Book Tuber

TUBERCULOSIS
Selected Internet Resources

Compiled and Edited by:
Noel Gonzlez Gotera (ngg@finlay.edu.cu) Armando Acosta Domnguez
(aracosta@finlay.edu.cu)
Mara Elena Sarmiento Garca-San Miguel

(mesarmientos@finlay.edu.cu)
Vicepresidency of Research Finlay Institute, La Habana, Cuba
Havana City, December, 2005
La
presente obra es una compilacin y seleccin, abarcadora pero no exhaustiva, de sitios web sobre tuberculosis, ordenados alfabticamente y provistos de sus vnculos (links) a los respectivos sitios en Internet. Esperamos que la misma resulte til a los interesados en informaciones relacionadas con esta temtica.
Sobre la presente edicin: Finlay Ediciones, 2005
ISBN: 959-7076-12-8
Finlay Ediciones Ave. 212 No. 3112 e/ 31 y 37, La Coronela, La Lisa,
Ciudad de La Habana, Cuba
THE UN SECRETARY-GENERAL KOFI A. ANNAN

Message on World TB Day, 24 March 2005.
Five thousand people die from tuberculosis every day, although the disease is both preventable and curable. Clearly, we must work harder if we are to achieve, by 2015, the Millennium Development Goal of halting and beginning to reverse the spread of TB as one of the worlds major diseases. Thanks to a massive scale-up of the DOTS strategy for TB control recommended by the World Health Organization, with 17 million persons treated in nine years, our prospects for reaching the goal have improved greatly. WHO reports that eight in 10 patients are successfully treated under DOTS programmes, and that 45 per cent of infectious patients were treated in 2003 -- up from 28 per cent in 2000. But huge obstacles remain, particularly in Africa -- in the form of weak health systems, a depleted health workforce, and an HIV/AIDS epidemic that is driving TB. As Nelson Mandela said, We cannot win the battle against AIDS if we do not also ght TB. TB is too often a death sentence for people with AIDS. I urge African leaders to make the ght against both diseases a priority. The Stop TB Partnership, with its 350 partner governments and organizations, is making a difference by forging consensus on strategies, coordinated responses, mechanisms for quality drug supply, and action for new diagnostics, drugs and vaccines. Governments, bilateral agencies, the Global Fund to Fight AIDS, TB and Malaria, and the World Bank are providing more resources. Still, to achieve worldwide impact, more is needed. And we must provide greater support for the increasingly wide range of caregivers who help nd people ill with TB and assist them with treatment. These providers include not just public health doctors and nurses, but also community leaders, former patients, womens groups, and many others. Such broad mobilization is our strongest weapon in the ght against the disease. On this world TB Day, let us rededicate ourselves to that mission.
Ko A. Annan
INTRODUCTION
According to a relatively recent study conducted by TeleGeography, global Internet trafc was set to increased by 67% during 2003 (Primetrica Inc., August 2003) and had been identied over 43 millions current registered domains (Cyveillance, May 2, 2003). Internet activity is alive and thriving outside of the World Wide Webs 6 billion pages or more, to include over 65 000 news groups (Cyveillance, May 12, 2003). The analysis of domain found a total of 19, 4 million live and 4, 3 million parked. Approximately 2, 5 million of the live domains contain more than 50 pages of content (Cyveillance, Breakdown of Registered Domains, March 2003). According to statistics valids to July 10, 2000, the number of unique pages on Internet was 2,1 billions and the amount of unique pages added per day reached the amazing gure of 7,3 million (Cyveillance, Sizing the Internet, July, 2000). Besides vast expanses of the Web are completely invisible (deep web and invisible web) to general-purpose search engines such as Altavista, HotBot, Yahoo, and Google. Even worse, this Invisible Web s in all likelihood growing signicantly faster than the visible Web that youre familiar with. Its not that the search engines and Web directories are stupid oven badly engineered. Rather, they simply cant see millions of high-quality resources that are available exclusively on the Invisible Web (The Invisible Web, Chris Sherman and Gary Price, ISBN 091096551X, 2001). An study reveals that the Internet searchers interested on the health topics nd what they want in a 48% (mostly) and 28% (always), according to Pew Internet Project, September 2002 Survey. Health searches and e-mail have become more commonplace, but there is room for improvement in searches and overall Internet access. Half of American adults have searched online for health information. Fully 80% of adult Internet users, or about 93 millions Americans, have searched for at least one of 16 major health topics on line (63% for specic diseases or medical problems). This makes the act of looking for health or medical information one of the most popular activities online,
2
after e-mail (93%) and researching a product or service before buying (83%). (Internet Health and Resources, Pew Internet & American Life Project, Susannah Fox and Deborah Fallows, 16 July, 2003). There are so many ways to access health information on the web and such a broad selection of content that the search process can seem overwhelming. However, searching for health information is easy if you know where to start. The following selected tuberculosis Web sites and links list (comprehensive but not exhaustive) offer some suggestions. We hope that you may nd it useful when looking specically for tuberculosis information on Internet.
THE AUTHORS La Habana, Cuba, May 2005.
TUBERCULOSIS SELECTED WEB SITES AND LINKS

(in alphabetical order)
1. ABC de la Tuberculosis - UITB - Unidad de investigacin en ... Informacion sobre tuberculosis, tratamientos, prevencion, vacunas, lineas y proyectos de investigacion, documentos, casos clinicos, novedades, congresos, ... www.imsb.bcn.es/uitb/ 2. About Tuberculosis Public information on the biology of tuberculosis from the Canadian Lung Association http://www.lung.ca/tb 3. Action TB 4. Aeras Global TB Vaccine Foundation http://www.aeras.org/ 5. Airborne Disease Weekly 6. A laymans guide to tuberculosis, atypical tuberculosis and ... Offers A to Z of Tuberculosis and includes general, mental health and medication side effects issues. Includes support and message board chat room. www.tbandu.co.uk/ 7. Amedeo.com, The Medical Literature Guide http://amedeo.com/index.htm 8. American Lung Association The American Lung Association (ALA) was founded in 1904 to combat tuberculosis. Today this organization ghts all forms of lung with special emphasis on asthma, tobacco control and environmental health. The ALA has worked to increase federal funding for tuberculosis research and control http://www.lungusa.org/diseases/lungtb.html 9. American Lung Association Tuberculosis Information (on PBS) 10. American Thoracic Society The American Thoracic Society [ATS] is an independently incorporated, international, educational and scientic society which focuses on respiratory and critical care medicine. ATS was once called the American Sanatorium Association. It maintains a focus on medical aspects of tuberculosis, whereas the parent organization, American Lung Association, concentrates on public health issues. Information links on tuberculosis at this site can identied after using the search button http://www.thoracic.org/ 11. Ask NOAH About: Tuberculosis Preguntale a NOAH Sobre la Tuberculosis Information in English and in Spanish presented by the New York Online Access to Health (NOAH) project.
12. Atlanta Tuberculosis Prevention Coalition Our Mission Collaborating Agencies Projects Screening Education Computerized TB registry Personnel Publications Training Funding Other TB related Sites TB & Medicaid General TB information Georgia TB reference guide... 13. ATS Journals Online... Ofcial Journals of the American Thoracic Society, Stanford University Libraries HighWire Press assists in the publication of ATS Journals Online ... www.atsjournals.org/ 14. Bill & Melinda Gates Foundation Grant-making foundation supports initiatives in education, world health and population, and community giving in the Pacic Northwest www.gatesfoundation.org/ 15. Books on Tuberculosis at Amazon.co.uk Find Genetics and tuberculosis (Novartis Foundation Symposium) and more at Amazon.co.uk. Read reviews, buy new and used titles... http://www.amazon.co.uk... 16. Brown University TB-HIV Research Laboratory www.brown.edu/Research/TB-HIV_
Lab/
17. BUBL LINK: Tuberculosis BUBL LINK Catalogue of Internet Resources. Tuberculosis. Titles. Descriptions. American Lung Association: Diseases A to Z ... cancer, tuberculosis, emphysema ... Internet resources relevant to the respiratory system. Author: OMNI, Nottingham University. Subjects: asthma, lung cancer, lungs, pneumonia, tuberculosis ... bubl.ac.uk/link/t/ tuberculosis.htm 18. California Tuberculosis Controllers Association 19. Canadas Role in Fighthing Tuberculosis - About Tuberculosis Public information on the biology of tuberculosis from the Canadian Lung Association. What is tuberculosis and how is it spread? This resource explains the biology of tuberculosis and the way in which we deal with it http://www.lung.ca/tb/abouttb/ 20. Case Western Reserve University Tuberculosis Research Unit and HIVNET Projects 21. CBC News - Tuberculosis: Anatomy of A Killer Includes facts, videos, reports, and links on Tuberculosis. Ever heard of White Plague? What about Potts disease? Lupus Vulgaris? Kings evil? No? Okay then, surely youve heard of Consumption. All of these diseases are actually the same disease, better known today as Tuberculosis or TB for short http://cbc. ca/news/indepth/background/tb.html... CBC News - Includes facts, videos, reports, and links on Tuberculosis 22. CDC Division of Tuberculosis Elimination News, reports, guidelines, and educational materials for health professionals http://www.cdc.gov/nchstp/tb 23. CDC National Prevention Information Network (NPIN) TB Resources 24. Center for Pulmonary and Infectious Disease Control University of Texas Health Center at Tyler 25. Charles P. Felton National Tuberculosis The goal is to meet the challenge of TB in Harlem by providing innovative prevention, treatment, and training programs to members community and healthcare providers serving the community http://www.harlemtbcenter.org
26. Clinicians Handbook of Preventive Services (TB Section) 27. Community Awareness Program for Tuberculosis Education from the Wetmore TB Foundation 28. Community Health and Anti -Tuberculosis Charity organisation supporting prevention, treatment and research into respiratory disease both internationally and in Australia http://www.chata.org.au 29. Core Curriculum on Tuberculosis: What the Clinician Should Know This is the 4th edition (2000) of this textbook from the U.S. Centers for Disease Controls Division of Tuberculosis Elimination. A note on the site states that The Internet (HTML) version of the Core Curriculum on Tuberculosis is updated periodically. Therefore, the Internet version may differ from the print version. 30. Cure-TB (US-Mexico Referral Program) (Exit DHFS) 31. Danida Assisted Revised National Tuberculosis Control Programme Provides information about the organization, initiatives, publications, a resource directory as well as the details about the disease itself. Our goal is o bring down the incidence of TB in India to levels where it will no longer be a public health problem http://www.dantb.org/ 32. DANTB - Danida Assisted Revised National Tuberculosis Control ... Information about the organization, initiatives, publications, a resource directory as well as the details about the disease itself. www.dantb.org/ 33. DEVELOPMENT OF VACCINES FOR BOVINE TUBERCULOSIS: REPORT OF THE ISG ... File Format: PDF/Adobe Acrobat ... a large number of local sites to have a signicant impact on TB in ... opportunities to identify tuberculosis vaccines that are more effective than ... www.defra. gov.uk/animalh/tb/pdf/vsssc.pdf 34. Division of Tuberculosis Elimination - Institute of Medicine (IOM ... regimens would have the greatest impact on the TB problem in the near term. ... for Tuberculosis Vaccine Development.39 The strategy should specify ... www.cdc.gov/nchstp/tb/pubs/iom/iomresponse/ goal3.htm 35. DNAvaccine.com... dnavaccine.com/ 36. Draft Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Settings, 2005 available for public comment. 37. Duke Funding Alert: October 10, 2003 ... e-mail address or telephone number); and 3) one common Web site for all Federal ... applications for Tuberculosis Vaccine Testing Research Materials. ... www.ors.duke.edu/nd/announce/alert/archive/03/03oct10.htmlhttp:// fedbizopps.cos.com/cgi-bin/getRec?id=20031006a8... ttp://fedbizopps.cos.com/cgi-bin/ getRec?id=20031006a8 38. EQUI-TB Knowledge Programme Details the international research program into pro-poor strategies in tackling Tuberculosis http://www.equi-tb.org.uk 39. eMedicine Health - Tuberculosis Consumer health resource center providing information on the causes, symptoms, and treatment of TB. http://www.emedicinehealth.com/articles/17621-1.asp
40. Emerging Infectious Diseases... ftp.cdc.gov/pub/EID/ 41. Escuela Centro de Tuberculosis de New Jersey Nacional Mdico 42. Eugene Bell Foundation Since 1997, Eugene Bell has concentrated on delivering tuberculosis assistance in the form of medication, equipment, and supplies to all of North Koreas thirteen TB hospitals and sixty-three TB care centers http://www.eugenebell.co.kr/ english/index.htm 43. EuroTB http://www.eurotb.org/ 44. External Tuberculosis Resources External Tuberculosis Resources. This is a list of other web sites that have information about tuberculosis. The resources have been categorized by the ... http://www.cpmc.columbia.edu/resources/tbcpp/extre... 45. FAQ about BCG Frequently asked questions about the BCG immunisation - a review article. www.priory.com/cmol/bcg.htm 46. FindArticles search?tb=art&qt...
search
for
BCG
vaccine
http://www.ndarticles.com/p/
47. Florida Department of Health (select Tuberculosis in the Subject Choices box) 48. Francis J. Curry National Tuberculosis Center 49. FREE Internet Encyclopedia - MacroReference MacroReference. Free Internet Encyclopedia. Copyright 2004 by Clifton Davis. Reproduction in whole or part of this arrangement of links only with permission. ... American Lung Association: TB FAQ. Peoples Plague: Tuberculosis in America (PBS special)(c ... www.cam-info.net/enc/macro.t.html 50. GFATM (PAHO/AMRO) resource page for Latin America and the Caribbean 51. Glaxo Wellcome and Healthcare - Global http://www.glaxowellcome.co.uk/health/odyssey/tuberc/tuberc3.html 52. Global Alliance for TB Drug Development Seeks to develop and ensure equitable access to new tuberculosis drugs. Features organization information, disease information, new drug development, and news http://www.tballiance.org 53. Global Fund to ght AIDS, tuberculosis and malaria (GFATM) 54. Hardin MD : Tuberculosis From the University of Iowa, the *best* lists of Internet sources in tuberculosis. www.lib.uiowa.edu/hardin\md/tuberculosis.html 55. Health and Development Initiative 56. healthnder - your free guide to reliable health information AIDS alt med cancer diabetes food safety Medicare tobacco more . . . the latest government health news health media online special events calendars prevention and self-care choosing quality care online health information fraud and... 57. Health Communication Partnership Tuberculosis Related Internet Sites. CDC Division of Tuberculosis Elimination Education and Training Resources Web Site. Tuberculosis ...
International Union Against Tuberculosis and Lung Disease ... www.hcpartnership.org/Topics/tuberculosis.php

58. How to obtain Surveillance of Drug Resistance in Tuberculosis Software from the Internet How to obtain Surveillance of Drug Resistance in. Tuberculosis (SDRTB3) Software from the Internet. Download and install the software. Before downloading the software, please read all three steps in the instructions. www.who.int/emc/SDRTB_software/instructions.html 59. Huff & Puff Victoria - Lung Disease Links Australian respiratory support group with international links to lung disease, medical sites, hospitals and respiratory support groups. http://www.vicnet.net.au/~huffpuff 60. Imperial College School of Medicine at St.Marys Medical Microbiology 61. Infectious Disease Society of America IDSA is a medical society representing more than 5,500 physicians and scientists devoted to patient care, education, research, and community health planning in the area of infectious diseases. IDSA members care for many of the patients with tuberculosis (TB) in the United States. This site summarizes ISDA activities related to tuberculosis http://www.idsociety.org/mo/adv/actions%5Ftuberculosis.htm 62. Initiative for Vaccine Research File Format: PDF/Adobe Acrobat ... Advisory Committee on new tuberculosis vaccines (TBVAC) ... information and knowledge management for vaccine R&D: websites, ... www.who.int/vaccines-documents/DocsPDF05/16317.pdf 63. Institute for Tuberculosis Research - Dedicated to the discovery and development of new effective, low-cost, therapeutics for the treatment of tuberculosis. Includes description of research projects, facilities, and methods, and welcomes donations to sponsor drug discovery. 64. International Union Against TB and Lung Disease 65. IUATLD Secretariats Tuberculosis Division 66. Japan Anti-TB Association Services include information about the disease itself, referrals to doctors and hospitals, plus its treatment and medical expenses. 67. Johns Hopkins Center For Tuberculosis Research Features research, epidemiology, treatment, drug information, forum, news, articles, and resources http://www.hopkinstb.org/news/ 68. Journal of Occupational and Environmental Medicine - Fulltext ... ... Journal of Occupational & Environmental Medicine... www.joem.org/pt/re/joem 69. Journal of Thoracic Imaging - Fulltext: Volume 18(1) January 2003 ... Www.thoracicimaging.com/pt/re/ jti/ 70. KNCV (The Royal Netherlands TB Association) KNCV Tuberculosefonds Informatie over tuberculose. Wat het is, wat de symptomen zijn, hoe tuberculose wordt behandeld en begeleid, of het te genezen is, of het besmettelijk is. www.tuberculose.nl/ 71. Korean National Tuberculosis Association (KNTA) Works with the government in treatment, health worker training and public education on TB, and conducts various technical and educational projects. www.knta.or.kr/
72. LARG Health Tuberculosis Patient Resources 73. Liga Argentina Contra la Tuberculosis y Enfermedades Regionales Institucin privada de bien pblico, sin nes de lucro, fundada en 1935. Cuenta con informacin institucional y una amplia documentacin sobre la problemtica ... www.laclatyer.org.ar/ 74. Links Links to Tuberculosis Sites. Line. Click here to link to the Division of Tuberculosis Elimination Web Site, TB-Related Links . ... http://www.phppo.cdc.gov/PHTN/tbmodules/ links.htm 75. Links to other TB Websites http://www.health.state.hi.us/doh-work/doh/resourc... 76. Links Mycos Research provides PPDs and links to other Mycobacterium Tuberculosis sites http://www.mycosresearch.com/links.htm 77. Links to other TB Websites Links to Other Tuberculosis Sites... http://www.health. state.hi.us/doh-work/doh/resourc... 78. Links to material available in languages other than English TB 79. Links ... Tuberculosis Sites. Action TB; Ask NOAH About: Tuberculosis from the New York Online Access to Health (NOAH); Atlanta TB Prevention Coalition ... http://www.umdnj. edu/~ntbcweb/links.htm 80. Los Angeles County TB Control Program 81. L.R.S. Institute of Tuberculosis & Respiratory Diseasesases About the institute, its objectives, functions, and activities http://lrsitbrd.nic.in/ 82. LSUMC Wetmore Foundation Tuberculosis Education 82. MedHist: The gateway to Internet resources for the History of Medicine ... The gateway to Internet resources for the History of Medicine. Top>Diseases>Tuberculosis. Tuberculosis ... Association for the Study and Prevention of Tuberculosis. It was set up to ... 128.243.217.106/ browse/mesh/detail/D014376.html 82. MedlinePlus: Tuberculosis Directory of factsheets, news, andarticles http://www.nlm.nih.gov/medlineplus/tuberculosis.html 83. Millennium indicators database 84. Minority Lung Disease Data - Tuberculosis (TB) A fact sheet from the American Lung Associations Lung Disease in Minorities 1999 booklet. The site covers recent U.S. historical trends. However, the most recent statistics listed are from 1996. A source of U.S. T.B. statistics from 1999 is the Division of Tuberculosis Eliminations 1999 Surveillance Report. 85. Molecular Characterization of Mycobacterium Tuberculosis, NYU 86. Multidrug-resistant Tuberculosis Annotated Bibliography Multidrug-resistant Tuberculosis (MDR-TB) - Annotated bibliography J. Woodruff 3/94 (Brief description of what kind of document this is, and what`s in it, what it`s for) Outline Reviews Epidemiology and High Risk Groups Diagnosis Treatment...
87. Multidrug-Resistant Tuberculosis Fact Sheet From the American Lung Association 88. Mycobacterial Genome Workshop, Division of Microbiology and ... ... tuberculosis research at or near the present level for about another ve years.... The development of an improved tuberculosis vaccine is of extreme ... www.niaid.nih.gov/dmid/tuberculosis/execsum. htm 89. MycDB, a Mycobacterium Database 90. Mycobacterium tuberculosis information Diseases Database Mycobacterium Tub erculosis,TB,Tuberculosis, Disease Database Information ... 3 synonyms or equivalents were found. Mycobacterium tuberculosis. aka/or ... Search using Internet medical databases; Search using Internet search engines (non-specialist); ... www.diseasesdatabase.com/ddb8515.htm 91. Mycobacterium tuberculosis : sites et documents francophones ... Dnition [MeSH Scope Note ; traduction CISMeF] : Espce de bactries, arobies, responsables de la tuberculose chez lhomme, les primates, ... http://www.chu-rouen.fr/ssf/organ/mycobacteriumtub... 92. MYCOS Research - A Colorado limited liability company providing custom mycobacterial research materials. Features products, services, company information, and research. 93. National Center for Infectious Diseases, Division of AIDS, STD, and TB Laboratory Research 94. National Institute of Allergy and Infectious Diseases Home Page (NIAID), National Institutes of Health NIAID Home | About NIAID | News & Information | Activities | Opportunities NIAID welcomes your comments and suggestions. Please click here to send us an email message, or write to us at: NIAID Ofce of Communications and Public Liaison Buildin... 95. National Institute for Occupational Safety and Health (NIOSH) 96. National Institutes of Health The National Institutes of Health [http://www.nih.gov/] contains a variety of sites related to tuberculosis research. Most programs lie within the National Institute of Allergy and Infectious Diseases [NIAID, http://www.niaid.nih.gov/]. The National Heart, Lung and Blood Institute [NHLBI, http://www.nhllbi.nih.gov/] also supports tuberculosis research. Within the NIAID, there are two divisions supporting tuberculosis research. These are the Division of Microbiology and Infectious Diseases 97. National Jewish Center for Immunology and Respiratory Medicine 98. National Jewish Medical and Research Center 99. National Library of Medicines Online Health Services 100. National Tuberculosis Center in Newark, New Jersey 101. National Tuberculosis Controllers Association - http://www.ntca-tb.org/
The home page of the National Tuberculosis Controllers Association (NTCA) and its associated organization, the National Tuberculosis Nurse Consultant Coalition (NTNCC). The NTCA and NTNCC were created in 1995 to bring together the leaders of the tuberculosis control programs of all 50 states as well as many county and city health departments which organize their own TB control activities
10
102. National Tuberculosis Nurse Consultant Coalition - http://www.ntca-tb.org/ The home page of the National Tuberculosis Controllers Association (NTCA) and its associated organization, the National Tuberculosis Nurse Consultant Coalition (NTNCC). See above. 103. Nature Medicine: Tuberculosis WebFocus Includes an historical overview, full-text research articles from Nature Medicine, reviews, news items, commentaries, and links to other sites 104. NIAIDs Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF) http://www.taacf.org/ 105. NIH Tuberculosis Research Materials and Vaccine Testing 106. NJMS National Tuberculosis Center - An institution performing research on the prevention and treatment of tuberculosis, particularly in inner-city environments in the United States... NJMS National TB Center - Links Page Tuberculosis Sites. Action TB. Atlanta TB Prevention Coalition. Brown Universitys TB/HIV Lab. CDCs Division of TB Elimination... http:// www.umdnj.edu/ntbcweb/links_frm.html and http://www.umdnj.edu/ntbcweb/tbsplash. html 107. North West TB Nurses Forum - The Northwest TB Nurses Association consists of nurses who specialise in the prevention and treatment of Tubercolis in the North West of England. 108. Occupational Exposure to Tuberculosis (NYCOSH) 109. Occupational Safety and Health Administration (OSHA) OSHA: Tuberculosis Links to regulation, compliance, and other issues about occupational exposure to tuberculosis from the U.S. Occupational Safety & Health Administration 110. OI: Turberculosis -- GIS A comprehensive resource on tuberculosis and HIV infection, from AEGIS. www.aegis.com/topics/oi/oi-tb.html 111. Pan American Health Organization (PAHO) Tuberculosis http://www.paho.org/ English/HCP/HCT/TUB/tuberculosis.htm 112. Pathology of Tuberculosis a mini-tutorial from Florida State University College of
Medicine
113. Philippine Tuberculosis Society Inc.... Dedicated to the prevention, treatment and control of TB in the country. Includes information about the disease and the organization http://www.ptsi.org.ph 114. PHRI Russian TB Control Program 115. Preguntale a NOAH Sobre la Tuberculosis Information in English and in Spanish presented by the New York Online Access to Health (NOAH) project. 116. Princeton Project 55 Princeton Project 55 Tuberculosis Initiative a wealth of documentation about TB 117. Public Health Laboratory Service (PHLS), UK - Tuberculosis 118. Public Health Research Institute Tuberculosis Center The Public Health Research Institute (PHRI) Tuberculosis Center was created to address the re-emergence of tuberculosis
11
and the spread of multidrug resistant (MDRTB) strains in New York City. Today it focuses on understanding and treating tuberculosis with activities in basic research, molecular epidemiology, and treatment of tuberculosis http://www.phri.org/tb.htm
119. Pulmonology Comprehensive database of pulmonological disorders www.fpnotebook.com/LUN.htm 120. PulmonologyChannel In 1993, WHO (the World Health Organization) declared tuberculosis a global emergency. Tuberculosis (TB) is responsible for the deaths of more youths and adults than any other infectious disease http://www.pulmonologychannel.com/tuberculosis... 121. Quantitative Analysis of TB, Los Alamos National Laboratory... 122. Questions and Answers About TB http://www.cdc.gov/nchstp/tb/faqs/qa.htm 123. Rapid Blood Tests: Infectious Diseases, Tuberculosis, HIV, AIDS, STD Prsentation dune ligne de tests rapides RAPID 1-2-3 HEMA, sur le sang total proposs par HDS. VIH, hpatites, dengue, maladie de Chagas, paludisme, ... www.rapid123.com/ 124. Registre de Tuberculosi Guia per al compliment del full de declaraci de cas de tuberculosi. Programa de prevenci i control de la tuberculosi a Andorra. www.col-legidemetges.ad/docs/fulltb.html 125. Research Institute of Tuberculosis Conducts research and treatment of TB. Located in Kiyose City, Tokyo http://www.jata.or.jp/eindex.htm 126. Research on Tuberculosis, New York State Department of Health 127. Resources for PPD antigens 128. Singapore Anti-Tuberculosis Association 129. Smart Computing Directory Of Web Sites: Diseases ... You will also nd links to tuberculosis sites, the latest information on conferences, a preventive therapy database, and numerous reports. ... http://www.smartcomputing.com/input/websites/viewl... 130. Stanford Center for Tuberculosis Research 131. Stanford Center for Tuberculosis Research Guestbook ... Websites with good pictures related with TB will help very much. ... Near infrared spectroscopy for the analysis of tuberculosis antimicrobials. ... www.stanford.edu/group/molepi/guestbook.html 132. Stop TB Canada Initiative 133. Stop TB Initiative The Stop TB Initiative is a partnership for global action. The mission of Stop TB is to ensure that every person with TB has all the necessary information and access to treatment and cure; to protect vulnerable populations from TB and http://www. stoptb.org 134. Texas Center for Infectious Diseases (TCID) 135. Texas Department of Health - Tuberculosis Elimination Division
12
136. Translated Education Materials TB educational material in many languages from the Minnesota Department of Health 137. TB Alert Details about this charity which supports health projects worldwide and promotes awareness of tuberculosis. Includes publications, a newsletter and links http:// www.tbalert.org 138. TB Alliance 139. TbandU A laymans guide to Tuberculosis, including all other health and medication issues. 140. TB Control India An information site providing vital information about the status of the RNTCP, Revised National Tuberculosis Programme being implemented in India. http:// www.tbcindia.org 141. TB Education Center Resources for Patient Care/Management - Texas Center for Infectious Disease 142. TB Education & Training Resources resources from the U.S. CDC 143. TB/HIV Research Laboratory, Brown University 144. TB/HIV WHO activity around tuberculosis and AIDS 145. TB News: Current News Article http://www.hopkins-id.edu/tb_news/tb_news_
17.html
146. TB Patient Incentive Program (American Lung Association of Wisconsin web site) 147. TB Policies: Classication of TB http://www.cpmc.columbia.edu/tbcpp/i-classt.html 148. TB Research at Case Western Reserve University 149. TB Resources on the Internet Text-Only Site. State Directory. Agencies A-Z. About Oregon.gov. Advanced. Help. Tuberculosis Control. About Us. Contact Us. Tuberculosis Control. Fact Sheets. Guidelines egov.oregon.gov/DHS/ph/tb/links.shtml 150. TB Weekly, a tuberculosis news weekly 151. TBXrays.com - A graphics only site of x-rays and images of patients with tuberculosis and other lung disease. 152. The Associate of North West TB Nurses The Northwest TB Nurses Association consists of nurses who specialize in the prevention and treatment of Tuberculosis in the North West of England http://www.tbinfoline.co.uk/ 153. The Hong Kong Tuberculosis, Chest and Heart Diseases Association Provides an introduction to the associations services and patient-oriented information on tuberculosis, heart diseases and hypertension http://www.ha.org.hk/org/antitb/ 154. The Indian Journal of Chest Diseases and Allied Sciences ... www.indegene.com/ijcd/ 155. The Indian Journal of Tuberculosis mohfw.nic.in/lrs/IJTB/
13
156. The International Journal of Tuberculosis and Lung Disease a ... ... The International Journal of Tuberculosis and Lung Diseases... www.ingentaconnect.com/content/ iuatld/ijtld/ 157. The International Union Against Tuberculosis and Lung Disease The International Union Against Tuberculosis and Lung Disease [IUATLD] is a non-prot, non-governmental organization with members throughout the world. It is dedicated to the prevention and control of tuberculosis and lung disease http://www.iuatld.org/ 158. The Lupin Group Tuberculosis Lupin is a national leader in anti-TB drugs. This site features anti-T.B. drugs produced by the company, frequently asked question, news, directory of tuberculosis links, and discussion group http://www.lupinworld.com/antitb.htm 159. The Meaning of a Positive Tuberculosis Test / AAFP Patient Inform... http://home.aafp. org/patientinfo/tbtest.html 160. The Peoples Plague: Tuberculosis in America, PBS Online 161. The Sequella Foundation The Sequella foundation promotes basic and clinical research to facilitate the development new tools for TB control by providing support to the research community and interested companies http://www.sequellafoundation.org/ 162. The TB Investigation Project A 2002 study investigating tuberculosis in Russia, the USA, and the UK. Analysis of both the human and the scientic stories behind the ght against TB. Includes TB links http://tbproject.tripod.com 163. The Tuberculosis Coalition for Technical Assistance (TBCTA) 164. The Vaccine Fund - Press Releases ... malaria and tuberculosis vaccines that are so desperately needed.... www.vaccinefund.org/ 165. Tinplate Hospital (BCG Vaccine) BCG Vaccine, Prevention of Tuberculosis, Vaccine, BCG background, General guideline of BCG, Benets of BCG http://www.tinplatehospital. com/bcg.asp 166. Treatment of Tuberculosis - revised recommendations (American Thoracic Society web site) (PDF, 515 KB) 167. TubercuList Database on Mycobacterium tuberculosis genetics. Provides a complete dataset of DNA and protein sequences linked to the relevant annotations and functional ... genolist.pasteur.fr/TubercuList/ 168. Tuberculosis Tuberculosis and Public Health for Health Care Professionals. Reviews on issues in tuberculosis, applied epidemiology, and courses. An afliation of the International Union Against Tuberculosis and Lung Disease http://www.tbrieder.org 169. Turberculosis A comprehensive resource on tuberculosis and HIV infection, from AEGIS. http://www.aegis.com/topics/oi/oi-tb.html 170. Tuberculosis & Airborne Disease Weekly - A weekly publication with searchable ar-
chives
14
171. Tuberculosis and HIV, HIVemir (HIV: An Electronic Media Information Review) 172. Tuberculosis and HIV, Project Inform Hotline 173. Tuberculosis and Related Infections Unit 174. Tuberculosis and Related Infectious Disease - Watson W. Wise ... ... Tuberculosis Sites (Univ. of Medicine and Dentistry, New Jersey); Tuberculosis & HIV (The Body: An AIDS and HIV Information Resource) ... http://library.uthct.edu/tb.htm 175. Tuberculosis Antimicrobial Acquisition & Coordinating Facility (TAACF) 176. Tuberculosis Association of Ohio County Provides programs and services to Ohio County, WV http://www.tboc.org/ 177. Tuberculosis Clinical Resources Health: Diseases and Conditions: Tuberculosis. Additional Tuberculosis Sites (These sites have not been reviewed.) ... http://capstoneclinic-dl.slis. ua.edu/clinical/pulm... 178. Tuberculosis Clinical Resources Additional Tuberculosis Sites (These sites have not been reviewed.) YAHOO - Health:Medicine:Respiratory Diseases ... http://ruralnurseorganization-dl.slis.ua.edu/clini... 179. Tuberculosis Control in Chicago A comprehensive information site for tuberculosis, a mycobacterial infectious disease, that is developed and maintained by local volunteers. www.tbchicago.org/ 180. Tuberculosis Control India This site provides information about tuberculosis and its control in India http://www.tbcindia.org/ 181. Tuberculosis Control Program (New York City Department of Health) 182. Tuberculosis Control Program Website internet URL http://www.med.upenn.edu/ TBPA/tbcp.html ... This web site has been created at the University of Pennsylvania Health System as part of a project entitled Tuberculosis Education in an Academic Health System, funded through the National Heart, Lung and Blood Institute at NIH. 183. Tuberculosis Facts Factsheet with cause, symptoms, risk factors, diagnosis, complications, treatment, and prevention. http://www.astdhpphe.org/infect/tb.html... 184. Tuberculosis Fact Sheet, Maryland Department of Health 185. Tuberculosis Facts Factsheet with cause, symptoms, risk factors, diagnosis, complications, treatment, and prevention. www.astdhpphe.org/infect/tb.html 186. Tuberculosis http://www.afscme.org/afscme/wrkplace/tbfs1.htm 187. Tuberculosis http://www.seanet.com/~tzhre/tuber.htm 188. Tuberculosis in Children - Keep Kids Healthy Tuberculosis information and answers to common questions about TB in children, including the difference between tuberculosis infection and disease, ... www.keepkidshealthy.com/welcome/ infectionsguide/tuberculosis.html
15
189. Tuberculosis - Index- Pulmonology In 1993, WHO (the World Health Organization) declared tuberculosis a global emergency. Tuberculosis (TB) is responsible for the deaths of more youths and adults ... www.pulmonologychannel.com/tuberculosis/ 190. Tuberculosis Information ... and Site Hosting - Web Hosting - Internet Store and Ecommerce Solution Provider - High Speed Internet. Popular Searches: Tuberculosis Information ... ccfdca.www1.50megs.com/TB.htm 191. Tuberculosis-Informacin Bsica www.netsalud.sa.cr/ms/estadist/enferme/tuberc.
htm
192. Tuberculosis Information Management System (TIMS) 193. Tuberculosis - Information / Diagnosis / Treatment / Prevention The Complete Guide to Health Care Resources on the Internet ... Search millions of published articles for news on Tuberculosis. The HighBeam_ Research newspaper and magazine archive ... healthcyclopedia.com/.../mycobacterial/tuberculosis.html 194. Tuberculosis.net - THE Source for Tuberculosis Teaching Materials Tuberculosis.net strives to provide information about tuberculosis to the public and health-care community http://tuberculosis.net/ 195. Tuberculosis.Net Forum Resources for tuberculosis education, including a TB forum, images, FAQs http://tuberculosis.net 196. Tuberculosis, New York Online Access to Health (NOAH) 197. Tuberculosis News - Topix.net - Latest news stories on the disease. 198. Tuberculosis, North Eastern Health Care Network, Melbourne Australia 199. Tuberculosis - Patient Oriented Resource http://johns.largnet.uwo.ca/largh/patients/
tb.html
200. Tuberculosis Primary Care Teaching Module, UCSF & Stanford 201. Tuberculosis pulmonar Informacin general, datos, manifestaciones, sntomatologa, tratamiento y enlaces http://www.geocities.com/hmiguelito/indicede.htm 202. Tuberculosis Research Centre studying effective treatment in India 203. Tuberculosis Research Unit, Case Western Reserve University 204. Tuberculosis Resources Columbia University`s website with information about tuberculosis, TB testing and treatment. Spanish and English http://www.cpmc.columbia.edu/ resources/tbcpp 205. Tuberculosis Resources - Information about tuberculosis Up-to-date information about tuberculosis written by the Bureau of Tuberculosis Control of the New York City Department of Health is now available via New York Online Access to Health (NOAH). Information includes what you need to know about tuberculosis, the tuberculin skin test, treatment to prevent tuberculosis and TB: getting cured http://www.cpmc.columbia.edu/resources/tbcpp/
16
206. Tuberculosis Resources on the Internet Source:HealthNet. Title. URL. Publisher(s) Comments. PubMed. http://www.ncbi.nlm.nih.gov/ entrez/ query.fcgi. National Center for Biotechnology Information at the National Library of Medicine ,NIH ... and presented by Johns Hopkins Cener for Tuberculosis Research ... part 2 of Table II. Global Tuberculosis Control Report ... www.psgaidsinfo.org/tuberculosis_resurces_on_the_internet.htm 207. Tuberculosis Screening Services (TSS) Information on services including TB skin testing, pre-employment screenings, and Hepatitis B vaccinations with evening appointments and group rates. All services satisfy Louisiana State Health Department requirements http:// www.tbtest.com/ 208. Tuberculosis (TB) 209. Tuberculosis Tuberculosis and Public Health for Health Care Professionals. Reviews on issues in tuberculosis, applied epidemiology, and courses. An afliation of the International Union Against Tuberculosis and Lung Disease http://www.tbrieder.org 210. Tuberculosis, The Luxembourg Health Server SANTEL 211. Tuberculosis - Topix.net - News on tuberculosis. [RSS] 212. Tuberculosis - Tuberculosis and Public Health for Health Care Professionals. Reviews on issues in tuberculosis, applied epidemiology, and courses. An afliation of the International Union Against Tuberculosis and Lung Disease. 213. Tuberculosis, Yahoo Web Database 214. Tuberculosis Vaccines: State of the Science, Tuberculosis Research...
http://www.niaid.nih.gov/dmid/tuberculosis/tbvacci...
215. Tuberculosis Vaccine Action Plan, Blueprint for Tuberculosis Vaccine Development, National Institute of Allergy ... http://www.niaid.nih.gov/publications/blueprint/pa... 216. Tuberculosis Web Sites http://www.lib.siu.edu/websites/health/tb.html 217. Tuberculosis Web Sites ... Consumer Health Sites. Enfermedades - Tuberculosis. This Spanish language page from the Centers for Disease Control contains links to pamphlets including Tuberculosis - !Enterese! ... Core Curriculum on Tuberculosis is updated periodically. Therefore, the Internet version may differ ... www.lib.siu.edu/hp/divisions/sci/health/tb.html 218. Tuberculosis - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Tuber-
culosis
219. Tuberculosis workplace standards related to TB from the U.S. Occupational Safety and Health 220. www.tuberculosis.ru/ 221. Understand and Fight Tuberculosis - Information for health care professionals From the Tuberculosis Division of the International Union Against Tuberculosis and Lung Disease (IUATLD) http://www.tbrieder.org/
17
222. Unidad de investigacin en Tuberculosis de Barcelona... Informacion sobre tuberculosis, tratamientos, prevencion, vacunas, lineas y proyectos de investigacion, documentos, casos clinicos, novedades, congresos, eventos y cursos http://www.imsb.bcn.es/uitb/ 223. Unit de Gntique Molculaire Bactrienne ... projects is also available via the web sites at Integrated Genomics, live tuberculosis vaccines Mycobacterium bovisBCG and Mycobacterium microti. ... www.pasteur.fr/recherche/unites/Lgmb/mycogenomics.html 224. USDA Funded Projects ... Develop candidate tuberculosis vaccines for cattle and deer; 3. ... www.nal.usda.gov/awic/pubs/TB/USDAFunded.htm 225. Vaccines, Division of Microbiology and Infectious Diseases http://worldaidsday.nih. gov/dmid/vaccines... 226. Veiled Face of Tuberculosis - Find the authors attitude towards diagnostics of renal tuberculosis, the way the investigations were performed, studied samples, and a note on the author. Site is in English and Croatian 227. Wadsworth Center (New York State Department of Health) 228. Welcome on the TB Vaccine Cluster Site Click on to enter. Updated : Tue, Jun 13, 2000. Site realised by Marie Guibert. http://www.pasteur.fr/recherche/EC_TBvaccine/ 229. WHO Tuberculosis - Prevention and Control Web Site This World Health Organization site includes several publications and fact sheets with an international focus, including the 2002 Global Tuberculosis Control Report, Treatment of Tuberculosis: Guidelines for National Programmes (available in English, French, and Spanish), TB/HIV: A Clinical Manual, Tuberculosis in Prisons (available in English and Russian), and information about drug-resistant TB. 230. World Bank - tuberculosis 231. World Health Organization Tuberculosis http://www.who.int/tb/en/ 232. World Health Organization Global Tuberculosis Programme 233. World TB Day, March 24, 2005 information from the U.S. CDC
18
List of Noted Tuberculosis Victims

From Wikipedia, the free encyclopedia. (Redirected from List of famous tuberculosis victims). This is a list of famous people and celebrities who had, or are believed to have had, tuberculosis.
Writers and poets: Jane Austen, Honor de Balzac, Anne Bront, Charlotte Bront, Emily Bront, Charles Farrar Browne, Elizabeth Barrett Browning, Robert Burns, Lord Byron, Albert Camus?, Anton Chekov, Tristan Corbire, Stephen Crane. Ren Daumal, Jean de Brunhoff, Guy de Maupassant, Fyodor Dostoevski, Paul Laurence Dunbar, Ralph Waldo Emerson, Dashiell Hammett, Saima Harmaja, Robert Heinlein?, Miguel Hernndez, Washington Irving, Helen Hunt Jackson, Alfred Jarry, Samuel Johnson, Franz Kafka, John Keats, Charles Kingsley, Sidney Lanier, D. H. Lawrence, Betty MacDonald?, Katherine Manseld, Somerset Maugham, Molire, Eugene ONeill, George Orwell, Walker Percy, Edgar Allan Poe, Alexander Pope, Llewelyn Powys, Winthrop Mackworth Praed, John Reed, Edmond Rostand Jean-Jacques Rousseau John Ruskin, Albert Samain, Friedrich Schiller, Sir Walter Scott, Percy Bysshe Shelley ?, Tobias Smollett, Laurence Sterne, Robert Louis Stevenson, Alan Sillitoe, Dylan Thomas, Francis Thompson, Henry David Thoreau, Leo Tolstoy?, Voltaire, Thomas Wolfe, Ji Wolker. Artists: Frdric Bartholdi, Marie Bashkirtseff, Aubrey Beardsley, Harry Clarke, Paul Gauguin, Amedeo Modigliani, Elizabeth Siddal ?, Pamela Anderson. Composers: Frdric Chopin, Stephen Foster, Wolfgang Amadeus Mozart, Niccolo Paganini, Giovanni Battista Pergolesi, Henry Purcell, Johann Schein, Cat Stevens?. Religious gures: John Calvin, Cardinal Richelieu, St Thrse de Lisieux, St Bernadette Soubirous. Leaders: Simn Bolvar, Edward VI of England, Ulysses S. Grant, Andrew Jackson, Muhammed Ali Jinnah, Sir Wilfrid Laurier, Louis XIII of France, Louis XVII of France, Nelson Mandela, Napoleon II of France, Manuel L. Quezon, Eleanor Roosevelt, Dmitri Pavlovitch Romanov, Alexander Stephens, Tutankhamun, John Young.
19
Others: Niels Abel, mathematician Rene Adore, Beulah Annan, Frdric Bastiat, Alexander Graham Bell, Sarah Bernhardt, Louis Braille, James Burke, Anders Celsius, Cheng Man-ching, Tai Chi Chuan master, Charlie Christian, Arline Feynman, W. C. Fields, Augustin-Jean Fresnel, Brenda Fricker, Abel Gance, Jay Gould, Emmett Hardy, Richard Harris (actor)?, Doc Holliday, Immanuel Kant, Freddie Keppard, Ren Lannec French physician; inventor of the stethoscope, Vivien Leigh, Christy Mathewson, Dmitri Mendeleev?, James Bubber Miley jazz trumpeter, Barry Morse?, Anne Neville (queen consort of Richard III) (probably), Florence Nightingale, Mabel Normand, Etti Plesch?, Joseph Mary Plunkett, Virginia Eliza Clemm Poe (wife of Edgar Allan Poe), Herman Potonik, Gavrilo Princip, Jimmie Rodgers, Bernhard, Riemann, mathematician Erwin Schrdinger, Takasugi Shinsaku (1839-1867), samurai Okita Soji (1844-1869), Japanese swordsman and troop captain in the Shinsengumi, Baruch Spinoza, Adrianus Turnebus, Georges Vezina, Lev Vygotsky, Rube Waddell, William Winchester (son of Oliver Winchester, husband of Sarah Winchester), Link Wray, Eugene Wigner?.
Note: ? died of something unrelated to tuberculosis.
Fictional characters: Ukyo Tachibana from the Samurai Shodown video game series Sayo from the Rurouni Kenshin anime, Hyatt from the Excel Saga anime, Helen Burns from Jane Eyre by Charlotte Bront, Little Nell from The Old Curiosity Shop (Charles Dickens), Mimi from La Bohme (Giacomo Puccini et. al.), Violette from Verdis La Traviata, Buddy Willard from The Bell Jar by Sylvia Plath, Lin Dai-yu from The Story of Stone by Cao, Satine from Moulin Rouge.
Reference: Rothman, Sheila M. (1994). Living in the Shadow of Death: Tuberculosis and the Social Experience of Illness in American History. ISBN 0801851866 .
20
SOME CUBAN MASTER PAINTERS VICTIMS OF TB...

... AND HIS WORKS
Fidelio Ponce de Len: Was born in 1895, at Camagey city, Cuba, and dies on February 19th, 1949, Havana city. Initiated studies in San Alejandro Academy from 1913 through 1918, year in which disappeared until 1923. He moved to a suburb neighborhood where he teaches drawings to poor kids and works on commercial arts. Return to Havana in 1930, alcoholic and with tuberculosis symptoms. The Ponces style, thematics and formal treatment, combines to create very pasty and milkies oil canvass, with lengthly and poorly denited human gures, and characterized also by his monochromatism, abstractions, and melancholic feelings related with diseases, death and religion. Ponce, which had a great personality, was a student of Master Leopoldo Romaach and his work was inuenced by his academic procedures. He was obsessed with the white color, which he used to call pintura nacarada in order to project light color from it. He enjoyed Kandinskys famous words: ...white is a great silence full of possibilities. In 1934, participated in the XVII Saln de Bellas Artes with his work Paisaje. His rst exhibitions at the Lyceum, becomes a great success for him. His work Las Beatas is awarded with a prize from El Salon Nacional, as well as prizes from El Salon de Arte Moderno in Havana, in 1937, during this period belongs also his superb work Tuberculosis. At this time his career is in a roll; traveled to New York and open exhibitions in the Delphis Studio. Again, received rst prize for his work Los Nios from the Salon Nacional, and then disappeared until 1940. The Museum of Modern Art in New York obtain his work: Mujeres as part of its permanent collection. In 1944, Ponce participated in the Cuban Painters Exposition at the Museum of Modern Art in New York (San Ignacio de Loyola); in 1946 in the Cuban Modern Paint, Bellas Artes Palace at Mexico City; in 1947 in the Cuban Painters, Bellas Artes Museum, Buenos Aires; and in 1947 in Cuban Modern Painters, Washington Collections, Washington, D.C. The Havana Lyceum organized an exposition about all his work in April, 1949; and in 1995, the National Museum, Bellas Artes Palace, at Havana city, organized a comprehensive exhibition about his work, commemorating his centenary. 21
Tuberculosis
Carlos Enrquez (1900 - 1957)

El Rapto de las Mulatas / Brown girls abduction
Arstides Fernndez (1904-1934)

Autorretrato / Self-Portrait Lavanderas / Washing Women
22
WHO | Tuberculosis
All WHO This site only
Home About WHO Countries Health topics Publications Research tools WHO sites TB home Data and country profiles DOTS TB control strategy TB/HIV TB publications About us Events Links
Tuberculosis (TB)
WHO > WHO sites
Tuberculosis
This website describes the work of the Stop TB Department
A partnership housed by WHO Global Drug Facility
Tuberculosis (TB) is primarily an illness of the respiratory system, and is spread by coughing and sneezing. Each year about 2 million people die from this curable disease.
Public-Private Mix for DOTS: Towards scaling up The third meeting of the global Public Private Mix Subgroup for DOTS Expansion (PPM DOTS Subgroup) was held in WHO 's Western Pacific Regional Office in Manila, Philippines, on 4-6 April 2005. The proceedings of the meeting have just been published. Read more
TB DATA COLLECTION 2004 Annual TB notification reports were received from 199 countries. Data are now available. Global TB database
TB PUBLICATIONS WHO publications on tuberculosis Most recent
Damien Foundation Bangladesh
26 May 2005 Shaping the future of TB control Full text 22 March 2005 TB cases and deaths linked to HIV now at alarming levels in Africa Full text
:: TB features archive
WHO Report 2005: Global Tuberculosis Control Read online
:: TB epidemiology and surveillance - VIRTUAL WORKSHOP :: UN millenium indicators database :: Tuberculosis fact sheet
TB guidelines
http://www.who.int/tb/en/ (1 of 2) [23/08/05 16:42:20]
WHO | Tuberculosis
:: Other tuberculosis-related WHO web sites Treatment of tuberculosis: guidelines for national programmes
DOTS The internationally-recommended TB control strategy is DOTS. More information Community care for tuberculosis There is growing interest in the role of communities in TB control. More information Global DOTS Expansion Plan The global TB network agreed to develop a Global DOTS Expansion Plan (GDEP) at the first DOTS Expansion Working Group meeting in Cairo in November 2000. More information An Expanded DOTS Framework The expanded strategy reinforces the five essential elements of the DOTS strategy. More information Drug- and multidrug-resistant tuberculosis (MDR-TB) MDR-TB is a specific form of drugresistant TB due to a bacillus resistant to at least isoniazid and rifampicin, the two most powerful anti-TB drugs. More information
Practical Approach to Lung Health (PAL) The Practical Approach to Lung health (PAL) is a syndromic approach to the management of patients who attend primary health care services for respiratory symptoms. More information Public-Private Mix for DOTS Expansion In many countries, private health care providers are the gateway to health services for people with symptoms of TB. More information Tuberculosis in prisons TB is not an unavoidable consequence of incarceration and can be controlled through the application of DOTS based programmes and improvements in prison conditions. More information Tuberculosis and gender In most of the world, more men than women are diagnosed with TB and die from it. TB is nevertheless a leading infectious cause of death among women. More information
Tuberculosis Giving a human face to the TB epidemic. Advocacy report and film
HIV/AIDS, Tuberculosis and Malaria (HTM) Newsletter View most recent
:: Contact us
Employment | Other UN Sites | Search | Suggestions | RSS | Privacy World Health Organization 2005. All rights reserved
http://www.who.int/tb/en/ (2 of 2) [23/08/05 16:42:20]
Canada's Role in Fighting Tuberculosis, Yesterday, Today, and Tomorrow.
CANADA's ROLE in FIGHTING TUBERCULOSIS

About Tuberculosis What is tuberculosis and how is it
spread? This resource explains the biology of tuberculosis and the way in which we deal with it.
Tuberculosis History in Canada Tuberculosis

is one of the oldest diseases of humans. Find out how it use to be fought, through sanatoria and mass community surveys.
Tuberculosis in Canada Today A "cure" was found

Teaching Resources Site Credits Glossary
This digital collection was produced under contract to Canada's Digital Collections program, Industry Canada. The website was produced by a CDC team at the Saskatchewan Lung Association.
for tuberculosis in the 1940s, but it is not gone from Canada. Why does TB remain and what are Canadians doing about it?
http://www.lung.ca/tb/ [23/08/05 17:08:30]
Aeras Global TB Vaccine Foundation
q q
Two billion people - one third of the world's population - have been infected with TB. Someone is newly infected with TB every second. Nearly 2 million people die of TB every year.
Distinguished scientist M.M. Sharma of Mumbai, India, has been named to the Aeras Board of Directors. Read more... The G8 Summit's final communique commits the world's wealthiest nations to boost action to combat TB and other killer diseases in Africa. Read the G8 communique on Africa. Aeras applauds G8 commitments to PublicPrivate Partnerships and new tools to fight TB and Danida, the Danish development agency, other diseases. Read announced an agreement to support development of a vaccine trial site in South Africa. Aeras will more... partner with Medicon AS, a leading Danish Aeras and partners urge research company, and the South Africa TB leaders of the G8 nations Vaccine Initiative (SATVI) to develop the site. to support Public-Private Read more
Denmark Becomes First European Country to Support Aeras
Partnerships working on new drugs, diagnostics and vaccines for global diseases of poverty. Read more
http://www.aeras.org/ (1 of 2) [23/08/05 17:10:36]
Aeras Global TB Vaccine Foundation
Aeras and UCLA have executed a non-exclusive license agreement for a new TB vaccine technology that will allow Aeras to develop and market the vaccine in the developing world. The new vaccine, known as rBCG30, was developed by Dr. Marcus Horwitz at UCLAs David Geffen School of Medicine. Read more Aeras and Statens Serum Institut of Copenhagen, Denmark, have announced a new collaboration on the pre-clinical and clinical development of SSI's tuberculosis vaccine candidate, HyVac4, which will be developed as a booster vaccine to extend the protection of the currently available TB vaccine, BCG. Read more
2004 Aeras Global TB Vaccine Foundation, 7500 Old Georgetown Road, Suite 800, Bethesda, MD 20814, USA Phone: +1-301-547-2900 info@aeras.org privacy policy
http://www.aeras.org/ (2 of 2) [23/08/05 17:10:36]
AMEDEO, The Medical Literature Guide - Scientific Information in Medicine
Home
HIV Medicine
FAQ
Unsubscribe
Change Email
Policy
About
Flying Publisher
Free Medical Information: Doctor = Publisher

PDF, 98 pages, 1.1 MB
Subscription procedure 1) Select a topic 2) Define your favourite journals 3) Fill out the form ..and you'll receive
q the weekly AMEDEO literature newsletters with an overview of new articles published in your personal journal subset (example)
q a weekly update of your Personal AMEDEO Web page displaying the abstracts of your journal subset articles (example)
In addition, AMEDEO presents

q weekly overviews of the new publications (example HIV Infection) and
q the last 12 to 24 months of medical literature grouped by journals (example Critical and Intensive Care).
Search
1. Infectious Diseases A. Viral Diseases AIDS / HIV Hepatitis Hepatitis C Cytomegalovirus Infection Herpes simplex Infection Influenza B. Bacterial Infections and Mycoses Sepsis Sexually transmitted diseases Tuberculosis Urinary Tract Infection C. Parasitic Diseases Malaria D. Vaccines E. Drug Resistance F. Travel Medicine 2. Disorders of the Cardiovascular System Arrhythmias Heart Failure Heart Transplantation Hypertension Ischemic Heart Disease Pulmonary Hypertension Valvular Heart Disease Venous Thrombosis 3. Disorders of the Respiratory System Lung Cancer Obstructive Lung Diseases Asthma 4. Disorders of the Kidney Chronic Renal Failure Kidney Transplantation 5. Disorders of the Gastrointestinal System Biliary Tract Disease Cirrhosis Colorectal Cancer Gastric Cancer Inflammatory Bowel Diseases Irritable Bowel Syndrome Liver Diseases
8. Oncology Bladder Cancer Breast Cancer Cervical Cancer CNS Cancer Colorectal Cancer Gastric Cancer Head and Neck Cancer Lung Cancer Malignant Melanoma Ovarian Cancer Prostate Cancer 9. Endocrinology and Metabolism Diabetes Dyslipidemia Hyperlipoproteinemias Osteoporosis Diseases of the Thyroid 10. Neurologic Disorders Alzheimer's Disease Cerebrovascular Diseases CNS Cancer Epilepsy Migraine Multiple Sclerosis Parkinson's Disease Sleep disorders 11. Psychiatric Disorders Depression Schizophrenia 12. Women's Health Gynecology Contraception Pregnancy Disorders Breast Cancer Ovarian Cancer 13. Neonatology 14. Men's Health Andrology Erectile Dysfunction Prostate Cancer 15. Dermatology Dermatology Malignant Melanoma
http://amedeo.com/index.htm (1 of 2) [23/08/05 17:12:42]
AMEDEO, The Medical Literature Guide - Scientific Information in Medicine
Liver Transplantation Pancreatitis Peptic Ulcer 6. Immunology Autoimmune Disorders Hypersensitivity Reaction Rheumatoid Arthritis 7. Hematology Anemia Bone Marrow Transplantation Leukemia Malignant Lymphoma Stem Cell Research
16. Ophthalmology 17. Otorhinolaryngology 18. Surgery Fractures Neurosurgery Thoracic Surgery Vascular Surgery 19. Dentistry Dental Implants Periodontology 20. Emergency Medicine 21. Intensive Care Anesthesia Critical and Intensive Care Pain Management Poisoning 22. Rehabilitation Medicine 23. Diagnostic Procedures Diagnostic Imaging Nuclear Medicine 24. Nutrition Anorexia Nutrition Obesity 25. Substance Abuse Alcoholism Smoking
All AMEDEO services are free of charge. This policy was made possible thanks to generous unrestricted educational grants provided by AMGEN, AstraZeneca, Berlex, Boehringer Ingelheim, Novartis, Pfizer, Roche, Schering AG.
Design:
http://amedeo.com/index.htm (2 of 2) [23/08/05 17:12:42]
Stop TB
Links
Error 404: The page or file you have requested cannot be found.
Website improvements under way
We have been improving our website and as such, some files may have been moved. Please use the menus on our site, our site map or search our website to find what you are looking for. If you do not find what you are looking for, please contact our website administrator. We regret any inconvenience this may cause.
Global Drug Facility
Partners' Directory
Calendar of Events Subscribe to the Stop TB Mailing List
Partner Highlight
The Oxford International Biomedical Centre (OIBC) is a humanitarian charity that focuses on the sharing of knowledge. The mission of OIBC is
http://www.stoptb.org/errorpages/404.asp (1 of 2) [05/12/05 22:15:20]
Stop TB
to improve health and the quality of life across the globe by promoting access to learning and research. Services related to TB: OIBC has launched a trans-continental research project on the selection of plants with potential for antituberculosis drug development (SOPAT). For more information, contact the coordinator of this project, Dr Leonard E. Newton, Department of Botany, Kenyatta University, P.O. Box 43844, Nairobi 00100, Kenya; email: ellyen@yahoo.com
View their partner profile
Privacy Policy | Site Search | Site Map | Contact Us | Link to our site | Compatibility | Jump to top of page
http://www.stoptb.org/errorpages/404.asp (2 of 2) [05/12/05 22:15:20]
WHO | <em>Tuberculosis</em>
Tuberculosis (TB)
WHO > WHO sites > Tuberculosis (TB) > WHO publications on tuberculosis
printable version
Tuberculosis
Advocacy report
WHO/CDS/TB/2003.321 ISBN 92 4 259070 3 (NLM classification: WF 310) The publication, prepared for the World Health Organization by editors and photographers from Colors magazine, puts a human face on the TB epidemic and the deadly interaction between TB and HIV. Outlining the efficacy of the DOTS programme, the report makes clear that continued commitment and expanded resources are vital to combat TB. Despite eight million new cases of TB being reported annually and two million deaths a year the report reveals the many misconceptions people have about the disease and how this ignorance is reflected in the misery of those infected with TB across the world. THE FILM Tuberculosis An informational film based on the report Tuberculosis. :: View the film THE REPORT Tuberculosis :: Photo gallery :: Press release :: Report - text only [html] :: English/French [pdf 1.1mb] :: English/Spanish [pdf 1.1mb]
"The images are disturbing," said Colors editor-in-chief Renzo di Renzo, "but in fact they give just a mere glimpse of the enormous challenges faced every day by TB health care workers."
http://www.who.int/tb/publications/advocacy_report_2003/en/index.html [05/12/05 22:16:01]
WHO | TB cases and deaths linked to HIV now at alarming levels in Africa
Tuberculosis (TB)
WHO > WHO sites > Tuberculosis (TB) > TB features archive
printable version
TB cases and deaths linked to HIV now at alarming levels in Africa

Rising rates contrast sharply with accelerated progress in other regions
London/Geneva - 24 March, 2005 - In most areas of the world, the battle against tuberculosis is being successfully fought, but in Africa the disease has reached alarming proportions with a growing number of TB cases and deaths linked to HIV, the World Health Organization said in a new report released today. :: News release :: Access the full report online :: Report summary (English) [pdf 81kb] :: Report summary (French) [pdf 95kb] :: Report summary (Spanish) [pdf 89kb]
The Global Tuberculosis Control report for 2005 finds that global TB prevalence has declined by more than 20% since 1990 and that incidence rates are now falling or stable in five of the six regions of the world. The glaring exception is Africa, where TB incidence rates have tripled since 1990 in countries with high HIV prevalence and are still rising across the continent at a rate of 3-4% annually.
Even Uganda, an African HIV reduction success story, is today curing fewer TB patients than it did four years ago. More than half of all people with TB in Uganda remain without access to life-saving DOTS* services due to strained general health facilities. "Evidence in this report provides real optimism that TB is beatable, but it is also a clear warning," said WHO Director-General Dr LEE Jong-wook. "As Nelson Mandela has said, we can't fight AIDS unless we do much more to fight TB, and it is time to match his words with urgent action in Africa on the two epidemics together." There has been major progress in China and India, which account for one third of the global TB burden. Both are leading the accelerated response to TB control by rapidly scaling up DOTS. As a result, the number of cases treated under DOTS worldwide rose 8% in 2003 compared to the previous year. Other countries such as Indonesia and the Philippines are showing similar progress. Assuming strong commitment and resources are sustained, four regions - the Americas, Eastern Mediterranean, South East Asia and Western Pacific - are on track to reach the United Nations Millennium Development Goal of reducing TB incidence by 2015. The two exceptions are Africa due to the TB/HIV coepidemic, and Europe where there are high levels of multidrug-resistant TB and slow advances in DOTS in countries of the former Soviet Union.
http://www.who.int/tb/features_archive/wtbd2005/en/index.html (1 of 2) [05/12/05 22:21:30]
WHO | TB cases and deaths linked to HIV now at alarming levels in Africa
"Dedicated frontline health workers are making a difference, reaching out to the most vulnerable," said Dr Mario Raviglione, Director of WHO's Stop TB Department. "But we need to push even further, to work with new partners in both public and private health sectors, and in all regions, to reach more than half of all patients that are still without access to DOTS treatments." Since 1995, over 17 million people with TB have benefited from effective treatment under DOTS. But more could be achieved within countries, and in research into new diagnostics, drugs and vaccines, if the annual US$ 1 billion funding gap for TB control was filled. The urgency of addressing TB has been highlighted in the UK-led Commission for Africa, which linked improved TB control to strengthened health systems, as well as calling for full funding of WHO's 'Two Diseases, One Patient' strategy for improved TB and HIV intervention. "It is a remarkable achievement that we are on target to reach the goal of halving TB cases by 2015 in most places," said the UK's International Development Secretary, Hilary Benn. "The Department for International Development is a strong supporter of TB programmes in some of the countries which have been making the fastest progress. However, as both the Global TB Control report and the Commission for Africa report stress, the destructive link between TB and AIDS in Africa is causing an increase in cases. I call on the international community to step up efforts to tackle both of these diseases together." *DOTS is the internationally recommended strategy for controlling TB, consisting of five elements:
q q q q q
Government commitment to TB control Diagnosis through bacteriology and an effective lab network Standardized short-course chemotherapy with full patient support throughout treatment Uninterrupted supply of quality-assured drugs Recording and reporting to measure patient and programme outcomes
World TB Day on 24 March is a Stop TB Partnership initiative aimed at raising TB awareness internationally. WHO is one of 325 members of the Stop TB Partnership committed to controlling and ultimately eliminating TB as a public health problem. Since the Partnership's formation in 2001 the number of patients detected for TB has increased by two thirds. :: Access the full report online
For more information, please contact:

q q q
Geneva: Michael Luhan Stop TB Partnership, + 41 22 791 1379 luhanm@who.int London: Glenn Thomas WHO Stop TB, +41 79 509 0677 thomasg@who.int; Paris: Michael Aublanc for Stop TB Partnership, +33 1 69 286 286, M.aublanc@public-info.org:
http://www.who.int/tb/features_archive/wtbd2005/en/index.html (2 of 2) [05/12/05 22:21:30]
: The AMEDEO Literature Guide
Home
HIV Medicine
FAQ
Unsubscribe
Change Email
Policy
About
Flying Publisher
Hepatitis
New 07.12.2005 articles 30.11.2005 23.11.2005 16.11.2005 09.11.2005 02.11.2005 26.10.2005 19.10.2005 12.10.2005 You may choose a subset of the following journals and subscribe to our free e-mail service. Every week you will receive an e-mail with bibliographical details and links to available abstracts. Example: Amedeo Bacterial Infections For a complete list of topics, see the Amedeo homepage. Furthermore, we will assign you a free personal Web page for the one-time downloads of all available abstracts (see example for Amedeo Hypertension). Your personal literature Web page is located on one of our servers and will be updated for you once weekly. For further detailed bibliographic information, we recommend the PubMed site.
Sponsored by
Free Subscription 1. Journals Select your favorite journals. 1. AIDS (112) 2. Am J Epidemiol (3) 3. Am J Gastroenterol (123) 4. Am J Med (31) 5. Ann Intern Med (48) 6. Arch Virol (25) 7. Blood (24) 8. BMJ (21) 9. Cancer (14) 10. Clin Exp Immunol (19) 11. Clin Infect Dis (153) 12. Dig Dis Sci (58) 13. Drugs (11) 14. Dtsch Med Wochenschr (15) 15. Eur J Epidemiol (19) 16. Eur J Gastroenterol Hepatol (78) 17. Gastroenterol Hepatol (43) 18. Gastroenterology (142) 19. Gut (79) First Name: AMEDEO code: (optional)
If this is your first subscription to Amedeo, please leave the field blank. In the future, using your Amedeo code, you will not need to fill out the rest of the form.
2. E-mail Service Our E-mail service is free of charge. You may select any of the journals listed on the left side, and you will receive every week a list of articles published in your journal subset. To register, fill out the following form and click the "Submit" button. At any time you may renew your request choosing another subset of journals. Please use the same e-mail address.
2.1. Account Information E-mail:
Name:
http://amedeo.com/medicine/hep.htm (1 of 4) [05/12/05 22:22:12]
20. Hepatology (337) 21. Int J Cancer (18) 22. Int J STD AIDS (19) 23. J Clin Gastroenterol (90) 24. J Clin Microbiol (102) 25. J Hepatol (358) 26. J Immunol (35) 27. J Infect Dis (90) 28. J Interferon Cytokine Res (18) 29. J Med Virol (199) 30. J Pediatr (11) 31. J Rheumatol (12) 32. J Viral Hepat (193) 33. J Virol (260) 34. JAMA (24) 35. Lancet (37) 37. MMWR (2) 38. N Engl J Med (56) 39. Nature (23) 40. Pediatr Infect Dis J (27) 41. Pediatrics (7) 42. Scand J Infect Dis (24) 43. Science (11) 44. Transplant Proc (143) 45. Transplantation (67) 46. Vaccine (114) 47. Virology (71) 48. Z Gastroenterol (30) 2.3.2. Healthcare non-clinical Profession:
Biomedical Scientist
Affiliation:
2.2. Location Country:

Select country
City:
2.3. Profession Information Click one button AND make a selection from the appropriate pick lists:
2.3.1. Medical/Clinical Profession:

Physician
Specialty:
General primary care
Phone number: (optional)
2.3.3. Student 2.3.4. Pharmaceutical Company 2.3.5. Press/Media 2.3.6. Consumer/Other
2.4. We welcome your comments
How did you hear about us?

select one
Comments and suggestions:
2.5. Additional Information I agree to receive information from the sponsoring company. Yes No I agree that my personal data be communicated to the sponsoring company. Yes No
I wish to be informed about new activities of the Amedeo Group (i.e. www.amedeo.com, Free Medical Journals, HIV Medicine). Yes No
2.6. Submit Click the button below, and we'll register you to the free AMEDEO Literature service.
Submit
Thank you for your interest in scientific medicine.
This AMEDEO Service was made possible thanks to the generous unrestricted educational grants provided by F. Hoffmann-La Roche.
Design:
Home
HIV Medicine
FAQ
Unsubscribe
Change Email
Policy
About
Flying Publisher
Hepatitis
Free Subscription
Articles published in Eur J Epidemiol Retrieve available abstracts of 19 articles: HTML format
Single Articles
1. KUBO N , Furusyo N, Nakashima H, Kashiwagi K, et al
January 2005
Strenuous physical labor is important as a cause of elevated alanine aminotransferase levels in Japanese patients with chronic hepatitis C viremia. Eur J Epidemiol 2005;20:251-61. PubMed Related articles Abstract available January 2004
2. CATALANI C , Biggeri A, Gottard A, Benvenuti M, et al
Prevalence of HCV infection among health care workers in a hospital in central Italy. Eur J Epidemiol 2004;19:73-7. PubMed Related articles Abstract available
3. MEHR AJ , Ardakani MJ, Hedayati M, Shahraz S, et al
Age-specific seroprevalence of hepatitis A infection among children visited in pediatric hospitals of Tehran, Iran. Eur J Epidemiol 2004;19:275-8. PubMed Related articles Abstract available
4. ERDOGAN MS , Otkun M, Tatman-Otkun M, Akata F, et al
The epidemiology of hepatitis a virus infection in children, in Edirne, Turkey. Eur J Epidemiol 2004;19:267-73. PubMed Related articles Abstract available
5. ARVANITIDOU M , Mamassi P, Vayona A
Epidemiological evidence for vaccinating wastewater treatment plant workers against hepatitis A and hepatitis B virus. Eur J Epidemiol 2004;19:259-62. PubMed Related articles Abstract available
6. FISKER N , Mygind LH, Krarup HB, Licht D, et al
Blood borne viral infections among Danish health care workers--frequent blood exposure but low
http://amedeo.com/medicine/hep/eurjepid.htm (1 of 3) [05/12/05 22:22:37]
prevalence of infection. Eur J Epidemiol 2004;19:61-7. PubMed Related articles Abstract available
7. SCHINAIA N , Kodra Y, Sarmati L, Andreoni M, et al
Prevalence of HHV-8 infection in Albanian adults and association with HBV and HCV. Eur J Epidemiol 2004;19:467-9. PubMed Related articles Abstract available
8. DJEBBI A , Mejri S, Thiers V, Triki H, et al
Phylogenetic analysis of hepatitis C virus isolates from Tunisian patients. Eur J Epidemiol 2004;19:555-62. PubMed Related articles Abstract available
9. ZALLER N , Nelson KE, Aladashvili M, Badridze N, et al
Risk factors for hepatitis C virus infection among blood donors in Georgia. Eur J Epidemiol 2004;19:547-53. PubMed Related articles Abstract available
10. SENCAN I , Sahin I, Kaya D, Oksuz S, et al
Assessment of HAV and HEV seroprevalence in children living in post-earthquake camps from Duzce, Turkey. Eur J Epidemiol 2004;19:461-5. PubMed Related articles Abstract available
11. GHABOULI MJ , Sabouri AH, Shoeibi N, Bajestan SN, et al
High seroprotection rate induced by intradermal administration of a recombinant hepatitis B vaccine in young healthy adults: comparison with standard intramuscular vaccination. Eur J Epidemiol 2004;19:871-5. PubMed Related articles Abstract available
12. DENIS F , Ranger-Rogez S, Alain S, Mounier M, et al
Sreening of pregnant women for hepatitis B markers in a French Provincial University Hospital (Limoges) during 15 years. Eur J Epidemiol 2004;19:973-8. PubMed Related articles Abstract available
13. BUTLER T , Kariminia A, Levy M, Kaldor J, et al
Prisoners are at risk for hepatitis C transmission. Eur J Epidemiol 2004;19:1119-22. PubMed Related articles Abstract available January 2003
14. BACKMUND M, Meyer K, Wachtler M, Eichenlaub D
Hepatitis C virus infection in injection drug users in Bavaria: risk factors for seropositivity. Eur J Epidemiol 2003; 18: 563-8. PubMed Related articles Abstract available
15. CHLABICZ S, Grzeszczuk A, Lapinski TW, Prokopowicz D, Panasiuk A
Search for hepatitis delta virus (HDV) infection in hepatitis C patients in north-eastern Poland. Comparison with anti-HDV prevalence in chronic hepatitis B. Eur J Epidemiol 2003; 18: 559-61. PubMed Related articles Abstract available
16. GOGOS CA, Fouka KP, Nikiforidis G, Avgeridis K, Sakellaropoulos G, Bassaris H et al
Prevalence of hepatitis B and C virus infection in the general population and selected groups in SouthWestern Greece.
Eur J Epidemiol 2003; 18: 551-7. PubMed Related articles Abstract available
17. JAIN A, Rana SS, Chakravarty P, Gupta RK, Murthy NS, Nath MC et al
The prevalence of hepatitis C virus antibodies among the voluntary blood donors of New Delhi, India. Eur J Epidemiol 2003; 18: 695-7. PubMed Related articles Abstract available
18. LA TORRE G, De Vito E, Langiano E, Petta P, Colarossi G, Cipriani L et al
Epidemiology of hepatitis C virus antibodies in blood donors from the province of Latina, Italy. Eur J Epidemiol 2003; 18: 691-4. PubMed Related articles Abstract available
19. REDA AA, Arafa MA, Youssry AA, Wandan EH, Ab de Ati M, Daebees H
Epidemiologic evaluation of the immunity against hepatitis B in Alexandria, Egypt. Eur J Epidemiol 2003; 18: 1007-11. PubMed Related articles Abstract available
Thank you for your interest in scientific medicine.
This AMEDEO Service was made possible thanks to the generous unrestricted educational grants provided by F. Hoffmann-La Roche.
Design:
Canada's Role in the Fight Against Tuberculosis Today.
CANADA's ROLE in FIGHTING TUBERCULOSIS Tuberculosis in Canada Today

The Resurgence of a Beaten Disease Who is Fighting Tuberculosis in Canada? Diagnosis of Tuberculosis in Canada Treatment of Tuberculosis in Canada Prevention of Tuberculosis in Canada
http://www.lung.ca/tb/tbtoday/ [07/12/05 4:06:17]
:: ABC de la Tuberculosis - UITB - Unidad de investigacin en tuberculosis de Barcelona ::
english version
ESTE SITE HA CAMBIADO DE SITIO. POR FAVOR ACTUALICE SUS ENLACES: http://www.aspb.es/uitb/
Su navegador le redigir en unos segundos a la nueva direccin, para hacerlo de forma manual pinche aqu.
Unidad Temtica Concedida por el Fondo de Investigaciones Sanitarias (FIS) en 1995 12257 visitantes. Visitas por das y por pases (ltima actualizacin: 13 de Diciembre 2005 )
http://www.imsb.bcn.es/uitb/ [03/01/06 23:37:35]
english version
Unidad Temtica Concedida por el Fondo de Investigaciones Sanitarias (FIS) en 1995 12258 visitantes. Visitas por das y por pases (ltima actualizacin: 13 de Diciembre 2005 )
Objetivos de la UITB
Produccin de conocimiento cientfico de relevancia sobre el control, diagnstico, tratamiento y prevencin de la TBC.
Requisitos generales
En 1994, el fondo de Investigaciones Sanitarias de la Seguridad social abra la posibilidad de solicitar una unidad Temtica de Investigacin en Tuberculosis, de acuerdo con estos requisitos: 1. Existencia de un Proyecto Integrado (Epidemiologa, Clnica y Microbiologa) enfocado sobre las siguientes reas de conocimiento: TBC en general, TBC y SIDA. 2. Exigencia de contar con todos los recursos y los enfermos de tuberculosis del area de referencia.
Red de Unidades de Investigacin (REUNI) Unidad de Investigacin en Tuberculosis

Tuberculosis en general/sida Epidemiologa
Clnica
Microbiologa
http://www.aspb.es/uitb/ (1 of 2) [03/01/06 23:38:42]
Evolucin cronolgica
Ya en 1987, en una reunin cientfica sobre Programas de Vigilancia y Control celebrado en Bilbao, se evidenci la necesidad de impulsar la investigacin sobre Tuberculosis. La Conferencia Nacional de Consenso de 1991 tambin puso de manifiesto esta necesidad. En 1994 se present al FIS el primer proyecto integrado de la Unidad deInvestigacin en Tuberculosis de Barcelona, la cual empez a ser operativa a partir de finales de 1995. Taller sobre Programas de vigilancia de la TBC en Espaa
Conferencia de consenso
Reuniones, grupos de trabajo
1er proyecto integrado*
Aprobacin memoria cientfica
Aprobacin ayuda infraestructura
Disponibilidad recursos infraestructura
1987
1991
1990-92
V-94
VI-95
IX-95
I-96
*Finalmente no hubo recursos para unidades temticas
Para ver las estadsticas de uso de esta web
Honduras Sites!
El directorio de Mxico
Bsqueda Google
http://www.aspb.es/uitb/ (2 of 2) [03/01/06 23:38:42]
A laymans guide to tuberculosis, atypical tuberculosis and mycobacterial disease.
The site now includes tuberculosis GUIDELINES covering diagnosis, treatment, medication, health & safety and many other issues The Facts of Tuberculosis can now be automatically translated in 16 languages by clicking A to Z of Drugs on any floating flag. AtoZ of General Health Welcome to TB and U I feel I should state immediately the fact that this site is NOT run by medical professionals or sponsored by medical companies but is solely run by an individual. The A to Z of TB aim of the site is to bring together the best web links on Tuberculosis, Atypical Tuberculosis and other mycobacterial diseases. The links have been carefully chosen; the majority of which are Chelonae layman or patient friendly whilst others are to help people research the general field of Books about TB mycobacterial diseases. The site includes a forum, message board and medically related games. Centre for Disease Accreditation to the Health on the Net rules of conduct can be checked by clicking on HON link below or by Clicking Here Drug Side Effect
FAQ Tuberculosis FREE TB NEWS Games Pages Hypocratic Oath John Hopkins Uni Latent TB Med Encyclopedia Medical News Today Message Board NHS Direct Pregnancy and TB TB Guide TB Guidelines TB HIV and Aids
What do you think you know about tuberculosis? Try a quiz Easy TB Quiz Medium TB Quiz Hard TB Quiz
Please vote and rate this site

Brilliant
Click here to Vote for this site
Atypical TB Ask a Question Atypical (What is?) Chelonae Chelonei Gordonae Haemophilum Johns Hopkins TB Kansasii MAC (Avium-Intracell) Marinum MOTT(other than TB) Nontuberculous(NTM) Xenopi Relaxation and games Weekly TB News Would like to ask NHS Direct Relaxation TB Guide TB HIV and Aids
http://www.tbandu.co.uk/ (1 of 2) [04/01/06 0:00:08]
A laymans guide to tuberculosis, atypical tuberculosis and mycobacterial disease.
UK Health News
UK Health News
DISCLAIMER
This site is NOT run by a medical professional and therefore does not give personal advice with the exception of
IF YOU HAVE ANY MEDICAL CONCERNS SEE YOUR DOCTOR OR HEALTH ADVISOR. Nothing in the TBandU website is intended to be used as a way of medical diagnosis or a substitute for consultation with a qualified healthcare professional.
About TBandU. Attribution. Authority. Authorship. Complementarity. Confidentiality. Justifiability. Sponsorship. Honesty.
This page was last modified undefined

auntie_biotic@tbandu.co.uk
Webmistress: Ms S Roberts
http://www.tbandu.co.uk/ (2 of 2) [04/01/06 0:00:08]
American Thoracic Society
ATS Highlights January 2006

Palm Tips: Make Peace between Palm OS and Windows Mobile Devices Best of the Web: Smoking Cessation Clinical Case: Pleuroparenchymal Disease In A Ship Repair And Maintenance Worker PC Assembly Journal Club RNS Basic Science Journal Watch More Highlights...
Quick Links Search
With more than 13,000 members, the American Thoracic Society is a leading medical association dedicated to advancing lung, critical care and sleep medicine.
61 Broadway New York, NY 10006-2755 Voice: 212-315-8600 Fax: 212-315-6498 Questions or comments? Contact Us. Copyright 2006 American Thoracic Society Web Site Requirements
http://www.thoracic.org/ [04/01/06 0:06:16]
Bill & Melinda Gates Foundation
WEDNESDAY, JANUARY 4, 2006
Investing in Children
Too many children in Washington state lack the basics to succeed in school and life. Together with many partners, we address the problem in a new early learning strategy.
Dec 19, 2005 Teacher Training Program Extends to New West Side High... Dec 18, 2005 Statement by Bill and Melinda Gates About Being Named... Dec 16, 2005 New Investment to Help Improve Quality of Education... More...
Foundation Facts Learn more about our work On the Issues Read speeches & commentary by foundation leaders In Our Region Local giving program takes on early learning Seeking Funding? Review our grant eligibility guidelines
Wired in the Wilderness

Cyber-libraries connect six communities in the remote Canadian Northwest Territories to the rest of the world.
Advanced Search
Global Health Education Global Libraries Pacific Northwest Grantee Profiles For Grant Seekers Newsroom
Priority Diseases & Conditions | Breakthrough Science | Other Initiatives Increasing U.S. Graduation Rates | Scholarships | Research & Evaluation U.S. Library Program | International Library Initiatives Early Learning | Supportive Housing | Community Grants | For Grant Seekers | Evaluations Global Health | Education | Global Libraries | Pacific Northwest Eligibility Overview | Frequently Asked Questions Announcements | Fact Sheets | Speeches | Publications
http://www.gatesfoundation.org/default.htm (1 of 2) [04/01/06 1:48:56]
Bill & Melinda Gates Foundation

About Us Grant Highlights | Leadership | Jobs | Contact Us | Privacy Policy
Promoting greater equity in global health, education, public libraries, and support for at-risk families in Washington state and the greater Portand area. 2005, Bill & Melinda Gates Foundation, All Rights Reserved
http://www.gatesfoundation.org/default.htm (2 of 2) [04/01/06 1:48:56]
Amazon.co.uk: low prices in Electronics, Books, Music, DVDs & more: Amaz...vantage, Associates Site of the Week, Books, Help, Jobs at Amazon.co.uk
HOW TO INTERNATIONAL ORDER
GIFT CERTIFICATES
SELL YOUR STUFF
Hottest Offers
HARRY POTTER
All Products
Wish you'd asked for cash? Sell your unwanted Christmas presents on Amazon.co.uk. Find out how. Star Choice January Sale
Hello! Already a customer? Sign in to get Instant Recommendations.
Portable Storage
Get up to 50% off CDs, including Africa Unite by Bob Marley. Our Price: 7.97
Browse
q q q q q q q q q q q q q q q
Transfer files between computers with the SanDisk Cruzer Micro 1GB USB 2.0 Flash Drive. See more in Computer Peripherals. Our Price: 29.99
Change Your Life and Save Up To 50%
Books DIY & Tools DVD DVD Rental Electronics & Photo Garden & Outdoors Gifts Home & Garden Kitchen & Home Music PC & Video Games Personal Care Software Toys & Games Video Used Auctions zShops
You Are What You Eat Cookbook

Synopsis My aim is for you to make simple changes that will begin to take effect almost immediately and will last for life' The You Are What You Eat Cookbook puts Dr Gillian McKeith's healthy food philosophy into action. The McKeith Diet of Abundance is not about telling you what not to eat, rather it... Read more
Find the inspiration for selfimprovement in 2006 with our fabulous New Year,
Our Price: 5.99 You Save: 9.00 (60%) Used & New from 5.95
New You promotion on hundreds of books, including The Money Diet. Our Price: 3.99
WHAT'S NEW
q q q
Already a customer? Sign in to see your New for You recommendations. Your Shopping Basket You have 0 items in your Shopping Basket.
New Releases
Books
Up to 70% off January bargains New Year New You Professional & Academic--up to 50% off Best of 2005
DVD
Up to 40% off bestsellers TV box sets for less s off in Special Offers Hot 100 DVDs
Electronics & Photo

MP3 players Digital cameras DVD players and recorders Kit out your computer
Marketplace Got something to sell? List it on our website. Associates Link to Amazon.co.uk from your website and earn money. Advantage A profitable way for authors, publishers, labels, and studios to enhance their sales. Web Services Gain more from building
Now That's What I Call Music! Vol 62

More Categories
Compilations Fiction Health, Family & Lifestyle DVD Science Fiction & Fantasy DVD Comedy
http://www.amazon.co.uk/exec/obidos/tg/browse/-/468294/026-8428682-2182811 (1 of 4) [04/01/06 1:51:59]
websites, applications or tools. See all services
PC & Video Games

25% off new releases s off in Special Offers Hardware and accessories Hot 100 games
Music
Chart CDs from 8.49 New & future releases s off in Special Offers Compilations from 12.99
Home & Garden

Kitchen & Home Personal Care DIY & Tools Garden & Outdoors
More New Releases

Amazon.co.uk Hot 100 Books Updated Hourly
MORE TO EXPLORE
January Bargains: Up to 70% off DVD
Wish List Make it easy to find that perfect gift--create or find a Wish List. DVD Rental by Post The new way to rent DVDs. Gift Certificates Send an Amazon.co.uk gift certificate to friends and family or colleagues. Currency Converter Display our prices in another currency. Amazon.co.uk Anywhere Browse and buy from your WAP mobile phone. Amazon.co.uk MasterCard Typical 12.9% APR (variable) Apply now to start earning loyalty points. More info. Awards See the latest nominees and winners for all the major awards. Virgin.net Broadband From only 14.99 per month. Up to 2 Mbps. No 12 month contract. More info.
Check out more amazing bargains: 4 DVDs for 20 Up to 50% off box sets DVDs from 3.97
Check out our January DVD Bargains: up to 70% off thousands of top titles.
1.
Dr Gillian McKeith's Ultimate Health Plan: The Diet Programme That WILL Keep You Slim for Life ~ Gillian McKeith
(53%)
2.
Does Anything Eat Wasps?: And 101 Other Questions ~ "New Scientist" (52%) You Are What You Eat Cookbook ~ Gillian McKeith (60%)
3.
q q q q
See full list Amazon.co.uk Hot 100 Music Updated Hourly
January Offers--Portable Audio
1. 2. 3.
First Impressions Of Earth ~ The Strokes 8.49 Whatever People Say I Am, That's What I'm Not ~ Arctic Monkeys 8.49 Eye to the Telescope ~ KT Tunstall (Artist) 8.99
q q
ATMT 1.8" 20GB MP3 Player Our Price: 109.99 Logic3 i-Station Docking Station for iPods and other MP3 Players Our
See full list
Price: 39.99 New & Used from 39.99

q
ATMT LITE MP130SL 256MB MP3 Player - Silver Our Price: 19.99
New & Used from 19.14 See more Electronics offers
Best Reads of 2005
Top 5 Questions
We have had a lot of fun choosing our Best of 2005 reads and hope that you'll enjoy reading them just as much--titles include:The Da Vinci Code, Talk to the Hand, and What Your Clothes Say About You.
1. How do I order? 2. Our Security Guarantee 3. How much will postage and packing cost? 4. Using a gift certificate 5. Making changes to my order
More to Explore in Books:
q q q q q q q
Up to 70% off Hundreds of Books 40% off New Releases Up to 50% off New Year, New You Titles 40% off Diaries, Calendars & Annuals Up to 50% off Professional and Academic Books Up to 40% off Humour books Visit our Chronicles of Narnia store
Dynamite DVD Deals
Brilliant Box Sets

Up to 50% off Box Sets Amazon.co.uk Exclusives TV & Documentary Science Fiction
s Off Children's DVDs

Children's Special Offers Bestselling Kid's DVDs Animation Educational DVDs
Cracking Comedy
Comedy Special Offers Comedy Bestsellers TV Comedy Classic Comedy
More Marvellous DVDs
Superb Special Offers

New Special Offers 4 DVDs for 20 Up to 50% off Box Sets DVDs from 3.97
Awesome Action Movies

Action Special Offers Action Bestsellers Heroes & Heroines Martial Arts
Super Sports & Fitness DVDs

Sport Special Offers Fitness DVDs Sports Bestsellers Football
Up to 50% off Health & Fitness
Weightwatchers 8976U Glass Body Monitoring Precision Electronic Scale Our Slendertone Start Female Abdominal Trainer Our Price: 29.97 Salter 144 SVBKDR Extended Full View Dial Mechanical Bathroom Scales Black/Silver Satin Our Price: 14.97 New & Used from 14.97
Price: 24.97
q q
Up to 50% off Health & Fitness
Where's My Stuff? track your recent orders view or change your orders in Your Account
Delivery and Returns see our delivery rates and policies thinking of returning an item? (See our Returns Policy)
Need Help? forgot your password? Click here redeem or buy a gift certificate still have questions? Visit our Help Pages
Search our shops
for
All Products
Text Only Top of Page
International Sites: United States |
Germany |
France |
Japan |
Canada |
China
Join Associates |
Join our staff |
About Amazon.co.uk |
Help pages |
Contact us
Our Privacy Notice, Conditions of Use & Sale 1996-2005, Amazon.com, Inc. and its affiliates
Welcome on the TB Vaccine Cluster Site
Updated : Tue, Jun 13, 2000 Site realised by Marie Guibert
http://www.pasteur.fr/recherche/EC_TBvaccine/ [04/01/06 1:55:08]
USDA Funded Projects
USDA FUNDED PROJECTS
ACCESSION NO: 0194743 SUBFILE: CRIS PROJ NO: CALV-MORRIS01-01Z029 AGENCY: CSVM CALV PROJ TYPE: STATE PROJ STATUS: TERMINATED START: 01 SEP 2001 TERM: 31 AUG 2002 FY: 2002 Investigator: Tell, L. A. Performing Institution: Medicine & Epidemology University of California (Vet-Med) Davis, California 95616 THE SUITABILITY OF POLYMERASE CHAIN REACTION FOR THE SCREENING OF MYCOBACTERIA IN AVIAN FECES NON-TECHNICAL SUMMARY: Mycobacteriosis is an insidious disease which causes mortalities in birds and is also a zoonotic concern. Affected birds shed organisms in their feces that remain viable in the environment for months to years and poses a threat to domestic animals, other birds and humans. This project will help to develop a more rapid and reliable screening method for the detection of Mycobacteria avium complex bacteria than conventional culture methods. OBJECTIVES: This project tests the hypothesis that polymerase chain reation (PCR) testing using extracted mycobacterial deoxyribonucleic acid (DNA) from avian feces can provide a more rapid and realiable screening method for the detection of Mycobacteria avium complex bacteria than conventional culture methods. APPROACH: Potential diagnostic procedures using extracted DNA for PCR from clinical samples have been plagued by the presence of various inhibitors of the PCR reaction. This study is specifically designed to assess three different DNA extraction protocols of avian feces for the presence or absence of these potential PCR inhibitors and the overall efficiency and the suitability of the resulting DNA for PCR reactions. Once an optimal method is identified, it will be used to evaluate the extraction and detection of DNA from feces spiked with living Mycobacterium avium complex cells. PROGRESS: 2001/09 TO 2002/08 This study was designed to assess four DNA extraction protocols of avian feces for the presence or
http://nal.usda.gov/awic/pubs/TB/USDAFunded.htm (1 of 38) [04/01/06 2:04:35]
absence of potential PCR inhibitors, thus defining an optimal method for DNA extraction from bird fecal samples. The first experiment compared three DNA extraction methods and heat treatment of the extracted fecal DNA samples for their ability to overcome fecal PCR inhibition. Methods for extracting DNA from feces of healthy Japanese quail (Coturnix coturnix japonica) included (a) bead beating + EL (BB+EL), (b) bead beating + silicone dioxide (BB+SiO2), and (c) bead beating + phenol/chloroform. To evaluate each extraction methods' ability to overcome PCR inhibition, extracted fecal DNA samples were spiked with control M. avium subsp. avium DNA and quantitative real-time TaqMan PCR analysis was performed. The BB+EL and BB+SiO2 methods returned positive PCR results. BB+EL resulted in the highest purity and number of mycobacteria. Heating samples before PCR analysis decreased the mean number of mycobacteria for all fecal DNA extraction methods. In the second experiment, living M. avium subsp. avium cells were mixed with feces from healthy Japanese quail at concentrations of 1 x 106 CFU/g, 10 x 106 CFU/g, or 60x 106 CFU/g. Samples underwent DNA extraction using BB+EL, followed by quantitative TaqMan PCR. Heated and unheated samples were analyzed. The mean number of mycobacteria detected in feces with a spiking concentration of M. avium subsp. avium of 1 x 106 CFU/g was only 1 (range, 0 to 2.3) for both heated and unheated samples. Thus, the lower limit of detection for quantitative PCR using the methods described is approximately 1x106 CFU/g or less. In summary, this study demonstrated that DNA extraction methods used in sample preparation can have a substantial impact on the DNA yield, purity, and amplification during subsequent PCR analysis on avian fecal samples. The best preparation method tested incorporated bead beating and enzymatic lysis using a commercial kit designed for use on stool samples. The lower limit of detection on avian fecal samples spiked with M. avium subsp. avium was 1 million CFU/gram, so this test may be of most use in identifying highly infective birds. IMPACT: 2001/09 TO 2002/08 Mycobacteriosis is a bacterial disease that causes morality in birds and can cause human disease as well. Affected birds shed organisms in their feces that may remain viable in the environment for months to years. Currently, infected birds are identified by culturing mycobacteria from fecal samples, a process taking weeks for results. This study assessed a DNA based assay system that could detect high numbers of the bacteria within one day of sample processing, and thus could help in the rapid screening of contagious animals. PUBLICATIONS: 2001/09 TO 2002/08 Lisa A. Tell, Wayne L. Smith, Christian M. Leutenegger, Janet E. Foley, Richard L. Walker, Martha L. Needham, Katheryn J. Jones, and James C. Cullor 2003. The suitability of polymerase chain reaction testing for the identification of Mycobacterium avium subsp. avium in avian feces. Submitted to Journal of Veterinary Diagnostic Investigation PROJECT CONTACT: Name: Tell, L. A. Phone: 530-752-1363 Fax: 530-752-0414
Email: latell@ucdavis.edu
ACCESSION NO: 0098139 SUBFILE: CRIS PROJ NO: COL00627 AGENCY: CSREES COL PROJ TYPE: HATCH PROJ STATUS: EXTENDED START: 01 JUL 1997 TERM: 30 JUN 2003 FY: 2002 Investigators: Nett, T. M.; Blair, C. D.; Bowen, R. A.; Orme, I. M.; Pearson, L. D.; Salman, M. D. Performing Institution: Microbiology, Immunology and Pathology Colorado State University Fort Collins, Colorado 80523 CONTROL OF INFECTIOUS DISEASES OF LIVESTOCK OBJECTIVES: 1. Determine the molecular epidemiology of bluetongue virus, vesicular stomatitis virus, Mycobacterium bovis, and other important livestock pathogens in Colorado and exploit this information for development of new control strategies for these diseases. 2. Develop a new generation of DNA based vaccines, antipathogen therapies, and diagnostic techniques for viral and bacterial livestock pathogens. 3. Apply modern molecular and quantitative techniques to identify, characterize, and control arthropod vectors and vector-borne and parasitic diseases of livestock. 4. Characterize the immunologic and molecular bases and identify specific genes and gene products that condition disease, disease resistance and protection in livestock and develop new virus and molecular expression systems to characterize relevant pathogen and host genes. APPROACH: Molecular, immunological, and biochemical approaches will be used to elucidate the pathogenetic mechanisms of infectious diseases of livestock and to develop new vaccines, therapies, and diagnostics for important veterinary pathogens. This information will be exploited to develop new control strategies for these important diseases. New technologies, such as polymerase chain reaction amplification, randomly amplified polymorphic and mitochondrial DNA, phylogenetic analyses, molecular epidemiologic approaches will be used to identify risks and propose management approaches to maximize animal productivity. PROGRESS: 2002/01 TO 2002/12 Multidrug resistant S. enterica serotype Newport isolates from the CSU Veterinary Diagnostic Laboratory encode antibiotic resistance markers on a large, resident plasmid and some of these markers are located within a class 1 integron. This is the first report of the occurrence of this particular class 1 integron in S. Newport isolates. Previously, this particular class 1 integron had only been reported in other drug resistant Enterobacteriaceae, such as Klebsiella pneumoniae, Citrobacter freundii, Serratia
marcescens, and Escherichia coli. The S. Newport class 1 integron was found to encode resistance to trimethoprim, spectinomycin/streptomycin, and sulfonamides; and contained a defective version of the quaternary ammonium compound resistance gene. The resident plasmid in these isolates also contained genes for tetracycline and b-lactam and cephalosporin resistance, although these genes were not contained within the class 1 integron. The results of these studies indicate that, unlike multidrug resistant S. typhimurium DT104 (whose antibiotic resistance is encoded within an integron located on the chromosome), multidrug resistance of S. Newport isolates is due to genes encoded on a resident plasmid. The significance of this finding is that these resistance markers could presumably be transferred to other Salmonella serotypes by conjugation and emphasizes the need to understand transfer of drug resistance in Salmonella. Range and feedlot cattle with a high intake of sulfur can develop polio-encephalomalacia (PEM), a neurological condition of ruminants characterized by necrosis of the cerebral cortex. An important factor in the development of PEM is the sulfur reducing capacity of the ruminal microflora. Little is known about the microbial population(s) involved in the production of neurotoxic concentrations of H2S. In this study, the natural ruminal ecosystem was studied by comparative 16S ribosomal RNA analysis followed by specific analysis of sulfate-reducing bacteria using DNA extracted from rumen fluid collected from test cattle before, during, and after transition to high sulfur water. 16S rDNA was cloned and 50 clones were analyzed from each rumen sample with restriction enzymes. Extreme diversity was observed both within a time point among different animals and between time points. Sulfate-reducing bacteria (SRB) belonging to the genera Desulfovibrio and Desulfomicrobium were detected in all of the animals. In addition, Desulfobulbus species were detected in animals during the second time point when ruminal H2S became maximal. Reverse Southern Analysis to determine the abundance of bacterial species in the rumen failed to reveal any particular dominant species in cattle consuming high sulfur concentrations. IMPACT: 2002/01 TO 2002/12 Drug resistant bacteria are becoming more of a health concern in animal products. The finding that multidrug resistance occurs in S. enterica serotyp Newport indicates that such resistance is spreading to several genera of bacteria. The occurrence of drug resistance in this species indicates that the resistance may be transferred to other species of Salmonella and indicates the importance of developing a better understanding of the transfer of drug resistance across species. It was demonstrated that the many microbes in the rumen of cattle are associated with production of toxic levels of hydrogen sulfide. Therefore, strategies to control complex populations of ruminal microbes, rather than a single species will be necessary to control polioencephalomalacia in cattle. PUBLICATIONS: 2002/01 TO 2002/12 1. Kurowski, P., Locke, A., and C. Gentry-Weeks. May 19, 2002. Characterization of integrons in Salmonella enterica serovar Newport, Abstract A-106. In Abstracts of the 102nd General Meeting of the American Society for Microbiology, 102nd General Meeting of the American Society for Microbiology, Salt Lake City, UT. 2. Allen, T.E., Sherrill, K.J., Crispell, S.M., Perrott, M., Carlson, J.O., DeMartini, J.D. The Jaagsiekte Sheep Retrovirus Envelope Gene Induces Transformation of the Avian Fibroblast Cell Line DF-1 but Does Not Require a Conserved SH2 Binding Domain. Journal of General Virology., 83: 2733-2742 (2002)
3. M.J. Magill1, D.H. Gould1, J.J. Wagner2, N.M DuTeau1; Characterization of Ruminal Microflora Associated With Pathologic Hydrogen Sulfide Production in Cattle Exposed to High Levels of Dietary Sulfur. American Society for Microbiology 102nd General Meeting, May 19-23, 2002, Salt Lake City, UT 1Colorado State University, Fort Collins, CO, 2Continental Beef Research, Lamar, CO 4. Thesis; Colorado State University: Magill, Molly Jean. Characterization of ruminal microflora associated with pathologic hydrogen sulfide production in cattle exposed to high levels of dietary sulfur / submitted by Molly Jean Magill. 2002. PROJECT CONTACT: Name: Nett, T. M. Phone: 970-491-7051 Fax: 970-491-2250 Email: tnett@cvmbs.colostate.edu
ACCESSION NO: 0182439 SUBFILE: CRIS PROJ NO: IDA01179 AGENCY: CSREES IDA PROJ TYPE: HATCH PROJ STATUS: TERMINATED START: 01 JUL 1999 TERM: 30 JUN 2002 FY: 2002 Investigators: Zaugg, J. L.; Bulgin, M. S.; Anderson, B. C.; England, J. J. Performing Institution: Animal & Veterinary Science University of Idaho Moscow, Idaho 83843 BIOLOGY AND CONTROL OF EMERGING DISEASES SHARED BY LIVESTOCK AND WILDLIFE NON-TECHNICAL SUMMARY: Diseases (brucellosis, tuberculosis and scrapie) of profound importance to the livestock industry have emerged as having actual, or potential interaction with wildlife. The purpose of this study is to investigate key aspects of the biology and control of bovine brucellosis, tuberculosis and scrapie emerging diseases shared by livestock and wildlife. OBJECTIVES: 1. Determine if mule deer are experimentally susceptible to scrapie infection. 2. Evaluate the utility of the palpebral site to test for tuberculosis in cervids. 3. Determine if Brucella abortus RB51 vaccine, delivered orally, will stimulate an immune response in bison and elk. APPROACH: 1. Intracerebrally inoculate mule deer fawns and domestic lambs with scrapie-infected
brain tissue. Montior for illness. Screen palpebral lymph nodes for prions at 18 and 24 months, and full necropsy at 36 months post inoculation. 2. Inoculate elk and mule deer with Mycobacterium avium organisms. Compare hypersensitive reactions to tuberculin intradermal inoculation made in the upper eyelids, to those standard test sites in the cervical region. 3. Elk will be fed Brucella RB51 vaccine as a top dressing in four, five-day series. Blood samples will be taken and evaluations conducted to determine if, and when an immune response is achieved. PROGRESS: 1999/07 TO 2002/06 Nothing was accomplished in this time period because we were awaiting the availability of mule deer fawns from Fish and Game in the late spring. IMPACT: 1999/07 TO 2002/06 The results of the investigation will have significant impact on disease management of range sheep and wildlife management. PUBLICATIONS: 1999/07 TO 2002/06 No publications reported this period PROJECT CONTACT: Name: Zaugg, J. L. Phone: 208-454-8657 Fax: 208-454-8659 Email: jzaugg@uidaho.edu
ACCESSION NO: 0401517 SUBFILE: CRIS PROJ NO: 3625-32000-034-00D AGENCY: ARS 3625 PROJ TYPE: USDA INHOUSE PROJ STATUS: TERMINATED START: 01 OCT 1997 TERM: 26 OCT 2001 FY: 2001 Investigators: Whipple D L; Waters W R; Palmer M V; Miller J M; Performing Institution: National Animal Disease Ctr Ames, Iowa 50010 PATHOGENESIS, DIAGNOSIS, AND EPIDEMIOLOGY OF BOVINE TUBERCULOSIS OBJECTIVES: Characterize interactions between various host species, such as cattle and white-tailed deer, and Mycobacterium bovis; develop and evaluate improved tests for diagnosis of M. bovis infection
in animals; and develop improved methods for differentiation of M. bovis isolates. NEW FUND OBJ: Identify candidate antigens that would be efficacious in a mucosal vaccine for prevention of tuberculosis in cattle, cervids (deer), and other wildlife. APPROACH: Animals will be experimentally challenged w/M. bovis and blood and tissue samples will be collected at different times to determine response of host to the organisms. Bacteriologic, histopathologic, and immunologic methods will be used to characterize host responses. Tissue samples w/b collected from naturally infected animals to determine distribution/characteristics of lesions. A gamma interferon assay for diagnosis of TB in deer and elk is being developed; w/b evaluated to determine test sensitivity/specificity. Blood samples from infected and noninfected animals w/b used for test evaluation. A method using the polumerase chain reaction w/b developed for rapid detection of M. bovis in tissue samples. Methods for DNA fingerprinting M. bovis isolates will be improved by using different DNA probes and enzymes. A method using PCR for direct detection and typing of M. bovis in fresh tissue samples w/b modified for use w/formalin-fixed tissues. NADC,AmesIA:Bldg2A12,BL1-3 IBC-0193 Apprvd to 6/29/00;-0224 Apprvd to 6/3/00; -0239 Apprvd to 12/26/00 PROGRESS: 2000/10 TO 2001/09 1. What major problem or issue is being resolved and how are you resolving it? Bovine tuberculosis, which is caused by Mycobacterium bovis, is an infectious disease that affects many species of animals as well as human beings. Animals infected with M. bovis can shed organisms as they exhale or cough and in various secretions including saliva, milk and urine. Elimination of animals infected with M. bovis is important to prevent the spread of disease among animals and to human beings. The United States initiated a program to eradicate tuberculosis from cattle in 1917 when the prevalence of disease was approximately 5%. In general, the eradication program has been successful and today, less than 0.002% of cattle are infected with M. bovis. However, a low prevalence of disease has persisted over the last 1015 years and it has not been possible to eradicate bovine tuberculosis from the United States using available technology. Improved diagnostic tests and control measures are needed to detect and eliminate the few remaining cattle and herds that have bovine tuberculosis. In addition, tuberculosis has been detected in captive deer and elk and in wild white-tailed deer, coyotes, raccoons, bear, bobcat, opossum, and fox. In some cases, there is epidemiological evidence to suggest that tuberculosis has been transmitted from deer to cattle. The presence of tuberculosis in wildlife poses a serious threat to the national eradication program. Other countries with tuberculosis in wildlife species have been unable to eradicate the disease from the domestic livestock population. The Bovine Tuberculosis research project at the National Animal Disease Center (NADC)is conducting research to develop a better understanding of the interactions between various host species and M. bovis. This information will be used to develop improved diagnostic tests and vaccines. Methods to identify and differentiate strains of M.bovis are being developed and used to aid in epidemiological investigations of outbreaks of tuberculosis in animals. 2. How serious is the problem? Why does it matter? Bovine tuberculosis is considered a public health threat because human beings can become infected with M. bovis through contact with infected animals or by ingestion of contaminated food and milk. Elimination of tuberculosis from cattle is important to provide food and milk to the public that is free of M. bovis. Eradication of tuberculosis from wildlife is important to prevent transmission of disease from wildlife to domestic livestock. Elimination of bovine tuberculosis from domestic livestock also is important to maintain free trade with the many trading
partners of the United States. Trade restrictions between the United States and Canada and between Mexico and the United States have occurred because of bovine tuberculosis in animals. 3. How does it relate to the National Program(s) and National Component(s)? The Bovine Tuberculosis research project is assigned to the Animal Health National Program (103) and relates to the vision of this program to ensure animal health through improved disease detection and control. The objectives of the project are to 1) develop and evaluate improved tests for diagnosis of tuberculosis in cattle, deer and other species,which relates to the National Program Component on Pathogen Detection; 2) develop improved methods for differentiation of M. bovis isolates, which relates to the National Program Component on Epidemiology of Disease; 3) define the interactions between various host species and M. bovis, which relates to the National Program Component on Host/Pathogen Interactions and 4) develop and evaluate vaccines for control and prevention of tuberculosis in animals, which relates to the National Program Component on Disease Control Strategies. 4. What were the most significant accomplishments this past year? A. Single Most Significant Accomplishment during FY 2000 year: Improved tests for diagnosis of tuberculosis are needed so that animals infected with M. bovis can be identified and eliminated as a source of infection to other animals and human beings. ARS scientists at NADC conducted experiments to examine the immune responses of animals infected with M. bovis to identify characteristics that could be used for diagnosis of infection. We developed a rapid diagnostic test that can be used for detection of M. bovis infection in multiple species of animals. After further validation and approval, the test may be used for the national program to eradicate tuberculosis from animals in the United States. B. Other Significant Accomplishment(s), if any: In order to conduct controlled studies on tuberculosis in animals, a system to experimentally infect animals with M. bovis is needed so that they develop signs of disease that are similar to those observed in naturally infected animals. ARS scientists at NADC developed a method to experimentally infect white-tailed deer, cattle, and other animals with aerosolized M. bovis. We determined that animals experimentally infected with aerosolized develop lesions and other signs of disease that mimic those seen in naturally infected animals. M. bovis The new method for experimentally infecting animals with M. bovis is being used for controlled studies on tuberculosis in animals. C. Significant Accomplishments/Activities that Support Special Target Populations: None to report. 5. Describe the major accomplishments over the life of the project including their predicted or actual impact. Since 1998, bovine tuberculosis has been detected in 16 herds of cattle in northeast Michigan where tuberculosis is endemic in the wild white-tailed deer population. ARS scientists at the NADC experimentally infected white-tailed deer and allowed cattle to have access to feed that had been offered to the deer and to pens that had been soiled by the deer. We determined that cattle can become infected with M. bovis through indirect contact with experimentally infected white-tailed deer. These results provide evidence that cattle do not need to have direct contact with infected white-tailed deer in order for them to develop bovine tuberculosis and helps explain how cattle in Michigan became infected with M. bovis. ARS scientists at the NADC experimentally infected a group of deer and monitored routes of shedding and transmission to other deer. We determined that deer infected with M. bovis shed organisms in saliva, nasal secretions, urine and feces and that infection is readily transmitted from experimentally challenged deer to other deer sharing the same pen. These results explain how tuberculosis is transmitted within a population of deer and will be used to develop strategies for control of the disease. Current surveys to determine the prevalence of tuberculosis in wild whitetailed deer are based on examination of tissues in the head to detect lesions. In a study that involved detailed examination of the entire deer carcass, we determined that about 50% of the infected deer did
not have lesions in the head. These results indicate current methods to detect tuberculosis in wild whitetailed deer underestimate the prevalence of disease by 50% and that improved methods for detection are needed. Supplemental feeding and baiting of white-tailed deer in the winter in Michigan has been practiced for many years and is thought to contribute to the spread of M. bovis among deer. ARS scientists at the NADC experimentally inoculated samples of six feeds typically used for baiting deer and stored them for various lengths of time at different temperatures. We determined that M. bovis survives on all feeds when frozen for at least 4 months. These results have been used by regulatory officials to make recommendations regarding feeding and baiting of deer in Michigan. A new test for detection and identification of M. bovis in tissue samples that are collected for microscopic examination was developed. When animals are slaughtered, meat inspectors collect tissue samples from animals that are suspected of having tuberculosis. Tissue samples are examined for microscopic evidence of tuberculosis and for the presence of organisms. Stains used to detect M. bovis in a tissue sample also stain other organisms so that it is not possible to identify the organism in the sample. The new test detects a specific piece of DNA that is present only in organisms that cause tuberculosis. The new test permits more accurate and rapid identification of animals with tuberculosis than was previously possible. The test is used extensively at the request of state and federal regulatory officials to confirm suspected cases of tuberculosis in animals. We adapted and standardized methods for differentiation of strains of M. bovis. Differences among various strains of M. bovis can be identified by using specific genetic markers. Using these markers, it is possible to determine if different animals are infected with a common strain or different strains of M. bovis. This information is used by epidemiologists to determine possible sources of infection in outbreaks of tuberculosis in animals. 6. What do you expect to accomplish, year by year, over the next 3 years? FY 2002: 1) Further characterize the disease produced when cattle and deer are experimentally challenged with aerosolized M. bovis. 2) Determine if M. bovis can be transmitted from experimentally infected raccoons to uninfected penmates. 3) Determine routes of transmission of M. bovis from does to fawns. 4) Begin to characterize immune response of white-tailed deer to M. bovis. 5) Determine the sensitivity and specificity of a new diagnostic test 6) Continue research to develop improved methods for differentiation of M. bovis isolates. FY 2003: 1) Further characterize the progression of disease and immune responses of white-tailed deer infected with M. bovis. 2) Continue research to determine the sensitivity and specificity of a new diagnostic test. 3) Identify potential vaccines that can be used for prevention and control of tuberculosis in wildlife and domestic animals. 4) Continue research to develop improved methods for differentiation of M. bovis isolates FY 2004: 1) Determine the safety and effectiveness of candidate vaccines. 2) Continue research to develop and evaluate improved diagnostic tests. 7. What science and/or technologies have been transferred and to whom? When is the science and/or technology likely to become available to the end user (industry, farmer, other scientists)? What are the constraints if known, to the adoption & durability of the technology product? ARS scientists assigned to the Bovine Tuberculosis Research Project routinely presented research findings to scientists, state and federal action agencies, and industry groups. In some cases, results of research conducted by ARS scientists are used as the basis for regulatory action. ARS scientists received invitations to present results of research to specfic groups, such as the Michigan Department of Natural Resources, because of the direct impact that the research findings have on recommendations of the group. ARS scientists are members of several organizations, committees, and working groups and provide scientific expertise on a broad range of issues relating to bovine tuberculosis. A patent has been approved for a new test that was developed by ARS scientists for
diagnosis of tuberculosis. (Invention Report No. 0152.01 "Diagnosis of Tuberculosis Infection Through Analysis of Nitrite Production of Leukocytes Stimulated with Mycobacterial Antigens") 8. List your most important publications in the popular press (no abstracts) and presentations to non-scientific organizations and articles written about your work Presented results of research on CMU Public Television program "Bovine Tuberculosis in Michigan: The Controversy," Spring, 2001. Presented talks entitled "Use of the gamma-interferon assay for diagnosis of tuberculosis in cattle," "Naturally occurring tuberculosis in white-tailed deer" and "Raccoons and Mycobacterium bovis: Maintenance or Spill-Over Host" to participants of Bovine Tuberculosis in Michigan, conference 2001, March 5- 6, 2001, Lansing, Michigan. Registered participants of the conference included state and federal animal health officials, departments of natural resource and community health, livestock industry groups, private land owners, hunt clubs, state legislators, congressional representatives, and members of the press. Presented talk entitled "Emergence of tuberculosis in wildlife: Impact on animal agriculture and public health" at Beltsville Symposium "Healthy Animals 2000", September, 2000. PUBLICATIONS: 2000/10 TO 2001/09 1. Palmer, M.V., Whipple, D.L., Waters, WR. Experimental deer to deer transmission of Mycobacterium bovis. American Journal of Veterinary Research. 2001. v. 62. p. 692-696. 2. Palmer, M.V., Whipple, D.L. Deer to deer transmission of Mycobacterium bovis. 43rd annual meeting of the American Association of Veterinary Laboratory Diagnosticians. 2000. p. 22. 3. Waters, W.R., Palmer, M.V., Pesch, B.A., Olsen, S.C., Wannemuehler, M.J., Whipple, D.L. MHC class II-restricted, CD4+ T cell proliferative responses of peripheral blood mononuclear cells from Mycobacterium bovis-infected white-tailed deer. Veterinary Immunology and Immunopathology. 2000. v. 76 p. 215-229. 4. Waters, W.R., Palmer, M.V., Pesch, B.A., Olsen, S.C., Wannemuehler, M.J., Whipple, D.L. Lymphocyte subset proliferative responses of Mycobacterium bovis-infected cattle to purified protein derivative. Veterinary Immunology and Immunopathology. 2000. v. 77. p. 257-273. 5. Waters, W.R., Palmer, M.V., Pesch, B.A., Olsen, S.C., Wannemuehler, M.J., Whipple, D.L. Lymphocyte subset proliferative responses of Mycobacterium bovis-infected cattle: gd TCR+ and CD4+ cells are the predominant cells responding. The Great Lakes International Imaging and Flow Cytometry Association Meeting, Detroit, MI 2000. Abstract No. 14. 6. Waters, W.R., Palmer, M.V., Whipple, D.L. Lymphocyte subset proliferative responses of tuberculous cattle and white-tailed deer to Mycobacterium bovis purified protein derivative. In: Proceedings of the Keystone Symposia entitled Molecular and Cellular Aspects of Tuberuclosis Research in the Post Genome Era, Taos, NM. 2001. Abstract p. 98. 7. Whipple, D.L., Palmer, M.V., Slaughter, R.E., Jones, S.L. Comparison of purified protein derivatives and effect of skin testing on results of a commercial gamma interferon assay for diagnosis of tuberculosis in cattle. Journal of Veterinary Diagnostic Investigation. 2001. v. 13. p. 117-122.
ACCESSION NO: 0404179 SUBFILE: CRIS PROJ NO: 3625-32000-034-03R AGENCY: ARS 3625 PROJ TYPE: USDA INHOUSE PROJ STATUS: TERMINATED
START: 01 DEC 2000 TERM: 31 OCT 2001 FY: 2001 Investigators: Whipple D L; Waters W R; Palmer M V Performing Institution: National Animal Disease Ctr Ames, Iowa 50010 TRANSMISSION AND DIAGNOSIS OF MYCOBACTERIUM BOVIS INFECTION IN ANIMALS OBJECTIVES: Transmission of Mycobacterium bovis deer to cattle by exposure to feed contaminated by tuberculous white-tailed deer; in utero transmission of M. bovis in white-tailed deer; milk containing M. bovis as a source of infection for white-tailed deer fawns; and evaluation of the gamma interferon assay for diagnosis of bovine tuberculosis. APPROACH: Deer will be experimentally challenged with M. bovis and offered excess feed in a portable bunk. After deer have eaten, the bunk with feed will be moved to a pen with cattle. This will be repeated daily for up to 4 weeks. Cattle will be monitored for infection using standard diagnostic tests. Pregnant white-tailed deer will be challenged with M. bovis. About 1 week before due date, fawns will be delivered by cesarean and samples will be collected for isolation of M. bovis. Bottle-raised fawns will be fed goat milk replacer that contains different doses of M. bovis on 5 consecutive days. Fawns will be monitored for immune responses and shedding of organisms for 6 months. Animals will be necropsied and samples will be collected to evaluate distribution of lesions and organisms. The gamma interferon assay will be evaluated by comparing of the assay with those of skin testing, culture and histopathology. PROGRESS: 2000/10 TO 2001/09 1. What major problem or issue is being resolved and how are you resolving it? 2. How serious is the problem? Why does it matter? 3. How does it relate to the National Program(s) and National Component(s)? 4. What were the most significant accomplishments this past year? D. Progress Report This report serves to document research conducted under a reimbursable agreement between ARS and the USDA, Animal and Plant Health Inspection Service. Additional details can be found in the report for the parent project, 3625-32000-034-00 D, Pathogenesis, diagnosis, and epidemiology of bovine tuberculosis. Tuberculosis caused by Mycobacterium bovis has been detected in free-ranging white-tailed deer in northeast Michigan. This is the first wildlife reservoir of tuberculosis identified in the United States. Since 1998, tuberculosis has been diagnosed in 16 herds of cattle in the affected region of Michigan and white-tailed deer have been identified as the likely source of infection. Because little is known about the transmision of infection from white-tailed deer to other animals, we initiated the following research projects during FY 2001: 1) Transmission of M. bovis from white-tailed deer to cattle by exposure to feed contaminated by tuberculous deer; 2) maternal transmission of M. bovis in whitetailed deer; and 3) milk containing M. bovis as a source of infection for white-tailed deer. We are also conducting research to examine the use of the gamma interferon assay for diagnosis of tuberculosis in cattle. All of these projects are currently underway and results will be reported during FY 2002. 5.
PUBLICATIONS: 2000/10 TO 2001/09 No publications reported this period.
ACCESSION NO: 0405020 SUBFILE: CRIS PROJ NO: 3625-32000-063-00D AGENCY: ARS 3625 PROJ TYPE: USDA INHOUSE PROJ STATUS: NEW START: 27 OCT 2001 TERM: 26 OCT 2006 FY: 2002 Investigators: Whipple D L; Palmer M V; Waters W R Performing Institution: National Animal Disease Ctr Ames, Iowa 50010 DIAGNOSIS AND CONTROL OF TUBERCULOSIS IN LIVESTOCK AND WILDLIFE OBJECTIVES: Develop and evaluate improved tests for diagnosis of Mycobacterium bovis infection in different animal species; Develop improved methods for differentiation of M. bovis isolates; Characterize M. bovis infection in domestic livestock and wildlife. APPROACH: Sensitivity and specificity of tests for detection of M. bovis infection in live animals will be determined. We will determine if new antigens can be used to improve skin tests and in-vitro diagnostic tests. Improved PCR assays for direct detection of M. bovis in various specimens will be developed by modification of existing tests. Improved methods for isolation of M. bovis from various samples will be developed by changing processing methods and decontaminants. Improved methods for DNA fingerprinting of M. bovis isolates will be developed by adapting published methods. Animals will be exposed to M. bovis by different routes and clinical signs, immune system parameters, and lesion distribution will be monitored. Routes of transmission of M. bovis from infected animals to uninfected animals will be assessed by periodic sampling of oral and nasal secretions, urine, and feces. BSL-1-3-N; Certified through April 10, 2002.
ACCESSION NO: 0405543 SUBFILE: CRIS PROJ NO: 3625-32000-063-01R AGENCY: ARS 3625 PROJ TYPE: USDA INHOUSE PROJ STATUS: NEW START: 01 FEB 2002 TERM: 30 SEP 2003 FY: 2002 Investigators: Whipple D L; Waters W R; Palmer M V
Performing Institution: Agricultural Research Service Ames, Iowa 50010 DIAGNOSIS AND PATHOGENESIS OF TUBERCULOSIS IN ANIMALS OBJECTIVES: Evaluate immune responses of reindeer sensitized to Mycobacterium bovis BCG; Evaluate immune responses and diagnostic tests in reindeer experimentally infected with pathogenic M. bovis; Evaluate lesions in reindeer experimentally infected with M. bovis; Evaluate immune respones and lesion development in white-tailed deer experimentally infected with M. bovis. APPROACH: A group of reindeer will be sensitized with M. bovis BCG and matched with a group of non-sensitized control animals. Blood samples will be collected and skin tests will be conducted periodically throughout the study period. Various immune function assays will be conducted to monitor immune responses. In the second study, reindeer will be challenged with virulent M. bovis. Blood samples will be collected and skin tests will be conducted similar to the first study. In addition, tissue samples will be collected at various times to characterize the progression of disease in reindeer. Whitetailed deer will be experimentally challenged with M. bovis using two routes of inoculation and three dosages. Immune responses will be monitored by evaluating blood collected at various times and conducting skin tests. Lesions will be characterized at the conclusion of the study. BSL-1-3-N; Certified through April 10, 2002.
ACCESSION NO: 0174613 SUBFILE: CRIS PROJ NO: LAV-1856-SVM AGENCY: CSVM LA.V PROJ TYPE: STATE PROJ STATUS: EXTENDED START: 01 JUN 1995 TERM: 30 JUN 2003 FY: 2002 Investigator: Groves, M. G. Performing Institution: Pathobiological Sciences Louisiana State University Baton Rouge, Louisiana 70893 SCREENING OF COMPOUNDS FOR ANTI-TUBERCULOSIS ACTIVITY OBJECTIVES: Numerous novel synthetic compounds and natural products made available from the repositories of the NCI will be evaluated for anti-tuberculosis activity. APPROACH: Compounds are screened against M. tuberculosis H37Rv and single drug-resistant strains
of M. tuberculosis by evaluation of minimum inhibtory concentration, minimum bactericidal concentration and post-antibiotic effect, using the BACTEC 460 radiorespirometric system. Promising compounds are subsequently tested in tissue culture for cytotoxicity and ultimately in infected mice. Highly efficacious compounds may ultimately be developed as animal drugs, targeting tuberculosis in production animal medicine. PROGRESS: 2002/01 TO 2002/12 At least one-third of the world population is infected with Mycobacterium tuberculosis (Mtb) with an esitmated 3 million deaths per year. Our project is an urgent response to the need to replace our best antiTB drugs which have been rendered ineffective by the widespread prevalence of multiple drug resistance (MDR) seen in the widespread increase of TB in association with the AIDS pandemic. In the largest TB drug discovery program in the world this past year we have screened approximately 10,000 compounds of synthetic or natural origin for anti-tuberculosis (TB) activity, bringing the total tested in 5 years to more than 68,000.This program represents a unique cooperation between government agencies (NIAID,NCI, FDA), the pharmaceutical industry and international sources to coordinate and funnel test compounds for testing in the special facilities of the LSU VETMED Biocontainment Level-3 laboratory. Compounds are run through a multi-level screening program. In the primary test all compounds are tested for anti-TB efficacy in an in vitro culture screening phase to establish minimum inhibitory concentrations (MIC). Effective compounds are tested for potential toxicity in a tissue culture cytotoxicity system. Finally, effective (Low MIC) and non-cytotoxic compounds are tested for efficacy against intracellular Mtb in infected cell cultures of mononuclear phagocytes the preferred host cell of the TB bacillus.Candidate compounds that pass through all 3 test phases are referred to another lab for testing in animal models of TB. Another 10,000 compounds are being tested in a 1 year extension of this project. IMPACT: 2002/01 TO 2002/12 Failure to control the spread of MDR tuberculosis will result in a public health disaster for developed as well as developing countries. The development of new drugs is essential to control TB. PUBLICATIONS: 2002/01 TO 2002/12 No publications reported this period
ACCESSION NO: 0174625 SUBFILE: CRIS PROJ NO: LAV-1967-SVM AGENCY: CSVM LA.V PROJ TYPE: STATE PROJ STATUS: EXTENDED START: 01 JUN 1996 TERM: 30 JUN 2003 FY: 2002 Investigator: Klei, T. R. Performing Institution:
Pathobiological Sciences Louisiana State University Baton Rouge, Louisiana 70893 MAINTENANCE OF AN ARMADILLO COLONY FOR LEPROSY RESEARCH OBJECTIVES: The nine-banded armadillo is a permissive host for leprosy and is essential for providing enormous numbers of Mycobacterium leprae as a research resource. The production of M. leprae allows for the purification and production of skin test antigens for detecting new cases of clinical disease. The objective of this project is to identify, condition and screen armadillos to determine their suitability for in vivo propogation of M. leprae. APPROACH: Armadillos will be captured in the wild from areas non-enzootic for armadillo leprosy. Animals' suitability for inclusion in the colony will be determined by normal hematology, serology and fecal exams, freedom from Mycobacterium sp infections, and negative for M. leprae based on antibody titer and PCR. An assisted breeding program will be developed for captive armadillos. PROGRESS: 2002/01 TO 2002/12 Leprosy is a chronic debilitating infectious disease caused by Mycobacterium leprae. Though significant progress has been made in its treatment using multiple drug regimes, more than 850,000 new cases occurred globally in 1999. Thus technologies are needed to interrupt the transmission of leprosy and eliminate it as a public health problem. In addition, with recognition of persistence of leprosy in human populations.there has been new appreciation for the importance of detection of sub-clinical infection and occult reservoirs. A major obstacle to these lines of investigation is the fact that the leprosy bacillus cannot be cultrured in vitro. However, M. leprae can be propagated in the tissues of the infected nine banded armadillo, the only animal host known to be highly susceptible to leprosy. Through contact with NIAID we maintain a colony of more than 100 M. leprae-infected armadillos to provide the scientific community with its principal source of Mycobacterium leprae and associated research reagents. Several different strains of M. leprae are maintained and we continue a quality assurance testing program on these tissues and are refining our protocols with new research on aspects of inoculum control, animal selection, susceptibility to leprosy and testing and management of experimental infections. The highly bacilliferous tissues produced are shared principally with another contractor at Colorado State University and secondarily with other investigators around the world. IMPACT: 2002/01 TO 2002/12 The leprosy bacillus cannot be cultured in vitro. We are the world's sole source of sufficient batches of armadillo-derived M. leprae for development of skin test antigens, a potential leprosy vaccine and immunologically specific antigens required to study the basic pathogenesis of this disease. PUBLICATIONS: 2002/01 TO 2002/12 No publications reported this period
PROJECT CONTACT: Name: Klei, T. R. Phone: 225-578-9903 Fax: 225-578-9916 Email: klei@vetmed.lsu.edu
ACCESSION NO: 0190303 SUBFILE: CRIS PROJ NO: MICL01999 AGENCY: CSREES MICL PROJ TYPE: HATCH PROJ STATUS: NEW START: 01 SEP 2001 TERM: 31 AUG 2006 FY: 2002 Investigators: Bolin, S. R.; Maes, R.; Grooms, D.; Mullaney, T.; Bolin, C.; Kiupel, M.; Kaneene, J. Performing Institution: Pathobiology & Diagnostic Investigation Michigan State University East Lansing, Michigan 48824 DIAGNOSIS AND EPIZOOTIOLOGY OF EMERGING INFECTIOUS DISEASES OF LIVESTOCK AND POULTRY NON-TECHNICAL SUMMARY: Critical information is needed to detect, diagnose, and predict transmission of newly emerged infectious disease. This project will obtain information on pathogenesis and transmission of newly emerged infectious diseases of livestock and poultry. OBJECTIVES: Objective 1: Develop methods for diagnosis of emerging and reemerging diseases of livestock and poultry. The infectious agents targeted for research include bovine enteric calicivirus (BECV), Michigan rabbit calicivirus (MRCV), and porcine circovirus (PCV). Objective 2.: Determine pathogenesis, modes of transmission, and distribution of emerging diseases of livestock and poultry. The diseases targeted for research are postweaning multisystemic wasting syndrome of swine, neonatal diarrhea of cattle, and Michigan rabbit hepatitis/hemorrhagic disease. Objective 3: Determine effects of sample handling on laboratory test s for diagnosis of bovine tuberculosis. APPROACH: A) Derivation of cell lines. Primary cell lines will be derived from embryonic tissues of several species and tested for use in virus isolation. The embryos will be obtained from pregnant animals that are brought to the Animal Health Diagnostic Laboratory for necropsy examination. Either filtered fecal samples known to contain BECV, or liver homogenates know to contain MRCV, will be used to inoculate the cells. Convalescent antiserum and polymerase chain reaction (PCR) tests will be used to detect viral replication in cells. B) Expression of viral proteins. Viral proteins produced in eukaryotic
and/or prokaryotic expression systems will be used for detection of antibody against viruses that do not grow in cell culture. The baculovirus expression system has proven very useful for expression of foreign proteins and will be used extensively for production of recombinant protein. C) Nucleic acid based diagnostic tests including PCR tests and in situ hybridization will be developed for newly emerged diseases. D) Standard procedures for determining pathogenetic mechanisms, modes of disease transmission, and disease distribution will be applied to newly emeerged diseases such as postweaning multisystemic wasting syndrome and Michigan rabbit viral heaptitis. E) Determine the effects of sample handling on laboratory tests for bovine tuberculosis. The gamma interferon whole blood test for bovine TB requires viable and functional white blood cells. Blood will be subjected to conditions that affect viability white blood cells or function of white blood cells. Pokeweed mitogen will be used as a positive control to assess effects of harsh conditions on white blood cell function. PROGRESS: 2002/01 TO 2002/12 In January of 2001, an outbreak of fatal disease occured in a rabbitry in Michigan. A calicivirus was detected in tissue emulsions using negative staining and transmission electron microscopy. The nucleic acid sequence for the virus has been derived and it indicates a new group of rabbit caliciviruses has been identified. The virus did not replicate in cell culture; therefore, the gene encoding the capsid protein for that virus was cloned into a baculovirus expression system for production of intracellular antigen in cultured insect cells. This has allowed development of a diagnostic test for detection of antibody against the calicivirus in rabbit serum. The whole blood gamma interferon test for bovine tuberculosis, a reemerging disease in Michigan, was recently approved in the U.S. for use as an ancillary diagnostic procedure. During 2002, 30 cattle were sensitized with antigen from Mycobacterium bovis to evaluate effects of sample handling on performance of the gamma interferon test. Optimal holding and transport temperature for blood used in the gamma interferon test was determined to be between 4 and 15 degrees celsius. West Nile Virus (WNV) emerged in Michigan in 2001 with minimal impact on human or animal health, other than death of several crows. However, in 2002, there were numerous fatal cases of WNV infection in humans and in horses. Fatality rates also were high in several avian species in zoological collections in Michigan. Equipment has been obtained and facilities modified to allow serological surveys for WNV acitivity in 2003. IMPACT: 2002/01 TO 2002/12 The development of a diagnostic test for rabbit calicivirus has allowed screening of rabbits for viral infection before purchase for research purposes. Determining the effects of sample handling, especially holding and transport temperature for blood, has been reported to the Tuberculosis Committee of the U.S. Animal Health Association. Blood obtained as part of the tuberculosis control program in Michigan is now held between 4 and 15 degrees celsius. This has had a beneficial impact on testing cattle for tuberculosis. PUBLICATIONS: 2002/01 TO 2002/12 No publications reported this period PROJECT CONTACT:
Name: Bolin, S. R. Phone: 517-432-9926 Fax: 517-353-4426 Email: bolins@ahdl.msu.edu
ACCESSION NO: 0184774 SUBFILE: CRIS PROJ NO: MICL07645 AGENCY: CSREES MICL PROJ TYPE: SPECIAL GRANT PROJ STATUS: TERMINATED CONTRACT/GRANT/AGREEMENT NO: 00-34427-8853 PROPOSAL NO: 2000-03132 START: 01 JUN 2000 TERM: 31 MAY 2002 FY: 2002 GRANT YR: 2000 GRANT AMT: $159,035 Investigator: Kaneene, J. B.; Fitzgerald, S.; Wolf, C. Performing Institution: Population Medicine Center Michigan State University East Lansing, Michigan 48824 EPIDEMIOLOGY AND RISK ANALYSIS OF MYCOBACERIUM BOVIS IN WILD AND DOMESTIC ANIMALS IN MICHIGAN NON-TECHNICAL SUMMARY: Wild white-tailed deer in northeastern Michigan have developed a sustained bovine tuberculosis infection, which poses health threats for other wildlife, livestock, and human beings. Research on how the disease became established in deer, and how the disease is being passed from deer to other animals, is needed by state and federal agencies for the development of programs to eradicate this disease. The research is divided into three projects - epidemiological studies, an experimental study, and a risk analysis for bovine TB in northeastern Michigan using information from the first two projects. The first project, epidemiological studies, seeks to find the relationship between supplemental feeding and TB in deer; the second study looks to see if TB contamination by infected deer can be found in the environment; the third looks at other wildlife to see if they can carry TB infections; and the fourth is an epidemiological study to look at conditions that promote the spread of TB. The second project experimentally tests whether common pigeons can become infected with TB and whether they can spread the infection over large areas. The third project, the risk analysis, will develop mathematical models to describe and predict the spread of TB from deer to cattle and humans. OBJECTIVES: The research will consist of three integrated projects. Project 1: Epidemiological study of Mycobacterium bovis in wild and domestic animals - Hypothesis: The spatial distribution of TB occurrence in wild white-tailed deer is associated with the spatial distribution of supplemental feeding, physical landscape factors, and location-specific human activity. Specific Aims: A. Determine the spatial
relationships in the transmission of bovine TB in white-tailed deer, relating to supplemental feeding habits, factors in the physical landscape such as land use and land cover, and location-specific human activity. B. Determine the survivability of M. bovis in the environment (in feces, feeds, water, soils, and other substrates) C. Determine if there are other wild or domestic hosts for M. bovis transmission through epidemiologic studies of naturally infected hosts D. Determine the factors that influence the transmission of M. bovis within and across species, both captive/domesticated (deer, cattle, sheep, goats, dogs, cats) and wild (deer, elk, coyote, raccoons, opossums, mustelids, bear, bobcats) Project 2: Experimental inoculation of M. bovis into Pigeons - Hypothesis: Pigeons (Columba livia) are not highly susceptible to M. bovis infection by oral inoculation, and will not shed the organism and contribute to the spread of tuberculosis between wild and domestic mammals. Specific Aims: A. Study the relative susceptibility of pigeons inoculated with M. bovis of deer-origin by oral and intraperitoneal routes B. Attempt to isolate M. bovis from inoculated pigeons through fecal culture at multiple times post-inoculation, and from various organ tissues at multiple times post-inoculation. C. Evaluate organ tissues microscopically at multiple times post-inoculation, to understand the pathogenesis of M. bovis infection in pigeons. D. Compare experimental results on pigeons with previous studies conducted on crows and starlings. Project 3: Risk analysis of bovine TB for surveillance and control programs - Hypothesis: Risk analysis models for M. bovis infection from wildlife sources to livestock and humans will be generated. Specific Aims: A. Develop a risk analysis model of M. bovis infection in cattle and other domestic livestock, captive cervids, and humans in Michigan. B. Capture spatial and dynamic aspects of disease through wildlife and livestock populations. C. Use epidemiological parameters from Project 1 to parameterize the risk model. APPROACH: Project 1: Specific Aim A: A retrospective epidemiological study will be conducted, examining the association between M. bovis and various factors, including data on supplemental feeding, physical landscape factors, and deer. Specific Aim B: Environmental samples, including soils, feeds, water sources, and fecal material, will be taken from deer feeding sites identified in Specific Aim A. Sample materials will be collected and shipped to NVSL for bacterial isolation, identification, and typing. Specific Aim C: A cross-sectional study using information from wildlife surveillance will be used to identify different species with bovine TB. Necropsies will be conducted when possible, tissues will be examined grossly, and selected tissues will be harvested for bacterial isolation and routine histopathology and acid-fast staining. The presence of M. bovis will be confirmed through culture and PCR analysis of tissues collected at necropsy by the NVSL. Routes of infection and shedding will be assessed based on necropsy results. Specific Aim D: A retrospective epidemiological analysis will be conducted by examining the association between the transmission of M. bovis and various risk factors, including M. bovis prevalence in deer, supplemental feeding, and physical landscape factors. Project 2: M. bovis from Michigan will be propagated for use as an inoculum. Pigeons will be inoculated with by oral gavage or intraperitoneal inoculation. A second room will contain non-inoculated control birds. All birds will have fecal cultures performed pre-inoculation and on days 1, 30, 60 and 90 days. Oral-inoculated birds and control birds will have additional fecal cultures performed on days 2 and 3. Body weights will be recorded at days 0, 15, 30, 45, 60, 75, and 90. Groups of two oral-inoculated birds, two IP-inoculated birds, and two control birds will be humanely euthanized by intravenous pentobarbital on days 30, 60 and 90 pi. At necropsy, total body weights, liver, lung and spleen weights will be recorded; all tissues examined grossly; and selected tissues will be harvested for mycobacterial isolation and formalin-fixed for routine histopathology and acid-fast staining. Attempts will be made to isolate M. bovis at 30, 60, and
90 days post-inoculation, from fecal culture and various organ tissues. Organ tissues will be evaluated microscopically at 30, 60, and 90 days post-inoculation. Project 3: Risk analysis of bovine TB for surveillance and control programs Risk assessment: A prospective stochastic simulation model will be developed to estimate the risk of a dairy or beef cattle herd developing TB infection, utilizing cattle herdrelated factors, deer-related factors, and other geographic factors. Results from the risk assessment model will be forwarded to federal and state agencies, which can use this information to improve TB eradication programs, and extension which can disseminate this information to the public. The results will also be used in a proposed farm-level risk management model which will interface with the risk simulation model. PROGRESS: 2000/06 TO 2002/05 Project 1: Epidemiological study of M. bovis in wild and domestic animals Specific aims: determine 1) spatial relationships of bovine TB to deer feeding, environmental conditions, and location-specific human activity; 2) environmental survivability of M. bovis; 3) conduct studies of naturally infected hosts; 4) determine factors that influence the transmission of M. bovis in domestic and wild animals. A study was conducted to examine the association between TB in deer and location, environment, and supplemental feeding. Spatial clusters of TB were seen, and associations between risk factors and TB prevalence were found. Preliminary results have been presented at conferences, and final results are being prepared for submission to a refereed journal. Environmental samples (soil, feed, water, feces) collected at feeding sites and TB-positive farms were tested for the M. bovis by the National Veterinary Services Laboratories: 200+ samples were tested for and none yielded M. bovis. The lag time from sample collection to processing may have affected our ability to recover M. bovis. Data on other wildlife species from TB surveillance were reported (Bruning-Fann et al., 2001). Results of an epidemiological study of a cat with M. bovis will be published (Kaneene et al., 2002b). Cats and other wildlife species may contract TB through consumption of infected deer carcasses. Project 2: Experimental inoculation of M. bovis into pigeons Specific aims: 1) study the susceptibility of pigeons inoculated with M. bovis by oral and intraperitoneal routes; 2) isolate M. bovis from inoculated pigeons from feces and various organ tissues; 3) evaluate organ tissues microscopically to understand the pathogenesis of M. bovis infection in pigeons; 4) compare results on pigeons with previous studies on crows and starlings. 12 pigeons inoculated with M. bovis (6 by oral gavage and 6 by intratracheal injection) and 6 control birds were in the study. Two birds shed M. bovis 1 day post-inoculation and 0 were shedding at 30 days. One intratracheally-inoculated bird developed granulomatous pneumonia with acid-fast bacilli, and tissues were culture-positive for M. bovis. Pigeons can passively shed M. bovis in feces following inoculation. Pigeons appear refractory to oral infection, but intratracheal inoculation may lead to active disseminated infection. Results have been prepared for publication (Zwick et al., 2002). Project 3: Risk analysis of bovine TB for surveillance and control programs Specific aims: 1) develop a risk analysis model of M. bovis in Michigan livestock; 2) capture dynamic spatial aspects of disease in wildlife and livestock; 3) use results from Project 1 to parameterize the risk model. An epidemiological study of M. bovis in cervid ranches was conducted and has been published (Kaneene et al., 2002a). A case-control study of cattle herds with M. bovis was done to identify risk factors for inclusion in the risk model, and results of the study have been accepted for publication (Kaneene et al., 2002c). The risk analysis model has been developed, and a stochastic simulation model to predict herd risk for TB based on management practices is being developed.
IMPACT: 2000/06 TO 2002/05 Results of this project show that, in wildlife, supplemental feeding and the presence of specific deer habitats were associated with levels of bovine tuberculosis in the deer population, TB-infected deer were the source of infection for other wild animals, including domestic cats, and pigeons are capable of shedding M. bovis after being experimentally infected. Livestock farmers can reduce the chances of their herds becoming TB-infected by using practices that keep wildlife away from cattle and feed, such as maintaining good fencing and keeping feed and water away from wildlife. PUBLICATIONS: 2000/06 TO 2002/05 1. Bruning-Fann, C.S., Schmitt, S.M., Fitzgerald, S.D., Fierke, J.S., Friedrich, P.D., Kaneene, J.B., Clarke, K.A., Butler, K.L., Payeur, J.B., Whipple, D.L., Cooley, T.M., Miller, J.M., and D.P. Muzo. 2001. Bovine Tuberculosis in Free-ranging Carnivores from Michigan. J. Wildlife Dis. 37(1): 58-64. 2. Butler, K.L., Fitzgerald, S.D., Berry, D., Church, S., Reed, W.M., and J.B. Kaneene. 2001. Experimental Inoculation of European Starlings (Sturnus vulgaris) and American Crows (Corvus brachyrhynchos) with Mycobacterium bovis. Avian Dis. 45:709-718. 3. Kaneene, J.B., VanderKlok, M., Bruning-Fann, C.S., Palmer, M.V., Whipple, D.L., Schmitt, S.M., and R. Miller. 2002a. Prevalence of Mycobacterium bovis infection in cervids on privately-owned ranches. J Am Vet Med Assoc. 220(5):656-659. 4. Kaneene, J.B., Bruning-Fann, C.S., Granger, L.M., Miller, R., and B.A. Porter-Spalding. 2002c. Environmental and management factors associated with bovine tuberculosis on Michigan cattle farms. J Am Vet Med Assoc. (in press). 5. Kaneene, J.B., Bruning-Fann, C., Dunn, J., Mullaney, T.P., Berry, D., Massey, J., Thoen, C.O., Halstead, S., and K. Schwartz. 2002b. An Epidemiological Investigation of Bovine Tuberculosis in a Cattery. Am J Vet Res. (in press). 6. Miller, R., Kaneene, J.B., Fitzgerald, S.D., Schmitt, S.M. Evaluation of the Influence of Supplemental Feeding of White-Tailed Deer (Odocoileus virginianus) on the Prevalence of Bovine Tuberculosis in the Michigan Wild Deer Population. J Wildlife Dis. (in press, 2001). 7. Butler, K.L., Fitzgerald, S.D., Berry, D.E., Church, S.V., Reed, W.M., Sikarskie, J.G., and J.B. Kaneene. 2002. Experimental Inoculation of North American Opossums (Didelphis virginiana) with Mycobacterium bovis. J. Wildl. Dis. (in press). 8. O'Brien, D.J., Schmitt, S.M., Fierke, J.S., Hogle, S.A., Winterstein, S.R., Cooley, T.M., Moritz, W.E., Butler, K.L., Fitzgerald, S.D., Berry, D.E., and J.B. Kaneene. 2001. Some epidemiologic aspects of Mycobacterium bovis in free-ranging white-tailed deer, Michigan, USA, 1995-2000. Prev Vet Med. (in press). 9. Zwick, L.S., Fitzgerald, S.D., Berry, D., Church, S., Kaneene, J.B., Reed, W.M. Experimental inoculation of pigeons (Columba livia) with Mycobacterium bovis. 2002. Avian Dis. (in preparation). PROJECT CONTACT: Name: Kaneene, J. B. Phone: 517-353-5941 Fax: 517-432-0976
Email: kaneene@cvm.msu.edu
ACCESSION NO: 0174717 SUBFILE: CRIS PROJ NO: MO-VMRB0514 AGENCY: CSREES MO. PROJ TYPE: HATCH PROJ STATUS: TERMINATED MULTISTATE PROJ NO: NC-107 START: 01 OCT 1996 TERM: 30 SEP 2001 FY: 2001 Investigator: Estes, D. M. Performing Institution: Veterinary Medicine University of Missouri Columbia, Missouri 65211 BOVINE RESPIRATORY DISEASE: RISK FACTORS, PATHOGENS, DIAGNOSIS AND MANAGEMENT OBJECTIVES: Define molecular mechanisms of pathogenesis of bovine respiratory tract disease. APPROACH: Our studies are designed to delineate in vivo in the SCID-bo mouse, the contribution of helper and cytotoxic T cells and the cytokines they produce to elimination or control of replication of the model organism, Mycobacterium bovis. Our working hypothesis to be tested in this proposal is that resistance to or control of infection will correlate with the development of a TH1-like response (IFN- and IL-12 produced and not IL-4 or IL-10) in vivo which will augment both macrophage activation/microbicidal activities and intracellular killing of M. bovis by cytotoxic (either CD4 or CD8+) cells. We propose that in the later stages of disease, IFN- is key to maintenance and enhancement of cytotoxic T cell activity (CTL) which is required to eliminate the organism from persistently infected cells. Second, we will focus on the transcriptional control and kinetics of expression of cytokines known to function in this capacity in vivo in the manipulated (cell subset-depleted) or unmanipulated SCID-bo mouse during the innate (acute disease; first 20-30 days) and acquired response (chronic disease, >30 days). We will examine organ and local cytokine mRNA expression in vivo over time for those modulators known to serve as "early" differentiation factors for TH0 lymphocytes to potentially either TH1 or TH2-type, specifically IL-4, IL-10, IL12-p40 and IFN- .--All studies involving cytokine expression will be correlated with bacterial. PROGRESS: 1996/10 TO 2001/09 Our laboratory is evaluating DNA vaccine approaches to induction of naive and memory cytolytic T cell (CTL) to subunit antigens. This project is currently evaluating responses to an antigenic target from Mycobacterium bovis, the causative agent of bovine type tuberculosis. One potential readout following vaccination with costimulatory molecule(s) and antigen is to evaluate antigen specific CTL lines for
effector capabilities following DNA immunization under the various protocols. Thus, the first sets of experiments we performed in the chimeric mouse model were proof of concept experiments related to the practical limitations of obtaining sufficient numbers of cells of the appropriate specificity to generate T cell lines or clones. We have successfully generated antigen-specific T cell lines from immunized animals. IMPACT: 1996/10 TO 2001/09 DNA vaccines are an ideal platform for delivering antigens into the class I pathway and thus eliciting potent CTL responses. Species differences in responsiveness to CpG motifs and the resulting inflammatory response suggest the potential need for added costimulation. This series of studies have examined this requirement in part and set the stage for continuing studies in large animals. PUBLICATIONS: 1996/10 TO 2001/09 1. Zhang, Y., L.K.M. Shoda, D.M. Estes, G.H. Palmer and W.C. Brown. 2001. Activation of B lymphocytes, monocytes and macrophages of cattle by a CpG oligoedeoxynucleotide (ODN 2059) containing the GTCGTT motif. J. Inter.& Cytokine Research 21:871-881 2. 5th Annual Conference on Vaccine Research, Baltimore, MD., May 2002. Mycobacterium bovis BCG vaccination of cattle: activation and proliferation of lymphocyte subsets upon stimulation with mycobacterial antigens. W.R. Waters, B.J. Nonnecke, T.E. Rahner, M.V. Palmer, D.L. Whipple, M.R. Foote, A.C. Maue, and D.M. Estes.
ACCESSION NO: 0194275 SUBFILE: CRIS PROJ NO: MONB00032 AGENCY: CSREES MONB PROJ TYPE: ANIMAL HEALTH PROJ STATUS: NEW START: 01 OCT 2002 TERM: 30 SEP 2005 Investigator: Quinn, M. T. Performing Institution: Veterinary Molecular Biology Montana State University Bozeman, Montana 59717 ANALYSIS OF BISON INNATE DEFENSE AGAINST MICROBIAL PATHOGENS NON-TECHNICAL SUMMARY: The American Bison (Bison bison) is a wild/semi-domesticated ruminant that encounters serious infectious diseases, such as tuberculosis and brucellosis. This project studies the types of antimicrobial proteins present in bison neutrophils and how active they are against several relevant pathogens. A better understanding of these proteins could potentially lead to practical applications to controlling infectious disease in bison and other wildlife.
OBJECTIVES: We hypothesize that bison neutrophils contain mobilizable proteins, which have direct antimicrobial properties with therapeutic potential against persistent bison diseases such as tuberculosis. To address this hypothesis, we propose the following aims: 1) Characterize biochemically and functionally the types of antibacterial proteins present in bison neutrophils and 2) Probe for and clone selected bison neutrophil antimicrobial proteins. APPROACH: Objective 1 will require the collection of blood from captive bison and further isolation and purification of neutrophils. We will then use one or more procedures to extract a subset of proteins, which is likely to contain neutrophil antimicrobial proteins (AMPs), as determined by bacterial killing assays. Finally, we will systematically screen the proteins we have extracted, for killing activity against E. coli, S. aureus, and M. bovis BCG. Following completion of objective 1, we hope to have identified one or more proteins that have interesting antimicrobial activity; we then propose to find and clone the gene(s) for these proteins, so that they can be produced as recombinant proteins for further detailed mechanistic and microbiological testing. One possibility is that the protein of interest is one of the bison bactenecins, which we have already begun to characterize, and we will continue cloning these genes as described below. If the protein does not appear to be one of the bactenecins, we will use N-terminal sequencing to obtain sufficient code to design primers for further sequencing/cloning. PROJECT CONTACT: Name: Quinn, M. T. Phone: 406-994-5721 Fax: 406-994-4303 Email: mquinn@montana.edu
ACCESSION NO: 0186991 SUBFILE: CRIS PROJ NO: NYC-433333 AGENCY: CSREES NY.C PROJ TYPE: ANIMAL HEALTH PROJ STATUS: NEW START: 01 JUN 2000 TERM: 30 SEP 2004 FY: 2002 Investigator: Russell, D. G. Performing Institution: Veterinarian Microbiology & Immunology Cornell University Ithaca, New York 14853 PATHOGEN MYCOBACTERIA: M.TUBERCULOSIS, M. BOVIS, AND M. AVIUM
NON-TECHNICAL SUMMARY: Mycobacterial species are important pathogens in both animals and humans. Study into the lifestyles of mycobacteria species pathogenic to animals and humans such as M. tuberculosis, M. leprae, M. bovis and M. avium reveals extensive parallels in their mechanisms of intracellular survival and persistence. The laboratory is devoted to the study of microbial pathogens that exploit the macrophage as their host cell. OBJECTIVES: The laboratory is dedicated to the study of pathogen mycobacteria. The primary area of interests are as follows: 1. Analysis of the biology of the interaction between the macrophage and the bacillus with respect to the intracellular environment and the regulation of host cell function. 2. The elucidation of the metabolism of the intracellular bacillus and its exploitation as possible targets of drug action. 3. The appreciation of the modulation of the infection foci and the role of the granuloma in the persistence of infection. APPROACH: Cell Biology of Intracellular Infections by Mycobacterium avium: This delicate interplay between the bacterium, and its potentially microbicidal host cell is little understood. Previous work in the laboratory has fostered the belief that, with respect to the interaction with macrophages and the immune responses at site of infection, there are many parallels between pathogenic mycobacteria species, including Mycobacterium bovis. For this reason emphasis is also placed on exploitation of genetic approaches available for other mycobacterial species, notably M. tuberculosis and M. bovis, for the resolution of mechanisms common to all pathogenic mycobacteria. 2. Elucidation of Intermediate Metabolism and Carbon Source Acquisition by M. bovis and M. tuberculosis: We have extensive experience in modelling intracellular infections by both prokaryote and eukaryote pathogens and propose to apply this expertise to determining the contribution of the glyoxylate shunt pathway to infection. 3. Formation and Maintenance of the Granuloma and it role in Infection by Mycobacterium spp: We have carried out a systematic analysis of bacterial lipidoglycans released and trafficked through infected macrophages. These comprise 7 major species of lipids some, or all, capable of inducting granulomas in mice. The ability of these lipids to expand the influence of the bacteria beyond the infected macrophages and induce granuloma formation suggest that they play roles key to the evolution of this response. Our recent development of an in vivo model exploiting these lipids will enable the functional determination of the roles of these molecules in granuloma induction. PROGRESS: 2002/01 TO 2002/12 Mycobacterium tuberculosis is a phenomenally successful pathogen that infects approximately 1/3 of its host species, mankind. Its success lies in its capacity to establish and maintain its infection within the hosts' phagocytes. In the short term this is achieved through arresting the normal maturation of its phagosome and blocking its fusion with acidic, hydrolytic lysosomes. We have been studying this aspect of the pathogen's biology through the isolation of transposon-mutagenized bacteria defective in arresting the maturation of the phagosome. Mutants isolated in this screen demonstrate an altered intracellular distribution and are attenuated for survival inside macrophages. In the longer term the continuation of infection relies on the bacterium's capacity to respond to and to modulate the changing environment within the immune host. The bacterium's metabolism appears geared to respond to environmental shifts experienced in activated versus resting macrophages. In resting macrophages the bacterium replicates freely and appears to rely extensively on the TCA cycle, however upon activation of the macrophage the
bacterium mobilizes the glyoxylate cycle, usually associated with a dependence on fatty acids as primary carbon source. The promoter for the gene encoding the glyoxylate cycle enzyme isocitrate lyase appears regulated tightly by factors such as oxygen tension and carbon source. We have adopted a genetic approach that exploits this regulation to identify environmental factors and the bacterial sensors and effectors responsible for this shift. Finally, the tissue surrounding the infected macrophages develops into a granuloma. This structure, the tubercle, fulfills functions for both pathogen and host. For the host the granuloma walls off the infection and restricts spread, but for the bacterium the granuloma actually ensures persistence of the infection. The bacterium is able to persist because the granuloma structure ensures that the lymphocytes capable of activating the macrophages are maintained as a mantle or cuff around the periphery of the granuloma, away from the infected macrophages in the center. Bacterial cell wall lipids are released by intracellular bacteria and appear to play an active role in the formation and maintenance of this structure. The biological activities of these lipids are being explored in an in vivo granuloma model. IMPACT: 2002/01 TO 2002/12 Infections by Mycobacterium spp. continue to be a serious problem for the health of both humans and livestock. Results of these studies will provide a better understanding of the pathogen's biology through the isolation of transposon-mutagenized bacteria defective in arresting the maturation of the phagosome. PUBLICATIONS: 2002/01 TO 2002/12 1. Beatty, W., Rhoades, E.R., and Russell, D.G. 2002. Association of a macrophage galactose-binding protein with Mycobacterium-containing phagosomes. Cell. Microbiol. 4. 167-176. 2. Smith, C.V., Huang, C-C., Miczak, A.M., Russell, D.G., Sacchettini, J.C., and Honer zu Bentrup, K. 2003. Biochemical and Structural studies of Malate synthase from Mycobacterium tuberculosis. J. Biol. Chem. 278. 1735-1743. 3. Russell, D.G., Mwandumba, H.C., and Rhoades, E.R. 2002. Mycobacterium and the coat of many lipids. J. Cell. Biology. 158. 421-426 4. Liu, K., Yu, J. and Russell, D.G. 2003. pckA-deficient mutants of Mycobacterium bovis BCG show attenuated virulence in mice and in macrophages. Microbiology. 149. 1829-1835 5. Rhoades, E.R., Hsu, F-F., Torrelles, J.B., Chatterjee, D. and Russell, D.G. 2003. Identification and macrophage-activating activity of glycolipids released from intracellular Mycobacterium spp. Mol. Microbiol. 48. 875-888 PROJECT CONTACT: Name: Wood, J. R. Phone: 607-253-3759 Fax: 607-253-3756 Email: jrw7@cornell.edu
ACCESSION NO: 0187063 SUBFILE: CRIS PROJ NO: NYCV-433338 AGENCY: CSREES NYCV PROJ TYPE: ANIMAL HEALTH PROJ STATUS: NEW START: 01 JUN 2000 TERM: 30 SEP 2004 FY: 2002 Investigator: Russell, D. G. Performing Institution: Microbiology and Immunology Cornell University Ithaca, New York 14853 PATHOGEN MYCOBACTERIA: M. TUBERCULOSIS, M. BOVIS, AND M. AVIUM NON-TECHNICAL SUMMARY: Study into the lifestyles of mycobacteria species pathogenic to animals and humans such as M. tuberculosis, M. leprae, M. bovis and M. avium reveals extensive parallels in their mechanisms of intracellular survival and persistence. The laboratory is devoted to the study of microbial pathogens that explit the macrophage as their host cell. OBJECTIVES: The laboratory is dedicated to the study of pathogen mycobacteria. The primary area of interests are as follows: 1. Analysis of the biology of the interaction between the macrophage and the bacillus with respect to the intracellular environment and the regulation of host cell function. 2. The elucidation of the metabolism of the intracellular bacillus and its exploitation as possible targets of drug action. 3. The appreciation of the modulation of the infection foci and the role of the granuloma in the persistence of infection. APPROACH: Cell Biology of Intracellular Infections by Mycobacterium avium: This delicate interplay between the bacterium, and its potentially microbicidal host cell is little understood. Previous work in the laboratory has fostered the belief that, with respect to the interaction with macrophages and the immune responses at site of infection, there are many parallels between pathogenic mycobacteria species, including Mycobacterium bovis. For this reason emphasis is also placed on exploitation of genetic approaches available for other mycobacterial species, notably M. tuberculosis and M. bovis, for the resolution of mechanisms common to all pathogenic mycobacteria. 2. Elucidation of Intermediate Metabolism and Carbon Source Acquisition by M. bovis and M. tuberculosis: We have extensive experience in modelling intracellular infections by both prokaryote and eukaryote pathogens and propose to apply this expertise to determining the contribution of the glyoxylate shunt pathway to infection. 3. Formation and Maintenance of the Granuloma and it role in Infection by Mycobacterium spp: we carried out a systematic analysis of bacterial lipidoglycans released and trafficked through infected macrophages. These comprise 7 major species of lipids some, or all, capable of inducting granulomas in mice. The ability of these lipids to expand the influence of the bacteria beyond the infected macrophages and induce granuloma formation suggest that they play roles key to the evolution of this response. Our recent development of an in vivo model exploiting these lipids will enable the functional determination
of the roles of these molecules in granuloma induction. PROJECT CONTACT: Name: Wood, J. R. Phone: 607-253-3759 Fax: 607-253-3756 Email: jrw7@cornell.edu
ACCESSION NO: 0190583 SUBFILE: CRIS PROJ NO: ORE00031 AGENCY: CSREES ORE PROJ TYPE: ANIMAL HEALTH PROJ STATUS: REVISED START: 01 JUL 2003 TERM: 30 SEP 2004 FY: 2002 Investigator: Kent, M. L. Performing Institution: Microbiology Oregon State University Corvallis, Oregon 97331 CHARACTERIZATION OF MYCOBACTERIUM SPP. FROM FISHES OF OREGON NON-TECHNICAL SUMMARY: Diseases impact both wild and captive fishes. One of these is a bacterial disease called 'fish mycobacteriosis' or 'fish tuberculosis.' Many strains or species of Mycobacterium occur in fish, and we will use both traditional methods and molecular biology to resolve their identity. The project examines the taxonomy of Mycobacterium pathogenic bacteria in fishes in Oregon This study has demonstrated that several more Mycobacterium spp. infect fishes than previously thought. Some of these strains may be related to pathogens of humans. OBJECTIVES: Our overall objectives are 1) to continue to resolve the taxonomy of Mycobacterium species infecting various commercially important fishes in Oregon, focusing on a more variable region of the rDNA gene (ITS), 2) to evaluate the virulence of selected strains using macrophage assays, and 3) to develop PCR-based diagnostic tests using these isolates. Such tests would ultimately be employed by fish health researchers and diagnostic laboratories in the Department of Microbiology, the College of Veterinary Medicine, and Oregon Department of Fisheries & Wildlife. Moreover, with we will evaluate the potential virulence of the strains in culture to mammals and fish using in vitro macrophage models. Using human, mouse and fish cell lines we will evaluate whether strains from fish are pathogens to both mammals and humans, fish pathogens only, or merely opportunists
APPROACH: rDNA sequences.. We will obtain rDNA sequences using both direct PCR from tissues and PCR from isolated colonies In addition, we will continue to use our new primers for amplification of problematic samples, especially fish tissue samples, as they amplify smaller products and thus appear to be more sensitive for certain samples These primer sets provide SSU sequence, and to more precisely characterize and differentiate our isolates (e.g., the closely related salmonid isolates), we will examine a more variable region of the gene (the ITS) using published primers After the various isolates are sequenced, we will compare sequences using BLAST Search to compare with existing strains in GenBank. Furthermore, we will conduct phylogenetic comparisons using standard molecular systematics programs available through PAUP, etc. Virulence. We will characterize the virulence of representative strains obtained from our epidemiological and taxonomy studies using in vitro macrophage assays. To evaluate the ability of the bacterium to infect and survive in macrophages, we propose to employ the systems currently in use in Dr. Bermudez's laboratory. We plan to determine: (1) efficiency of invasion and (2) the ability of survive and replicate inside macrophages. For those experiments we propose to use carp macrophage cell line, the zebrafish macrophage cell line we have recently established from zebrafish spleens, and mouse macrophage cell line RAW 246.7. We also plan to use as controls for the experiments a human isolate of Mycobacterium avium, a fish derived Mycobacterium marinum (also a human isolate) and a non-virulent Mycobacterium smegmatis. The strain to be tested and the controls will be cultured and then used to infect macrophages in a ratio of 0.1 to 1, 1 to 1 and 10 to 1 (bacteria:macrophage). Invasion will be determined after 1 hour. The inoculum will be plated onto 7H11 agar plates to determine the number of bacteria. Infected macrophage monolayers will be washed several times with buffer in order to remove extracellular bacteria and then the monolayers will be lysed by incubating them with water for 10 min as described (Bermudez and Young 1988; Bermudez et al. 1994). Then 0.025% SDS will be added to the suspension for 10 additional minutes to prevent clumping. The suspension will be plate onto 7H11 plates to determine the number of viable intracellular bacteria. The efficiency of invasion will be calculated as a percentage of the initial inoculum used to infect the monolayers. To determine the ability of the bacteria to grow intracellularly, monolayers will be established and infected in a similar manner as described above. The intracellular bacteria will be allowed to grow and 4 and 7 days after infection the monolayers will be lysed and the number of intracellular bacteria quantified as reported (Wagner et al. 2002). The bacterial growth or decrease of the number of intracellular bacteria will be calculated as the variation of the number of bacteria inside macrophages 1 h after infection. PROGRESS: 2002/01 TO 2002/12 NEW PRIMERS: We have had moderate success amplifying 16s rDNA using the Talaat primers which worked well for cultures, but we obtained mixed results with tissue samples. We designed new primer sets, dividing this region into two sections. These sets proved to be more sensitive and we were able to obtain product from difficult tissues. ZEBRAFISH ISOLATES: (Facility 1) Using the 16S primers and restrictive enzyme approach for identification of fish mycobacteria we identified the first zebrafish isolates that we investigated as M. marinum. In contrast, when we sequenced this specimen, it clustered as a sister taxon to M. haemophilum, a human pathogen not recognized as a pathogen of fishes. We considered that this may be a terrestrial contaminant, but refuted this hypothesis as we obtained identical sequence from a PCR product amplified from the heart of additional fish from the same colony. Infected fish exhibited massive invasion and associated tissue reaction in the visceral organs. In addition, some of
the fish with the M. haemophilum-like infection showed an unusual pathological condition with numerous mycobacteria colonies within the central nervous system not associated with inflammatory changes. (Facility 2.) A second research facility suffered a massive outbreak of mycobacteriosis in which the entire colony was ultimately destroyed. Using our new 16s rDNA primers and those of Talaat et al. (1997), we also obtained 16s rDNA sequence from two zebrafish from this epizootic. This isolate cluster within a clade was comprised of M. septicum and M. peregrinum. These species are related to M. fortuitum, forming a clade of fast growing bacteria known to be pathogens of humans. (Facilty 3.) We maintain a sentinel fish monitoring program at the two zebrafish facilites at the University of Oregon Zfish Facility - i.e., exposing zebrafish to effluent water from the entire system. Although no outbreaks have been observed, we recently detected mycobacteiosis in a few sentinel fish based on histology. We have obtained an isolate from these fish in culture, and it will be added to our phylogenetic analyses. (Salmon Isolates.) We obtained five isolates from salmonids from the OSU fish pathogen culture culture at the Hatfield Marine Science Ctr . All salmonid isolates, including one from Australia were very closely related, showing only a maximum sequence difference of 4 bp over about 850 bp of the 16S rDNA. These isolates cluster together as a group, near M. chelonae, a recognized pathogen of fishes. (Marine Fish Isolates.) We obtained a culture from a moribund sable fish maintained at the Hatfield Marine Science Ctr. which was clustered with the salmonid isolates near M. chelonae. We have several kidneys (frozen) from rockfishes with Mycobacterium infections. To date we have not been able to culture Mycobacterium spp. from these tissues. However, direct PCR using new primers that we designed allowed us to obtain about 850 of reliable sequence. This specimen was identical to M. monteflorense, a recently described Mycobacterium species from moray eels from Florida. This is the first report of the infection in another fish species and from the Pacific Ocean. IMPACT: 2002/01 TO 2002/12 The genus Mycobacterium causes several diseases in animals, including tuberculosis in humans (i.e. M. tuberculosis). Particularly with emergence of AIDS, in recent years many new Mycobacterium species have been recognized as virulent or opportunistic human pathogens. Our study has revealed that several other species of Mycobacterium can cause disease in fishes than what was previously recognized, including human pathogens such as M. haemophilum. These results provide further evidence that fishes may be reservoirs for Mycobacterium infections that are potential pathogens for humans. PUBLICATIONS: 2002/01 TO 2002/12 Kent, M.L., V. Watral, J.L. Matthews, C.M. Whipps. Proceedings of the 43rd Western Fish Disease Workshop. 25- 26 June 2002. Corvallis, Oregon, p. 11. PROJECT CONTACT: Name: Kent, M. L. Phone: 541-737-5088 Fax: 541-737-2166 Email: Michael.Kent@orst.edu
ACCESSION NO: 0195831 SUBFILE: CRIS PROJ NO: ORE00275 AGENCY: CSREES ORE PROJ TYPE: HATCH PROJ STATUS: NEW START: 01 OCT 2002 TERM: 30 SEP 2007 Investigator: Kent, M. L. Performing Institution: Microbiology Oregon State University Corvallis, Oregon 97331 INFECTIOUS DISEASES OF IMPORTANCE TO WILD AND CULTURED FISHES NON-TECHNICAL SUMMARY: Fishes represent various important economic commodities in the Pacific Northwest. As with terrestrial animals, diseases may severely impact the well-being and economic viability of fish industries. This study investigates the host and geographic range, pathogenesis, taxonomy, modes of transmission, and treatment of infectious diseases of importance to wild and cultured fishes, particularly those afflicting fishes in the Pacific Northwest region. The ultimate goal of this research is to provide information to assist fish health managers and veterinarians to minimize the impact of these diseases OBJECTIVES: 1. Characterize diseases of importance to salmonids, zebrafish and rockfish. 2. Elucidate the taxonomy and phylogenetics of these diseases. 3. Develop sensitive and specific diagnostic tests for these diseases. APPROACH: 1.Diseases of importance in these fishes will be determined by complete necropsy and subsequent laboratory analyses, including pathology, bacteriology, and virology. Conducting in vivo transmission studies will elucidate the pathogenesis of various pathogens. 2.Molecular systematic approaches will lead studies on identifications and phylogenetic relationships of the pathogens in study. In addition, traditional morphology and culture characteristics will be included. 3.For bacteria and parasites, will focus on using ribosomal DNA sequences for the development of sensitive and specific PCR based tests. PROJECT CONTACT: Name: Kent, M. L. Phone: 541-737-8652 Fax: 541-737-2166 Email: michael.kent@oregonstate.edu
ACCESSION NO: 0173019 SUBFILE: CRIS PROJ NO: TEX08409 AGENCY: CSREES TEX PROJ TYPE: HATCH PROJ STATUS: EXTENDED START: 07 OCT 1996 TERM: 06 OCT 2002 FY: 2002 Investigator: Adams, L. G.; Davis, D. S.; Ficht, A. R. Performing Institution: Veterinary Pathobiology Texas A&M University College Station, Texas 77843 BOVINE & CERVID TUBERCULOSIS: DIAGNOSIS, VACCINATION, PATHOGENESIS, AND GENETIC DISEASE RESISTANCE NON-TECHNICAL SUMMARY: Tuberculosis in cattle and wildlife causes economic and public health concerns. The purpose of this project is to: 1.) Develop new diagnostic tests; 2.) Develop candidate tuberculosis vaccines for cattle and deer; 3.) Develop fundamental understanding of cattle and deer tuberculosis disease processes; and 4.) Produce cattle and deer genetically resistant to tuberculosis. OBJECTIVES: 1. Develop new diagnostic tests. 2. Develop candidate tuberculosis vaccines for cattle and deer. 3. Develop fundamental understanding of cattle and deer tuberculosis disease processes. 4. Produce cattle and deer genetically resistant to tuberculosis. 5. Assess impacts of optimally implement new technologies for control of tuberculosis. APPROACH: 1. Develop rapid and sensitive tests that permit multiple testing of the same animal and do not require repeated handling, including: PCR based tests for M. bovis specific DNA; cytokine profiles; and restriction fragment length polymorphism (RFLP) analysis of M. bovis DNA. 2. Develop a marker deletion vaccine with companion diagnostic for a specific antigen which is normally produced by the wild-type disease agent but is deleted from the vaccine strain, thus the diagnostic test recognizes only animals infected with wild-type field strains of M. bovis but not marker-deletion TB vaccinated animals. 3. Define the host-pathogen relationships that are critical to infection and development of disease following exposure of livestock to M. bovis. 4. Define major new host genes encoding factors important in the disease pathogenesis of tuberculosis infection vs. disease in these farmed species. 5. Predict the epidemiologic and economic impact and application of existing and potential strategies for eradication of TB from animals. PROGRESS: 2002/01 TO 2002/12 A search for bovine macrophage genes differentially expressed after Mycobacterium bovis infection was done by Differential Display Reverse Transcription Polymerase Chain Reaction (DDRT-PCR). The
differential expression of eight clones was confirmed by reverse Northen blot and ribonuclease protection assays. Most of the genes identified were associated with an overexpression pattern after infection. Differential gene expression was observed at all the time points studied (0, 12, 24h), however the majority of the changes in gene expression occurred at the early stages post-infection. A GenBank sequence database search identified the differentially expressed genes as the putative bovine homologues of serum amyloid A protein (SAAP), legumain, signaling lymphocytic activation molecule (SLAM), alveolar macrophage-derived chemotactic factor II, ferritin heavy-chain and osteopontin. Results from this study reveal that M. bovis modulates the gene expression of bovine macrophages shortly after infection. IMPACT: 2002/01 TO 2002/12 Better understanding of the regulation of gene expression in the bovine host target cell, the macrophage, particularly genetically controlled factors controlling survival of Mycobacterium bovis, provide the rationale for improved control of tuberculosis. PUBLICATIONS: 2002/01 TO 2002/12 1. Adams, L. G. 2001. In vivo and in vitro diagnosis of Mycobacterium bovis infection. Rev. sci. tech. Off. Int. Epiz. 20:302-324. 2. Gutierrez-Pabello, Jose A., David N. McMurray, and L. Garry Adams. 2002. Upregulation of Thymosin of B-10 by Mycobacterium bovis Infection in Bovine Macrophages is Associated with Apoptosis. Infection & Immunity, 70:2121-2127. 3. Chacon, O., Z. Feng, N.B. Harris, N.E. Caceres, L.G. Adams, and R.G. Barletta. 2002. Mycobacterium smegmatis D-alanine racemase mutants are not dependent of D-alanine for growth. Antimicrobial Agents and Chemotherapy. 46:47-54. PROJECT CONTACT: Name: Adams, L. G. Phone: 979-845-9816 Fax: 979-862-1088 Email: gadams@cvm.tamu.edu
ACCESSION NO: 0190294 SUBFILE: CRIS PROJ NO: VA-135642 AGENCY: CSREES VA. PROJ TYPE: HATCH PROJ STATUS: NEW START: 01 JUL 2001 TERM: 30 JUN 2003 FY: 2002 Investigators: Smith, S. A.; Hrubec, T. C.; Densmore, C. L. Performing Institution:
College of Veterinary Medicine Virginia Polytechnic Institute Blacksburg, Virginia 24061 DEVELOPMENT OF A TOOL TO ASSESS BACTERIAL INFECTIONS IN HYBRID STRIPED BASS NON-TECHNICAL SUMMARY: Aquaculture is one of the top 30 agricultural commodities; however, monetary losses from diseases and disease control efforts are significant. Aquaculture is hampered by a lack of tools to accurately diagnose disease. This research proposes to develop hematology and blood biochemistry as a diagnostic tool to assess bacterial diseases in hybrid striped bass and will allow producers to assess and monitor the health of their stock. OBJECTIVES: This study has 5 specific objectives: 1) Determine progressive hematologic changes associated with MAS infection by analyzing blood collected at set intervals post infection. 2) Determine any change (either activation or suppression) in macrophage function because of bacterial infection (macrophages play a crucial role in defense from bacterial pathogens). 3) Determine the pathophysiology (uptake, dissemination and tissue damage) of Aeromonas hydrophila in the tissues by histopathological evaluation. 4) Correlate the pathophysiology with changes in blood analytes, 5) Establish which blood changes, if any, are characteristic of MAS infection allowing diagnosis of diseased individuals and populations. Developing a tool for the early detection of bacterial diseases would decrease the incidence and economic loss from disease in production hybrid striped bass and would result in greater numbers of fish reaching marketable size. Additionally the results of this study will assist in the diagnosis of infectious disorders in other species of fish. APPROACH: Hybrid striped bass will be housed in 1000 gal recirculating system in a separate building from the bacteria exposed fish to prevent accidental infection of stock fish. Isolates of A. hydrophila will be obtained from the National Fish Health Research Laboratory and cultured with non-selective media. Three experimental groups of fish will be used based on route of exposure: water borne, intramuscular (IM) and saline injected controls. For the water borne challenge, bacterial suspensions will be added to the water, fish will be exposed for 30 min to the bacteria and then bacteria flushed out of the system. For the IM injections, fish will be sedated with MS-222 (150 mg/L) and injected IM with bacteria. The saline injected group will be handled similar to IM infected fish. A total of 72 fish will be used in each treatment group with18 fish placed in four replicate tanks. Fish will be acclimated to the experimental tanks for 3 weeks prior to initiating the experiment. Blood and tissue samples will be collected at 7 equally spaced time intervals following bacterial exposure and analyzed for hematological and blood biochemical parameters, macrophage activity and tissue histopathology. Fish will be rapidly netted and placed in aerated, buffered MS-222 anesthetic. When anesthetized, fish will be bled from the caudal vessels. Sampled fish will not be returned to the tanks to prevent repeat sampling of fish. For hematologic analysis, blood will be placed into individual EDTA blood tubes held on ice and analyzed for: packed cell volume, plasma protein, total red and white cell counts, differential white cell counts, hemoglobin and red cell indices (mean cell volume, mean cell hemoglobin, and mean cell hemoglobin concentration). For biochemical analysis, blood will be placed into individual heparinized tubes held on
ice. The tubes will be centrifuged immediately and the plasma removed to analyze the following with an automated chemistry analyzer: total protein, albumin, globulin, creatinine, total bilirubin, alkaline phosphatase, aspartate aminotransferase, glucose, cholesterol, sodium, chloride, potassium, calcium, magnesium, and phosphorus. Hematologic reference intervals will be determined for the stock group of fish and will be used as the standard of comparison for any changes in blood values due to the bacterial infections. Macrophages will be isolated from the spleen and pronephros of control and exposed fish at the 7 sampling times. Flow cytometry will be used to determine macrophage function and activation by monitoring chemiluminescence and phagocytic activity. Additionally, tissue samples will be collected and fixed in 10% neutral buffered formalin, paraffin embedded, sectioned, and stained with hematoxylin and eosin and Gram stain. Tissue sections will be analyzed for the presence of bacteria and pathological changes associated with the bacterial infection. The general linear model function of SAS System will be used to perform analysis of variance to test for treatment effects, time effects and treatment time interactions. Correlation will be used to associate tissue pathology with hematologic changes. PROGRESS: 2001/10 TO 2002/09 Cultured juvenile hybrid striped bass and cultured juvenile summer flounder were exposed to Mycobacterium marinum by inoculation and water borne routes, respectively. At various times postexposure, a sample of fish was collected, humanely euthanized and necropsied. Tissues were submitted for standard histopathology and a pathological description developed for the time course of the pathology associated with the infection. Both species of fish had tissue pathology as a result of the infection, but had differing courses and amounts of pathology. The hybrid striped bass typically had the classical granulomas, while the summer flounder typically had a severe granulomatous inflammatory response without discrete granuloma formation. The time course for pathology in both species was described. IMPACT: 2001/10 TO 2002/09 This study documents the progressive pathological changes in fish associated with a specific bacterial disease, mycobacteriosis, and provides a diagnostic description for assessing the health of fish in the face of this infection. As a result, veterinarians and other fish health professionals will have a method for evaluating chronic disease changes in hybrid striped bass and summer flounder. PUBLICATIONS: 2001/10 TO 2002/09 1. Hughes, K.P, R.B. Duncan. and S.A. Smith. 2002. Renomegaly associated with a mycobacterial infection in summer flounder, Paralichthys dentatus. Fish Pathology 37:83-86. 2. Hughes, K.P., R.B. Duncan, S.A. Smith. 2002. Mass in oral cavity of cultured summer flounder, Paralichthys dentatus. Lab Animal 31:25-27. 3. Wolf, J.C. and S.A. Smith. 1999. Comparative severity of experimentally-induced mycobacteriosis in striped bass Morone saxatilis and hybrid tilapia Oreochromis spp. Diseases of Aquatic Organisms. 38:191-200. PROJECT CONTACT: Name: Schurig, G. G.
Phone: 540-231-4992 Fax: 540-231-5815
ACCESSION NO: 0190298 SUBFILE: CRIS PROJ NO: VA-137185 AGENCY: CSREES VA. PROJ TYPE: ANIMAL HEALTH PROJ STATUS: NEW START: 01 JUL 2001 TERM: 30 JUN 2004 FY: 2002 Investigators: Smith, S. A.; Pasnik, D. J.; Schurig, G. G. Performing Institution: College of Veterinary Medicine Virginia Polytechnic Institute Blacksburg, Virginia 24061 IMMUNOMODULATORY EFFECTS OF RECOMBINANT MYCOBACTERIAL VACCINE IN FISH NON-TECHNICAL SUMMARY: Mycobacteriosis is a devastating bacterial disease of wild, and more importantly, cultured food fish species such as striped bass and flounder. The production of a safe, effective mycobacterial vaccine will reduce the incidence and severity of this infectious disease in commercial food fish populations allowing healthier fish to reach the market. OBJECTIVES: The goal of this project is to create a safe, effective vaccine for piscine mycobacteriosis, an important chronic, progressive bacterial disease of fish causing systemic granulomas in virtually any tissue and often leading to death of the fish. Using an established vaccine vector and protocol proven successful for a commercial brucellosis vaccine (RB51), a mycobacterial vaccine will be constructed for an aquatic strain of Mycobacterium marinum. Striped bass, an economically-important cultured food fish species shown to be highly susceptible to mycobacteriosis, will be immunized with the vaccine and both humoral and cell-mediated immunity will be monitored post-exposure. After determining the optimum concentration and route of administration necessary to generate an immune response in the fish, the effectiveness of the mycobacterial vaccine will be tested with a live bacterial challenge of immunized and non-immunized fish. Ultimately, a safe, effective mycobacterial vaccine would decrease the aquaculture industry's dependence on antibiotics, improve the overall immunocompetence and health of the fish, and decrease financial losses due to this fish disease. APPROACH: A vaccine for fish mycobacteriosis will be constructed using the M. marinum 85A protective antigen and strain RB51 of B. abortus overexpressing the Cu/Zn superoxide dismutase (SOD) antigen. The recombinant strain will be obtained by transforming strain RB51 with a pBBR1MCS-based plasmid containing the genes for SOD (sodC) and the 85A antigen (fbpA). The basis for the selection of
the 85A antigen is threefold: 1) the 85A antigen is one of the major secreted fibronectin binding proteins of all mycobacterial species including M. bovis and M. marinum, 2) the 85A antigen induces an effective protection against infection in other mycobacterial species, and 3) the 85A antigen shows high homology with various mycobacterial species suggesting that the antigen may be cross-protective against other mycobacterial species. Expression of sodC will be driven by its own promoter while that of fbpA will be driven by the groE heat shock promoter of Brucella. The fbpA from M. marinum will be obtained by amplification via PCR from the genomic DNA. Overexpression of SOD and expression of the 85A antigen in the recombinant RB51 strain will be confirmed by Western blot analysis. The recombinant strain will be subjected to heat-shock by incubating the cultures for 30 minutes at 42 degrees C to upregulate the production of the mycobacterial protein. After treatment, the bacteria will be washed in PBS, resuspended to obtain approximately 1011 colony forming units (CFU) per ml, and frozen at -80 degrees C. When the fish are ready for immunization, the bacteria will be subjected to 300 krad of radiation which renders the bacteria completely inactivated without any effect on its adjuvant and antigenic properties. Thus, the mycobacterial recombinant vaccine will be rendered completely non-infectious without changing its immunomodulatory effects. Two routes of immunization, intraperitoneal injection (IP) and water immersion (WI) will be tested. Juvenile striped bass will be divided into 5 groups/route of 140 fish each and individually identified. One group for each route will be sham-immunized with sterile saline, while the other four groups will receive concentrations of x10E8, x10E9, x10E10, and x10E11. On Days 0, 14, 28, and 42, fish will be bled and the serum analyzed by indirect ELISA for humoral antibodies to the RB51 strain of B. abortus and the M. marinum 85A antigen. The cell-mediated response will be evaluated by a lymphoproliferative assay where splenocytes will be harvested on Days 28, 42, 90, and 120 and cultured in 96-well plates in the presence of M. marinum 85A antigen, B. abortus RB51 crude extract, concanavalin A (positive control), or no additives (negative control). The cells will be cultured for 3-5 days and then pulsed with 1 micron Ci of [3H] thymidine/well for 18 hours, harvested, and placed in a liquid scintillation counter to evaluate [3H] thymidine incorporation. On Days 42, 90, and 120, fish from each group will also be challenged with M. marinum. Tissue samples of fish from this study will be routinely processed, stained with hematoxylin and eosin (H & E) and Zeihl-Neelson stain, and examined by microscopy for granulomas or other pathology. PROGRESS: 2001/10 TO 2002/09 A DNA vaccine for fish mycobacteriosis was constructed against the M. marinum 85A protective antigen using standard protocols. The basis for the selection of the 85A antigen is threefold: 1) the 85A antigen is one of the major secreted fibronectin binding proteins of all mycobacterial species including M. bovis and M. marinum, 2) the 85A antigen induces an effective protection against infection in other mycobacterial species, and 3) the 85A antigen shows high homology with various mycobacterial species suggesting that the antigen may be cross-protective against other mycobacterial species. Two routes of immunization, intraperitoneal injection (IP) and intrmuscular injection (IM) were tested. Juvenile striped bass were divided into 5 groups/route of 140 fish each and individually identified. One group for each route was sham-immunized with sterile saline, while the other four groups received concentrations of 108, 109, 1010, and 1011. On Days 0, 14, 28, and 42, fish were bled and the serum analyzed by indirect ELISA for humoral antibodies to the M. marinum 85A antigen. The cell-mediated response were evaluated by a lymphoproliferative assay where splenocytes were harvested on Days 28, 42, 90, and 120 and cultured in 96-well plates in the presence of M. marinum 85A antigen, concanavalin A (positive
control), or no additives (negative control). The cells were cultured for 3-5 days and then pulsed with 1uCi of [3H] thymidine/well for 18 hours, harvested, and placed in a liquid scintillation counter to evaluate [3H] thymidine incorporation. On Days 42, 90, and 120, fish from each group were challenged with M. marinum. Tissue samples of fish from this study will be routinely processed, stained with hematoxylin and eosin (H & E) and Zeihl-Neelson stain, and examined by microscopy for the presence of granulomas or other pathology. To date, hybrid striped bass have been immunized with the DNA vaccine and their humoral and cell-mediated immune responses have been documented. These responses appear to be dose-dependant, with higher vaccine doses eliciting stronger immune responses. Preliminary histopathology results suggest that the vaccine may have some protective effects against live bacterial challenge. IMPACT: 2001/10 TO 2002/09 As mycobacteriosis is a serious bacterial disease of cultured fish, the construction of an effective vaccine against this pathogen will protect the fish ensuring that healthier and greater numbers of fish reach marketable size. In addition, since these bacteria are potential zoonotic pathogens, a vaccine should decrease the exposure of humans to this infectious agent. PUBLICATIONS: 2001/10 TO 2002/09 No publications reported this period PROJECT CONTACT: Name: Schurig, G. G. Phone: 540-231-4992 Fax: 540-231-5815
Return to Contents
ATS Journals Online
American Journal of Respiratory and Critical Care Medicine
American Journal of Respiratory Cell and Molecular Biology
Proceedings of the American Thoracic Society
ATS GUEST SUBSCRIPTION PROGRAM FOR DEVELOPING COUNTRIES
Official Journals of the
Stanford University Libraries' HighWire Press assists in the publication of ATS Journals Online
Copyright 2005 American Thoracic Society.
http://www.atsjournals.org/ [04/01/06 2:08:11]
BUBL LINK: Tuberculosis
BUBL LINK Catalogue of Internet Resources

Home | Search | Subject Menus | Countries | Types | BUBL UK | Index
A|B|C|D|E|F|G|H|I|J|K|L|M|N|O|P|Q|R|S|T|U|V|W|X|Y|Z
Tuberculosis
Titles
1. American Lung Association: Diseases A to Z 2. Base de Dados Tropical 3. CDC (Centers for Disease Control) National Prevention Information Network 4. LungNet 5. National Jewish Medical and Research Center 6. Nursing Bibliographies 7. OMNI Subject Listing for Respiratory System 8. Respiration: International Journal of Thoracic Medicine 9. Stanford Center for Tuberculosis Research 10. TB/HIV Research Laboratory
Descriptions
American Lung Association: Diseases A to Z Information on lung cancer, tuberculosis, emphysema and A1AD related emphysema, pneumonia, sarcoidosis, influenza, HIV / AIDS and lung disease, covering the causes, types, symptoms, and treatment of each.
Author: American Lung Association Subjects: bronchitis, influenza, lung cancer, lungs, pneumonia, tuberculosis DeweyClass: 616.2 Resource type: documents
Base de Dados Tropical Bioinformatics databases and links to information on biodiversity, biotechnology and public health available in Portuguese and English. Information concentrates on issues pertaining to Brazil.
Author: Andre Tosello Foundation Subjects: biodiversity, biotechnology, brazil, tropics, tuberculosis DeweyClass: 570 Resource type: documents, index
Comments: bubl@bubl.ac.uk
CDC (Centers for Disease Control) National Prevention Information Network A national reference, referral and distribution service offering advice and help for the prevention of HIV / AIDS, STDs and TB. Includes synopses of key scientific articles and media reports, and provides details of publications on topics such as legal issues, people of colour, women, substance abuse, testing and counselling, viruses and transmission, youth, workplace issues, and treatment and care.
Author: National Center for HIV, STD and TB Prevention Subjects: aids news, hiv, tuberculosis DeweyClass: 613 Resource type: documents
LungNet Information about lung health for healthcare professionals and the public. Includes chronic bronchitis and emphysema, cystic fibrosis, influenza, lung cancer and tuberculosis.
Author: Australian Lung Foundation Subjects: bronchitis, cystic fibrosis, influenza, lung cancer, lungs, pneumonia, tuberculosis DeweyClass: 616.2 Resource type: documents
National Jewish Medical and Research Center Founded in 1899, National Jewish is a non-profit institution dedicated to enhancing prevention, treatment and cures through research, and to developing and providing innovative clinical programs for treating patients regardless of age, religion, race or ability to pay. National Jewish is the only medical and research centre in the United States devoted entirely to respiratory, allergic and immune system diseases, including asthma, tuberculosis, emphysema, severe allergies, AIDS, cancer and autoimmune diseases, such as lupus.
Author: National Jewish Medical and Research Center Subjects: allergies, asthma, diseases, preventive medicine, tuberculosis DeweyClass: 616.0 Resource type: documents
Nursing Bibliographies Regularly updated nursing bibliographies on over 100 subjects, including AIDS/HIV, bereavement, computers in nursing, infant feeding, osteoporosis, tuberculosis and women's health.
Author: Southampton University Subjects: bereavement, nursing, tuberculosis DeweyClass: 610.73
http://www.bubl.ac.uk/link/t/tuberculosis.htm (1 of 2) [04/01/06 2:18:06]
BUBL LINK: Tuberculosis

Resource type: bibliography
OMNI Subject Listing for Respiratory System Set of links to selected, evaluated and annotated Internet resources relevant to the respiratory system.
Author: OMNI, Nottingham University Subjects: asthma, lung cancer, lungs, pneumonia, tuberculosis DeweyClass: 616.2 Resource type: index
Respiration: International Journal of Thoracic Medicine Online version of the journal covering clinical and experimental investigations of the respiratory system. Features tables of contents of the latest issue, and full text versions of back issues from 1998 onwards.
Author: Karger Subjects: asthma, bronchitis, lungs, pneumonia, tuberculosis DeweyClass: 616.2 Resource type: journal
Stanford Center for Tuberculosis Research Aims to foster international collaborations between tuberculosis researchers. Includes a message board, a summary of research and access to software developed for use in molecular epidemiologic studies.
Author: Stanford University Subjects: epidemiology, tuberculosis DeweyClass: 616.9 Resource type: documents, software
TB/HIV Research Laboratory Dedicated to research into the prevention and treatment of Tuberculosis and HIV.
Author: Brown University Subjects: aids research, hiv, tuberculosis DeweyClass: 616.9 Resource type: documents
http://www.bubl.ac.uk/link/t/tuberculosis.htm (2 of 2) [04/01/06 2:18:06]
What You Need to Know About Tuberculosis, Consumption, the White Plague.
CANADA's ROLE in FIGHTING TUBERCULOSIS About Tuberculosis

What is Tuberculosis? How Does Pulmonary Tuberculosis Develop? How Can I Tell if I have Tuberculosis? Other Forms of Tuberculosis Tuberculosis in Animals Mulitiple-Drug Resistant Tuberculosis (MRTB)
http://www.lung.ca/tb/abouttb/ [04/01/06 2:19:35]
Division of Tuberculosis Elimination (DTBE) - Home Page
January 4, 2006
Contents Home Questions and Answers About TB TB Guidelines Surveillance Reports Slide Sets TB-Related MMWRs & Articles Education/Training Materials Newsletters World TB Day Resources State TB Control Offices Order Publications International Notification of TB Cases TB Education & Training Network (TB ETN) TB Information Management
News and Updates Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Settings,2005 MMWR 2005; 54 (No. RR-17, 1-141)
( December 30, 2005 )
Mycobacterium tuberculosis Transmission in a Newborn Nursery and Maternity Ward New York City, 2003 MMWR 2005; 54 (No. RR-50, 1280-1283)
( December 22, 2005 )
Guidelines for the Investigation of Contacts of Persons with Infectious Tuberculosis: Recommendations from the National Tuberculosis Controllers Association and CDC MMWR 2005; 54 (No. RR-15, 1-37)
( December 15, 2005 )
q q
Appendix A: Glossary Appendix B: Recommendations for the Investigation of Contacts of Persons with Infectious Tuberculosis (TB)
Guidelines for Using the QuantiFERON-TB Gold Test for Detecting Mycobacterium tuberculosis Infection, United States MMWR 2005; 54 (No. RR-15, 49-55)
( December 15, 2005 )
http://www.cdc.gov/nchstp/tb/ (1 of 3) [04/01/06 2:32:42]
TB Trials Consortium TB Epidemiologic Studies Consortium Laboratory Services Regional Training and Medical Consultation Centers (RTMCCs)
Links
Controlling Tuberculosis in the United States Recommendations from the American Thoracic Society, CDC, and the Infectious Diseases Society of America MMWR 2005; 54 (No. RR-12)
( November 3, 2005 )
MMWR: Errata: Treatment of Tuberculosis MMWR 2005; 52, (No. RR-11)

( January 10, 2005 )
MMWR: Update: Adverse Event Data and Revised American Thoracic Society/CDC Recommendations Against the Use of Rifampin and Pyrazinamide for Treatment of Latent Tuberculosis Infection MMWR 2003; 52 (No. 31)
( August 8, 2003 )
Highlights Regional Training and Medical Consultation Centers (RTMCCs) TB Guidance for Hurricane Katrina Workers and Evacuees Interactive Core Curriculum on Tuberculosis Webbased course TB Education and Training Resources Federal TB Task Force Plan in Response to the IOM Report MMWR: Treatment of Tuberculosis TB Treatment Guidelines in PDA Format CDC's Response to Institute of Medicine (IOM) TB Report
TB-Related Links HIV/AIDS Prevention STD Prevention
DTBE Search
Search
Back to Top of Page
You will need Adobe Acrobat Reader v3.0 or higher to read pages that are in PDF format. Download the Adobe Acrobat Reader. If you have difficulty accessing any material on the DTBE Web site because of a disability, please contact us in writing or via telephone and we will work with you to make the information available. Division of Tuberculosis Elimination Attn: Content Manager, DTBE Web site Centers for Disease Control and Prevention 1600 Clifton Rd., NE Mailstop E-10 Atlanta, GA 30333 (404) 639-8135 E-mail: tbinfo@cdc.gov
Home | What's New | Search | Site Map | Subscribe | Contact Us Accessibility | Privacy Policy Notice | FOIA CDC Home | Search | Health Topics A-Z
Centers for Disease Control & Prevention National Center for HIV, STD, and TB Prevention Division of Tuberculosis Elimination Please send comments/suggestions/requests to: tbinfo@cdc.gov
Home Page
CHATA
Community Health and Tuberculosis Australia is a charity organisation supporting prevention, treatment and research into respiratory disease at a national and international level. CHATA's mission is to develop and support innovative and effective approaches to research and development in lung health and to improve lung health in communities, with emphasis on disadvantaged groups.
Nurse training in Kiribati CHATA has completed nurse training in early 2005 at the Tungara Hospital. Click here to learn more.
2006 CHATA Research Grants
News & Events

MANDELA ON TB AND AIDS: We can't fight Aids unless we do much more to fight TB as well. Click here to read the entire speech.
CHATA funded research into an improved TB vaccine One third of the world's population is infected with tuberculosis. It's easy to see the potential benefits that a longer-lasting, more potent vaccine could bring. Click here to learn more. Improving lung health in Indonesia CHATA is funding work to minimise chronic lung disease in the Mimika District in Western Papua. Click here to learn how.
Contacting CHATA
http://www.chata.org.au/ (1 of 2) [04/01/06 5:08:20]
Home Page
If you would like to make a donation (donations of AUD$2.00 and over are tax deductible), become a member or want more information, you can contact us in any of the following ways: Mailing Address: PO Box 200 Rose Bay NSW 2029 Office Address: Norwich House Suite 2, 2 Norwich Road Rose Bay NSW 2029 Telephone: (61 2) 9371 7952 Fax: (61 2) 9371 9768 Email us on chata@chata.org.au
http://www.chata.org.au/ (2 of 2) [04/01/06 5:08:20]
Welcome to the Charles P. Felton National Tuberculosis Center
15 West 136th Street, 6th Floor New York, NY 10037
Adherence to Treatment for Latent Tuberculosis Infection: A Manual for Healthcare Providers ::View it ::Order It
http://www.harlemtbcenter.org/ (1 of 5) [04/01/06 22:19:54]
DANTB - Danida Assisted Revised National Tuberculosis Control Programme
http://www.dantb.org/ [04/01/06 22:22:20]
DEVELOPMENT OF VACCINES FOR BOVINE TUBERCULOSIS: REPORT OF THE ISG VACCINE SCOPING SUB-COMMITTEE
JULY 2003
CONTENTS. Contents Chairmans Introduction Recommendations Badger Vaccines Cattle Vaccines References Appendix 1 Appendix 2 Appendix 3 Appendix 4 Appendix 5 Appendix 6 Appendix 7 Appendix 8 Appendix 9 Appendix 10 Appendix 11 Appendix 12 Appendix 13 Appendix 14 Appendix 15 PAGE 2 3 6 8 13 16 17 23 29 39 45 48 53 58 62 69 72 82 101 106 108
Epidemiological investigations into bovine TB the potential for the use of vaccines in cattle and wildlife. Badger vaccination: ecological and epidemiological considerations BCG vaccination of wildlife BCG in wild-life and domestic livestock; virulence and efficacy Protocols for the development and evaluation of BCG vaccination against M.bovis infection in badgers Vaccines for the control of bovine tuberculosis: commercial product development and regulatory approval Issues relating to the procurement of badgers for vaccine research Feasibility & costs for providing accommodation for badgers Immunological assays to support the development and evaluation of a vaccine against badger tuberculosis Requirements of a field trial to test BCG in badgers Vaccination of badgers against bovine TB ecological considerations Vaccination of cattle with BCG to protect against M.bovis Chairmans discussion paper on format of final report Vaccination of cattle against TB Terms of Reference & Committee Members
1. CHAIRMANS INTRODUCTION. 1.1 Bovine TB is a serious disease of cattle in Great Britain. The incidence of the disease is increasing and extending beyond the traditionally TB infected areas in the West Country. It is a disease of complex epidemiology involving a wildlife reservoir of infection, the size and contribution of which to the disease in cattle, is not known. Control of the disease is ultimately likely to require a multi-faceted approach which will require a better scientific understanding of the disease in both cattle and wildlife. To achieve this, Defra has put in place a broad based programme of research on which it can be expected that future control policy options will be based. 1.2 Vaccination of either cattle or wildlife is considered to be a potential, long term, policy option. The Independent Scientific Group on Cattle TB (ISG) has previously commented on the importance of vaccine research and advised that this option should be kept under active consideration. Vaccines are often talked about in simplistic terms that ignore the paucity of scientific information available, and the financial and time dimensions required for developing a successful vaccine. This reflects a presumption that a vaccine strategy, for cattle or badgers, is scientifically, technically and operationally easy to put in place. In response to a request from ministers to better inform them on the development needs and potential value of vaccines the ISG established a Sub-Committee comprising some ISG members plus external experts (Appendix 15) to carry out an objective review of the feasibility for pursuing a TB vaccination strategy for either cattle or wildlife. Consideration was given to ongoing research and to identify further research which would be needed to develop and test vaccines and successfully extend their use into the field. 1.3 The Sub-Committee approached the task by identifying questions and issues that needed to be considered and inviting members of the SubCommittee and other external experts to prepare position papers to aid its discussions and deliberations. To fully record the approach adopted by the Sub-Committee and to illustrate the breadth of its discussions these documents form Appendices to this report. The Sub-Committee also recognised that as technology develops and new scientific data become available, further reviews are likely to be needed; the prepared position papers will form a useful reference point for future deliberations. 1.4 From an operational perspective the field use of a cattle vaccine should present few problems since there is direct access to the target species and the vaccine could be given directly to each individual animal by injection. However there are difficult scientific questions that need to be considered as well as policy issues before use of a vaccine in the field could be contemplated; it is worthy of note that all other countries with an intransigent cattle TB problem have rejected the option of using currently available cattle vaccines (in effect, only BCG is available) on the grounds of its relatively poor efficacy and that its use would limit the ability to export breeding cattle. 1.5 We recognise that the demands of an ideal cattle vaccine are particularly severe since the vaccine would need to prevent the establishment of
persistent infection and eliminate transmission. Such ideal demands will be difficult to meet and it may be that the best that can realistically be achieved is a reduction in pathology and transmission. Under current testing regimes, a vaccine should also not give a positive reading in the tuberculin skin test since this would confuse the regular herd testing procedures and create serious regulatory problems. Although it may be possible to develop a diagnostic test that distinguishes between vaccinated and infected animals, the more important issue is whether vaccinated animals, even if fully protected, may respond positively in a diagnostic test following challenge with M. bovis. This is particularly relevant, given the likelihood that a wildlife reservoir of TB infection will persist in the environment. The development of a diagnostic test that meets these requirements may prove difficult. 1.6 Currently we do not feel that a suitable candidate vaccine is available for use in cattle. Nevertheless, we believe that the option to use a cattle vaccine in the future should be retained, and ongoing research to develop candidate vaccines should continue to be supported. We recognise that adoption of vaccination would require not only more effective vaccines but also the development of improved diagnostic tests. 1.7 We have considered the potential future use of new improved vaccines in cattle either in conjunction with a new diagnostic test or on their own in the absence of herd testing. We accept that such vaccine strategies, applied either nationally or zonally, would require a significant change to TB disease control policy. Dispensing with herd testing would place greater demands on other measures for protection of public health and could require tightening of regulations concerning the sale of non-pasteurised milk products and carcass inspection in slaughterhouses. The anticipated increasingly stringent EU rules on visible lesioned carcasses would place even greater demands on a vaccine in order to avoid wasteful carcass condemnation. 1.8 The primary goal of a badger vaccine would be to reduce the rate of transmission of TB to cattle rather than to protect each individual badger. Because of this, vaccination of wildlife would require a less demanding vaccine than vaccination of cattle. Nevertheless, there are significant scientific hurdles that have to be considered and overcome, even to get to the point of conducting a field trial. Such a vaccine of course would only be effective if most cattle TB infection derived from badgers, a point that is currently being investigated in the Randomised Badger Culling Trial (RBCT). 1.9 Before serious consideration could be given to using a badger vaccine in the field, it would be necessary to establish that the vaccine will influence the course of the disease in badgers. Only then could a field trial be considered. Then the logistics of successfully vaccinating a badger population in the wild would need to be considered; this would present a major challenge and could not be undertaken lightly. It would also need to avoid non-target species. Large-scale vaccination of badgers would be necessary to have a significant impact on the disease in cattle. This would be logistically difficult to achieve without an oral vaccine, although this in turn creates its own challenges, both
in terms of developing an oral vaccine which stimulates an effective immune response and its effective delivery. 1.10 One of the problems in developing a vaccine strategy for badgers is the limited knowledge of the epidemiology and dynamics of TB in badgers. Some new epidemiological data will be forthcoming from the ongoing RBCT and other related research, which will indicate how vaccines in the field may best be utilised. There are still important issues to resolve and at the moment any attempt to model the disease, so as to provide better information on the design of potential vaccine strategies and to predict their likely outcome, has serious limitations. 1.11 The report and its appendices consider these issues, highlight the questions that the Sub-Committee has needed to address and illustrate the complexity of adopting vaccination-based TB control policies for either cattle or wildlife. The option of the use of vaccines should in our view be retained. Most of the necessary research has been commissioned, is in place and very effectively linked to an International TB vaccine development programme involving both veterinary and medical research workers. However, we have identified areas of research that we believe are necessary to ensure that progress towards taking a vaccine into the field is optimised. It is, nonetheless, clear that there is no quick fix or short cut that can be taken to speedily put in place a vaccine control policy option. In the short, or even longer term, alternative control options will need to be adopted in order to achieve better control of the disease in cattle. 1.12 I wish to thank members of the Sub-Committee and its Secretariat, for their hard work and diligence in carrying out their task. I am particularly grateful to the authors of papers that appear in the report. I hope that the report is clear and comprehensive and that it has realistically considered and presented the vaccine option. 1.13 Finally it is with great sadness that we learned of the premature and sudden death of Dr Jo Colston. Jo was a close friend to many of us. Not only was he a valued and extremely active member of the Sub-Committee but he also played a significant and important part in supporting the work of the ISG in other areas of its activity and had provided sound scientific advice to Defra, particularly on its vaccine research programme. John Bourne July 2003
2. RECOMMENDATIONS. 2.1 Badgers. 2.1.1 BCG may be of value to protect badgers but before a field trial of BCG can be put in place it is essential to await the outcome of vaccine protection studies that are currently being carried out on a population of housed wild badgers in the Republic of Ireland (RoI). We advise that even if a degree of protection is shown in these studies that success in the field cannot be guaranteed and that a field trial would inevitably have to be put in place and designed on a large scale and continue for an extended time period, in order to demonstrate its effect on the incidence of TB in cattle. 2.1.2 It will also be necessary to await the outcome of the RBCT in order to obtain essential epidemiological data on TB in the badger and the impact of badger culling on cattle TB before deciding on whether or not to proceed with a field trial. 2.1.3 A field vaccine for badgers will need to be delivered as an oral bait. Priority needs to be given to development of oral/respiratory delivery systems that are effective in stimulating protective immune responses without capture of badgers. 2.1.4 There is additional preparatory work that could be undertaken in order to enable a field trial to be in place as soon as badger vaccine protection and field trial data become available. We recommend that oral bait formulation studies be continued, and that field studies be initiated on bait uptake and bait targeting in badgers and the level of bait uptake by non-target species including cattle. 2.2 Cattle. 2.2.1 BCG is the only currently available vaccine candidate that could be considered for practical use. Experimental challenge of vaccinated cattle has demonstrated very variable protection of up to 70%, as judged by reduction in pathology, but lower levels of protection against establishment of infection. Field trials have generally provided poor protection. It is our view that BCG in its present form would not provide an effective cattle vaccine and that cattle vaccination could only be considered when an improved vaccine is available. 2.2.2 It will be imperative to maintain the current effort on development and testing of vaccines, which relates to both cattle, including neonates, and badgers, with emphasis on testing in the target species (cattle). The well developed and effective international collaborations with scientists working on vaccines for both animal and human TB must be maintained and built on. 2.2.3 We also recommend studies on the oral sensitisation of cattle with BCG and on the effect of vaccinating already infected animals particularly with respect to lesion development.
2.2.4 We recommend that greater priority be given to developing improved diagnostic tests for both cattle and badgers. 2.3 Other. 2.3.1 A large body of data on BCG safety in a number of wildlife species, based on laboratory experimentation, already exists. We recommend that an extensive literature search is carried out to collate these data.
3. BADGER VACCINES. 3.1 Introduction. 3.1.1 In its report of 1997, the Kreb's Committee recommended1 that a research programme aimed at developing a vaccine against tuberculosis for use in cattle should be implemented, although the option of developing a vaccine for use in wildlife (badgers) should also be retained. A vaccine targeted at badgers would not be required to protect individual badgers against TB, but would need to reduce transmission to cattle. Thus a vaccine which reduces the severity of the disease and/or reduces shedding of the bacteria from infected badgers could have the desired effect of reducing transmission to cattle. Of course, such a vaccine would have the additional requirement of being safe, both for the target species (badgers) and for nontarget species including domestic animals, wildlife and humans (Appendix 1). In principle developing a wildlife vaccine may be regarded as a more realistic and less long-term option than developing a cattle vaccine. However, it should be noted that, implementing a field trial to measure the effect of a wildlife vaccine on TB in cattle presents considerable challenges, and cannot be done quickly. Moreover, while there is reasonable evidence that virtual elimination of badgers has been shown to have an impact on TB in cattle, the influence of reducing the numbers of infected badgers and/or the severity of disease in affected badgers on the risk of TB in cattle is not known. Thus, any decision to proceed towards a field trial of a vaccine targeted at badgers (or other wildlife species) should await the outcome of the ongoing RBCT. We do however advise that preparatory work is put in place to inform on matters such as bait uptake and improved vaccine formulations, and thus prepare for the possibility of a trial. 3.2 Epidemiological considerations and vaccination strategies. 3.2.1. Developing and testing a vaccine for badgers remains a considerable undertaking. Even with an appropriate vaccine candidate, many hurdles remain, and even if these hurdles are overcome, there can be no guarantee of success. The development of a vaccine strategy targeted at badgers would need to address the following issues: 3.2.1.1 The expected efficacy of the vaccine, as determined by experimental protection studies. 3.2.1.2 The extent of the badger population to be covered and the optimal area of coverage required to have a measurable impact on the disease in cattle. 3.2.1.3 The route of delivery of the vaccine would need to be easy and inexpensive, and while providing the maximum possible take-up rate in badgers, it should avoid immunisation of non-target species and particularly cattle.
3.2.1.4 How would a badger vaccine be used in the field? What are the frequency and duration of vaccine application that would be required. What proportion of badgers would eat the bait? What is the duration of immunity? 3.2.2 Given the extent of the TB problem in cattle, it is likely (assuming current studies confirm that badgers are an important source of infection) that vaccination would need to be applied over large areas to have a significant impact on the problem. The rapid turnover of the badger population and the fact that vaccination is unlikely to confer complete protection also means that a vaccine would need to be administered at regular intervals (probably at least annually) over a prolonged period of time. While trapping of badgers in order to administer vaccine by injection may be justifiable under certain circumstances (e.g. to deal with small, well-circumscribed pockets of disease), it would be impractical for the more extensive application of vaccination that is required to address the problem. Such a vaccination programme would require an oral vaccine that could be delivered in the form of a bait. 3.2.3 There is currently insufficient knowledge of the epidemiology of the disease in badgers and the route and frequency of transmission to cattle, to produce simulation models for predicting the level of vaccine efficacy and determining the optimal vaccination strategy required to interrupt transmission to cattle (Appendix 2). While the RBCT will provide useful epidemiological data, quantitative information on a number of parameters relating to transmission of infection, which would be particularly useful for model construction, are extremely difficult to obtain. For these reasons the only realistic way of determining whether or not a vaccine (even if effective in badgers) has an impact on TB in cattle is to conduct a field trial to measure the effect of vaccination on the incidence of cattle herd breakdowns. The limitations in producing precise mathematical models for TB in badgers also make it impossible, at present, to predict the long-term impact of vaccination on TB in the badger population, and whether or not it might be possible to achieve eradication in local populations of badgers. 3.2.4 Considering the current situation regarding vaccine candidates, the only vaccine which is currently available and which is likely to be available within the medium term is the human vaccine, BCG (Bacille Calmette-Guerin). BCG was developed during the early part of the 20th Century. It was derived from a strain of virulent Mycobacterium bovis which became attenuated following prolonged passage in laboratory culture medium. BCG was introduced as a human vaccine on a large scale during the second half of the 20th Century and is currently one of the most extensively used vaccines available (Appendices 3 and 4). 3.2.5 Unfortunately, it has now become evident that the efficacy of BCG against the major form of TB in humans is extremely variable, ranging from 0% to approximately 80% in different trials. The basis for this variability is not fully understood. BCG has been tested in experimental conditions in a wide variety of animal species, both for efficacy against TB and for possible virulence (Appendices 3 and 4). This extensive testing of BCG in a wide variety of mammalian species has failed to reveal any substantive evidence
that the organism can cause disease (Appendix 3). At the same time, most species which have been used in experimental efficacy studies have been found to exhibit some level of protection against challenge with virulent M. tuberculosis or M. bovis. 3.2.6 The most relevant information on the potential of BCG to protect wildlife against M. bovis infection, and interrupt transmission to cattle comes from work carried out (Appendix 5) in New Zealand (NZ). In NZ the Brushtail possum is a major wildlife reservoir for M. bovis infection. In preliminary experimental studies, BCG administered to Brushtail possums by a variety of routes, including orally, gave low level protection against experimental infection with M. bovis. Subsequently a field study was carried out in which vaccinated and unvaccinated control possums were released into a study area and the amount of TB in the possum population was monitored for 2 years. The results, which because of inadequate experimental design are difficult to interpret, confirmed that BCG gave some protection to possums against M. bovis infection in this field situation although the effects on cattle TB could not be measured. Thus, these limited studies are the only grounds for considering trialing BCG for protection against TB in badgers. However, even with evidence of significant protection in badgers, it would be difficult to predict how this translates to protection of cattle. Therefore, it would be critical to design a trial to measure the impact of badger vaccination on TB in cattle. 3.3 Towards a trial of BCG vaccination of badgers. 3.3.1 Given that there is some available evidence to suggest that BCG might have a rle in the vaccination of badgers, the Sub-Committee felt it would be useful to document the steps required in developing a field trial protocol. In many ways this represents a best case scenario. Given the widespread use of BCG in the human population and the considerable background information on its safety in many species and optimal modes of administration, gaining approval to implement a field trial is likely to be considerably more straightforward than would be the case for a completely novel vaccine. 3.3.2 Regulatory considerations. 3.3.2.1 The fact that BCG has been so widely used in man, and has been extensively studied for efficacy and toxicity in a large number of wildlife and domestic species, means that many of the steps involved in authorising its use in field trials will be considerably less demanding than would be the case for a completely novel vaccine formulation. The probable steps required for authorisation have been set out (Appendix 6). 3.3.2.2 As part of the regulatory requirements for the use of BCG as a wildlife vaccine, it would be necessary to demonstrate safety and efficacy against the target species under laboratory conditions (see below); this would mean obtaining uninfected badgers from the wild for experimental purposes. The legal aspects of the Badger Act on the procurement of badgers for research purposes (see below) have been described (Appendix 7). It would also be
10
necessary to demonstrate safety in a number of non-target species that might be exposed to the vaccine. Evidence of safety could include information from previously published studies. In addition to the requirements under the Home Offices Animals (Scientific Procedures) Act of 1986, there may also be issues related to the procurement of protected species for these purposes. 3.3.3 Scientific Considerations. 3.3.3.1 Regarding experimental infection and vaccination studies, although some preliminary work has been carried out on looking at immune responses in badgers vaccinated with BCG, and on experimental infection of badgers, more work is required to demonstrate proof of principle of protection. Such work would require a source of uninfected badgers and facilities for accommodating experimental badgers, including Category 3 containment facilities. The types of experiments that would be required are set out (Appendix 5), and include a need to establish the effect of BCG vaccination not only when administered prior to infection but also when given to already infected animals. The implications for establishing experimental badger facilities are discussed (Appendix 8). Establishing experimental badger facilities would have major financial and logistical implications, particularly as Containment Level 3 facilities would be required. 3.3.3.2 An alternative option would be to make use of the information generated at the experimental badger facility in the RoI. The RoI facility has been explicitly established with a view to carrying out experimental infection and vaccinology studies. Good collaborative links already exist between UK groups (VLA) and the RoI group. A compromise strategy would be to have limited experimental facilities available in the UK to carry out vaccine dosage, vaccine delivery and purely immunological studies, but to rely on the RoI group to carry out the experimental protection studies. It is our view that duplication of the facilities is not currently justified. However since the RoI research programme is designed to address their own needs and their animal holding capacity is limited, their priorities may diverge from those required in the UK. Thus, there may be a need to review this policy in future. 3.3.3.3 Considering the delivery of BCG to badgers, the only practical means of delivering a vaccine to badgers on a wide scale, is by the oral route. Methods that combine oral and aerosol delivery are in development. In general much larger doses are required for immunisation by the oral route as opposed to delivery by injection. Although initial experimental work on the effects of immunisation with BCG is likely to involve delivery by injection to provide proof of principle, considerable research will be required to determine the optimal procedures for oral immunisation. A limitation of both oral and parenteral vaccine strategies is the difficulty of vaccinating pre-emerging cubs below ground and preventing early transmission of infection from adults in the same sett (pseudo-vertical transmission). 3.3.3.4 Regarding the diagnosis of TB in badgers, currently available badger diagnostic tests lack sensitivity. Improved tests would be extremely valuable and could be used to support epidemiological studies on the extent and
11
distribution of TB in badgers and also to develop a range of vaccination strategies. For example it has been suggested that a potential vaccination strategy for TB in badgers would be to target vaccination around infected badger social groups, communities or local populations, coupled to the coincidental culling of infected animals. Such a strategy would require a highly sensitive, cage-side diagnostic test which could be performed on living badgers; if applied along with vaccination on more than one occasion, the test would also need to distinguish between vaccinated and infected animals. However, even if this strategy was practical, it would need to be applied over a large number of local sites to have a significant impact on TB in cattle and thus would be extremely costly. Nevertheless, an improved diagnostic test that distinguished infected from vaccinated animals would also be of value for larger-scale vaccination programmes using baited vaccines, by allowing the effect of vaccination to be monitored in samples of vaccinated animals (Appendix 9). 3.4 Field trials. 3.4.1 Following successful experimental proof of principle in laboratory conditions, it would then be necessary to carry out a field trial. Some of the requirements of a field trial to test efficacy of BCG in badgers have been set out (Appendix 10 and 11). It is worth noting that it would be essential to design a badger vaccine trial which would enable the impact on TB incidence in cattle to be measured. This would be the major constraint in determining the location, size and duration of the trial. Some indication of these factors could be deduced from the on-going RBCT. As with a vaccine field trial, the culling trial is measuring the impact on the incidence of TB in cattle of an intervention from wildlife; thus one might anticipate that a vaccine trial would need to be of a scale similar to that of one of the three treatments within the culling trial. Surveying of badger setts would be required for delivery of vaccine baits, but once completed vaccination could be applied rapidly. However, because several years of vaccination may be required to have maximal effect on TB in the badger population, the effects of vaccination of badgers on TB transmission to cattle are likely to take longer to have an effect than badger culling (Appendix 2). The statistical approach would be similar to that described for the RBCT (ISG 2nd Annual Report2). 3.5 Support studies. 3.5.1 In addition to the work described above, the ability to carry out an effective vaccine trial in badgers will depend on a number of additional areas of research support. These include: 3.5.1.1 Research on vaccine delivery. For large scale vaccination of badgers, oral delivery of vaccine will be the only practical option. Research to identify appropriate baits and optimal doses of vaccine, and methodologies to measure bait uptake will be required (Appendix 11). 3.5.1.2 Immunological monitoring of effective immunisation of badgers. No information is available on the responses induced following administration of
12
BCG to wildlife in the form of an oral bait. It would be necessary, prior to a trial, to carry out experimental studies of immune responses induced following oral vaccination, in order to identify responses that can be used as markers to evaluate vaccine take (i.e., that the vaccine has successfully induced an immune response similar to that seen under experimental conditions) in samples of vaccinated badgers (Appendix 9). 3.5.1.3 The effect of exposure of non-target species to an oral vaccine. The method of vaccine delivery employed must avoid, as far as possible, uptake of bait by non-target species including domestic animals, wildlife and humans. The potential effect of vaccine uptake by the oral route in these species must also be considered. 3.6 Constraints on carrying out a vaccine field trial for badgers. 3.6.1 The cost and staff resource required to carry out the scientific studies prior to the field trial, the field trial itself, and the necessary support work is likely to be high. An estimate of costs of surveying for badger setts and bait application can be made from costs of the RBCT. An estimate of the cost of vaccination and the potential financial benefits that could result from vaccination should be possible when the method and frequency of vaccine administration are better defined. However, an accurate cost/benefit analysis could only be carried out after a field trial was completed. 3.6.2 A trial is likely to be lengthy as well as costly. It should be stressed that demonstration of vaccine efficacy under experimental conditions is no guarantee of effectiveness under field conditions and vaccination alone may not solve the problem. As a consequence the implementation of other control measures must not be relaxed. 3.6.3 Uptake of baited vaccine by cattle could potentially result in false positive tuberculin tests. While there is some evidence that oral vaccination of cattle with BCG does not result in skin-test conversion, this would need to be investigated thoroughly with the precise vaccine formulation used in the trial. 3.6.4 Other constraints to consider would be farmer compliance, interference with field operations and the practicality of baiting large areas of the countryside. 4. CATTLE VACCINES. 4.1 Introduction. 4.1.1 The requirements of a vaccine which targets cattle are somewhat different from those which target wildlife (Appendices 12 and 13). Operationally, delivering a vaccine to cattle would be much easier since it would be possible to deliver the vaccine by injection to individual animals, guaranteeing widespread coverage of the target species. Operational considerations aside however, a vaccine for cattle poses considerable difficulties. A cattle vaccine would not only have to reduce substantially
13
transmission from infected to uninfected animals but also prevent the establishment of persistent infection. None of the vaccines that have been tested so far for effectiveness against bovine TB, are efficient at preventing persistent infection. Of greater concern for the use of cattle vaccination is the likelihood that a wildlife reservoir of TB infection will persist in the environment and vaccinated cattle, even if fully protected, might respond immunologically when exposed to natural infection from this wildlife source. These animals might react positively to the skin test, or any other immunological test that might be used for diagnosis, and so with current control policy trigger a herd breakdown. 4.1.2 Vaccination of cattle against TB would require either a vaccine that is compatible with the diagnostic assay currently used for herd testing, or changes in control policies that would allow the use of alternative vaccine strategies. An over-riding consideration in introducing any new vaccine strategy would be that it did not compromise protection of human health. Thus, development of a successful vaccine strategy targeting cattle is likely to require both significant scientific advances for the development of novel candidate vaccines and diagnostics, and new approaches to disease control. 4.2 The current situation regarding vaccine candidates. 4.2.1 As discussed above, the only vaccine that is likely to be available for use in the field over the next few years is BCG. Although vaccination of cattle with BCG has been shown to reduce the severity of pathology following challenge with virulent M. bovis, a significant proportion of the vaccinated animals continue to harbour viable bacteria and have visible pathological lesions (Appendix 12). Moreover, animals vaccinated with BCG give a positive reaction in the tuberculin skin test, and hence cannot be distinguished from infected animals. Thus, current research activities aimed at generating novel candidate vaccines should be continued, but in the short term vaccination of cattle does not present a viable option. 4.3 Potential use of vaccination of cattle in the longer term. 4.3.1 Successful vaccination of cattle is likely to require significant scientific developments and changes to strategies for control (Appendix 14). For the last 50 years control of bovine TB in the UK and the rest of Europe has relied on herd testing to identify and remove infected animals. This strategy was originally adopted with the aim of eradicating the disease. The only available vaccine, BCG, was not sufficiently effective for vaccination to be considered as a primary strategy to achieve eradication, and BCG could not be used in conjunction with herd testing because of interference with interpretation of the skin test. Looking to the future, development of new diagnostics and vaccines might allow alternative control strategies incorporating vaccination to be considered. 4.3.2.1 Vaccination in conjunction with an alternative diagnostic test. Leaving aside the issue of vaccination, there is a need to improve the sensitivity of the diagnostic assay used in herd testing. Substantial research effort, funded by
14
Defra, is currently being devoted to the development of TB-specific interferongamma (IFN-) assays incorporating defined M. bovis antigens. As with the skin test, the IFN- assay measures the immunological response to M. bovis; however using state-of-the-art genomic analysis it has been possible to identify antigens which are present in M. bovis but absent in environmental mycobacteria and also absent in BCG. Thus, such an assay is likely to be more specific in defining TB infection than the existing skin test. In the short term, it is envisaged that such assays could be used in conjunction with the skin test to improve the efficiency of herd testing. It is likely that an IFN- assay with similar or superior sensitivity to that of the skin test will be developed over the next few years. If sensitivity can be achieved along with a high level of specificity, serious consideration should be given to replacing the skin test with the IFN- assay as the primary diagnostic assay for herd testing. Such a laboratory-based assay would allow improved standardisation of TB testing and require only one farm visit per test (as compared to two at present). 4.3.2.2 A diagnostic assay based on the use of defined M. bovis antigens would also potentially allow the use of vaccines that did not contain the antigens used in the diagnostic assay. For example, many of the candidate diagnostic antigens are absent from BCG but present in wild-type M. bovis, so using such a test should differentiate between infection with M. bovis and vaccination with BCG. Thus, either live attenuated or sub-unit vaccines could be considered. However, as discussed elsewhere (see 4.1.1), the diagnostic assay would not only need to distinguish infected from vaccinated animals but also infected from vaccinated immune animals that have been exposed to challenge with M. bovis. The latter might be difficult to achieve but is amenable to experimental investigation. 4.3.3 Vaccination without herd testing. Current resources for control of TB are focused on identification of animals once they have become infected with the causative organism. If wildlife is confirmed as a major source of infection and if measures to control infection in wildlife prove to be impractical, unacceptable or ineffective, this control strategy will have a limited impact on the problem and will continue to consume a large amount of resource. An alternative, though radical approach would be to use vaccination of cattle as the primary means of control in affected regions, dispense with routine herd testing and focus resources on detection of infected carcasses in slaughterhouses coupled with a ban on the consumption of raw milk. Such a strategy would require a highly effective vaccine, which reliably prevents systemic infection and substantially reduces pathology and bacterial excretion. The principal aim would be to protect human health, by reducing bacterial excretion to a level that poses negligible risk to humans in contact with the live animal and limits pathology to avoid lesions that would lead to condemnation of the carcass at post mortem, slaughterhouse, inspection. This approach would require a vaccine with a protective effect superior to that of BCG. 4.3.4 An advantage of vaccine development in cattle is that any vaccine candidate considered suitable for field use can be tested rigorously for 15
efficacy under experimental conditions. The logistics of undertaking a field trial are also more straightforward than for badgers, in that large numbers of animals can be vaccinated rapidly and the impact of vaccination on the incidence of disease can be measured directly. However, in the case of a vaccine applied along with a new diagnostic test, information on the performance of the diagnostic test under field conditions would be required before proceeding with a vaccine trial. Trials of vaccines intended for use in the absence of herd testing would need to incorporate close monitoring of animals destined for slaughter. 4.3.5 These new vaccination strategies are dependent on advances in diagnostics and vaccine development and would require rigorous experimental and field-testing of the candidate vaccines before they could be implemented. Legislative changes would also be required to allow new TB control policies to be adopted. Nevertheless, in view of the uncertainty concerning the impact of other approaches to improving control of bovine TB, we consider that the options for vaccination of cattle need to be retained. In any event, much of the work on testing vaccine candidates is relevant to both badgers and cattle. Unlike the situation regarding development of badger vaccines, experimental bovine models for characterising TB allowing rapid testing candidate vaccines in natural target species are already in use in the UK. 5. REFERENCES. 1. Krebs, J.R (1997). Bovine Tuberculosis in Cattle and Badgers. MAFF Publications, PB3423, London. 2. An Epidemiological Investigation into Bovine Tuberculosis (1999). Second Annual Report of the Independent Scientific Group on Cattle TB. MAFF Publications, PB4870, London.
16
APPENDIX 1. EPIDEMIOLOGICAL INVESTIGATIONS INTO BOVINE TB THE POTENTIAL FOR THE USE OF VACCINES IN CATTLE AND WILDLIFE. John Bourne ISG, Location 105, 1A Page Street, London SW1P 4PQ 1. INTRODUCTION. 1.1 The ISG in co-operation with Defra has put in place a range of studies to gain more information on the epidemiology of TB in both cattle and wildlife since it is our view that only through this knowledge can sustainable control policies be developed. 1.2 Full details of the scientific approach taken and the research now in place, which includes vaccine research, can be found in the Groups reports to Ministers (2000, 2001). 1.3 The use of vaccines in either cattle or badgers remains a potential policy option, although we regard this option as offering prospects only in a long term context and also caution that success cannot be guaranteed. The demands of an acceptable cattle vaccine are particularly severe since it would need both to prevent the establishment of persistent infection and to eliminate transmission. Additionally, it should not give a positive reading in the tuberculin skin test since this would confuse the regular herd testing procedure and create serious regulatory problems. However, an additional concern about the use of cattle vaccination in Great Britain relates to the strong likelihood that a wildlife reservoir of TB infection will persist in the countryside environment, and exposure of cattle protected by a successful vaccine to this source of infection would result in immunological responses which may compromise the skin test. 1.4 Any diagnostic test based upon detecting an immune response would need therefore to distinguish immune responses generated following infection from those elicited following challenge of a protected vaccinated animal. This would be difficult to achieve. In addition, to being highly sensitive such a test would have to have a high level of specificity for it to be acceptable, since false positive reactions would trigger a herd breakdown control response. 1.5 Nonetheless, we support continuation of the cattle vaccine research and its co-ordination with human TB research, since new technologies are continually developing which may be applicable to cattle vaccine development. Experimental infection of cattle with TB also provides a model of the natural disease, which will provide information on the immunology and pathogenesis of bovine TB relevant to vaccine development for both cattle and badgers and also to the development of improved diagnostics.
17
1.6 By contrast with the cattle situation, vaccination of wildlife would require a less demanding vaccine since, although widespread coverage would be the target, protection of each individual animal would not be essential. The primary rle of a wildlife vaccine would be to reduce the severity of disease in the target species and the consequent rate of transmission to cattle. However, a wildlife vaccine would only be effective in controlling TB in cattle if most cattle TB infections derived from wildlife, a point that at present is in doubt. 1.7 If an effective vaccine was available for wildlife, the logistics of vaccinating a badger population in the wild presents enormous challenges. The effectiveness of vaccination is likely to be greatly influenced by the route of administration, but there are practical constraints on which route can be employed; oral vaccination is likely to be the preferred route for use in the badger but by this route it may be difficult to achieve a protective immune response. 1.8 If the strategy of badger vaccination is to be seriously pursued, experimental facilities to conduct pathogenesis and vaccination challenge studies would have to be made available. This will necessitate sourcing TBfree badgers and possibly rearing offspring that can be used for experimental studies in disease secure high containment facilities. A more demanding requirement will be to validate the potential vaccine in the field and to determine how its success would be measured particularly as we currently have no reliable rapid live test for TB infection in badgers. A further consideration is the possibility of transmission of a wildlife vaccine to other wildlife, domestic animals, man and also to cattle, and the impact that that might have on tuberculin testing in cattle. 1.9 While there is strong pressure from some groups for successful vaccination of cattle or badgers to be considered as the preferred strategy there are many difficult issues to be addressed if this policy is to be pursued. 1.10 The purpose of the present exercise is to consider these issues and to assist the ISG in further advising Ministers on the requirements for pursuing the vaccination strategy. 1.11 There are two issues to consider, namely a badger vaccine and a cattle vaccine. 2. BADGER VACCINE. 2.1 We must consider the factors that could influence the impact of vaccination and these are listed below. 2.1.1 The contribution badgers make to bovine TB. 2.1.2 The extent of reduction in transmission to cattle achieved by vaccination.
18
2.1.3 The pattern of disease in badger populations, including prevalence, clustering, the rle of super-excretors, the proportion of badger populations that can be vaccinated or need to be vaccinated and cycles of infection. 2.1.4 The value of simple modelling. 2.2.1 Regarding vaccine candidates, BCG must be considered as it available from established sources, it is cheap, its safety in man has been established, it has been shown to influence disease in badgers and protect possums and it would allow a fast-track time-frame. 2.2.2 New vaccine candidates must be considered as research is on-going, but their time-frame is unknown. 2.3 The protective activity of candidate vaccines must be established. An immune effect and some protection can be demonstrated following intradermal vaccination of badgers with BCG, but effects on bacterial excretion and transmission has not been studied in detail and duration of immunity has not been determined. Pathogenesis / protection studies are required to provide information on protective potential. The following need to be considered. 2.3.1 The sourcing TB-free badgers. 2.3.1.1 The number of badgers required per year. 2.3.1.2 Should we use wild or captive badgers? 2.3.1.3 The need to establish a breeding colony. 2.3.1.4 The size and fecundity of captive badgers. 2.3.1.5 Badger genetic variability. 2.3.1.6 Ethical considerations must be considered. 2.3.1.7 English Nature licensing must be investigated. 2.3.2 The facilities for experimental work on badgers must be considered. 2.3.2.1 Disease containment would be an HSE responsibility. 2.3.2.2 The Home Office licensing requirements must be adhered to. 2.3.3 Experimental models must be considered. 2.3.3.1 We should consider an infectious disease and challenge model. 2.3.3.2 Immune reagents should be investigated; some are now available.
19
2.3.3.3 Previous exposure to M. bovis or environmental mycobacteria should be considered. 2.3.4 The costs and time frame must be examined. 2.4 The route of vaccine delivery must be investigated. Oral, might be preferable but might not immunise; aerosol is logistically difficult, but would injection be logistically impossible? 2.5 Field trial validation must be investigated. How are protective effects of vaccination on disease in badgers and cattle measured? 2.5.1 Current live tests to diagnose TB in the badger or other wildlife have low sensitivity; if sensitive tests were available, a large scale trial would be required to evaluate the impact on badger TB (is there dependence on prevalence?). 2.5.2 To measure the effect on cattle TB herd breakdowns would necessitate a field trial of similar scale and time-frame to the ongoing culling trial. 2.5.3 Interaction with environmental mycobacteria should be investigated. 2.5.4 The costs and time frame must be examined. 3. CATTLE VACCINE. 3.1 The potential value must be investigated. 3.1.1 This would require a highly effective vaccine. 3.1.2 We should investigate a differential diagnostic test that distinguishes infected animals from vaccinated animals, including successfully vaccinated animals exposed to challenge. 3.1.3 EU legislation and trade issues must be examined. 3.2 Vaccine candidates must be examined. 3.2.1 Is BCG sufficiently effective? 3.2.2 New vaccine candidates must be examined - research is already ongoing. 3.2.3 The time frame must be considered. 3.3 The protective activity of candidate vaccines should be established. 3.3.1 Some experimental facilities are available; is there a requirement for more?
20
3.3.2 Experimental challenge models should be established. 3.3.3 Are immune reagents available? 3.3.4 Relevant pathogenesis studies are now ongoing. 3.3.5 Rapid testing of promising vaccine candidates and diagnostic tests would be required. 3.4 Regarding vaccine delivery, easy administration by a variety of routes must be examined. 3.5 A field trial will need evaluation. 3.5.1 The design should be conventional. 3.5.2 The effect on cattle TB breakdowns should be measurable. 3.5.3 Are diagnostic tests on live animal available? 3.5.4 A differential test is required; infected/vaccinated, and vaccinated animals following field challenge? 3.5.5 The effect of environmental mycobacteria must be examined. 3.5.6 The costs and time frame must be examined. 4. GENERAL (APPLICABLE TO BOTH CATTLE AND WILDLIFE). 4.1 Safety. 4.1.1 The impact on the food chain is important. 4.1.2 Environmental contamination, excretion, the effect on other wildlife and domestic animals must be examined. 4.1.3 The compatibility with TB testing should be evaluated. 4.1.4 The experimental work needs to incorporate an evaluation of safety. 4.1.5 The time frame, costs and facilities must be considered. 4.2 Regarding registration / legislation: 4.2.1 Different for a Non GMO or GMO-based vaccine. 4.2.2 EU registration / legislation must be followed. 4.2.3 Time frame and cost must be considered.
21
4.2.4 VMD and industry input must be considered. 4.3 An economic and cost/benefit analysis should be undertaken, and who pays? 4.4 Other considerations are: 4.4.1 Political acceptability. 4.4.2 To be effective will vaccination of wildlife have to be complemented by culling? 4.4.3 We must consider the New Zealand control model. 4.4.4 We must consider the opportunities to be gained from collaboration with other workers. 4.4.5 Southern Ireland (badger studies) will be relevant. 4.4.6 New Zealand (possum studies) will be relevant. 4.4.7 Do we need to wait for culling Trial data / results before advising on the commitment of significant expenditure? 4.4.8 The public perception of food products from vaccinated cattle must be considered. 4.4.9 The long term production of disease susceptible populations must be considered.
22
APPENDIX 2. BADGER VACCINATION: CONSIDERATIONS ECOLOGICAL AND EPIDEMIOLOGICAL
Rosie Woodroffea and Christl Donnellyb a. Department of Wildlife, Fish and Conservation Biology, University of California, One Shields Avenue, Davis, CA95616-8751, USA. b. Department of Infectious Disease Epidemiology, Imperial College School of Medicine, St. Mary's Campus, Norfolk Place, London, W2 1PG 1. INTRODUCTION AIMS OF A VACCINATION PROGRAMME. 1.1 In judging the likely effectiveness of a badger vaccination programme, it is important to bear in mind precisely what such a programme might be expected to achieve. Administration of vaccines might have one or two possible impacts on individual badgers, leading to different population effects and, potentially, to different impacts on cattle exposure to M. bovis. First, vaccination might be intended to render badgers immune to M. bovis infection. This classical effect of vaccination could be expected to control (and, given sufficient coverage and efficacy, ultimately to eradicate) M. bovis infection in the badger population, hence reducing exposure of cattle to M. bovis. Alternatively, and less optimistically, administration of vaccines might be intended to reduce bacterial shedding by infected badgers. This effect a more realistic expectation of BCG vaccination could also reduce exposure of cattle (and other badgers) to infection. Reducing bacterial shedding might contribute to local eradication of infection; however it might also contribute to disease control even if eradication is not achieved, and is therefore worthy of consideration in its own right. 2. IF VACCINATION PROMOTES IMMUNITY: ERADICATING TB FROM BADGER POPULATIONS. 2.1 Many infectious diseases have been successfully eradicated by use of vaccination programmes. The eradication of rabies from populations of red foxes (Vulpes vulpes) on mainland Europe through oral vaccination is a frequently cited success story (e.g. Artois et al., 2001). 2.2 Understanding how vaccine-induced immunity leads to the eradication of infection demands an understanding of basic epidemiology. Pathogens can persist in host populations only if each infected host, on average, infects one or more susceptible hosts. If the average number of new hosts infected per case (termed R0 in a fully susceptible population) drops below one, then the pathogen population will die out. Persistence, then, requires a supply of susceptible hosts. By inducing immunity in hosts that have not been naturally infected, vaccination reduces the supply of susceptible hosts available to the pathogen. If a high enough proportion of hosts is rendered immune through vaccination, the average number of new hosts infected per case can be forced
23
below one, and the pathogen will die out. The higher R0, the greater the proportion of hosts that must be vaccinated to achieve eradication. Estimation of R0 is therefore vital to determine the proportion of hosts that must be kept immune through vaccination in order to achieve eradication. 2.3 Eradication of TB infection from closed badger populations is clearly theoretically possible. However, several technical barriers make it unlikely that eradication could be achieved at present. 2.3.1 The only vaccine currently available BCG has not been shown to confer immunity to experimental challenge with M. bovis. Twelve badgers vaccinated with BCG in captivity showed immune responses to vaccination (Stuart et al., 1988). However, when seven of these were subsequently challenged by intradermal injection of M. bovis they did become infected (though they lived longer, and shed fewer bacteria), than did three unvaccinated controls (Stuart et al., 1988), although it is not clear to what extent experimental intradermal infection mimics natural exposure. It is possible that reduced bacterial excretion by infected but vaccinated badgers could reduce transmission and help to control the disease; however, in the absence of any data on TB transmission routes among badgers, and on how bacterial excretion influences infectiousness, it is impossible to make quantitative predictions. 2.3.2 Estimation of the proportion of animals to be vaccinated requires an estimate of R0. This requires basic epidemiological data which are, unfortunately, not currently available for TB in badgers. Existing models (e.g. White & Harris, 1995; Smith et al., 1995) do predict population density and group size thresholds for the persistence of TB in badgers. Unfortunately these models largely fail to capture the observed distribution of infection (disease persists in much lower-density populations than predicted). This suggests either that some component of disease dynamics, such as social perturbation effects (Swinton et al., 1997) or infection from alternative host species, is important in the natural system but missing from the base models, or that models have been incorrectly parameterised, due for example to the sparse data available from a limited number of badger studies. In either case, these models currently have limited predictive value but data generated by the randomised badger culling trial (RBCT) may lead to the use of more accurate parameter values of similar models, and may allow estimation of the proportion of badgers that would have to be made immune to TB to reduce transmission rates below the required threshold. Such estimates would then need to be combined with measures of vaccine efficacy to allow approximate calculation of the vaccine coverage required to achieve eradication. In the absence of reliable data on either TB transmission rates within badger populations, or vaccine efficacy, it is impossible to know whether the bait uptake rates (and hence the potentially achievable vaccination coverages) reported in Appendix 11 are acceptably high. 2.3.3 Classical disease eradication through vaccine-induced immunity requires vaccinating individual hosts before they are exposed to infection. If initial exposure occurs in young cubs that have not yet emerged from the sett,
24
it would be virtually impossible to vaccinate prior to exposure. Hughes et al. (1996) suggest that cubs might be vaccinated through regurgitation of baits by their mothers, but, since regurgitation has been recorded only very rarely, this possibility remains speculative. Pre-exposure vaccination might become possible several years into a vaccination campaign, if transmission rates could be reduced such that animals were first exposed at a later age; however it is not possible to predict whether or when this might be possible. 2.3.4 While driving the average number of new hosts infected per case below one will eradicate infection eventually (in the absence of reinfection from outside sources), the process may be slow in a disease with a long infectious period. Given the longevity of badgers, the time course of eradication might be guesstimated to take more than a decade, and possibly longer. 2.3.5 Badgers are not the only species that becomes infected with TB. If badgers are the only major reservoir host for TB, then eradication of TB from badger populations could be expected to lead to disappearance of the infection from other wildlife species (as well as from cattle), just as rinderpest disappeared from African ungulate populations when it was eradicated from cattle (Plowright, 1982). Vaccination cover might be suspended at that point. However, badgers rle in maintaining TB infection in multi-host systems is currently unknown; thus it would probably be necessary to maintain vaccination coverage in the long term to avoid re-infection from other wildlife hosts, or from cattle. 3 IF VACCINATION REDUCES BACTERIAL SHEDDING: REDUCING CATTLE EXPOSURE. 3.1 As an alternative to TB eradication, vaccination of badgers might be used to reduce bacterial shedding and, hence, exposure of cattle (and other badgers) to M. bovis. BCG might fulfil this more limited rle but the potential effectiveness of such an approach cannot be predicted; ultimately, the only way to assess this would be to trial it over statistically meaningful numbers of farms but a cautious approach to this possibility would be warranted since: 3.1.1 The quantitative effect of vaccination on bacterial shedding is not well established (Stuart et al., 1988); more captive studies would be needed to further evaluate this. 3.1.2 Data are not currently available to determine how TB risk to cattle reflects bacterial shedding by badgers (or even TB prevalence in badgers). Hence it is currently impossible to know what level of shedding might be deemed sufficient to reduce cattle exposure. 4 OTHER CONCERNS ABOUT VACCINATING BADGERS. 4.1 The points raised above suggest that, at present, there can be little shortterm expectation of successfully controlling cattle TB by vaccinating badgers, irrespective of the aim of the vaccination programme. Several other concerns about these approaches also deserve attention.
25
4.1.1 What proportion of cattle TB cases originate in badgers? At present, the proportion of cattle TB cases originating in badgers is unknown. Hence, it is impossible to predict what proportion of cases might be prevented by vaccination. General models suggest that vaccination is likely to control infection more slowly and less effectively than culling (Barlow, 1996) although this would depend upon the completeness and effectiveness of vaccination compared with that of culling. Hence, as a first approximation, one might expect vaccination to be less effective than culling, unless the social disruption caused by culling greatly increases transmission rates (Swinton et al., 1997). Results of the RBCT and associated research on social disruption, should therefore help to provide a more informed picture of the possible impacts of badger vaccination on cattle TB, and thus permit a closer approximation of the potential cost-effectiveness of this approach. 4.1.2 How can the effects of vaccination be measured? Given the paucity of data on TB transmission between badgers and to cattle, and the consequent difficulties of building predictive models, at present not even the vaguest estimate of the effectiveness of badger vaccination could be achieved without a field trial. However, since general models suggest that vaccination is likely to control infection more slowly and less effectively than culling (Barlow, 1996), a vaccination trial would need to be of comparable scale, and probably greater duration, than the ongoing RBCT. Such a trial would require a very substantial investment of time and funding, with (in contrast to culling) not even anecdotal evidence to suggest a likely effect. Such an investment might be better delayed until ongoing studies provide better guesstimates of the possible effectiveness of badger vaccination in influencing cattle TB. 4.1.3 Safety concerns. Several delivery methods have been considered for badger vaccines (Appendix 11). However, remote delivery using oral baits or a combination of intranasal aerosol and conjunctival installation as used in possums (Appendix 3) is favoured, given the costs, difficulties, and variable effectiveness of capturing badgers (Hughes et al., 1996). Such remote delivery methods have the potential to expose other wildlife and of perhaps greater concern cattle to TB vaccine. Cattle vaccinated by accident in this way could be expected to react to the tuberculin test; hence badger vaccination has the potential to generate spurious and bogus breakdowns that could be extremely costly. The risks of such events need to be assessed carefully, since poorly designed or poorly implemented delivery systems could have the potential to make the situation worse rather than better. 5. CONCLUSIONS AND RECOMMENDATIONS. 5.1 The points discussed above indicate great uncertainty about the potential benefits of vaccinating badgers against TB. Using available data, it is currently impossible to predict, even in the vaguest way, whether vaccination might be expected to prove beneficial, ineffective, or damaging. While vaccination could reduce cattle exposure to M. bovis, poorly designed or laxly implemented delivery methods have the potential through accidental vaccination of cattle to cause as many TB incidents in cattle as they prevent.
26
One firm conclusion can be drawn: vaccinating badgers is not a quick fix that could be implemented outside the RBCT with any expectation of effectiveness in the short or medium term. 5.2 These discussions highlight the fact that many of the concerns about the potential effectiveness of badger vaccination stem from lack of data on the transmission of TB among badgers, and between badgers and cattle. Some of the necessary data will be provided by the ongoing RBCT and associated research. Hence, the outcome of the trial might inform expectations of the potential success of any vaccination programme and the extent to which vaccinating badgers might potentially influence cattle TB. In addition, the trial will provide much-needed data on TB epidemiology in badger populations that would help in the design of vaccination programmes. However even with trial data we will still lack some important information on transmission. 5.3 Given (i) a lack of confidence in the possible effectiveness of badger vaccination in controlling cattle TB; (ii) the cost and timescale of the field trial that would be necessary to evaluate the effectiveness of this measure; and (iii) the expectation that data from the ongoing RBCT, and associated research, will provide better estimates of what might be achievable, and how that might best be achieved, I recommend that field trials of badger vaccination are not to be carried out at this point, but that the situation be reassessed when results of the RBCT and other work become available. 6. ACKNOWLEDGEMENTS. 6.1 I would like to thank Sir David Cox for epidemiological advice during the preparation of this Appendix. 7. REFERENCES. Artois, M., Delahay, R., Guberti, V., Cheeseman, C. (2001). Control of infectious diseases of wildlife in Europe. Veterinary Journal, 162, 141-152. Barlow, N.D. (1996). The ecology of wildlife disease control: simple models revisited. Journal of Applied Ecology, 33, 303-314. Hughes, M.S., Neill, S.D., Rogers, M.S. (1996). Vaccination of the badger (Meles meles) against Mycobacterium bovis. Veterinary Microbiology, 51, 363-379. Plowright, W. (1982). The effects of rinderpest and rinderpest control on wildlife in Africa. Symposia of the Zoological Society of London, 50, 1-28. Smith, G. C., Richards, M. S., Clifton-Hadley, R. S., Cheeseman, C. L. (1995). Modelling bovine tuberculosis in badgers in England: Preliminary results, Mammalia, 59, 639-650.
27
Stuart, F.A., Mahmood, K.H., Stanford, J.L., Pritchard, D.G. (1988). Development of diagnostic tests for, and vaccination against, tuberculosis in badgers. Mammal Review, 18, 74-5. Swinton, J., Tuyttens, F., Macdonald, D. W., Nokes, D. J., Cheeseman, C. L. Clifton-Hadley, R. (1997). A comparison of fertility control and lethal control of bovine tuberculosis in badgers: the impact of perturbation induced transmission. Philosophical Transactions of the Royal Society, 264, 1-13. White, P. C. L., Harris, S. (1995). Bovine tuberculosis in badger (Meles meles) populations in Southwest England: the use of a spatial stochastic simulation model to understand the dynamics of the disease. Philosophical Transactions of the Royal Society of London, Series B, 349, 391-413.
28
APPENDIX 3. BCG VACCINATION OF WILDLIFE. Glyn Hewinson Veterinary Laboratories Agency, New Haw, Addleston, Surrey KT15 3NB 1. INTRODUCTION. 1.1 This appendix reviews current knowledge on the use and efficacy of BCG in wildlife species. It concentrates on the use of BCG in possums, ferrets and badgers although subcutaneous vaccination with between 104 to 107 cfu BCG has also been shown to confer significant protection against infection and disease in domesticated deer (Griffin et al, 1999). 2. BCG VACCINATION IN POSSUMS. 2.1 Challenge Model. 2.1.1 Two models have been developed for the evaluation of vaccines in possums. The first consists of an intratrachael inoculation of 100 - 1000 cfu of M. bovis (Aldwell et al, 1995 a & b). In this model lesions are confined to the lungs and lymph nodes of the thorax, except in the advanced stage of disease (Cooke et al, 1999). However, disease progression is more rapid than observed for natural infection and possums develop severe pneumonia six to eight weeks after challenge. More recently a low dose aerosol challenge model has been developed using an aerosol-generating chamber in which a dose of 104 cfu in the nebuliser produces eight to fifteen primary lesions resulting in a more natural time scale for disease progression (Skinner et al, 2001). In an attempt to develop a natural challenge model, vaccinated and non-vaccinated possums were housed with possums that had been experimentally infected with M. bovis using the intratrachael challenge model. In these experiments transmission of disease was highly variable with infection rates for in-contact possums ranging from 10% to 60%. This level of variation prevented interpretation of the protection results (Skinner et al, 2001; Corner, 2001). 2.2 BCG vaccination. 2.2.1 A number of vaccination studies have been undertaken in possums using BCG which have demonstrated a significant level of protection to experimental challenge. These studies have also indicated that the route of vaccination affects the protective efficacy achieved. In all of these studies vaccination has not prevented animals from developing tuberculous lesions but has conferred a significant reduction in the dissemination of M. bovis to the spleen and liver. Vaccination with BCG has also been shown to influence the immunopathology associated with M. bovis challenge. In comparison with the predominantly necrotic lesions present in non-vaccinated animals, the
29
lung lesions in vaccinated animals are mostly granulomas with minimal necrosis and few acid fast bacilli (Aldwell et al, 1995a). Vaccination with BCG might be expected to be more efficacious against natural infection where the challenge is less stringent, the possums less stressed and where the course of infection is longer. A recent field trial of BCG vaccination in possums suggests that this may be the case (see below). 2.2.2 In the first BCG vaccination study, groups of possums were vaccinated with 106 cfu BCG by the subcutaneous, intratrachael and intragastric routes of vaccination (Aldwell et al, 1995a). Subcutaneous and intratrachael vaccination resulted in a marked reduction in the severity of tuberculosis compared with that observed in the non-vaccinated controls and animals vaccinated intragastrically. Intragastric vaccination gave no protection against experimental intratrachael challenge with M. bovis. 2.2.3 In a second study designed to compare the efficacy of different routes of infection likely to be of use in the field, possums vaccinated intranasally by aerosol spray or by the subcutaneous route with 106 cfu BCG gave greater levels of protection against challenge compared to animals vaccinated orally with 108 cfu BCG (Aldwell et al, 1995b). In order to determine whether the lack of efficacy of oral vaccination was due to degradation of BCG in the stomach, the levels of protection against tuberculosis were compared between possums vaccinated with 108 cfu BCG intraduodenally and those vaccinated with the same sized inoculum via the intragastric route (Buddle et al, 1997). The animals vaccinated via the intragastric route had a 100-fold reduction in bacterial burden in the lungs and increased lymphocyte responses to PPD-B indicating that protection of live BCG from degradation in the stomach should improve efficacy. 2.3 Duration of protection. 2.3.1 One of the key requirements for vaccination of wildlife is that protection should be long lasting. In a recent study in captive possums, animal were vaccinated with a single dose of approximately 1 x 105 cfu of BCG by intranasal aerosol and challenged by intratrachael instillation of M. bovis 2, 6 or 12 months after vaccination (Corner et al, 2001). Vaccination induced moderate protection from challenge as determined by a decrease in pulmonary lesions and dissemination to body lymph nodes with intervals of 2 or 6 months between vaccination and challenge but a lower level of protection was observed when the interval was increased to twelve months. 2.4 Effect of Multiple doses of BCG. 2.4.1 Recently a vaccination regime combining intranasal aerosol and conjunctival instillation (total inoculum: 3 x 107 cfu BCG) has been used to study the effect of repeated doses on the protective efficacy of BCG in possums (Corner et al, 2002a). In these experiments captive possums were vaccinated either 12 times at weekly intervals, twice at 6-weekly intervals or once. Protection was greatest in the group vaccinated 12 times indicating that protection could be enhanced if vaccinations were repeated at weekly
30
intervals while no benefit or detriment resulted from revaccination after longer intervals (1-2 months). 2.5 Field trial of BCG in Possums. 2.5.1 To date one field trial using BCG has been completed in New Zealand (Corner et al, 2002b). A population of possums in which M. bovis infection was endemic within a 56 hectare site was vaccinated with 3 x 106 cfu BCG by a combination of intranasal aerosol and conjunctival instillation. Possums were revaccinated on average every 5 months and the population was monitored bimonthly over 2 years by capture and release. Over the 2 years 300 possums were recruited to the study, with 149 being allocated to the vaccination group. There were significantly fewer cases of tuberculosis in the vaccinated (4 cases) than in the unvaccinated group (13 cases; p=0.023). The vaccine efficacy was 69%. 2.5.2 Although the results are encouraging it is important to note that there were a number of limitations in the design and conditions that occurred during the study. The number of incident and prevalent cases at each trapping session declined progressively during the study. No new cases of TB were detected in the last 8 months of the study. This may have been caused by a steady decline in the population of the site over time due to a culling operation in the area surrounding the site. This encouraged dispersal of juvenile possums away from the site and prevented recruitment of juveniles from the surrounding area. At the conclusion of the study the susceptible population on the site was 25% of the long term mean population. At this density the transmission of infection appeared to be reduced. In an attempt to increase the statistical power of the study and elevate the incidence of disease in the population, possums experimentally infected with M. bovis of a unique molecular profile were released onto the site. However, this did not result in any additional cases of TB. 2.6 Formulations for oral delivery of BCG. 2.6.1 A number of encouraging studies using novel oral bait formulations for BCG have been performed in New Zealand (Aldwell et al., 2003b Bryce Buddle, personal communication). Although, BCG cultures delivered orally or intragastrically were relatively ineffective, BCG delivered intraduodenally or intragastrically with an ant-acid medication induced protection against an experimental challenge (Buddle et al. 2002). These encouraging results demonstrate that BCG could be effective if it was protected from degradation in the stomach. BCG encapsulated in a lipid matrix (Aldwell et al., 2003a) has been fed to possums and resulted in significant protection against an experimental aerosol challenge with M. bovis (Aldwell et al., 2003b). Currently a dose response trial is in progress to determine how much BCG is required in oral bait to induce optimal protection (Bryce Buddle, personal communication). 2.7 Vaccines other than BCG.
31
2.7.1 The very high susceptibility of possums to M. bovis infection and limited protection of possums against experimentally-induced infection provides opportunities to identify tuberculosis vaccines that are more effective than BCG. In one study, killed Mycobacterium vaccae mixed with live BCG and administered intranasally induced significantly greater protection than BCG alone (Skinner et al., 2002). In another study, vaccination with two newly derived attenuated M. bovis strains induced a higher degree of protection than that seen with BCG (Buddle et al., 2002). 3. BCG VACCINATION IN FERRETS. 3.1 Challenge Model. 3.1.1 The route of transmission of M. bovis to ferrets is usually by ingestion through the scavenging of infected carrion. Consequently an oral M. bovis challenge model has been used to assess the efficacy of BCG in ferrets. In this model ferrets are infected orally with 5 x 106 cfu by feeding with infected lung tissue (Qureshi et al, 1999; Cross et al, 2000). The outcome of challenge is determined twenty weeks after challenge by autopsy, histology and bacterial culture. This route of infection gives rise to progressive disease with lesions primarily in the mesenteric lymph nodes where the bacterial burden is highest and also in the head region lymph nodes. The pathology observed in this model mimics natural infection in the ferret. 3.2 BCG Vaccination Studies. 3.2.1 In a recent study ferrets were orally vaccinated with two doses of 5 x 108 cfu live BCG incorporated into dietary meat administered 4 weeks apart (Qureshi et al, 1999). Although oral vaccination did not prevent infection, significant manifestations of protection were observed most notably a reduction in the bacterial burden, incidence and severity of TB in the head lymph nodes. Interestingly, blood from only 2/9 vaccines gave tuberculin specific lymphocyte responses suggesting that systemic immune responses may have been less important than local immunity in mediating protection in this study. Subcutaneous vaccination of ferrets with 5 x 106 cfu BCG between the shoulder blades also induced protection against oral challenge but again did not prevent infection (Cross et al, 2000). In this case protection was characterised by a significant reduction in bacterial burden, the prevention of gross lesions in the mesenteric lymph nodes and reduced bacterial spread to thoracic lymph nodes. In contrast, to the favourable results in possums, vaccination by intraduodenal inoculation of 5 x 107 cfu BCG was not effective in reducing disease (Cross et al, 2000). Both subcutaneous and intraintestinal vaccination with BCG induced tuberculin-specific lymphocyte reactivity. 4. BCG VACCINATION IN BADGERS. 4.1 Introduction.
32
4.1.1 The early observation that badgers may survive for a number of years after natural or experimental infection (Mahmood et al., 1987; Newell et al, 1997) suggests that they are not especially susceptible to M. bovis infection. Preliminary studies of the badger immune response to experimental infection led to the conclusion that badgers exhibit an immune spectrum during tuberculosis akin to other mammalian species (Thorns and Morris, 1983). More recent studies on the pathology and immunology of tuberculous badgers suggest that they are capable of mounting a vigorous cell-mediated immune response even when heavily infected and that they can contain infection, possibly for several years (Newell et al, 1997; Gavier-Widen et al, 2001). 4.2 Challenge Model. 4.2.1 Protocols for the experimental infection of badgers with M. bovis have been developed at VLA in previous studies (Pritchard et al, 1988; Mahmood et al, 1987). Two groups of four badgers were challenged with either 103 or 104 M. bovis either intradermally or intratracheally. Two animals thus received each dose/route combination. The intratracheal challenge route failed to lead to tuberculosis in all cases and their immunological responses were the same as the control, uninfected animals. The four intradermally challenged animals all developed miliary tuberculosis accompanied by positive skin test and increases in lymphocyte transformation and anti-mycobacterial antibodies. These studies highlighted the need to develop an improved challenge model for badgers. 4.3 Development of a badger challenge model in the Republic of Ireland. 4.3.1 Development of an experimental M. bovis challenge model for badgers has started at the Badger Research and Observation Complex (BROC) facility in Abbotstown. In the first instance, groups of uninfected badgers held in the BROC facility were challenged intratracheally with M. bovis over a range of doses (ca. 100 10,000 cfu). After a set interval (15 weeks), all animals were sacrificed and the presence and extent of infection determined at post mortem. Lung lesions were observed in all animals receiving 10,000 cfu. This challenge dose of M. bovis is now being used to infect further groups of badgers in order to determine the reproducibility of the model and to examine the progression of disease over time. This will be measured immunologically, physiologically and pathologically by serial necropsy. VLA is providing support for the immunological aspects of this study through a Defra funded project. 4.4 BCG vaccination. 4.4.1 In a previous study performed at VLA, Stuart et al. (1988) reported the protective effect of BCG against M. bovis in badgers. An intradermal inoculation of 106 cfu of BCG was found to be non-pathogenic, was not excreted by the badgers and was not transmitted to in-contact animals. There was an increase in LTT response but no skin-test reaction or antibody increase in all vaccinated badgers. When seven of these badgers were subsequently challenged intradermally with 104 M. bovis, between 5 and 25
33
months after vaccination, the LTT response tended to fall and the antibody response rose. Skin-test responses became positive. The vaccinated badgers were shown to live longer, shed fewer tubercle bacilli and their inoculation sites healed more rapidly after challenge than a group of three control badgers. Thus, although only small numbers of badgers were involved, cell-mediated immunity did seem to be enhanced by BCG vaccination, leading to prolonged survival of the badgers and delayed excretion of tubercle bacilli. 4.4.2 In a recent study in the Republic of Ireland, the immunological responses were measured in a resident population of badgers following subcutaneous vaccination with BCG (Southey et al, 2001). Three doses of vaccine were administered 1 cm above right ear. An initial dose of 5 x 104 cfu BCG was followed 17 weeks later with a boost of 5 x 104 cfu and a second boost of 5 x 105 cfu at week 30. Cellular immune responses were only observed after the third dose of BCG (at week 42) and were characterized by lymphocyte blastogenic responses to PPD-B. Antibody responses to MPB83 (the Brock Test) were minimal. This study highlighted the need to optimise the dose and route of BCG vaccination for badgers before further field evaluation could be performed. It is clear that the testing of BCG in badgers is lagging some way behind that in possums and ferrets, not least because of the lack of facilities to perform such work. 5. POST-EXPOSURE VACCINATION. 5.1 Vaccination of badgers in the field will inevitably result in the vaccination of many badgers that have already been infected with M. bovis and have clinical or subclinical disease. It is possible that the ensuing immune response to vaccination may result in exacerbation of the disease (the Koch phenomenon). This might have two effects. First, if post-exposure vaccination exacerbates disease it might result in increased spread of infection. Second, vaccination might reveal occult disease which could confound interpretation of a field trial since the number of TB cases in the vaccinated population would be selectively increased compared to that in the untreated population. 5.2 A number of post-exposure experiments have been performed in mice using BCG (Turner et al, 2000; Moreira et al., 2002). When administered to mice already infected with M. tuberculosis a single dose of BCG did not exacerbate disease nor effect the bacillary loads in the organs of the infected mice. Neither did it have a therapeutic effect on the pre-existing infection. However, repeated BCG vaccination of infected mice resulted in exacerbation of the granulomatous response with detrimental pathologic changes in the lungs. The effect became more prolonged and severe if the vaccine was given twice or three times (at 15 day intervals) although there was no effect on the bacillary load in the lungs (Turner et al., 2000). 5.3 Exacerbation of TB following post-exposure vaccination with BCG has not been reported for any other species including man. There have not been reports of significant harm associated with boosters or revaccination with BCG
34
or harm associated with BCG vaccination of tuberculin skin test positive individuals with latent TB." (Egsmore, 1968). 6. CONCLUSIONS. 6.1 Although BCG does not induce sterilising immunity in possums, ferrets or badgers, it has been shown to induce a marked reduction in pathology, disease, bacterial burden and haematogenous dissemination of M. bovis. The only recorded field trial of BCG in possums has indicated that an efficacy of 69% can be achieved with repeated doses of BCG. 6.2 To date the published data suggest that subcutaneous and aerosol vaccination might be more effective than oral vaccination for BCG and that further work is required to produce formulations which protect BCG from the stomach acids. However, recent data have shown that some oral bait formulations under development in New Zealand may be as effective as subcutaneous vaccination, at least in possums. In humans, oral BCG vaccination required much larger doses (ca. 3,000 times the dose) and was hence more expensive. It also proved difficult to control the effective dose with oral administration as some viable bacteria were inactivated in the stomach and many passed right through the intestinal tract. If this were the case in badgers oral vaccination would increase the risk of exposure of sentinel animals including domestic livestock and other wildlife. 7. REQUIREMENTS FOR DEVELOPMENT OF BCG VACCINATION REGIMES FOR BADGERS. 7.1 Facilities for badger vaccination experiments. 7.2 M. bovis challenge model for badgers including studies on pathogenesis and kinetics of the immune response. 7.3 Optimised dose of BCG for use in badgers. 7.4 Proof of principle experiments to show that BCG can give demonstrable protection against M. bovis challenge in badgers and reduce bacterial excretion. 7.5 Safety data for BCG in badgers using a single dose, 10 x overdose, and a repeated dose. 7.6 Determination of duration of protective immunity and effect of boosting. 7.7 Development of effective systems for oral delivery of BCG to badgers. 7.8 Development of immunological assays to monitor field vaccination studies (including differential diagnostic assays to distinguish protected from infected badgers).
35
7.9 In addition to the above there may be a requirement to demonstrate that BCG does not exacerbate disease in pre-infected badgers. 8. ACKNOWLEDGEMENTS. 8.1 Bryce Buddle, Leigh Corner, Frank Aldwell and Eamonn Gormley provided unpublished data and information. 9. REFERENCES. Aldwell F.E., Keen D.L., Stent V.C., Thomson A., Yates G.F., de Lisle G.W., Buddle B.M. (1995a). Route of BCG administration in possums affects protection against bovine tuberculosis. NZ vet J, 43, 356-359. Aldwell F.E., Pfeffer A., DeLisle G.W., Jowett G., Heslop J., Keen D., Thomson A., Buddle B.M. (1995b). Effectiveness of BCG vaccination in protecting possums against bovine tuberculosis. Res Vet Sci., 58, 90-5. Aldwell F.E., Tucker I.G., de Lisle G.W., Buddle B.M. (2003a). Oral delivery of Mycobacterium bovis BCG in a lipid formulation induces resistance to pulmonary tuberculosis in mice. Infect Immun., 71, 101-8. Aldwell F.E., Keen D.L., Parlane N.A., Skinner, M.A., de Lisle G.W., Buddle B.M. (2003b). Oral vaccination with Mycobacterium bovis BCG in a lipid formulation induces resistance to pulmonary tuberculosis in brushtail possums. Submitted for publication. Buddle, B. M., Skinner M. A., Wedlock D. N., Collins D. M., de Lisle G. W. (2002). New generation vaccines and delivery systems for control of bovine tuberculosis in cattle and wildlife. Vet. Immunol. Immunopathol., 87, 177-185. Buddle B.M., Aldwell F.E., Pfeffer A., de Lisle G.W. (1994). Experimental Mycobacterium bovis infection in the brushtail possum (Trichosurus vulpecula): pathology, haematology and lymphocyte stimulation responses. Vet Microbiol., 38, 241-54. Buddle B.M., Aldwell F.E., Keen D.L., Parlane N.A., Yates G., de Lisle G.W. (1997). Intraduodenal vaccination of brushtail possums with bacille CalmetteGuerin enhances immune responses and protection against Mycobacterium bovis infection. Int J Tuberc Lung Dis., 1, 377-83. Cooke M.M., Buddle B.M., Aldwell F.E., McMurray D.N., Alley M.R. (1999). The pathogenesis of experimental endo-bronchial Mycobacterium bovis infection in brushtail possums (Trichosurus vulpecula). NZ vet J., 47 187-192. Corner L.A., Buddle B.M., Pfeiffer D.U., Morris R.S. (2001). Aerosol vaccination of the brushtail possum (Trichosurus vulpecula) with bacille Calmette-Guerin: the duration of protection. Vet Microbiol., 81,181-91.
36
Corner L.A.L. 2001. Natural transmission of bovine tuberculosis in captive brushtail possums (Trichosurus vulpecula). In Bovine tuberculosis in brushtail possums (Trichosurus vulpecula): Studies on vaccination, experimental infection and disease transmission. PhD Thesis, Massey University, New Zealand. Corner L.A., Buddle B.M., Pfeiffer D.U., Morris R.S. (2002a). Vaccination of the brushtail possum (Trichosurus vulpecula) against Mycobacterium bovis infection with bacille Calmette-Guerin: the response to multiple doses. Vet Microbiol., 84, 327-36. Corner L.A., Norton S., Buddle B.M., Morris R.S. (2002b). The efficacy of bacille Calmette-Guerin vaccine in wild brushtail possums (Trichosurus vulpecula). Res Vet Sci., 73, 145-52. Cross M.L., Labes R.E., Mackintosh C.G. (2000). Oral infection of ferrets with virulent Mycobacterium bovis or Mycobacterium avium: susceptibility, pathogenesis and immune response. J Comp Pathol., 123,15-21 Cross M.L., Labes R.E., Griffin J.F., Mackintosh C.G. (2000). Systemic but not intra-intestinal vaccination with BCG reduces the severity of tuberculosis infection in ferrets (Mustela furo). Int J Tuberc Lung Dis., 4, 473-80 Egsmore, T. (1968). The effect of BCG vaccination in naturally infected tuberculin-positive individuals. Scand. J. Resp. Dis. 49,123-140. Gavier-Widen D., Chambers M.A., Palmer N., Newell D.G., Hewinson R.G. (2001). Pathology of natural Mycobacterium bovis infection in European badgers (Meles meles) and its relationship with bacterial excretion. Vet Rec., 148, 299-304. Griffin J.F., Mackintosh C.G., Slobbe L., Thomson A.J., Buchan G.S. (1999). Vaccine protocols to optimise the protective efficacy of BCG. Tuber Lung Dis., 79, 135-43. Mahmood K.H., Rook G.A.W., Stanford J.L., Stuart F. A., Pritchard D.G. (1987). The immunological consequences of challenge with bovine tubercle bacilli in badgers (Meles meles). Epidemiology and Infection, 98, 155-163. Moreira A.L., Tsenova L., Aman M.H., Bekker L.G., Freeman S., Mangaliso B., Schroder U., Jagirdar J., Rom W.N., Tovey M.G., Freedman V.H., Kaplan G. (2002). Mycobacterial antigens exacerbate disease manifestations in Mycobacterium tuberculosis-infected mice. Infect Immun. 70, 2100-7. Newell D.G., Clifton-Hadley R.S., Cheeseman C.L. (1997). The kinetics of serum antibody responses to natural infections with Mycobacterium bovis in one badger social group. Epidemiology and Infection, 118, 173-80.
37
Pritchard D.G., Stuart F.A., Brewer J.I., Mahmood, K.H. (1987). Experimental infection of badgers (Meles meles) with Mycobacterium bovis. Epidemiology and Infection, 98, 145-154. Qureshi T., Labes R.E., Cross M.L., Griffin J.F., Mackintosh C.G. (1999). Partial protection against oral challenge with Mycobacterium bovis in ferrets (Mustela furo) following oral vaccination with BCG. Int J Tuberc Lung Dis., 3, 1025-33. Skinner, M. A., Keen D. L., Parlane N. A., Yates G. F., and Buddle B. M.. 2002. Increased protection against bovine tuberculosis in the brushtail possum (Trichosurus vulpecula) when BCG is administered with killed Mycobacterium vaccae. Tuberculosis 82,15-22. Skinner M.A., Wedlock D.N., Buddle B.M. (2001). Vaccination of animals against Mycobacterium bovis. Rev Sci Tech, 20, 112-32 Southey A., Sleeman D.P., Lloyd K., Dalley D., Chambers M.A., Hewinson R.G., Gormley E. (2001). Immunological responses of Eurasian badgers (Meles meles) vaccinated with Mycobacterium bovis BCG (bacillus calmette guerin). Vet Immunol Immunopathol., 79,197-207. Stuart F.A., Mahmood K.H., Stanford J.L., Pritchard D.G. (1988). Development of diagnostic tests for, and vaccination against, tuberculosis in badgers. Mammalian Review, 18, 74-75. Thorns C.J., Morris J.A. (1983). The immune spectrum of Mycobacterium bovis infections in some mammalian species: a review. Veterinary Bulletin, 53, 543-550. Turner J., Rhoades E.R., Keen M., Belisle J.T., Frank A.A., Orme I.M. (2000). Effective preexposure tuberculosis vaccines fail to protect when they are given in an immunotherapeutic mode. Infect Immun. 68, 1706-9.
38
APPENDIX 4. BCG IN WILD-LIFE AND DOMESTIC LIVESTOCK; VIRULENCE AND EFFICACY. Jo Colston (deceased) National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA 1. INTRODUCTION. 1.1 Extensive testing of virulence was carried out by Calmette and his colleagues during their development of BCG in the early part of the 20th century. In addition to this there has been extensive work carried out in wildlife or domestic livestock to investigate protective efficacy or immunogenicity of BCG, rather than virulence; these studies allow us to draw some conclusions about the virulence of BCG in these species. Calmette and colleagues also carried out experiments in which large doses of BCG were administered to animals which were already infected with M. tuberculosis; because of the potential importance of these studies, these have been included in the discussion (see section 3). 2. EXPERIMENTS ON THE VIRULENCE OF BCG CARRIED OUT BY CALMETTE AND COLLEAGUES. 2.1 Cattle. 2.1.1 In Calmette and Guerins original work, 100mg of BCG was administered intravenously to cattle. The recipients were reported to have developed a typhoid-like disease (Le seul effet de cette injection massive est de provoquer une maladie generale dallure typhique, qui gurit spontanement aprs 15 a 20 jours de fievre, sans produire la moindre lesion folliculair), but all recovered and remained healthy. 2.2 Guinea pigs. 2.2.1 Guinea pigs given 5-10mg of BCG intradermally or 3-5mg intraperitoneally remained healthy. 50-100mg administered into the stomach resulted in lymph node swelling but again the animals remained healthy. 2.3 Rabbits. 2.3.1 1-5mg BCG injected sub-cutaneously had no effect on the health of the rabbits. Intravenous injection of 100mg also had no effect. 2.4 Dogs. 2.4.1 A single 4Kg dog was given 0.5mg BCG intravenously, followed five days later with 1mg by the same route, and three months later 10mg
39
intraperitoneally. The dog remained healthy in spite of a slightly elevated temperature after the second and third injection. A post mortem examination carried out six months after the last injection revealed no gross lesions, but intact mycobacteria were detectable. 2.5 Monkeys. 2.5.1 A Macaque cynomolgus was given 2mg of BCG intraperitoneally, and four months later a further intraperitoneal injection of 4mg. The animal remained healthy, and there was no evidence of tuberculosis on post mortem examination. 2.6 Horses. 2.6.1 One horse was given 10mg BCG intravenously; the horse developed a slight fever 12 days later lasting for 6 days. A second horse received 100mg intravenously; this animal developed temperature oscillations between 39.5oC and 40oC for two weeks. The animal lost appetite, developed rapid breathing and a high pulse rate. There was evidence of pulmonary congestion between seven and eight days, but by six weeks the animal had fully recovered. Another horse was given 200mg intravenously and sacrificed two weeks later. Mycobacteria could be found in lymphoid tissue, but there was no evidence of tuberculosis-like lesions. 3. STUDIES ON EFFICACY AND IMMUNOGENICITY OF BCG. 3.1 With the exception of the work by Calmette et al, most of the work which has involved exposing wild-life or domestic livestock to BCG, has been carried out to investigate protective efficacy or immunogenicity, rather than virulence. Nevertheless, these studies do allow us to draw some conclusions about the virulence of BCG in these species. The information set out below summarises research on vaccination of different species of animals with BCG. 3.2 Cattle. 3.2.1 The original work of Calmette (see Section 2) would have involved doses of more than 1010 BCG. More recently doses have ranged from 104 to 108 viable BCG, usually given subcutaneously. One study (Buddle et al, 1995) involved intratracheal vaccination. Virtually all of these studies reported some level of protection in animals which were subsequently challenged with virulent M.bovis, although this appeared to wane after approximately 5 years (Bergeen, 1977). With the exception of the report by Calmette and Guerin (see 2.1.1), there have been no reports of adverse affects following the administration of BCG. 3.3 Deer. 3.3.1 Various experiments have been carried out in which BCG-vaccinated deer have been challenged with M.bovis BCG; dosage has ranged from 5 x 104 5 x 108 viable bacteria (Griffin et al, 2001; Miller et al, 1999; Slobbe et
40
al, 1999; Hook et al, 1996). As with cattle vaccination, all of these studies reported some level of protection and there were no reports of adverse affects from the vaccination. 3.4 Possums. 3.4.1 Possums have been vaccinated with BCG by a variety of routes, including subcutaneous, aerosol and intraduodenal (Aldwell et al, 1995; Buddle et al, 1997). One study involved a combination of intranasal aerosol and conjunctival instillation. No adverse effects of vaccination have been reported. In all experiments, there was a reduction in disease severity in the BCG vaccinated animals following challenge with viable M.bovis. 3.5 Ferrets. 3.5.1 BCG has been given orally to ferrets, followed by oral challenge with virulent M.bovis. There was significant reduction in gross lesions, and in culture and acid fast positive lymph nodes in the vaccinated groups. No adverse side effects of vaccination were reported (Qureshi et al, 1999). 3.5.2 In another series of experiments, ferrets were vaccinated with live BCG via subcutaneous injection or intra-duodenal inoculation. Only the subcutaneous route was effective in reducing disease (Cross et al, 2000). 3.6 Badgers. 3.6.1 Numbers of experimental studies have been carried out on vaccination of badgers with BCG (Stuart et al, 1988; Southey et al, 2001). Generally the route of administration has been intradermal or subcutaneous. No adverse effects have been reported and the experiments reveal an increase in cellmediated immunity against M.bovis. 3.7 Rabbits. 3.7.1 Tuberculosis in rabbits is claimed to resemble human TB more closely than TB in other common laboratory animals. Immunisation of rabbits with BCG has been carried out by a number of workers (Lurie et al, 1952; Dannenberg et al, 2001). BCG was usually administered intradermally using 106 107 viable bacilli. No adverse affects were reported and significant levels of protection against subsequent challenge with M.bovis observed. 3.8 Guinea pigs. 3.8.1 Guinea pigs have been widely used for experimental tuberculosis studies, and there are many reports of vaccination with BCG (e.g. Chambers et al, 2000). There are no reports demonstrating that BCG can cause progressive infections or have adverse side effects. 3.9 Mice.
41
3.9.1 Mice are the most commonly used experimental animals for testing vaccination against tuberculosis. BCG does not cause progressive infections in these animals. 4. ADMINISTRATION TUBERCULOSIS. OF BCG TO ANIMALS INFECTED WITH
4.1 Calmette and colleagues carried out a number of studies in which large doses of BCG were administered to animals already infected with M. bovis. Their general conclusion was that this did not produced aggravation of the tuberculosis (Lintroduction de bacilles bilies, meme a fortes doses plusieurs fois repetees, dans lorganisme des animaux deja tuberculises ne produit aucune aggravation de la maladie). 4.2 A PPD-positive cow was given 10mg of BCG intravenously, followed nine days later with 50mg, again intravenously. The animal was sacrificed and subjected to post mortem examination two and a half months later. Two small, caseous lung lesions were found, along with a number of calcified lesions in mediastinal lymph nodes; however these were considered to be old lesions, and there was no evidence of recent tuberculosis. Similar experiments carried out with guinea pigs and rabbits failed to reveal evidence of aggravation of the disease. 5. CONCLUSIONS. 5.1 Extensive testing of BCG in a variety of mammalian species has failed to reveal any evidence that the organism can cause disease or can exacerbate pre-existing tuberculosis. Many of these tests were carried out with very large doses of BCG given by a variety of different routes. However, it should be noted that lack of virulence of BCG is related to the immunological status of the host. Thus people with congenital defects in type 1 cytokines or their receptors may develop a disseminated, lethal BCG infection. Thus individual animals which are immunosuppressed, or species with more primitive immune systems could be highly susceptible to BCG infection. 6. REFERENCES. Aldwell F.E., Keen D., Stent V.L.C. et al. (1995). Route of BCG administration in possums effects protection against bovine tuberculosis. New Zealand Vet. Rec., 43, 356-359. Bergeen S.A. (1977) Incidence of tuberculosis in BCG vaccinated and control cattle in relation to age distribution in Malawi. Br. Vet. J., 133, 490-494. Buddle B.M., Keen D., Thomson G. et al. (1995). Protection of cattle from bovine tuberculosis by vaccination with BCG by the respiratory or subcutaneous route, but not by vaccination with killed Mycobacterium vaccae. Res. Vet. Sci., 59, 10-16.
42
Buddle B.M., Aldwell F.E., Keen D., et al. (1997). Intraduodenal vaccination of brushtail possums with bacille Calmette-Guerin enhances immune responses and protection against Mycobacterium bovis infection. Int. J. Tuberc. & Lung Dis., 1, 377-383. Chambers M.A., Williams A., Gavier-Widen, D. et al. (2000). Identification of a Mycobacterium bovis BCG auxotrophic mutant that protects guinea pigs against M. bovis and hematogenous spread of Mycobacterium tuberculosis without sensitisation to tuberculin. Infect. Immun., 68, 7094-7099. Cross M.L., Labes R.E., Griffin J.F.T., Mackintosh C.G. (2000). Systemic but not intra-intestinal vaccination with BCG reduces the severity of tuberculosis infection in ferrets (Mustelo furo). Int. J. Tuberc. & Lung Dis., 4, 473-480. Calmette A., Boquet A., Negre L. (1921). Contributions a letude du bacille tuberculeux bilie Extrait des Annales de lInstitut Pasteur. Septembre 1921, Tome XXXV. Dannenberg A.M., Bishai W.R., Parrish N. et al. (2001). Efficacies of BCG and vole Bacillus (Mycobacterium microti) vaccines in preventing clinically apparent pulmonary tuberculosis in rabbits: a preliminary report. Vaccine, 19, 796-800. Griffin J.F.T., Chinn D.N., Rodgers C.R., Mackintosh C G. (2001). Optimal models to evaluate the protective efficacy of tuberculosis vaccines. Tuberculosis, 81, 133-139. Hook S., Griffin F., MacKintosh C., Buchan G. (1996). Activation of an interleukin-4 mRNA-producing population of peripheral blood mononuclear cells after infection with Mycobacterium bovis or vaccination with killed, but not live, BCG. Immunology, 88, 269-274. Lurie M.B., Zappasodi P., Cardona-Lynch E., Dannenberg A.M. (1952). The response to the intracutaneous inoculation of BCG as an index of native resistance to tuberculosis. J. Immunol., 68, 369-387. Miller L.A., Johns B.E., Elias D.J., Killian G.J. (1999). Oral vaccination of white-tailed deer using a recombinant Bacillus Calmette-Guerin vaccine expressing the Borrelia burgdorferi outer surface protein A: prospects for immunocontraception. Am. J. Rep. Imm., 41, 279-285. Qureshi T., Labes R.E., Cross M.L., et al. (1999). Partial protection against oral challenge with Mycobacterium bovis in ferrets (Mustelo furo) following oral vaccination with BCG. Int. J. Tuberc. & Lung Dis., 3, 1025-1033. Slobbe L., Lockhart E., ODonell M.A., et al. (1999). An in vivo comparison of bacillus Calmette-Guerin (BCG) and cytokine-secreting BCG vaccines. Immunology, 96, 517-523.
43
Southey A., Sleeman D.P.S., Lloyd K., et al. (2001). Immunological responses of Eurasian badgers (Meles meles) vaccinated with Mycobacterium bovis BCG (bacillus Calmette-Guerin). Vet. Immunol. Immunopath., 79, 197207. Stuart F.A., Mahmood K.H., Stanford J.L., Pritchard D.G. (1988). Development of diagnostic tests for, and vaccination against, tuberculosis in badgers. Mammalian Rev., 18, 74-75.
44
APPENDIX 5. PROTOCOLS FOR THE DEVELOPMENT AND EVALUATION OF BCG VACCINATION AGAINST M. BOVIS INFECTION IN BADGERS. Glyn Hewinson and Mark Chambers Veterinary Laboratories Agency, New Haw, Addleston, Surrey KT15 3NB 1. INTRODUCTION. 1.1 Vaccinating badgers against infection with M. bovis is one possible strategy with which to break the transmission of tuberculosis, by reducing the burden of infection within the badger population and the level of shedding of the bacterium by infected individuals. 1.2 In Appendix 3 was outlined a number of steps that would be required for the development of BCG vaccination regimes for badgers. The main purpose of the study would be to provide proof of principle that BCG can protect against a stringent challenge with M. bovis and to determine the level of protection conferred by BCG in this model. Previous studies in other wildlife species have shown that, to date, the optimum level of protection for BCG has been achieved by subcutaneous vaccination (Appendix 3). Therefore it would be prudent to provide proof of principle that BCG can protect against M. bovis infection in badgers using this route of vaccination before embarking on the development of formulations and delivery systems for oral vaccination. The aim of this Appendix is to discuss the development of protocols to achieve this goal. 2. M. BOVIS CHALLENGE MODEL FOR BADGERS INCLUDING STUDIES ON PATHOGENESIS AND KINETICS OF THE IMMUNE RESPONSE. 2.1 The first objective would be to develop an M. bovis challenge model for badgers. The optimum dose for intratrachael challenge is being determined in the Republic of Ireland (RoI) by titrating doses of M. bovis (10, 100, 1000 cfu). The kinetics of the immune response and shedding during infection are being measured and pathology will be defined by post mortem examination. 2.2 The second objective would be to define the variation in the parameters that would be used for measuring protection against M. bovis challenge in this model. This would ensure that a minimum number of animals were used for subsequent vaccination and challenge studies. 2.3 Ideally, the experimental design would include a badger group size of between twelve and twenty animals. At least two pre-bleeds should be taken for each badger. The dose of M. bovis given would be determined from the experiments performed in RoI outlined above (2.1). All badgers would be kept 12-18 weeks after challenge or until they showed severe clinical signs of disease. A full post mortem would be carried out on each animal and
45
pathology, histopathology and cfu in lung, lymph nodes and other tissues would be determined. Pathology scores would be determined for lungs and lymph nodes using scoring systems developed for the bovine model of M. bovis infection. 2.4 The clinical markers to assess disease progression would be weight, haematology, blood biochemistry, survival, clinical signs (include lymph node enlargement). 2.5 Regarding immune markers of disease progression, badgers would be sampled at two to three-weekly intervals and tested for the following: 2.5.1 Serum IgG response (using the Brock Test, MAPIA/Lateral flow assays and Dachs ELISA; Appendix 9). 2.5.2 IgA response in tracheal aspirates and serum. 2.5.3 Lymphocyte transformation assay (Appendix 9) using PPD-M, PPD-A and specific M. bovis antigens that are present in M. bovis and absent from BCG (e.g. ESAT-6 and CFP10). 2.5.4 IFN ELISA and ELISPOT using PPDM, PPDA, ESAT-6, CFP10 and other antigens that might be useful in determining disease progression (Appendix 9). 2.6 Shedding of M. bovis would be detected by culturing urine, faeces and tracheal aspirates and by PCR. 2.7 The information gathered as a result of this experiment would be used to determine which parameters would be useful in determining protective efficacy, the variation in these parameters and hence the group size required for subsequent vaccination and challenge experiments. 3. PROOF OF PRINCIPLE EXPERIMENTS TO SHOW THAT BCG CAN GIVE DEMONSTRABLE PROTECTION AGAINST M. BOVIS CHALLENGE IN BADGERS AND REDUCE BACTERIAL EXCRETION. 3.1 Group size for a BCG vaccination and challenge experiment would be determined from the data obtained from the experiment outlined in 2. It should be noted that groups of six cows were sufficient to demonstrate 80 % protection (i.e. reduction in lesions) in BCG vaccinated animals compared to controls. This is the minimum group size that could demonstrate a statistically significant protective effect in cattle. 3.2 It is suggested that a commercial preparation of BCG that is licensed in GB (i.e. BCG Copenhagen; see Appendix 6) be used at a dose that has been efficacious for a wide range of species i.e. 106 cfu (Appendix 3). 3.3 Shedding of BCG prior to M. bovis challenge would be detected by culturing urine, faeces and tracheal aspirates and by PCR.
46
3.4 Immune responses of vaccinated badgers would be monitored as described in section 2.5 above. 3.3 It is suggested that there would be a rest between BCG vaccination and M. bovis challenge of ca. 8 weeks in the first instance. 3.4 The challenge experiment would be carried out as described in Section 2 above.
47
APPENDIX 6. VACCINES FOR THE CONTROL OF BOVINE TUBERCULOSIS: COMMERCIAL PRODUCT DEVELOPMENT AND REGULATORY APPROVAL. Steve Houghton Hoechst Roussel Vet Ltd., Walton Manor, Walton, Milton Keynes, MK7 7AJ 1. INTRODUCTION. 1.1 The expertise necessary to develop and license commercial TB vaccines lies with animal health companies collaborating with research institutes or laboratories. A commercial company involved in the development of vaccines will seek to make a return on investment whilst at the same time having to comply with regulatory requirements. This involves compliance with Good Manufacturing Practice (GMP) for production, Good Laboratory Practice (GLP) for experimental studies and Good Clinical Practice (GCP) for field studies. 2. PROJECT EVALUATION: HOW COMPANIES CHOOSE WHAT PRODUCTS TO DEVELOP. 2.1 In deciding what projects to progress, the following are taken into consideration: 2.1.1 The market. How many countries are involved and how widespread is the disease? What is the likely uptake of the vaccine (prohibition or prescription for use by control policies?), what are the manufacturing costs and anticipated selling price? 2.1.2 Technological feasibility. How likely is it that a useful vaccine can be developed? 2.1.3 Product profile. This sets the objectives for the project which primarily involves defining the following: 2.1.3.1 Type of vaccine: live, inactivated whole cells, subunit, extract, recombinant etc. 2.1.3.2 Adjuvant (usually only for inactivated vaccines). 2.1.3.3 Dosage regimen. 2.1.3.4 Method and route of application (by injection, oral etc). 2.1.4 Production methods/costs.
48
2.1.4.1 The more complicated the production process, the higher the costs. It is easier to predict the costs of a simple process, similar to established methodology. 2.1.4.2 The vaccine strain(s), notably the history (particularly with respect to culture conditions and TSE), and any IP issues are essential to address early on. 2.1.5 Consumer concerns. The release of live strains with potential zoonotic implications and perhaps the release of Genetically Modified Organisms (GMOs) as live vaccine strains in particular will undoubtedly present problems with consumer and regulatory acceptance. 3. RESEARCH AND DEVELOPMENT OF CANDIDATE TB VACCINES. 3.1 A successful project team is multidisciplinary consisting of R&D, Marketing, Registration, QA, QC and Production personnel throughout the duration of the development. 3.1.1 First and foremost Transmissible Spongiform Encephalopathy compliant production master and working seeds must be established and the method of production of the vaccine defined, otherwise all subsequent studies might be invalidated. 3.1.2 A validated, consistent, method of production is essential. Fermentation, culture conditions etc must be set. Culture media used at all stages of manufacture have to comply with Transmissible Spongiform Encephalopathy guidelines of the Committee for Veterinary Medicinal Products. An initial stage of vaccine development is undertaken with candidate vaccines prepared to a documented method and used to inoculate animals in challenge studies to evaluate efficacy and safety. This phase may also involve dose ranging. Data on vaccine stability are required and are initiated as soon as possible in development. 3.1.3 The seeds have to be tested for identity and purity. The maximum and minimum titre (for live vaccines) of the final product is set. If a range of titres is specified for the product, all efficacy studies are carried out using minimum titre and all safety studies at maximum titre. 3.1.4 Safety studies are carried out under GLP conditions and conducted in the most susceptible category of animal (e.g. neonates, pregnant) and include: 3.1.4.1 Safety of a single dose. 3.1.4.2 Safety of a repeated dose. 3.1.4.3 Safety of a 10 times (live) or double (inactivated) overdose. 3.1.4.4 Reversion to virulence (live).
49
3.1.4.5 Persistence and shedding (live). 3.1.4.6 Numbers of the order of 5/6 per group are usually sufficient. 3.1.5 Efficacy studies are carried out under experimental conditions and include studies which will enable the product claims to be substantiated involving: 3.1.5.1 Efficacy of the recommended dose regime, including onset of immunity, duration of immunity, booster vaccination. 3.1.5.2 Efficacy in the face of maternal antibodies (if given to neonates). 4. PRACTICAL CONSIDERATIONS IN TB VACCINE DEVELOPMENT. 4.1 An animal health company partner. Studies are not relevant for registration unless they involve the product manufactured in a manner representative of full-scale manufacture. 4.2 Target species only. Evaluation of vaccine candidates in guinea pigs or other laboratory animals may or may not be relevant to target species efficacy, but is certainly not acceptable as the only efficacy model. An early decision on which vaccine candidate is chosen and then work in the target species using the stated dose by the chosen route of application is key. Any amount of efficacy or safety in laboratory animals is at best supporting data and cannot replace studies in the target species(badgers or cattle). 4.3 Live GMO. In addition to centralised licensing, it would need to be registered with the Health and Safety executive (HSE) for contained release during development and deliberate release into the environment when in use commercially. 4.4.1 GMOs. These must be developed in containment facilities and licensed via the centralised system with the involvement of all 15-member states in the process. However, countries for which the product is intended can be nominated and those countries, where use of the product is prohibited by local control policies, can prevent national approval. 4.4.2 Centralised registration applies to not just live GMOs but also any material produced by a recombinant process - therefore even if the vaccine is inactivated or a sub-unit protein the same rules apply. 4.5 Field Trials. These can only be carried out in the UK under an Animal Test Certificate (ATC) according to GCP although trials could be done elsewhere. An ATC application requires data on quality and safety in the form of a dossier, but not efficacy. However as the definitive evidence of efficacy is by experimental challenge, field studies would be expected to provide supporting data at best for efficacy, and to confirm safety under field conditions.
50
5. BCG. 5.1 From all the studies conducted so far BCG is the only realistic vaccine candidate currently available. 5.2 BCG is a licensed product for humans in the UK, therefore there are no significant zoonotic implications. 5.3 Adopting this vaccine for use in badgers or cattle is likely to save years in development time. Collaboration and consent of the manufacturer would be necessary. 5.4 For badgers the oral route in bait is likely to be the method of application of choice. Efficacy and stability work would be necessary to develop this. 5.5 Ecology and the Environment. For any product a key part of the dossier is the assessment (called the ecotoxicity section) of impact on the environment and spread to other species. This assessment method is clearly described in regulatory guidelines and involves key studies of the vaccine and its stability. There is a wealth of published data on the safety and efficacy of BCG in numerous species, including man, cattle and laboratory animals and some in badgers. 6. REGULATORY STEPS. 6.1 The sequence involved depends on which of a number of options provides the best route: 6.1.1 Article 8 of Directive 2001/82/EC. As there is no licensed vaccine for animals it is possible (but, vide infra) that the human BCG vaccine could be used in badgers and cattle to combat a disease emergency, and the EU commission informed of this action. Given the current levels of TB in GB this route should not be ignored and for a badger vaccine this may be the ideal route to pursue as long as data on stability in bait can be developed. For cattle, tuberculin testing is required by Directive 64/432 and evidence that BCG does not interfere with this test would be necessary. However it is unlikely that TB in cattle would constitute a disease emergency and oral administration of BCG to badgers would not be a direct correlate of the use of BCG in other species and is unlikely to be approved without data to support its likely efficacy. 6.1.2 Cascade. Where there is no licensed product available, a veterinary surgeon may be permitted to administer to a small number of animals on a particular holding a product authorised for human beings. For badgers and selected cattle herds this would be acceptable. The same issues as in 6.1.1 above would apply but it is unlikely that this would be considered an option for justifying the use of BCG in badgers. The key point is that the animals are under the care of the prescribing veterinary surgeon, which is unlikely to apply to wildlife. This point is also relevant to 6.1.1.
51
6.1.3.1 Marketing Authorisation (MA) for BCG in Badgers. The sequence is laid out in Table 1 for badgers but as essentially the Quality section of the dossier would be provided by the licensed manufacturer(s) this would save considerable time in development. Published data and new studies would provide data for the safety and efficacy sections of the dossier. This would lead to a national marketing authorisation in the UK which could then be mutually recognised in Ireland or other interested Member States. Table 1- MA for BCG for Badgers. - Agreement with licensed manufacturer. - State product specification and profile, develop delivery system. - Develop challenge model. - Establish dose giving adequate efficacy in preliminary titration studies. With minimum effective dose perform further challenge studies. Support with published data. - Single dose, overdose, repeated dose studies in Badgers to GLP. - Compile dossier including safety and efficacy and quality data from manufacturer. - Submit to VMD for Animal Test Certificate i.e. field trials on a limited scale. - Complete Quality, Safety, Efficacy sections of dossier in EU format and submit to VMD. - Validation, followed by Questions from VMD Biologicals Committee. Following satisfactory answers, Veterinary Product Commission consulted before MA granted subject to resolution of outstanding points. 6.1.3.2 It is estimated that the procedure in Table 1 would take approximately 4-5 years providing there are no bottlenecks in animal availability or major technical problems. 6.1.3.3 The development of a novel TB vaccine (i.e. not BCG) would require a considerable amount of additional work. The early development and screening of candidate vaccine components and formulations, and establishing production and quality test methodologies in particular, would probably add at least another 2 to 3 years to the programme. 7. CONCLUSIONS. The provision of any vaccine to aid the control of Bovine TB, whether for use in cattle or badgers, would be most likely achieved by a close collaboration between a vaccine manufacturer and research institutes (perhaps several) from the beginning. Co-ordination of research activities to provide the science necessary to underpin the development programme, particularly with respect to novel vaccines, is essential. From manufacturing, vaccine development and probably regulatory/consumer acceptance perspectives, the use of BCG in badgers is the option that would be quickest to market.
52
APPENDIX 7. ISSUES RELATING TO THE PROCUREMENT OF BADGERS FOR VACCINE RESEARCH. Chris Cheeseman, Des Delahay & Gavin Wilson CSL Woodchester Park, Nympsfield, Stonehouse, Glos, GL10 3UJ 1. INTRODUCTION. 1.1 Captive badgers will be required for experimental research related to the development of a TB vaccine for badgers. Consequently badgers will need to be procured from the wild by live trapping. 2. GENERAL. 2.1 Badgers are social animals and therefore cannot be housed individually in captivity on a long-term basis. However, although housing singly is not desirable for welfare reasons, housing in pairs or groups will have implications for cross-infection between individuals in the course of the vaccination studies. Advice will be required from the relevant immunologists and statisticians on the desired characteristics of badgers to be procured for vaccine research, as this will influence the strategy for their capture. Are badgers to be kept in pairs? If so what age and sex distribution is required? Alternatively, will it be possible to house whole social groups? Will the badgers be required to come from locations of varying history of exposure to M. bovis? 3. AGE AND SEX. 3.1 There is likely to be a requirement for the sample of procured badgers to have a particular age and sex structure. One scenario is that badgers are held in pairs. In order to minimise disruption to existing social groups from which badgers are being removed, a small number of individuals should be taken. A maximum removal of one male and one female could probably be sustained by a normal group of five to eight individuals, as this is a minimal increase over the natural background mortality rate of approximately 30% per annum. However, this approach will require trapping of many setts in order to procure sufficient badgers, which will be labour intensive. There may be limits to the months when trapping can be carried out, to avoid the breeding season. It is obviously undesirable to bring pregnant females into captivity and lactating females cannot be removed from their cubs. It may also be necessary to carry out bait-marking surveys in the areas of interest to determine social group territories. 3.2 The intention only to partially deplete social groups to avoid disruption carries with it the need to assess group size, age and sex composition. For example, it would not be desirable to remove two badgers from a group of less than say five individuals. A possible alternative to this, if there were
53
appropriate facilities to house them, would be to capture whole social groups. In this scenario, trapping could be condensed, as the required number of badgers would be more quickly reached after fewer trap-events. As they are social animals, it may be less stressful (see Sections 8.1.3 and 9) for badgers if kept together as a group (see Section 8). 3.3 Advice received from people with experience of keeping captive badgers suggests that it may not matter how pairs are mixed according to sex or even social group origin. However, it is important to introduce them together, monitor the situation and be prepared to separate them again if conflict occurs. In order to overcome the potential problems of keeping pairs of adults together, it may be better to remove animals from the wild as cubs, as they settle into captivity much better than adults. The experience of badger rehabilitation centres is that cubs of both sexes mix well, but they do exhibit a behavioural change in the autumn where they spend much of their time trying to escape. This period coincides with the time of year that cubs in the wild become independent and disperse. 4. ESTABLISHING DISEASE STATUS. 4.1 Presumably known infected animals will be required as well as those of TB-free status. There are two available approaches to establishing the TB status of badgers; ELISA blood testing, and culturing of clinical samples. ELISA results can be returned in a matter of hours, but culturing takes several weeks. In theory, ELISA tests could be carried out on badgers held in holding cages in the field, to help establish disease status. Sensitivity and specificity issues must be considered when planning to use such techniques. If TB positive badgers are required, a single trap-side ELISA may be performed in the field. The high specificity of the test would allow identification of positive animals, which could then be removed to the laboratory. For disease free badgers, confirmation of negative status by repeat ELISA (see Forrester et al 2001) and clinical sampling could only be achieved in captivity. Consideration may have to be given to the quarantine of individuals until their disease status is confirmed. 5. PROCURING KNOWN NEGATIVE BADGERS FROM DISEASE FREE AREAS. 5.1 Although it is not possible to guarantee that procured badgers come from areas where infection is definitely absent, there are areas of the country where there is no history of infection in either badgers (although insufficient sample sizes may be a factor) or cattle. Targeting these areas would provide the best chance of obtaining disease free badgers. These areas would however be outside TB hotspots if this is an important consideration (see Genetic considerations). Confirmation of the disease-free status of these badgers could be achieved by repeat ELISA testing, plus clinical sampling.
54
6. PROCURING KNOWN POSITIVE BADGERS. 6.1 The best chances of identifying infected animals is in a population which has been subject to sequential sampling, such as the situation that exists at Woodchester Park. It follows therefore that the most efficient approach may be to set up such study areas well in advance of the requirement for procured badgers. 6.2 One possible scenario is that target setts are trapped repeatedly until sufficient animals of the desired disease status are caught. Badgers could be blood tested in the field at capture. The high specificity of the ELISA test means that any animal testing positive is highly likely to be infected. Positive individuals could be taken into captivity, where further testing could be carried out to confirm disease status. Culture of clinical samples from these badgers would also help confirm disease status. At the time of the initial capture, all badgers could be clinically sampled and given permanent identification marks. Culture of clinical samples from all badgers would provide a further opportunity to identify infection in animals not identified by the initial ELISA test. Any additional positive individuals could be selected in subsequent trapping operations. 7. PROCURING KNOWN TB NEGATIVE BADGERS FROM HOT SPOTS. 7.1 Procurement of known negative badgers from the same genetic stock as the known positive badgers may be required, which would involve capturing them in TB hot spots. The limitations of current TB diagnostic techniques will mean that it would be difficult to obtain disease-free badgers from these areas with a high level of confidence. 8. SELECTING WHOLE SOCIAL GROUPS. 8.1 An alternative approach to selecting a small number of badgers from many social groups would be to catch as many badgers as possible from a smaller number of groups, i.e. removal of entire groups if possible. The advantages of this would be the following. 8.1.1 Less trapping would have to be carried out to reach the numbers of badgers required. 8.1.2 The badgers would be captive therefore it would be easier to carry out repeated culture tests, and if necessary repeat ELISA tests. 8.1.3 The whole social group would be kept together, which might reduce stress to the target individuals. 8.2 However, this may be impractical due to the requirements of housing several badgers together. It should be noted that a current proposal allows for badgers to be held in captivity in pairs at a new facility (see Appendix 8). It
55
should also be noted that removal of badger from the wild by cage trapping is not 100% effective. 9. STRESS - WILD ANIMALS IN CAPTIVITY. 9.1 Experience suggests that there is a great deal of individual variation in how easily badgers accept captivity. In general, cubs seem better at settling into captivity than adults. Adults tend to spend more of their time and energy attempting to escape, and sometimes never settle completely. If they are to be held in pairs, the chances of them accepting each other are increased if they are introduced to their accommodation at the same time. Some badgers in captivity may remain intolerant of each other. This does not seem to be determined by whether they came from the same or different social groups, or whether they are males or females. Therefore there is likely to be an element of trial or error in successfully housing badgers in pairs. 9.2 The exact design of the accommodation needs to be considered carefully. The stress levels of the animals may affect their immune response. Therefore it will be very important to house the badgers in a way which reduces stress as much as possible. Before committing to the construction of a large number of enclosures, it may be worth considering a small-scale pilot study to establish a successful design for the accommodation (see Appendix 8, Section 6). 10. GENETIC CONSIDERATIONS. 10.1 Preliminary work suggests that the levels of genetic variability are very similar between trial areas. No such information is available for non TB hotspot areas. Also, it is as yet unknown what implications differences in genetic variability between areas would have for the immune response, or TB pathogenicity in badgers. Therefore genetic composition is an issue which cannot currently be resolved, and it is assumed that it will not be a consideration for badger procurement. 11. LEGAL CONSIDERATIONS. 11.1 Under the Protection of Badgers Act 1992, the killing or taking of badgers and/or interference with their setts is prohibited. Section 10 of the Act, however, makes provision for the issue of licences for specific purposes to carry out otherwise unlawful activities against badgers and their setts. Section 10(1) of the Act provides for the licensing of certain activities, including the killing or taking of badgers, and interference with setts, for scientific or educational purposes, or for the conservation of badgers. English Nature is the licensing authority for licences issued under this Section. 11.2 In addition, the Act provides an exemption to the above offences for the purpose of doing anything which is authorised under the Animals (Scientific Procedures) Act 1986 e.g. experimental procedures approved under licence to advance biological or behavioural knowledge.
56
11.3 One part of the Crown is, strictly speaking, unable to apply to another part of the Crown for a licence and it may be a Crown laboratory that would wish to carry out the research. In circumstances such as these it is usual for Crown staff to operate within the spirit of the law, and should a "licence" prove necessary, to submit an "application" and to comply with the conditions attached to any "licence" subsequently issued. 12. SECURITY CONSIDERATIONS. 12.1 Removal of animals from the wild for experimental purposes will attract the attention of animal rights activists, both in the field and at the captive facility. Consideration should be given to the possibility of procuring badgers from a secure, perhaps Ministry of Defence, site. 13. REFERENCE. Forrester G.J., Delahay R.J., Clifton-Hadley R.S. (2001). Screening badgers (Meles meles) for Mycobacterium bovis infection by using multiple applications of an ELISA. Veterinary Record, 149, 169-172. 14. BIBLIOGRAPHY. Pope and Burke, preliminary report 6th March 2002. Report to Defra.
57
APPENDIX 8. FEASIBILITY AND COSTS FOR PROVIDING ACCOMMODATION FOR BADGERS. 1. INTRODUCTION. 1.1 Work with badgers infected with bovine tuberculosis would require containment at Level 3. Appropriate containment is also required to protect local farming interests. As the work would require animals to be maintained in captivity for an extended period particular attention needs to be paid to their welfare and the conditions under which they would be held. 1.2 Given the containment and animal welfare considerations of this work a new facility would be required. Existing secure facilities are available which include sufficient open ground to accommodate a new unit while providing access to trained animal technicians and scientists. 2. STANDARDS. 2.1 To comply with Level 3 containment and Home Office Procedures the facilities must meet the following standards. 2.1.1 All rooms must be maintained to an air pressure negative to the atmosphere. 2.1.2 Extracted air must be filtered by a HEPA (high efficiency particulate absorption) filter. 2.1.3 Liquid waste should be discharged via a sealed and leak-proof drainage system into an impermeable holding or treatment enclosed tank within the designated area. 2.1.4 All areas must be sealable to permit disinfection. 2.1.5 An autoclave must be available within the facilities and all bedding, animal waste and bodies must be autoclaved before disposal. 2.1.6 When undertaking procedures, such as post mortem, a class 1 microbiological safety cabinet is required; the exhaust must go into the room extract system via a HEPA filter. 2.1.7 A dedicated staff changing area is required. 3. SERVICES. 3.1 Under The Animal (Scientific Procedures) Act 1986 all services should be installed in such away that they are either buried within the fabric of the building or clear of wall surfaces. Maintenance required to any services might disturb the animals. Therefore the design for services such as lighting must
58
be accessible from outside the holding area. All holding areas should have temperature and relative humidity control, which are carefully maintained. The temperature should be within the range appropriate for the species and the relative humidity would be maintained at 55%. Ventilation should provide sufficient air of an appropriate quality and reduce the levels and spread of odours, dust and infection; in order to comply with this recommendation 15-20 air changes per hour distributed throughout the holding area should be adequate. No procedures or euthanasia must be performed in the normal holding areas where animals are housed, i.e. there must be an adequate area provided to carry out these. 4. HOLDING AREA. 4.1 These requirements mean that infected badgers will need to be kept in an enclosed facility with no access to outdoor or grass runs. There is currently no available information on the welfare requirements of badgers to be kept under such containment conditions for an extended period of time. However, working on the assumption of two animals to be kept in each enclosure, and from experience with other species, it is suggested a holding area of 4.5m x 10m be an appropriate minimum. This area should be concrete floored with steel walls. Within this area the animals would be kept on a deep litter system and be provided with nest boxes. 4.2 A series of such enclosures would require access through a central corridor leading to a procedures room, post mortem area, autoclave facility and changing area. The area would require secure drainage. 5. COSTS. 5.1 Commercial construction of Category 3 facilities costs approximately 4,400 per square meter. Adding 15% to the floor area for corridors and circulation and each enclosure built to existing standards would involve a cost of 227,700. Such area-based costs might be higher than necessary given the large enclosed spaces required by the animals and should be viewed as a maximum. It might be possible to use cheaper alternatives or modular preconstructed units although these would require further investigation. A low end cost of 3,000 per square meter might be a minimum in these circumstances producing a cost of 155,250 per enclosure. The central procedures, autoclave, post mortem and changing areas would have an additional cost of approximately 440,000. No Enclosures each containing two badgers 10 25 50 Cost of Enclosures at 4,400 per m2 2,277,000 5,692,500 11,385,000 Cost of Enclosures at 3,000 per m2 1,552,500 3,881,250 7,762,500 Cost of Central Facilities at 4,400 per m2 440,000 440,000 440,000 Total price range
2.25-2.72m 4.32-6.13m 8.20-11.82m
59
5.2 In addition to the capital costs of construction there would also be staff, veterinary consultancy and running costs associated with the facilities. Approximate annual costs are outlined below. No Enclosures each containing two badgers 10 25 50 Staff Costs Veterinary Costs Running Costs Total
40,000 60,000 85,000
2,000 2,500 3,000
30,000 75,000 150,000
72,000 137,500 238,000
5.3 Holding animals in existing facilities while checking disease status would not change the above costs; these are largely determined by the number of simultaneous challenges that are required, not by how long the animals are held. If animals were to be held for a brief period to check disease status and then for up to a year in category 3 for the challenge work, there would be a slight saving in time, but not a significant one. Using holding pens would also raise issues of soil contamination, risking infection of subsequent animals and the surrounding environment. 5.4 These costings contain a number of uncertainties that require further investigation before reliance can be placed on the figures. In particular the standard of building required to provide containment at reasonable cost, and the conditions under which animals should be held to ensure their welfare both require further investigation. It is suggested that two lines of enquiry are needed to explore the options. 6. FURTHER ENQUIRY. 6.1 Firstly, there is limited information and expertise on keeping badgers under such conditions. A pilot study would be required to identify suitable protocols to maximise the health and welfare of animals. This would use uninfected badgers to obviate the need for containment. It is suggested holding two pairs of badgers in enclosures modified from existing low containment facilities. This pilot study should be carried out for 12 months to develop protocols for the following. 6.1.1 Optimum space requirements for housing. 6.1.2 Routine and experimental handling. 6.1.3 Food presentation and suitable sources of food. 6.1.4 Types of bedding and nesting material required. 6.1.5 Presentation of bedding and nesting material. 6.1.6 Water presentation. 60
6.1.7 Benefits of environmental enrichment. 6.1.8 To assess whether the badgers health and welfare is optimised, badgers would regularly be weighed and inspected for injury and behaviour monitoring would be conducted using standard techniques e.g. 24 hour time budgets once a month. Faecal cortisol levels would be measured weekly to provide an independent measure of stress. 6.1.9 It is anticipated that such a study would cost around 100,000 and could be completed in 15 months. 6.2 Secondly there is a need to explore the methods of containment and associated costs. As described earlier the typical cost of 4,400 per m2 for Category 3 containment might not be applicable to this situation. A study to assess the practicality and cost of other options such as pre-constructed modular units is needed before accurate designs and costings could be produced. It is suggested a contract to a building and containment specialist contractor would be needed to explore the available options and it is anticipated a cost of 20,000 would be made for such work.
61
APPENDIX 9. IMMUNOLOGICAL ASSAYS TO SUPPORT THE DEVELOPMENT AND EVALUATION OF A VACCINE AGAINST BADGER TUBERCULOSIS. Glyn Hewinson and Mark Chambers Veterinary Laboratories Agency, New Haw, Addleston, Surrey KT15 3NB 1. INTRODUCTION. 1.1 One of the stumbling blocks to vaccine development for badgers is the paucity of available immunological reagents that might be used to assess vaccine take and to monitor M. bovis infection and vaccine efficacy in the field. Over the past few years a number of immunological assays have been developed for badgers. The purpose of this appendix is to review the assays that are already available, to describe those that are in development and to outline how each assay might be used in a vaccine development and evaluation programme. 2. PROPOSED USES FOR IMMUNOLOGICAL ASSAYS. 2.1 Sensitive and specific detection of M. bovis infection in the target population.
Test
Rationale
ELISA for serological response to M. The existing Brock Test ELISA detects bovis-specific antigen(s). IgG antibody against a single antigen, MPB83, with a sensitivity of ca. 45%. Adding further M. bovis specific antigens has improved sensitivity to ca. 55% without a loss in specificity (Kampfer et al., 2003; Greenwald et al., 2003). Lymphocyte (LTA) transformation assay Measures T cell responses to either vaccination or infection. More sensitive than Brock Test (Dalley et al., 1999).
High performance and operational IFN ELISA with PPD-M and PPD-A, or ease based on experience of analogous test for cattle. antigen(s) specific to TB complex. Above tests used in combination. Improved detection of M. bovis infection has been reported using a combination of cellular and humoral assays (Griffin and Buchan, 1994).
62
2.2 Assessment of vaccine take. Test

As for 2.1 plus IFN ELISPOT assay.
Rationale
Use of an IFN ELISPOT assay would allow assessment of the magnitude of the memory response generated by vaccination (e.g. Vordermeier et al., 2002). Detection of IgA against M. bovis antigens would be especially useful for detecting mucosal immune responses.
IgA ELISA
2.3 Assessment of vaccine efficacy. Test

LTA or IFN ELISA using antigen(s) present in M. bovis but not in vaccine (e.g. ESAT-6 and CFP10, in the case of vaccination with BCG).
Rationale
Recent results in cattle have demonstrated that, following BCG vaccination, protected animals could be differentiated from those that were developing disease (Vordermeier et al., 2002) using this approach.
ELISA for serological response to M. Absence of seroconversion to MBB83 amongst vaccinated animals could bovis-specific antigen(s). indicate control of infection or disease progression, since BCG vaccinated animals do not mount a serological response against this antigen (Southey et al., 2001). 2.4 Trap-side diagnosis. Test Lateral flow-format serological assay. Rationale Seropositive badgers are at greatest risk of shedding M. bovis (Chambers et al., 2002, Clifton-Hadley et al., 1995). This assay would allow detection of super excretors within 15 minutes of capture.
63
3. PROGRESS MADE ON TEST DEVELOPMENT: AVAILABLE ASSAYS. 3.1 Lymphocyte transformation assay. 3.1.1 A comparative lymphocyte transformation assay (LTA) has been developed using bovine and avian tuberculin as antigen to detect cellmediated responses in M. bovis-infected badgers (Dalley et al., 1999). Todate the sensitivity of the comparative LTA is 91%. This compares favourably with the sensitivity of 50% for the existing indirect ELISA assay for the detection of tuberculous badgers (the Brock Test see below). However, the ELISA test gives a greater specificity (92% compared with 89% for the comparative LTA). Preliminary evidence suggests that for the comparative LTA, the blood cannot be stored overnight prior to testing as this procedure reduces the specificity of the assay to approximately 57%, although the sensitivity remains at approximately 86%. 3.2 Brock Test (indirect ELISA for detecting IgG antibodies against MPB83). 3.2.1 The only validated immunological test for the detection of tuberculosis in the badger is the Brock Test. This is an indirect ELISA for a serological response to MPB83, a 26 KDa protein antigen expressed by M. bovis (Goodger et al., 1994; Hewinson et al. 1997). Evaluation of the Brock Test for the detection of M. bovis infection in badgers gave the predictive value of a positive test result of 67.5% and the predictive value of a negative test of 84.6%. The sensitivity of the test was significantly higher in animals with gross tuberculous, which suggested the Brock Test may be useful for the detection of badgers most likely to be excreting M. bovis (Clifton-Hadley et al., 1995). The sensitivity of the test at the population level was 72.9%, compared with 40.7% at the level of the individual animal, suggesting the test could also be used to determine the burden of disease, at least for a population of badgers. 3.2.2 The serological responses in 102 badgers from social groups in Woodchester Park have been examined where M. bovis infection has been endemic since 1985. These responses were compared with culture from faeces, urine, tracheal aspirates and bite wound swabs taken from these animals whilst alive. The majority of culture-positive badgers excreted M. bovis intermittently over the period of study. As a result, there was only a 27.5% chance of detecting an infected badger by culturing M. bovis from clinical samples. In contrast, a positive ELISA result correctly predicted 68.2% of badgers with a history of excreting M. bovis. In the absence of alternative live tests for the badger, the Brock Test indirect ELISA should be more valuable than culture for measuring the effect of vaccination on reducing the number of badgers at risk of transmitting tuberculosis (Chambers et al., 2002). 3.2.3 In addition, animals vaccinated with BCG Pasteur do not mount a serological response to MPB83 (Southey et al., 2001) and so the Brock test could be used to detect M. bovis infected animals within a BCG vaccinated population.
64
3.3. Indirect ELISA for detecting IgA antibodies against MPB83. 3.3.1 Monoclonal antibodies against badger IgA have been raised and used to develop an indirect ELISA for detecting IgA antibodies against MPB83 in badgers. Preliminary data suggest that IgA responses can be detected in tracheal aspirates and sera of M. bovis infected animals. 3.4 Multi-Antigen Print ImmunoAssay (MAPIA). 3.4.1 The existing serological ELISA test (Brock Test) looks for an antibody response to a single mycobacterial antigen, MPB83, and has low sensitivity for surveillance purposes (Clifton-Hadley et al., 1995). Recent work using a technique known as Multi-Antigen Print ImmunoAssay (MAPIA) (Lyashchenko et al, 2000), identified a proportion (16%) of M. bovis culture-positive badgers that were negative by Brock Test but seropositive for their recognition of other M. bovis-specific antigens. This study suggests that modifying the Brock Test by incorporating a suitable cocktail of mycobacterial antigens results in enhanced test sensitivity (Greenwald et al., 2003). 3.5 Lateral flow-format seroassay. 3.5.1 The technology involved in the MAPIA approach described above is readily amenable to conversion to a lateral flow-format assay, in which a small volume (5 - 10l) of serum is placed on a wand onto which the target antigens are bound. Within 5 to 10 minutes a colour-change indicates firstly, that the test has worked, and secondly whether the test serum contains IgG (or IgA) antibodies to any of the target antigens. 3.5.2 Preliminary results from 178 badgers (Greenwald et al., 2003) showed that a lateral flow-format gave enhanced sensitivity and specificity over the Brock Test and MAPIA-based assay (sensitivity 53% vs 47% vs 49%; specificity 95% vs 89% vs 88%, respectively). 3.5.3 Although a lateral flow test is unlikely to have a sensitivity much beyond 55%, it is the only test that could be performed badger-side and should preferentially detect those animals at greatest risk of shedding M. bovis (Chambers et al., 2002). Such a test would enable a cull or vaccinate test strategy to be adopted in the field, should this be an option. 3.6. Multi-antigen BrockTest (the Dachs ELISA; Kampfer et al., 2003). The protocol used for the Dachs TB-ELISA is essentially the same as used in the Brock Test. The antigens used for the Dachs TB-ELISA are MPB83, MPB70, CFP10 and 16 kD antigen. In a preliminary evaluation of the test (Kampfer et al., 2003), the Dachs TB-ELISA gave higher sensitivity (a 33% improvement) than the Brock Test at the same specificity. These preliminary results suggest that serodiagnosis of badger TB can be enhanced with the new test. However, analysis of more sera with the Dachs TB-ELISA is required to reduce the confidence intervals to confirm its improved
65
performance over the Brock Test; which was originally evaluated on nearly two thousand sera (Clifton-Hadley et al., 1995). 4. PROGRESS MADE ON TEST DEVELOPMENT: ASSAYS UNDER DEVELOPMENT. 4.1 IFN ELISA. 4.1.1 Badger interferon-gamma (IFN) has been cloned and sequenced. Badger IFN was found to be most similar to canine IFN, with 88% aminoacid identity. Rabbits have been immunised with DNA encoding badger IFN and the resulting polyclonal antiserum demonstrated specificity for native badger IFN by intracellular staining and flow cytometry analysis of badger lymphocytes stimulated with PMA (Phorbol myristate acetate) and ionomycin. 4.1.2 At least 20 monoclonal antibodies have been generated that specifically recognise badger IFN, as demonstrated by flow cytometry on mitogenstimulated badger lymphocytes. These antibodies are being systemically evaluated in pair-wise combinations for their performance in the sandwich ELISA. 4.1.3 A prototype sandwich ELISA has been produced that detects the presence of badger IFN. However, the test requires further optimisation as the sensitivity is currently too low to be of practical use. Blood from badgers experimentally infected with M. bovis in the Republic of Ireland (RoI) will be used for this purpose. 4.1.4 The IFN assay is not anticipated to be available and validated until March 2005. 4.2 IFN ELISPOT. 4.2.1 Evaluation of a cross-reactive commercial ELISPOT kit for canine IFN (R&D Systems) lacked the required sensitivity and reproducibility for use in badgers. A promising prototype ELISPOT for badger IFN has been produced using a combination of monoclonal antibodies generated against badger IFN. However, this assay requires further optimisation. 5. USE OF M. BOVIS SPECIFIC ASSAYS TO DISCRIMINATE BETWEEN VACCINATED, INFECTED AND VACCINATED BUT INFECTED ANIMALS. 5.1 Analysis of cellular immune responses in cattle following M. bovis challenge has demonstrated that proliferative T cell and IFN- responses towards the M. bovis specific antigen ESAT-6 (whose gene is absent from BCG) were generally low in vaccinated animals, but high in all non-vaccinated calves. Importantly, the amount of ESAT-6 specific IFN- measured by ELISA after M. bovis challenge, but not the frequency of responding cells, correlated positively with the degree of pathology found 18 weeks after infection. However, diagnostic reagents based on antigens not present in BCG, like
66
ESAT-6 and CFP-10, were still able to distinguish BCG vaccinated/diseased animals from BCG vaccinated animals without signs of disease (differential diagnosis). These results suggest that the determination of ESAT-6 specific IFN-, whilst not a direct correlate of protection, constitutes a useful prognostic immunological marker predicting both vaccine efficacy and disease severity (Vordermeier et al., 2002). Preliminary data generated using the LTA assay suggest that T cells from infected badgers also recognise these antigens. Blood from badgers experimentally infected with M. bovis in the RoI will be used for further evaluation of M. bovis specific antigens in T cell assays. 6. REFERENCES. Chambers M.A., Pressling W.A., Cheeseman C.L., Clifton-Hadley R.S., Hewinson R.G. (2002). Value of existing serological tests for identifying badgers that shed Mycobacterium bovis. Vet. Microbiol., 86, 183-189. Clifton-Hadley R.S., Sayers A.R., Stock M.P. (1995). Evaluation of an ELISA for Mycobacterium bovis infection in badgers (Meles meles). Vet. Rec., 137, 555-558. Dalley D., Chambers M.A., Cockle P., Pressling W., Gavier-Widen D., Hewinson R.G. (1999). A lymphocyte transformation assay for the detection of Mycobacterium bovis infection in the Eurasian badger (Meles meles). Vet. Immunol. Immunopathol., 70, 85-94. Goodger, J., Nolan, A., Russell, W.P., Dalley, D.J., Thorns, C.J., Stuart, F.A., Croston, P., Newell, D.G. (1994). Serodiagnosis of Mycobacterium bovis infection in badgers: development of an indirect ELISA using a 25 kDa antigen. Vet. Rec., 135, 82-85. Greenwald R., Esfandiari J., Lesellier S. Houghton R., Pollock J.., Aagaarde C., Andersen P., Hewinson R.G., Chambers M.A., Lyashchenko K. (2003). Development of a Lateral-Flow Immunoassay for Rapid Detection of Mycobacterium bovis Infection in Badgers (Meles meles). Diagnostic Microbiology and Infectious Disease. In press. Griffin J.F., Buchan G.S. (1994). Aetiology, pathogenesis and diagnosis of Mycobacterium bovis in deer. Vet. Microbiol., 40, 193-205. Hewinson R.G., Michell S.L., Russell W.P., McAdam R.A., Jacobs W.R. Jr. (1996). Molecular characterization of MPT83: a seroreactive antigen of Mycobacterium tuberculosis with homology to MPT70. Scand J Immunol. 43, 490-9. Kampfer S., Dallet D., Hewinson R.G., Chambers M.A., Singh, M. (2003). Multi-Antigen ELISA Test for Enhanced Diagnosis of Badger TB. Vet Record. In press.
67
Lyashchenko K.P., Singh M., Colangeli R., Gennaro M.L. (2000). A multiantigen print immunoassay for the development of serological diagnosis of infectious diseases. J. Immmunol. Methods, 242, 91-100. Southey A., Sleeman D.P., Lloyd K., Dalley D., Chambers M.A., Hewinson R.G., Gormley E. (2001). Immunological responses of Eurasian badgers (Meles meles) vaccinated with Mycobacterium bovis BCG (bacillus calmette guerin). Vet. Immunol. Immunopathol., 79, 197-207. Vordermeier H.M., Chambers M.A., Cockle P.J., Whelan A.O., Simmons J., Hewinson R.G. (2002). Correlation of ESAT-6-specific gamma interferon production with pathology in cattle following Mycobacterium bovis BCG vaccination against experimental bovine tuberculosis. Infect. Immun. 70, 3026-32.
68
APPENDIX 10. REQUIREMENTS OF A FIELD TRIAL TO TEST BCG IN BADGERS. Ivan Morrison Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Roslin, Scotland EH25 9RG 1. INFORMATION REQUIRED BEFORE UNDERTAKING A TRIAL. 1.1 The following information would be highly desirable not only to justify a field trial with BCG but also to facilitate design of the trial and interpretation of the results. Some of this information might be available from the literature, but much of it would need to be generated from experimental studies. 1.1.1 Optimal dose and route of administration of BCG to achieve protection. 1.1.2 A reliable method to measure vaccine uptake, if administered remotely in bait. 1.1.3 Whether or not excretion of BCG occurs following vaccination. 1.1.4 Risk of uptake by, or transmission to, other species and potential pathogenic effects. 1.1.5 Level of protection obtained, in terms of reduced disease and bacterial excretion. 1.1.6 Types of immune responses induced by infected and BCG-vaccinated badgers, including immune responses that distinguish infected from vaccinated animals. 2. PARAMETERS THAT NEED TO BE MONITORED IN A TRIAL. 2.1 Essential parameters. 2.1.1 Badger population density and structure. This can only be estimated on the basis of survey data. It would be needed at outset to determine where vaccine baits should be laid and also needed during the course of a trial to ensure that the badger population does not change radically. 2.1.2 The rate of vaccine uptake. Methods would need to be tested and validated prior to a trial; this need only be done on a sample of badgers. 2.1.3 The incidence of cattle herd breakdowns. 2.1.4 Environmental impact. One would need to assess possible infection of other species with BCG and any potential deleterious effects. Ideally this
69
needs to be done prior to starting a trial; it could perhaps be done as a risk assessment based on information from experimental studies or it might require field experiments prior to a trial. 2.2 DESIRABLE PARAMETERS. 2.2.1 Immunological evidence of vaccine take. This would be dependent on assays that detect vaccine-induced immune responses similar to those detected in experimentally vaccinated badgers; it need only be done on a sample of badgers. 2.2.2 Prevalence of infection in the badger population. This would be dependent on having an assay that detects infected animals and distinguishes them from vaccinated uninfected animals; it need only be done on a sample of animals. 3. A TWO-PHASE OR SINGLE-PHASE TRIAL? 3.1 The success of any vaccination of badgers would ultimately be measured by whether or not it had an impact on the incidence of cattle herd breakdowns. Vaccination trials must therefore be conducted in areas where there is a high incidence of breakdowns. However, even in high incidence areas, such as those included in the current culling trial, the annual incidence of herd breakdowns is only about 10%. As each trial area (i.e. each individual member of a triplet) contains on average about 100 herds, vaccination of badgers would need to be applied over a large area to encompass sufficient numbers of breakdowns each year to measure the impact of the vaccine. Moreover, since the badger population takes 2-3 years to turn over, a substantial impact on TB in the badger may not be achieved until the population has received two or three annual vaccinations and, because of the lag between cattle becoming infected and detection of infection by testing, any effect on cattle herd breakdowns might not be apparent for a further year. Based on these assumptions, it is unlikely that meaningful information on the impact of badger vaccination on cattle herd breakdowns could be obtained without undertaking a relatively large scale trial over at least a four year period. 3.2 For similar reasons, a small-scale trial is also unlikely to yield reliable information on the effect of vaccination on prevalence of TB in the badger, (even assuming there were reliable assays to diagnose TB in the live animal). The prevalence of TB in most populations of badgers is probably less than 10%, it can vary considerably between local social groups and can also show cyclical variation over a period of several years. As discussed above, two or three years of vaccination might be required to have an impact on TB in the badger. Therefore, large numbers of badgers would need to be vaccinated and monitored by trapping and blood sampling over a prolonged period of time to obtain meaningful data. In any event, current assays for detection of infection by one-off sampling of live badgers have limited sensitivity and specificity and the likelihood and time-scale for developing such assays is uncertain.
70
3.3 For these reasons, it would be preferable to proceed directly to a largescale trial aimed primarily at examining the impact of vaccination on TB in cattle, assuming that the experimental studies provided evidence of efficacy. The precise design of the trial would depend on the area that would need to be covered to include the numbers of herd breakdowns required. This might be either a single large site or multiple sites, as in the current culling trial, with appropriately matched control sites. Indeed, the control areas, and possibly also the reactive areas (depending on the results), in the current culling trial might be suitable for such a trial. 3.4 However, there may be a need for limited scale, short-term experiments in the field to examine the feasibility of particular aspects of the trial, e.g. assessment of environmental risks, measurement of vaccine uptake or assessment of vaccine take.
71
APPENDIX 11. VACCINATION OF BADGERS AGAINST BOVINE TB: THE ECOLOGICAL CONSIDERATIONS. Chris Cheeseman, Des Delahay & Gavin Wilson CSL Woodchester Park, Nympsfield, Stonehouse, Glos, GL10 3UJ 1. INTRODUCTION. 1.1 Vaccination of wildlife presents particular challenges related to the ecological characteristics of the target population. The efficacy of the vaccine will be a product of the rates of uptake and immunisation that are achieved. Understanding the practical constraints imposed by ecological factors is essential for the development of an effective vaccine and a successful strategy for its delivery. 1.2 This appendix describes the potential influence of badger social organisation, population dynamics and the epidemiology of Mycobacterium bovis infection on the development and execution of any future vaccination programme, and discusses options for vaccine delivery strategies. 2. BADGER SOCIAL ORGANISATION AND POPULATION DYNAMICS. 2.1 In order to establish an effective vaccine delivery programme it is necessary to estimate the size and distribution of the target population (which may relate to either the number of badgers or their setts). Consequently, vaccination of badgers would require information on population density, social organisation and demographic structure (particularly if age or sex biased disease transmission occurs, e.g. pseudo-vertical transmission). In addition, information on population turnover rates (fecundity, mortality and emigration/immigration) would be required to determine the frequency of application that would ensure a fixed proportion of the population was always vaccinated. 2.2 Badger density varies widely throughout the UK, from less than a single animal / km2 in marginal habitats to more than 25 / km2 in optimal habitats (Wilson et al., 1997). The density of badgers in the TB cattle hotspot areas of South West England is probably medium to high, perhaps typically varying between 6-15 adults / km2 based on the presence of 1-2 social groups of moderate size / km2. However, it is likely that in many of these areas current population density is below carrying capacity as a result of previous culling operations. It will be necessary to assess the size of target populations for vaccination, and the methodology employed will depend on the proposed scale of operations. Current Defra funded projects are investigating the development of methods to estimate badger abundance. 2.3 Badger social organisation varies between populations. In undisturbed medium and high-density populations, badgers live in social groups and
72
collectively maintain territories. Although badgers may use several setts within the group territory, much activity is concentrated at the main sett. This stable pattern of social organisation allows the delineation of a target area for vaccination that is ecologically meaningful. 2.4 However, this stable pattern is disrupted to varying degrees in lower density and disturbed populations. Consequently, a more dynamic social system (e.g. more movement between groups and sett-sharing) may exist in populations that have been subjected to badger culling operations in the past. However, there is currently insufficient data on the social structure of disturbed populations to fully assess the likely implications for vaccination strategies. The demographic and epidemiological consequences of badger culling are the subject of another current Defra funded project. Nevertheless, evidence from studies of culled populations suggests that in the absence of further major disruption, numbers might have reached carrying capacity and a more stable social structure might have returned in many such areas by the time a vaccination strategy was employed. Following complete removal of 11 social groups (60 adults and yearlings, 11 cubs in total) from the high density Woodchester Park population it took 10 years for population density and social organisation to return to pre-cull levels (Cheeseman et al., 1993). Following the incomplete removal of eight social groups (29 badgers in total) in a lower density population at North Nibley, the disruption of social group organisation was largely limited to the first year post-BRO and density returned to pre-cull levels after only three years (Tuyttens et al., 2000 a & b). 2.5 Any vaccination strategy would need to be sustained over a protracted period of time and the interval between repeated applications would be determined by the rate of turnover of individuals in the population. Disease eradication could probably only be achieved over several decades (White & Harris, 1995; Smith et al., 2001). Fecundity, mortality, immigration and emigration determine population turnover rates. 2.6 Female badgers do not usually reproduce until they are two years old. However, although the majority of females mate and produce blastocysts, in many populations only a relatively small proportion produce litters. In badgers examined from South West England only 44% of females implanted (Cresswell et al., 1992). In high density populations (e.g. Woodchester Park) more females per social group produce litters than in lower density populations where suppression by dominant females is thought to be resource-related (Woodroffe & Macdonald, 1995). However, within high density areas the number of successful pregnancies (i.e. cubs weaned) might decrease as the number of adult females per group increases (Woodroffe & Macdonald, 1995). Generally, only one litter (typically of 2-3 cubs) is produced per social group each year. This gives an annual productivity of 0.5 to 0.8 cubs per badger in the UK (Smith, 2002). Cub mortality rates are high and variable (Cresswell et al., 1992; Rogers et al., 1997). Mortality rates of uninfected adults are more constant: 0.30 and 0.24 per year for males and females respectively (Wilkinson et al., 2000). This gives a per capita mortality rate of about 0.5 (Smith, 2002).
73
2.7 Rates of immigration into stable badger populations and those that are recovering from culling operations will influence the time scale for vaccine deployment on all but the largest of areas (e.g. at a regional level). In high density populations rates of movement of badgers between social groups are relatively low (Cheeseman et al., 1988a; Rogers et al., 1998). However, rates of movement within populations that are recovering from culling might be higher (Cheeseman et al., 1993; Tuyttens et al., 2000b). 2.8 Consequently, the intrinsic growth rate (r) of badger populations is relatively low; approximately 0.24 to 0.30 per year for moderate to high density populations (Anderson & Trewhella, 1985; Smith, 2002). Rates of population turnover need to be considered in conjunction with vaccine uptake rates in order to determine the optimal strategy for repeated applications. 3. THE EPIDEMIOLOGY OF TB IN BADGER POPULATIONS. 3.1 The distribution of infected badgers is spatially clustered. Social groups with endemic infection can be adjoined by groups where infection is absent (Cheeseman et al., 1988b; Delahay et al., 2000a). Also, the prevalence of infection might vary considerably both within and between badger populations, and over time (Cheeseman et al., 1981; Cheeseman et al., 1985; Delahay et al., 2000a). However, as there is currently no reliable, cost-effective and practical technique for accurately identifying such patterns, it might not be possible to target vaccine delivery accordingly. 3.2 Evidence from Woodchester Park suggests that the prevalence of infection in the badger population might not bear any linear relationship with density (Cheeseman et al., 1989; Rogers et al., 1999). However, no concurrent data exists on both badger density and TB prevalence from other sites. Mathematical models suggest that a threshold of about 8 badgers per social group is required for maintenance of infection over the moderate to long-term (i.e. up to 30 years) in a population (Smith et al., 1995). 3.3 Evidence from the Woodchester Park study suggests that the greatest risks of infection to cattle may be posed by a relatively small proportion of the population, consisting of persistently infectious animals (Cheeseman & Mallinson, 1981; Delahay et al., 2000a). Infected individuals can live for several years and breed successfully whilst excreting bacilli (Clifton-Hadley et al., 1993; R. Delahay, unpublished data). As the distribution of infected individuals can also be highly aggregated within populations, this argues for a spatially broad-based strategy for vaccination, since small foci of infection cannot be adequately identified. It is possible that a proactive campaign involving broad scale application of a vaccine could reach a high proportion of the target population. However, if small foci of infectious animals were missed (perhaps reflected in the persistence of local cattle breakdowns), then smallerscale, reactive applications of vaccine could be used to target these problem areas. Delivery of a vaccine over an extensive area might be best achieved by deployment of baits, whereas trapping and injection could be useful in intensive localised operations.
74
3.4 It is not yet known whether badgers can naturally mount an effective immune response to M. bovis capable of protecting against the development of disease and excretion of bacilli. There is some evidence from the Woodchester Park study, of a transient sero-positivity to M. bovis in badger cubs. However, it is unclear whether this is the result of maternally derived antibodies or prior exposure (Newell et al., 1997; Chambers et al., in press). Nevertheless, in the majority of badgers that exhibited transient sero-positivity as cubs, M. bovis could not be isolated from clinical samples during later life (R. Delahay & G. Wilson, unpublished data). Both Newell et al. (1997) and Chambers et al. (2002) reported that Western blotting may identify serum antibodies that are correlated with prolonged culture negativity in later life. However, at present there is insufficient information on the true immune status (cellular immunity in particular) of these animals to predict the likely effects of a vaccine. 3.5 It would also be important to consider what the effect of potential vaccines would be on individuals that were already infected. If cubs are infected at an early age by females (e.g. pre-weaning and/or pre-emergence from the sett) then this would probably make it impossible to deliver a vaccine to them prior to infection. However, in order for a badger vaccine to reduce the incidence of TB in cattle it might only need to reduce the severity of disease rather than protect against infection. It might be possible to reduce the rate of transmission from badgers to cattle by either stopping or decreasing the excretion of bacteria in infectious badgers. However, if the vaccine had no effect on infected individuals, then this would suggest the necessity of frequent follow up vaccination campaigns to prevent these animals from causing new cases. 4. VACCINE DELIVERY. 4.1 The most likely options for successful delivery of a vaccine to wildlife are by injection, by an aerosol spray, by ingestible bait or by an orally administered bait with the capacity to deliver an aerosol to the respiratory tract. The likelihood of successful immunisation resulting from each potential delivery route will depend on the characteristics of the vaccine. For example some vaccines might not survive passage through the gastro-intestinal tract. The survival of the vaccine in the environment and its likely effects on nontarget species would also influence the choice of delivery vehicle. The pattern of vaccine deployment would influence the proportion of the population that could be reached, and this in combination with the immunisation rate would determine the overall efficacy of the vaccine. 4.2 Delivery of a vaccine by injection would require the capture of badgers. Cage trapping is unlikely to be more than 80% efficient and would often be much lower (see Tuyttens et al., 1996), could be biased towards particular age and sex classes, would be extremely labour intensive over an extended area and would be prone to interference from objectors. In addition, capture related stress in trapped badgers could potentially adversely affect the immune response. However, administration by injection would eliminate the problems associated with non-target species and survival of the vaccine in the
75
environment. Capture of animals would also allow a specific dose to be delivered to each individual by a chosen route, and provide accurate data on numbers vaccinated. In addition, if a suitable badger-side diagnostic test was available then vaccination could be combined with selective culling of infected individuals. Modelling studies suggest that as culling is more effective in eradicating disease from the badger population than vaccination, a combined strategy (of culling and ring vaccination for example) would be likely to be more efficacious than vaccination alone (Smith et al., 2001). Alternatively, vaccination by injection could be employed as a fall-back strategy in specific problem areas, as an adjunct to bait delivery. 4.3 Badger setts are relatively conspicuous structures that could be used to target delivery of a vaccine. Delivery of bait into the setts themselves would limit opportunities for exposure to non-target species. Identification of setts for bait delivery would require labour intensive surveys much like those already carried out in treatment areas for the Randomised Culling Trial. Main setts can often be identified (although not always with certainty), but at any given time some badgers are also likely to be occupying other setts. Also, rates of movement between setts might be higher in areas that have been the subject of some disturbance in the past (Tuyttens et al., 2000b) and might change seasonally. It is likely therefore, that in order to maximise uptake, bait would have to be delivered to all active setts within the target area over a period of several days, and that re-surveying for active setts would be required before each subsequent application. 4.4 Bait uptake rates in carnivores have been monitored throughout Europe and North America as part of strategies to control wildlife rabies by vaccination. Bait uptake rates can be influenced by a variety of environmental factors, including prevailing weather conditions, the availability of natural foods and season. It might also take sometime for populations of bait nave animals to become accustomed to a novel food source, so uptake might improve with repeated applications. 4.5 The strategy of bait delivery to badgers would need to minimise the opportunity for a few animals to monopolise the vaccine. This is also the aim when carrying out studies of badger social organisation with marked bait. In this case bait containing plastic markers is placed in badger setts and also distributed in the immediate proximity of the holes at bait points under stones and logs. This maximises the opportunity for all occupants of the sett to take bait, protects it from the elements and reduces opportunities for exposure to non-target species (Delahay et al., 2000b). Such a strategy could also be employed to deliver a bait containing a vaccine. 4.6 In a field trial in Cork, Republic of Ireland, chocolate-coated gelatine capsules containing dead Mycobacterium vaccae were added to peanut and syrup baits placed in shallow pits near sett entrances (McCarthy, 1993). To date, only limited work has been carried out on bait uptake rates by badgers and the results have been variable. Southey et al., (2001) reported rates of bait uptake by badgers that varied widely between sites (between 20 and 82 %), and suggested that uptake by non-targets, weather conditions, time of bait
76
deployment and the local availability of natural foods might have been influential. 4.7 The strategy might need to minimise exposure of non-target species to baits, if the vaccine was likely to have any pathological effects, or if uptake rates in the target population could be adversely affected. Placing baits in badger setts would reduce exposure to non-target species, but cannot eliminate it as some mammals (e.g. foxes, rabbits, rats, mice and, in rarer cases, otters) might also be resident. 4.8 A bait that would be taken orally (whether or not it contains an effervescent component) would need to be highly palatable to badgers. In bait preference tests, a formulation consisting of plant and animal protein, fish oil, a synthetic polymer and coated in chocolate was readily accepted by captive badgers (OCallaghan, 1996). Scented attractants could also be used to improve bait uptake (e.g. synthetic fermented egg in fox baits). 4.9 It is important that the vaccine had no detrimental effects if taken several times by the same badger, as this would be extremely difficult to avoid. If delivery of a specific dose was required, then this would seriously constrain the options for use of an oral bait and could arguably rule it out. However, it might be possible to use the principles of conditioned taste aversion (CTA) to limit bait uptake by individuals. This would involve incorporating a CTA agent in each bait, to induce nausea in any animal that consumed it. Work on foxes and ferrets carried out by CSL suggests that this could induce a short-term aversion to consuming further similar baits (G. Massei, unpublished data). Trapping and injection would allow each captured animal to receive a known dose and if these animals were marked in some way then re-dosing could be avoided. 4.10 Monitoring rates of bait uptake during vaccination operations would be a substantial undertaking, and would be likely to only be possible on a relatively small sub-sample of the population. The development of a potentially effective bait delivery strategy would require research on uptake rates with respect to variations in season, weather, habitat and badger density. 4.11 In New Zealand, vaccine delivery trials have been undertaken using a mechanical device that sprays an aerosol at possums visiting a bait station . Using this approach in badgers would require the development of suitable technology, the vaccine would need to remain viable during storage in the bait station and suitably prepared for reliable aerosolisation. However, automated vaccine delivery systems could be prone to mechanical failure and it might be difficult to monitor numbers receiving the vaccine. It is likely that a large number of such devices would be required and it is not clear how delivery of a specific dose and avoidance of multiple dosing could be assured, but it might be possible to substantially reduce exposure of non-target species by such a method. 4.12 Once a vaccine candidate and delivery route were identified then firstorder estimates of its effectiveness in the badger population could be obtained
77
from modelling studies. Following experimental dose-response and challenge studies on captive badgers, field trials would be required to monitor the immune responses in vaccinated and control animals in the wild, and the effects of vaccination on patterns of disease prevalence. A field trial would also provide the only measure of the efficacy of a badger vaccine in reducing TB breakdown rates in cattle. 5. CONCLUSIONS. 5.1 It is difficult to judge the relative importance of many of the ecological factors described in this appendix, in the absence of information on the properties of the candidate vaccines. 5.2 The characteristics of the vaccine (e.g. persistence in the environment, effects on non-targets, duration of protection afforded) would also influence the optimal strategy for delivery. 5.3 Characteristics of an ideal vaccine might be that it provides long-term protective immunity and some therapeutic value for infected animals at a range of doses, whilst being safe in non-targets that could be delivered in an oral bait. 5.4 Successful delivery of a vaccine to wild badger populations throughout the TB affected areas of England and Wales, would be likely to be aided by their typical organisation into social groups based around relatively conspicuous communal setts. 5.5 At present, an orally delivered bait appears to be the most practical option for vaccination (see Annex). However, the limited studies undertaken to date suggest that rates of bait uptake could vary widely (e.g. G. Smith, unpublished data; Southey et al., 2001), so further work would be required to identify optimal strategies. 5.6 Potentially promising strategies include annual broad scale application of a vaccine followed by localised, intensive, follow-up vaccination operations in problem areas, and vaccination in combination with selective culling. 5.7 Field studies on the effects of a vaccine in wild badgers would require one or more populations for which the prevalence of infection, social organisation and demographic characteristics were already known. 6. REFERENCES. Anderson R.M. & Trewhella W. (1985). Population dynamics of the badger (Meles meles) and the epidemiology of bovine tuberculosis (Mycobacterium bovis). Philosophical Transactions of the Royal Society of London B, 310, 327-381. Chambers M.A., Pressling W.A., Cheeseman C.L., Clifton-Hadley R.S. & Hewinson, R.G. (2002). Value of existing serological tests for identifying
78
badgers that shed Mycobacterium bovis. Veterinary Microbiology 86, 183189. Cheeseman C.L., Jones G.W., Gallagher J. & Mallinson P.J. (1981). The population structure, density and prevalence of tuberculosis (Mycobacterium bovis) in badgers (Meles meles) from four areas in south-west England. Journal of Applied Ecology, 18, 795-804. Cheeseman C.L. & Mallinson P.J. (1981). Behaviour of badgers (Meles meles) infected with bovine tuberculosis. Journal of Zoology, 194, 284-289. Cheeseman C.L., Little T.W.A., Mallinson P.J., Page R.J.C., Wilesmith J.W. & Pritchard D.G. (1985). Population ecology and the prevalence of tuberculosis in badgers in an area of Staffordshire. Mammal Review, 15, 125-135. Cheeseman C.L., Cresswell W.J., Harris S. & Mallinson P.J. (1988a). Comparison of dispersal and other movements in two badger (Meles meles) populations. Mammal Review, 18, 51-59. Cheeseman C.L., Wilesmith J.W., Stuart F.A. & Mallinson P.J. (1988b). Dynamics of tuberculosis in a naturally infected badger population. Mammal Review, 18, 61-72. Cheeseman C.L., Wilesmith J W. & Stuart F.A. (1989). Tuberculosis: the disease and its epidemiology in the badger, a review. Epidemiology and Infection, 103, 113-125. Cheeseman C.L., Mallinson P.J., Ryan J. & Wilesmith J.W. (1993). Recolonisation by badgers in Gloucestershire. In Hayden, T. J. (ed.). The Badger, 78-93. Royal Irish Academy, Dublin. Clifton-Hadley R.S., Wilesmith J.W. & Stuart F.A. (1993). Mycobacterium bovis in the European badger (Meles meles): epidemiological findings in tuberculous badgers from a naturally infected population. Epidemiology and Infection, 111, 9-19. Cresswell W.J., Harris S., Cheeseman C.L. & Mallinson P.J. (1992). To breed or not to breed: an analysis of the social and density-dependent constraints on the fecundity of female badgers (Meles meles). Philosophical Transactions of the Royal Society of London Series B, 338, 393-407. Delahay R.J., Langton S., Smith G.C., Clifton-Hadley R.S. & Cheeseman C.L. (2000a). The spatio-temporal distribution of Mycobacterium bovis (Bovine Tuberculosis) infection in a high density badger (Meles meles) population. Journal of Animal Ecology, 69, 428-441. Delahay R.J., Brown J.A., Mallinson P.J., Spyvee P.D., Handoll, D., Rogers, L.M. & Cheeseman C.L. (2000b). The use of marked bait in studies of the territorial organisation of the European badger (Meles meles). Mammal Review, 30, 73-87.
79
McCarthy J. (1993). The badger vaccination trial in West Cork: Progress report. In Hayden, T. J. (ed.). The Badger, 181-188. Royal Irish Academy, Dublin. Newell D.G., Clifton-Hadley R.S. & Cheeseman C.L. (1997). The kinetics of serum antibody responses to natural infections with Mycobacterium bovis in one badger social group. Epidemiology and Infection, 118, 173-180. OCallaghan W. (1996). Responses of badgers and other mammals to different food flavours. National University of Ireland, Cork, Ireland. Rogers L.M., Cheeseman C.L., Mallinson P.J. & Clifton-Hadley R. (1997). The demography of a high density badger (Meles meles) population in the west of England. Journal of Zoology, 242, 705-728. Rogers L.M., Delahay R.J., Cheeseman C.L., Langton S., Smith G.C. & Clifton-Hadley R.S. (1998). Movement of badgers (Meles meles) in a high density population: individual, population and disease effects. Proceedings of the Royal Society Lond. B., 265, 1-8. Rogers L.M., Delahay R.J., Cheeseman C.L., Smith G.C. & Clifton-Hadley R.S. (1999). The increase in badger (Meles meles) density at Woodchester Park, south-west England: a review of the implications for disease (Mycobacterium bovis) prevalence. Mammalia, 63, 183-192. Smith G.C., Richards M.S., Clifton-Hadley R.S. & Cheeseman C.L. (1995). Modelling bovine tuberculosis in badgers in England: preliminary results. Mammalia, 59, 639-650. Smith G.C., Cheeseman C.L., Clifton-Hadley R.S. & Wilkinson D. (2001). A model of bovine tuberculosis in the badger Meles meles: an evaluation of control strategies. Journal of Applied Ecology, 38, 509-519. Smith G.C. (2002). The role of the badger (Meles meles) in rabies epizootiology and the implications for Great Britain. Mammal Review, 32, 1326. Southey A.K., Sleeman D.P., Prendergast J., OSullivan R.F.O. & Mulcahy M.F. (2001). Use of biomarkers to assess the feasibility of delivering a vaccine to badgers (Meles meles). Journal of Zoology, 253, 133-139. Tuyttens F.A.M., Macdonald D.W., Delahay R. J., Rogers L.M., Mallinson P.J., Donnelly C. A. & Newman C. (1996). Differences in trappability of European badgers Meles meles in three populations in England. Journal of Applied Ecology, 36, 1051-1062. Tuyttens F.A.M., Delahay R.J., Macdonald D.W., Cheeseman C.L., Long, B. & Donnelly C.A. (2000a). Spatial perturbation caused by a badger (Meles meles) culling operation: implications for the function of territoriality and the
80
control of bovine tuberculosis (Mycobacterium bovis). Ecology, 69, 815-828.
Journal of Animal
Tuyttens F.A.M., Macdonald D.W., Rogers L.M., Cheeseman C.L. & Roddam A.W. (2000b). Comparative study on the consequences of culling badgers (Meles meles) on biometrics, population dynamics and movement. Journal of Animal Ecology, 69, 567-580. White P.C.L. & Harris, S. (1995). Bovine tuberculosis in badger (Meles meles) populations in south-west England: an assessment of past, present and possible future control strategies using simulation modelling. Philosophical Transactions of the Royal Society of London B, 349, 415-432. Wilkinson D., Smith G.C., Delahay R.J., Rogers L.M., Cheeseman C.L. & Clifton-Hadley R S. (2000). The effects of bovine tuberculosis (Mycobacterium bovis) on mortality in a badger (Meles meles) population in England. Journal of Zoology, 250, 389-395. Wilson G., Harris S. & McLaren G. (1997). Changes in the British badger population, 1988 to 1997. Peoples Trust for Endangered Species. Woodroffe R. & Macdonald D.W. (1995). Female/female competition in European badgers (Meles meles): effects on breeding success. Journal of Animal Ecology, 64, 12-20. ANNEX TO APPENDIX 11. STAFF TIME REQUIRED FOR A STRATEGY BASED ON DELIVERY OF VACCINE IN BAIT. 1. This example assumes that the strategy will involve two applications of bait each year in the proximity of all the active badger setts in the target area. 2. Initially the area would need to be surveyed for all badger setts, in the same manner as was carried out for each treatment area in the randomised badger culling Trial. Between applications, follow-up surveys (directly comparable to the re-surveys carried out in proactive treatment areas of the Trial) would be required to identify any changes in sett use that may have taken place. The resource requirements for survey work in Trial areas are already known. 3. Experience at Woodchester Park suggests that one fieldworker with a Land Rover and driving access to within several meters, can feed bait at about 8-10 main setts each day. On average this will involve the placing of 25-30 individual baits in shallow pits covered with large stones. For the purposes of bait-marking studies, feeding continues for 8-10 consecutive days, although if each badger only needed to consume a single bait then this period could probably be shortened for vaccine delivery.
81
APPENDIX 12. VACCINATION OF CATTLE WITH BCG TO PROTECT AGAINST INFECTION WITH MYCOBACTERIUM BOVIS. John Pollock Veterinary Sciences Div, DARDNI, Stormont, Belfast BT4 3SD 1. INTRODUCTION. 1.1 This appendix seeks to trace the sequence of the main events in almost a century of attempts to develop cattle vaccines for bovine tuberculosis. Within that broad aim, the main areas of focus have been selected to be of relevance to the present need to assess potential strategies to address the ongoing problem with this disease. 1.2 Considerable numbers of studies have been performed in several countries and have been based generally on the use of Bacillus Calmette Gurin (BCG). Some studies have been constructed as experimental investigations, others as field trials of various magnitudes. Some have been reported in detail as carefully designed studies with adequate controls, others less so. This variation must be acknowledged when considering the relevance of individual studies to the current situation and the overall potential of vaccination. To that end, this appendix attempts to rationalise: 1.2.1 The problems the investigators were attempting to solve and the background. 1.2.2 Any flaws now apparent which may limit the strength of the conclusions. 1.2.3 The details of the vaccination strategy which was used. 1.2.4 The protocols by which vaccine efficacy was assessed. 1.2.5 The outcome and the conclusions which were reported. 1.3 In a number of the studies which have been reviewed, particularly the more historical ones, some of these details are difficult to ascertain. However, with the benefit of previous reviews in this area (Francis, 1958; Zuckerman, 1980; OReilly and Daborn, 1995; Skinner et al., 2001; Buddle, 2001), it is usually possible to fit each study into a perspective of how opinions and ideas have changed with time. 2. IDEAL FEATURES OF A VACCINE FOR BOVINE TUBERCULOSIS. 2.1 It is apparent that the ideal features of a vaccine to combat bovine tuberculosis depend on the prevailing conditions, including economics and disease prevalence. For example, the requirements of a vaccine to improve the situation in the early part of the 20th Century are likely to have been very 82
different from present requirements. Around 100 years ago, knowledge of the pathogenesis of the disease was in its infancy. At that time, up to a third of all cattle were infected with tuberculosis, and there had been little attempt to deal with the situation. Currently in the U.K., however, statutory programmes for eradication have been in place for decades and have greatly decreased disease prevalence. Additionally, it is become accepted that wildlife reservoirs may play a significant rle in the maintenance of bovine tuberculosis in particular areas (as reviewed by Krebs, 1997). 2.2 Within recent years, several authors have considered the features required of a vaccine to effectively address bovine tuberculosis in developed countries, like U.K. and New Zealand, where there are potential wildlife reservoirs of infection (badgers and possums, respectively). In such a situation, the vaccine could be targeted towards either cattle or wildlife, and the profile of the vaccine will be different in each situation. 2.3 Within a programme to control tuberculosis in domestic animals, the aim of a vaccine for wildlife species is, essentially, to prevent spread of infection to cattle. To that end, such a vaccine need not necessarily prevent establishment of infection in the target animal, but must prevent excretion of bacilli (Newell and Hewinson, 1995). It has been considered that a badger vaccine should reduce the number and infectiousness of animals with active tuberculosis, but that it is not a concern if vaccinated animals have persistent low levels of infection (Krebs et al., 1997). 2.4 The requirements of a vaccine to be used in cattle are much more stringent. It has been stated that such a vaccine must be capable of protecting against establishment of persistent infection and that an outcome of reduction in bacterial load in persistently infected animals, which may be a good outcome for badger vaccination, would be unacceptable for cattle (Krebs et al., 1997). Recent reviews from New Zealand (Buddle, 2001; Skinner et al., 2001) have set out the detailed requirements for a cattle vaccine in developed countries. As stated, the vaccine must establish a form of immunity which will allow the animal to resist infection. The vaccine should also be safe, and be acceptable to other countries which would be potential importers of vaccinated cattle or cattle products. As part of that requirement, it will be necessary to be able to differentiate vaccination from infection (Krebs et al., 1997). Skinner et al. (2001) set the standard that the ideal cattle vaccine should allow the animal to resist challenge without becoming positive to subsequent tuberculin skin tests. 3. BCG. 3.1 Historical development of BCG. 3.1.1 The initial Bacillus Calmette Gurin was developed from a strain of M. bovis, which had been isolated by Nocard from a case of tuberculous mastitis by 230 passages through glycerinated bile potato medium between 1908 and 1919 (Oettinger et al., 1999). The initial strain was dispersed to many countries in the 1920s and continuing maintenance in differing conditions
83
resulted in the production of a considerable number of substrains (such as Moreau, Tokyo, Gothenburg, Danish, Tice, Montreal, Connaught, Glaxo, Merieux and Pasteur). Importantly, it has been shown that the substrains of BCG do not have identical properties and differ, for example, in their antigenic repertoire (Behr et al., 1999). Indeed, several important T-cell antigens of M. bovis, such as MPB64, MPB70 and MPB83, are differentially expressed by substrains of BCG (Li et al., 1993; Matsuo et al., 1995; Wiker et al., 1996). These differences have the implication that the substrain of BCG that is selected for vaccination will determine the antigenic profile of the resulting immunological priming. To that end, it has been shown that different substrains of BCG induce differing immune responses in mice (Lagranderie et al., 1996). Therefore, it has been considered likely that the substrain selected, and other factors such as dose and route of vaccination, may influence the efficacy of BCG in cattle (Newell and Hewinson, 1995). 3.2 Use of BCG in human tuberculosis. 3.2.1 Around 3 billion doses of BCG have been used since 1921 as a safe, inexpensive, single-shot vaccine to protect people from tuberculosis, but the overall efficacy remains somewhat controversial (Colditz et al., 1994; Roche et al., 1995; Wilson, 2000; Fine, 2001). Over the years, many studies have investigated the benefits of BCG and protective efficacies ranging from 80% to less that 0% have been reported (Fine, 1995; Roche et al., 1995). Metaanalysis of available published data indicated that BCG decreased the risk of tuberculosis by 50% (Colditz et al., 1994). It is generally accepted that BCG protects best against childhood and disseminated tuberculosis, but is less effective against adult pulmonary tuberculosis, leading to a school of thought that it protects better against internal, blood-borne spread than against initial infection (Roche et al., 1995). 3.3 Potential of BCG for vaccinating cattle. 3.3.1 As an attenuated strain of M. bovis, the potential of BCG for vaccinating cattle against disease caused by wild-type M. bovis was obvious to Calmette and Gurin, who carried out early investigations in that species (Calmette and Gurin, 1911). As in human tuberculosis, the additional benefits of being safe and inexpensive mean that BCG has often been considered as an option to control bovine tuberculosis over the last century (as reviewed by OReilly and Daborn, 1995; Buddle, 2001 and Skinner et al., 2001). It is also clear that BCG has been the prototype vaccine for tuberculosis in domestic livestock and remains the standard against which novel candidate vaccines will be compared (Griffin, 2000). 4. EXPERIMENTAL AND FIELD INVESTIGATIONS INTO THE POTENTIAL OF BCG FOR CATTLE. 4.1 Early investigations. 4.1.1 Investigations have been made in several counties to determine whether BCG offers potential in the control and eradication of bovine
84
tuberculosis. The studies have been based either on vaccination followed by challenge with virulent M. bovis (vaccine-challenge experiments; Table 1) or on monitoring the effects of vaccination on field situations where cattle were exposed to M. bovis (field studies; Table 2). While it is not always obvious how individual studies should be ascribed, an attempt has been made in Tables 1 and 2 to rationalize the major published information in a chronological and geographical manner. 4.1.2 The first experiments with BCG in cattle were performed by Calmette and Gurin (1911; 1920 and 1924). Doses of BCG, up to 200 mg, were given intravenously and subcutaneously prior to challenge with M. bovis. At post mortem examination, tuberculous lesions were limited in number or absent, although guinea pig isolations were reported to be positive in some of the nonlesioned cases. It was concluded that BCG conferred protection and minimised lesion formation. The findings from subsequent French field trials (Calmette and Gurin, 1920; Gurin et al., 1927) were also very encouraging, with BCG vaccination reducing lesions or providing freedom from tuberculosis. 4.1.3 The results from the French investigations led to international interest in the possibility of eradicating bovine tuberculosis by vaccinating cattle with BCG. This was further stimulated by findings of an experiment in the Ukraine (Tzeknovitzer, 1927) which concluded that BCG induced resistance to tuberculosis in cattle. 4.1.4 Historically, the focus of investigations then moved to North America where the outcomes do not seem to have been so positive. In Canada, Watson et al. (1928) reported that investigations in an infected herd situation showed that BCG did not provide any benefit in terms of resistance to tuberculosis. A similar situation was reported in trials in USA, where live or dead BCG showed some benefit in decreasing internal spread of tuberculosis but did not prevent infection (Larson and Evans, 1929; Schroeder and Crawford, 1929). A series of experimental investigations was carried out in USA and is reported by Haring et al. (1930). BCG was given in large doses (up to 100 mg or 109 cfu) and animals were challenged intravenously or orally. It was found that live bacilli were preferable for the induction of protective immunity, but that the level of protection was insufficient. A trial in an infected herd also reported by Haring et al. (1930) found a degree of protection but concluded that BCG induced skin test reactivity and was not appropriate for tuberculosis eradication programmes. 4.1.5 An experimental study carried out in the 1930s in UK used BCG doses of 5 and 50 mg (Buxton and Glover, 1939). Variable protection (between 0 and 50%) was reported, with the higher dose providing better results. As reviewed by Francis (1958), in the 1930s there was also interest in the vole bacillus (M. microti) as a potential vaccine strain. This was investigated in calves and, after showing initial promise in inducing a relatively high degree of immunity to M. bovis (Young and Paterson, 1949), it was ignored subsequently due to concerns over virulence.
85
4.1.6 Zuckerman (1980) reviewed two trials which were carried out in UK in the 1930s and 1940s, which were stated not to have been widely published. The first trial was conduced in 4 herds infected with tuberculosis and lasted for 11 years. 47 animals were vaccinated at 6-month intervals. Ultimately, 25% of these were found to have tuberculosis lesions, compared with 50% of their contacts. The second trial involved more animals, but did not last as long due to the advent of the national test-and-slaughter programme. In that case, 30% of the vaccinated and 50% of the non-vaccinated animals were found to have lesions. 4.1.7 Glover and Richie (1953) report on a UK trial carried out in 2 infected areas. In that case, vaccination reduced the number of animals with lesions, and there was an indication that vaccination was most successful if calves were not subjected to early challenge. In another trial which was carried out in an infected herd, it was found that considerable numbers of vaccinated animals developed lesions, and it was concluded that test-and-slaughter was a more realistic option (Doyle and Stuart, 1958). In other European trials, however, more positive outcomes were reported. In two such programmes carried out in Germany in the 1950s, tuberculosis was successfully eradicated from herds which were known to have been infected (Schellner and Gaggermeier, 1955; Rolle and Wiethe, 1956). 4.1.8 Considering the variable outcomes which had been reported for the use of BCG in cattle up until the 1950s, an Expert Committee of the WHO/FAO (1959) stated that: generally speaking, vaccination has no place in the eradication of tuberculosis in cattle. This conclusion was based on a lack of proven effect and the fact that BCG vaccination compromises the tuberculin skin test. 4.1.9 In the situations which prevail in some countries, however, tuberculin testing followed by slaughter of reacting animals may not be an option and, in the face of a serious zoonotic problem, further work on BCG vaccination was performed in some African countries (Mares, 1972). Experimental investigations reported from Malawi in 1972 showed that BCG produced useful resistance to challenge with M. bovis, which was more apparent in Zebu cattle than in Zebu-cross (Waddington and Ellwood, 1972; Ellwood and Waddington, 1972). In Madagascar, Cheneau and Blancou (1975) compared the potential of vaccination with live BCG, killed BCG and a trypsin extract of the Koch bacillus and found the latter to provide greatest protection. Several field trials were carried out in Malawi in the 1970s using 2.6 x 109 cfu of BCG. Some reports from this phase (Ellwood, 1975; Moodie, 1977) concluded that BCG was effective in controlling spread of tuberculosis in cattle. However, other reports (Berggren, 1977; 1981) identified little benefit of BCG in protecting cattle from infection. Contrary to these findings, trials carried out in infected animals in USSR indicated that BCG had the potential to clear infected herds within a period of years (Sibgatullin, 1982). 4.2 Recent investigations.
86
4.2.1 The reports considered above provide a range of conclusions on the potential of BCG to be used effectively against bovine tuberculosis. Among the possible reasons for this variation, it is apparent that the studies were performed under a great range of conditions, using different types of cattle with different infection backgrounds, different vaccination strategies, different methods of assessment and different criteria for success. It has been recognised that improved animal models were needed to allow advancement of tuberculosis vaccine development (Griffin, 2000), and, in the 1990s, Buddle and co-workers modified the intra-tracheal method of experimentally infecting cattle with M. bovis to allow a more controlled and appropriate assessment of vaccines. 4.2.2 At that time in New Zealand, it was recognised that vaccination of cattle was a possible option of addressing a tuberculosis problem confounded by the presence of a reservoir of infection in possums. Furthermore, it had been recognised that previous studies had vaccinated cattle with massive doses of BCG, equivalent in many cases to in excess of 108 cfu (Skinner et al. 2001), while it had been postulated that a low dose of BCG would provide more effective protection by imprinting an appropriate pattern of immune response (Bretscher, 1994; Griffin et al., 1999). 4.2.3 An experiment reported by Buddle et al. (1995a) compared vaccination with 6 x 104 cfu BCG (low dose) with 6 x 106 cfu BCG (medium dose) in groups of calves which were subsequently challenge intratracheally with M. bovis. 10/16 of the non-vaccinated calves were found to have tuberculous lesions, while only 6/30 vaccinates were lesioned. It was concluded that either the low or medium dose of vaccine gave significant protection, but it is of importance that an additional 3 calves from the vaccinated groups were positive for M. bovis culture in the absence of lesions (i.e. overall 9/30 vaccinates were culture positive). 4.2.4 Further experiments were carried out in New Zealand to investigate the effects of route of administration of BCG and compare BCG with an alternative vaccine, killed M. vaccae (Buddle et al., 1995b). This study confirmed the ability of BCG to reduce lesion formation in experimentallyinfected cattle, but detected no such effect for M. vaccae. 4.2.5 A subsequent experiment identified a potentially very important feature, that cattle with pre-existing sensitisation to environmental mycobacteria may not become effectively protected by BCG (Buddle et al., 1999). In that study, cattle with pre-existing T-cell recognition of PPDA prior to immunisation with 5 x 105 cfu BCG had similar levels of lesion formation as the control group after challenge with M. bovis. 4.2.6 It has been suggested that the problem of pre-sensitisation is caused by inhibition of active metabolism of the viable vaccine strain and that a possible strategy to overcome this is to develop subunit vaccines (Brandt et al., 2002). An initial experiment to investigate such a vaccine in cattle has been reported from New Zealand (Wedlock et al., 2000). In that experiment, although BCG was found to give a significant level of protection from challenge with M. bovis,
87
the subunit vaccine (based on culture filtrate proteins of M. bovis and IL-2) was seen to enhance extrathoracic spread of infection compared to nonvaccinates. 4.2.7 An alternative strategy to circumvent any adverse effect of environmental pre-sensitisation may be to vaccinate animals while they are very young. Recent data from experiments carried out in New Zealand indicate that the approach of vaccinating neonatal calves with BCG holds considerable promise in protection from challenge with M. bovis (Bryce Buddle, personal communication). 5. CONCLUSIONS FROM FIELD STUDIES ON THE USE OF BCG IN CATTLE. 5.1 It has been demonstrated that vaccination with BCG can provide a considerable degree of protection from the development of tuberculous lesions following experimental challenge with M. bovis. However, this outcome has not always been reflected in field trials. Indeed, attempts to utilise BCG to control natural tuberculosis have often given disappointing results (OReilly and Daborn, 1995; Buddle, 2001; Skinner et al., 2001). The reasons for this overall lack of success in field situations are not clearly understood. A number of factors have been proposed relating to either the vaccine or the target cattle, and include: 5.2 Factors relating to BCG. 5.2.1 Very large doses of BCG (up to 1010 cfu) were used in many field trials. It is now considered that lower doses may induce more effective immunity (Bretchner, 1994; Griffin et al., 1999). 5.2.2 Differing substrains of BCG were used in different trials. It has been suggested that the lack of success in Malawi may relate to the use of BCG Glaxo, which does not produce the dominant antigen MPB70 (C. Foster, 1992 cited by OReilly and Daborn, 1995). Interestingly, individual strains of BCG have had very different efficacies in different trials against human tuberculosis (Fine, 1995). 5.2.3 The viability of the BCG vaccine is difficult to ascertain. In some cattle experiments, it has been shown that the BCG must be viable to induce effective immunity (Haring et al., 1930). In some trials, particularly in difficult situations, the conditions may not have been optimal for storage and presentation of the vaccine. 5.3 Factors relating to the cattle. 5.3.1 In human tuberculosis, it is considered that host genetics are relevant to the development of effective immunity in response to BCG (Fine, 1998). This may also be of fundamental importance in cattle, and it was noted by Ellwood and Waddington (1972) that Zebu cattle developed more effective immunity to BCG than cross breeds.
88
5.3.2 Factors such as stress may affect development of effective immunity. Griffin et al. (1999) have shown that modelling of stressful conditions by treatment with dexamethasone has a devastating effect on development of anti-BCG responses in deer. Other intercurrent infections may also have an adverse effect on immuno-competence. 5.3.3 In situations where bovine tuberculosis is endemic, cattle may be exposed to M. bovis prior to vaccination. The WHO/FAO Expert Committee (1959) considered that it was an essential condition that only animals free from infection should be vaccinated. 5.3.4 In studies of BCG in human tuberculosis, it has become apparent that geographical location, possibly relating to prevalence of environmental mycobacteria, has an effect on vaccine efficacy (Palmer and Long, 1966; Fine, 1995). It has been shown recently in mice that the effect of sensitisation to environmental mycobacteria is due, at least in part, to the inhibition of BCG activity (Brandt et al., 2002). In cattle experiments, it has been found that animals with pre-vaccination T-cell reactivity to PPDA, presumably through exposure to environmental organisms, do not develop effective immunity in response to BCG (Buddle et al., 1999). Potentially, this type of scenario could have had a profound effect on many of the vaccine trials which have been performed to date. 6. VACCINE DEVELOPMENT. 6.1 A lack of clear success for BCG along with the difficulty of addressing some of the factors listed above, have provided impetus towards the development of novel vaccines for bovine tuberculosis. This work has been developing in parallel with major initiatives to develop new vaccines for human tuberculosis and enormous potential for cross-discipline research has been recognised. 6.2 Recent scientific advances will facilitate greatly the development of new vaccines for bovine tuberculosis. For example, characterisation of the M. bovis genome will provide great advantage in rational production of novel vaccines such as sub-unit proteins, DNA vaccines, vector vaccines, M. bovis auxotrophs and recombinant strains of BCG. Also, progress in the field of bovine immunology will lead to greater understanding of protective immune responses and development of tests to differentiate between vaccinated cattle and those infected with M. bovis. 6.3 With regard to understanding protective immunity, recent experiments in New Zealand have shown that development of efficient protection is associated with an early post-vaccine IFN- response (Skinner et al., 2001). Also, in the same vein, it has been shown that post-challenge level of pathology is related to the magnitude of the IFN- response directed towards ESAT-6 (Vordermeier et al., 2002).
89
6.4 One major concern about vaccinating cattle with BCG has been that the tuberculin skin test, which is often a pre-requisite for international trade, is compromised (WHO/FAO, 1959). However, in the post-genomic era, it is known that the process by which BCG evolved from M. bovis resulted in deletion of defined stretches of DNA (Behr et al., 1999). This knowledge can be utilised in the development of tests which can differentiate BCG-vaccinates from cattle which have been exposed to M. bovis. Thus, only cattle which have been exposed to the virulent organism will have responses to dominant T-cell antigens such as ESAT-6 and CFP10, which are deleted from the genome of all substrains of BCG (Pollock and Andersen, 1997; Buddle et al., 1999; Vordermeier et al., 2002). 6.5 However, a possible category of animals, which have been effectively protected by BCG vaccination and subsequently exposed to M. bovis, must still be considered. Because of post-vaccine M. bovis exposure, these animals may develop T-cell responses to antigens such as ESAT-6 and CFP10 in the absence of disease or tuberculous pathology. It must be recognised that further advances will be required to allow accurate categorisation of such animals based on immunological parameters. 7. CONCLUSIONS. 7.1 As in human tuberculosis, BCG has many potential advantages for use against tuberculosis in cattle. It is a safe, inexpensive vaccine for which there is evidence of protective efficacy in experimental situations. However, a number of factors, which are not fully understood, appear to compromise field performance. Indeed, current expectations for BCG would probably fall well short of the 90% efficacy which was indicated as necessary to provide benefits in a mathematical model referred to by Krebs et al. (1997). It should also be remembered that in experimental studies, the protective benefit derived from BCG vaccination has often referred to limitation of lesions rather than the prevention of infection. It is now generally stated that to have an effective impact on bovine tuberculosis, a cattle vaccine must prevent establishment and maintenance of infection. Indeed, the previous lack of acceptable field performance for BCG may be a vindication of this current standard. 7.2 From the literature reviewed, it is apparent that further developments in vaccine application and possibly in vaccine selection are required to allow effective use against bovine tuberculosis. Such advances will require greater understanding of protective immunity and of several confounding factors such as pre-sensitisation with environmental mycobacteria. 7.3 Importantly, in terms of future expectations, it should be noted from human studies that even exposure to the complete tuberculosis organism may not guarantee total protection from subsequent challenge in all individuals (Fine, 1995) and, as suggested even from earliest times, it may be a reality that cattle are not capable of developing an immune response which equates to absolute protection against M. bovis (McFadyean, 1901 cited by Pritchard, 1988).
90
8. ACKNOWLEDGEMENT. The input of Dr Jim McNair (VSD, Belfast) in the production of this Appendix is gratefully acknowledged. 9. REFERENCES. Behr M.A., Wilson M.A., Gill W.P., Salamon H., Schoolnik G.K., Rane S., Small P.M. (1999). Comparative genomics of BCG vaccines by wholegenome DNA microarray. Science, 284, 1520-1523 Berggren S.A. (1977). Incidence of tuberculosis in BCG vaccinated and control cattle in relation to age distribution in Malawi. British Veterinary Journal, 133, 490-494. Berggren S.A. (1981). Field experiment with BCG vaccine in Malawi. British Veterinary Journal, 137, 88-96. Bretscher P.A. (1994). Prospects for low dose BCG vaccination against tuberculosis. Immunobiology, 191, 548-554. Brandt L., Feino Cunha J., Weinreich Olsen A., Chilima B., Hirsch P., Appelberg R., Andersen P. (2002). Failure of the Mycobacterium bovis BCG vaccine: some species of environmental mycobacteria block multiplication of BCG and induction of protective immunity to tuberculosis. Infection and Immunity, 70, 672-678. Buddle B.M., de Lisle G.W., Pfeffer A., Adwell F.E. (1995a). Immunological responses and protection against Mycobacterium bovis in calves vaccinated with a low dose of BCG. Vaccine, 13, 1123-1130. Buddle B.M., Keen D., Thomson A., Jowett A.G., McCarthy A.R., Heslop J., de Lisle G.W., Standford J.L., Aldwell F.E. (1995b). Protection of cattle from bovine tuberculosis by vaccination with BCG by the respiratory or subcutaneous route, but not by vaccination with killed Mycobacterium vaccae. Res Vet Sci., 59, 10-16. Buddle B.M., Parlane N.A., Keen D.L., Aldwell F.E., Pollock J.M., Lightbody K., Andersen P. (1999). Differentiation between Mycobacterium bovis BCGvaccinated and M. bovis-infected cattle by using recombinant mycobacterial antigens. Clin Diagn Lab Immunol., 6, 1-5. Buddle B.M. (2001). Vaccination of cattle against Mycobacterium bovis. Tuberculosis, 81, 125-132. Buxton J.B., Glover R.E. (1939). Experiments with calves on immunity conferred by single and double injections of BCG in an oily excipient. Journal of Comparative Pathology, 52, 47-56.
91
Calmatte A., Gurin C. (1911). Recherches exprimentales sur la defense delorgganisme contre linfection tuberculose. Annuals of the Institute of Pasteur, 25, 625-641. Calmatte A., Gurin C. (1920). Novelles recherches exprimentales sur la vaccination des bovids contre la tuberculose. Annuals of the Institute of Pasteur, 34, 553-560. Calmatte A., Gurin C. (1924). Vaccination des bovids contre la tuberculose et methode nouvelle de prophylaxie de la tuberculose bovine. Annuals of the Institute of Pasteur, 38, 371-398. Calmatte A., Gurin C. (1936). Tuberculosis in man and animals. In Linfection bacillaire et al tuberculose (A. Boquet & L. Ngre, eds). Masson et Cie, Paris, 1024 pp. Cheneau Y., Blancou J. (1975). Comparative values of live or killed BCG and trypsinised Kochs bacillus in the immunisation of zebu against tuberculosis. Rev. Elev. Md. Vt. Pays trop. 28, 1-7. Colditz G.A., Brewer T.F., Berkey C.S., Wilson M.E., Burdick E., Fineberg H.V., Mosteller F. (1994). Efficacy of BCG vaccine in the prevention of tuberculosis. Journal of the American Medical Association, 271, 689-702. Doyle T.M., Stuart P. (1958). Veterinary Journal, 114, 3-10. Vaccination of cattle with BCG. British
Ellwood D.C., Waddington F.G. (1972). A second experiment to challenge the resistance to tuberculosis in BCG vaccinated cattle in Malawi. British Veterinary Journal, 128, 619-626. Ellwood D.C. (1975). First results of the field use of BCG vaccine to control bovine tuberculosis in Malawi. British Veterinary Journal, 131, 186-189. Fine P.E. (1995). Variation in protection by BCG: implications of and for heterologous immunity. The Lancet, 346, 1339-1345. Fine P.E. (1998). Vaccines, genes and trials. Symposium, 217, 57-69. Novartis Foundation
Fine P.E. (2001). BCG: the challenge continues. Scandinavian Journal of Infectious Disease, 33, 243-245. Francis J. (1958). Tuberculosis in animals and man. A study in comparative pathology. Cassell and Co., London. pp357. Glover R.E., Ritchie J.N. (1953). Field trials with BCG for the immunisation of calves against tuberculosis. British Veterinary Journal, 109, 411-427. Griffin J.F.T., Mackintosh C.G., Slobbe L., Thomson A.J., Buchan G.S. (1999). Vaccine protocols to optimise the protective efficacy of BCG. Tubercle and Lung Disease, 79, 135-143. 92
Griffin J.F. (2000). Veterinary tuberculosis vaccine development. Infectious Diseases, 30, S3, 223-228.
Clinical
Gurin C., Richard A., Boissiere M. (1927). Essai de prophylaxie de la tuberculose bovine par le BCG dans une exploitation rurale infecte (19211927). Annuals of the Institute of Pasteur, 41, 233-253. Harring C.M., Traum J., Hayes F.M., Henry B.S. (1930). Vaccination of calves against tuberculosis with Calmette-Gurin culture, BCG. Hilgardia, 4, 307394. Krebs J.R., Anderson R.M., Clutton-Brock T., Morrison W.I., Young D., Donnelly C.A. (1997). Bovine tuberculosis in cattle and badgers. Ministry of Agriculture, Fisheries and Food (MAFF) Publications, London. Lagranderie M.R., Balazuc A.M., Deriaud E., Leclerc C.D., Gheorghiu M. (1996). Comparison of immune responses of mice immunised with five different Mycobacterium bovis BCG vaccine strains. Infection and Immunity, 64, 1-9. Larson W.P., Evans W.A. (1929). A two-year experiment with the Calmette method of vaccination. Journal of the American Veterinary Medical Association, 74, 580-585. Li H., Ulstrup J.C., Jonassen T.O., Melby K., Nagai S., Harboe M. (1993). Evidence for the absence of the MPB64 gene in some substrains of Mycobacterium bovis BCG. Infection and Immunity, 61, 1730-1734. Mares R.G. (1972). Control of bovine tuberculosis in Malawi by the use of BCG vaccination. The Veterinary Record, 90, 428-429. Matsuo T., Matsumoto S., Ohara N., Kitaura H., Mizuno A., Yamada T. (1995). Differential transcription of the MPB70 genes in two major groups of Mycobacterium bovis BCG substrains. Microbiology, 141, 1601-1607. Moodie P.A. (1977). Tuberculin reactions in BCG. British Veterinary Journal, 133, 642-645. Newell D.G., Hewinson R.G. (1995). Control of bovine tuberculosis by vaccination. The Veterinary Record, 136, 459-463. Novak D.D., Suyubaeva B.P. (1986). Assessment of postvaccinal immunity to tuberculosis (in calves inoculated with BCG and BK-Khartov vaccines). The Veterinary Bulletin, 56, 361 (Abstract 27640). Oettinger T., Jrgensen M., Ladefoged A., Haslv K., Andersen P. (1999). Development of the Mycobacterium bovis BCG vaccine: review of the historical and biochemical evidence for a genealogical tree. Tubercle and Lung Disease, 79, 243-250.
93
OReilly L.M., Daborn C.J. (1995). The epidemiology of Mycobacterium bovis infection in animals and man: a review. Tubercle and Lung Disease, 76, S1, 1-46. Palmer C.E., Long M.W. (1966). Effects of infection with atypical mycobacteria on BCG vaccination and tuberculosis. American Review of Respiratory Disease, 94, 553-568. Pollock J.M., Andersen P. (1997). The potential of the ESAT-6 antigen secreted by virulent mycobacteria for specific diagnosis of tuberculosis. Journal of Infectious Disease, 175, 1251-1254. Roche P.W., Triccas J.A., Winter N. (1995). BCG vaccination against tuberculosis: past disappointments and future hopes. Trends in Microbiology, 3, 397-401. Rolle M., Wiethe H. (1956). Results of BCG vaccination in cattle in Bavaria. The Veterinary Bulletin, 27, 105 (Abstract 663). Schellner H., Gaggermeier G. (1955). Vaccination of cattle in herds infected with TB with the strain P tubercle baccillus described by Grub. The Veterinary Bulletin, 26, 183 (Abstract 1117). Schroeder E.C., Crawford A.B. (1929). Studies concerning the CalmatteGurin method of vaccinating animals against tuberculosis. Journal of the American Veterinary Medical Association, 74, 733-782. Sibgatullin R.S. (1982). Eradicating tuberculosis from large cattle-breeding complexes using BCG vaccine. Veterinary Bulletin, 53, 731 (Abstract 5212). Skinner M.A., Wedlock D.N., Buddle B.M. (2001) Vaccination of animals against Mycobacterium bovis. Rev.Sci. Tech. Off.Int.Epiz., 20 112-132 Tzeknovitzer M. (1927). tude de la vaccination antotuberculose par le BCG. Annuals of the Institute Pasteur, 41, 322-357. Vordermeier H.M., Chambers M.A., Cockle P.J., Whelan A.O., Simmons J., Hewinson R.G. (2002). Correlation of ESAT-6-specific interferon production in cattle following Mycobacterium bovis BCG vaccination against experimental bovine tuberculosis. Infection and Immunity, 70, 3026-32. Waddington F.G., Ellwood D.C. (1972). An experiment to challenge the resistance to tuberculosis in BCG vaccinated cattle in Malawi. British Veterinary Journal, 128, 541-552. Watson E.A., MacIntosh C.N., Konst A. (1928). Research on Bacillus Calmette-Gurin and experimental vaccination against bovine tuberculosis. Journal of the American Veterinary Medical Association, 73, 799-816. Wedlock D.N., Vesosky B., Skinner M.A., de Lisle G.W., Orme I.M., Buddle B.M. (2000). Vaccination of cattle with Mycobacterium bovis culture filtrate
94
proteins and interlukin-2 against bovine tuberculosis. Infection and Immunity, 68, 5809-5815. Wiker H.G., Nagai S., Hewinson R.G., Russell W.P., Harboe M. (1996). Heterogeneous expression of the related MPB70 and MPB83 proteins distinguish various substrains of Mycobacterium bovis BCG and Mycobacterium tuberculosis H37Rv. Scandinavian Journal of Immunology, 43, 374-380. Wilson M.E. (2000). Applying experiences from trials of bacille CalmettGurin vaccine. Clinical Infectious Disease, 30, S3, 262-265. WHO/FAO Expert Committee on Zoonoses. (1959). Second Report. World Health Organisation Technical Report Series No 169. Young J.A., Paterson J.S. (1949). Studies on the vaccination of cattle as a measure against infection with tuberculosis with the living vole acid-fast bacillus. Journal of Hygiene (London), 4, 39-78. Zuckerman O.M. (1980). Badgers, cattle and tuberculosis. Report to The Right Honourable Peter Walker, MBE, MP.
95
TABLE 1. OVERVIEW OF VACCINE CHALLENGE EXPERIMENTS

Study Calmette and Gurin Calmette and Gurin 1911 1920 Country France France France Ukraine Strain BCG BCG BCG BCG Vaccine Dose 200mg 20mg 50-100mg Route I/V1 I/V S/C2 M.bovis Challenge I/V In-contact 5mg I/V 0.005mg Vallee 2mg I/V Assessment PM4 / GP5 PM / GP PM / GP PM Evidence for protection No lesions seen Limited thoracic lesions. GP -ve No lesions seen. GP+ve Visible lesions seen but were fewer in number compared to controls Moderate lesions in lungs and thoracic LN. GP +ve. Controls died of miliary TB Visible lesions in 3/4 calves, 4/4 control calves had extensive lesions Visible lesions, GP-ve Visible lesions, GP+ve Visible lesions 3/4 calves lesion positive Visible lesions in most vaccinated calves, GP Authors' Conclusion BCG prevents lesions but bacilli still excreted via the intestines BCG confers protection from incontact exposure In general, BCG confers resistance to experimental infection compared to nonvaccinated controls Live bacilli are necessary to develop a protective response. Dead bacilli provide little protection Insufficient protection using BCG
Calmette and Gurin 1924 Tzeknovitzer 1927
Haring et al
1930
USA
BCG
50-100mg
I/V-S/C
PM
USA
Killed, virulent BCG
1 gm
I/V S/C
2mg I/V Oral
PM PM / GP
USA
USA Buxton and Glover 1939 UK
BCG BCG BCG BCG BCG
100mg 1gm 100mg 1.2-3.5 x 109 cfu8 5 and 50mg
I/V Oral I/D10 S/C S/C
Oral Oral Oral Oral 5mg Oral
PM / GP PM / GP PM / GP PM / GP PM / GP
Differences between control and vaccinates groups insufficient to identify protection 5mg BCG failed to protect, 50mg induced moderate
96
Waddington & Ellwood 1972
Malawi
BCG Galaxo used according to the manufacturer's instructions
0.1mg S/C
PM / H / B
+ve. Protection 0-50%
variation BCG appears to produce a useful degree of resistance to progression of TB

protection with individual
Ellwood & Waddington 1972 Cheneau and Blancou 1975
Malawi
BCG Galaxo used according to manufacturer's instructions BCG 100mg S/C
0.1-0.5mg
PM / B
Fewer lesions and limited progression of lesions in vaccine group
Madagascar
I/V
BCG reduces the impact of virulent challenge. Greater protection in Zebu than Zebu cross Killed BCG and live BCG gave slightly lower protection than trypsin extract of Koch bacillus (25.2%, 28.5% and 34.6% respectively)
Novak and Suyubaeva 1985 Buddle et al 1995
USSR New Zealand
BCG, killed Koch, trypsin extract BCG BK Karkov BCG Pasteur BCG Pasteur BCG Pasteur
250mg 50mg In contact In contact 800 cfu I/T3 PM PM PM /H / B 53% developed lesions 15% developed lesions 20% vaccinated calves lesion +ve, 30% culture +ve; compared to 62.5% controls 37% of vaccinated calves were lesion and culture positive compared to 77% in the M. vaccae group. 66% of controls were lesioned and culture positive
6 x 104 cfu 6 x 106 cfu 2 x 105 cfu
S/C
BCG at 6 x 104 or 106 induced significant protection against virulent challenge
S/C S/C
800 cfu I/T 2 x 103 cfu I/T PM / H / B Killed M. vaccae induced no protection against virulent challenge but BCG did
Buddle et al
1995
New Zealand
97
Buddle et al
1999
New Zealand New Zealand
BCG Pasteur BCG Pasteur M. vaccae, killed BCG Pasteur BCG Pasteur
2 x 103 cfu 2 x 105 cfu 2 x 109 cfu 5 x 105
S/C I/T I/D S/C 1 x 103 cfu I/T 5 x 103 cfu I/T PM / H / B Lesions found in vaccinated and control calves 50% of vaccinated calves lesion +ve. All calves were bacteriology positive. 100% nonvaccinates were lesion positive 75% of calves lesion +ve. All calves were bacteriology positive. Fewer lesions were found in the vaccinated calves compared to controls BCG induced little protection in this study, possibly due to previous exposure to environmental mycobacteria CFP-IL2 vaccination can reduce the incidence of lesions but not as much as BCG. High dose CFP-IL2 can induce extra thoracic spread
Wedlock et al
2000
1 x 106
S/C
PM / H / B
CFP-IL29
200g1mg
S/C
Superscripts: 1 Intra-venous 2 Sub-cutaneous 3 Intra-tracheal 4 Post Mortem 5 Guinea-Pig 6 Histopathology 7 Bacteriology 8 Colony forming unit 9 Culture filtrate protein-Interleukin-2 10 Intra-dermal
98
TABLE 2. OVERVIEW OF CONTROLED FIELD TRIALS BASED ON BCG VACCINATION

Study Calmette and Gurin Gurin et al Watson et al 1920 1927 1928 Country France France Canada Strain BCG BCG BCG Vaccine Dose 20mg Route In-contact Infected herd Infected herd 100mg 0.5g S/C2 S/C Infected animals 50mg S/C Infected herd In-contact PM3 PM All cattle showed TB lesions 4/7 had TB 2/8 had TB 2/6 had TB Some degree of resistance from localisation and generalisation of TB No macroscopic lesions seen but some LN were bacilli positive BCG induced protection from infection with reduced numbers of lung lesions Slaughtered cattle were free from TB lesions There was no evidence in favour of the vaccinated animals nor any indicators of greater resistance Calmette method of vaccination had no value in protecting cattle M.bovis Challenge Assessment Evidence for protection Authors' Conclusion
Larson and Evans
1929
USA
BCG Killed bacilli No vaccine BCG
PM PM PM PM
Schroeder & Crawford 1929
USA
There was no immunity as measured by the prevention of infection Some protection was conferred but insufficient to use vaccination as a means of eradication. Skin reactivity to vaccination renders cattle unmarketable Vaccination proved successful when calves were not exposed too early post-vaccination
Haring et al
1930
USA
BCG
PM / GP4
Glover and Richie
1953
UK
BCG
50mg
I/V1
2 areas with infected herd Infected
PM / GP
Doyle and Stuart
1958
UK
BCG
100mg
S/C
PM / B5
8+27% of vaccinated calves were lesioned. Some LN were bacilli positive. 52% of control animals were affected by TB 10 / 25 vaccinated cattle
Test and slaughter is a more
99
herd Schellner & Gaggermeier 1955 Germany Strain P 28 infected herds
were lesioned. 15 cattle with no visible lesions where culture negative
practical eradication policy than vaccination Complete success was met with the Graub method (early inoculation, segregation, multiple vaccination) TB was eradicated from a severely infected herd over 7yrs BCG vaccination is an effective control measure for bovine TB in Malawi BCG confers protection against spread of TB BCG has no significant effect on the control of bovine TB nor does it reduce the incidence of meat condemnations BCG did not reduce the rate of infection nor the progression of lesions, gives little protection against the Afro-Asian strain of M.bovis Over a five year period a herd was declared free from TB
Rolle and Wiethe Ellwood
1956 1975
Bavaria Malawi
BCG BCG Galaxo BCG BCG Galaxo
50mg 2.6 x 109 cfu6 2.6 x 109 cfu 2.6 x 109 cfu
S/C S/C
Infected herd Infected herd Infected herd Infected herd
Meat inspection Meat inspection Meat inspection
Moodie Berggren
1977 1977
Malawi Malawi
S/C S/C
Berggren
1981
Malawi
BCG Galaxo
2.6 x 109 cfu
S/C
Infected herd
PM / B
11.9% of vaccinated calves were lesioned, 17.8% non-vaccinated were lesion positive Reduced numbers of reactor cattle With age matched vaccine and control groups there was no difference in the levels of protection Similar levels of lesion positive cattle were found in vaccine and non-vaccine groups
Sibgatullin
1982
USSR
BCG
Infected herd
Superscripts: 1. Intra-venous 2. Sub-cutaneous 3. Post Mortem 4. Guinea-Pig 5. Bacteriology 6. Colony forming unit
100
APPENDIX 13. CHAIRMANS DISCUSSION PAPER ON FORMAT OF FINAL REPORT. John Bourne ISG, Location 105, 1A Page Street, London SW1P 4PQ 1. INTRODUCTION. 1.1 The use of vaccines in either cattle or wildlife remains a potential policy option, although this option offers prospects only in the medium to longer term. A vaccine development programme is already in place. This involves a number of international collaborations which harness a global resource which includes a significant effort to develop a vaccine against the human form of TB. 1.2 For the future while success cannot be guaranteed, if a vaccine policy is to be pursued for either cattle or wildlife, it must be recognised that a demanding research programme would have to be put in place to provide proof principle that a vaccine is likely to be effective. But more importantly its value in the field must be validated before the Sub-Committee can appropriately advise. 1.3 There are I believe a number of important questions that need further discussion. The purpose of this Appendix is to revisit some of the major questions. 2. WHAT IS AN EFFECTIVE CATTLE VACCINE? 2.1 Introduction. 2.1.1 We need to discuss under what circumstances could a cattle vaccine be used and would BCG fit the bill? 2.1.2 The demands of an acceptable cattle vaccine are particularly severe since it would be expected to both prevent the establishment of infection and to eliminate transmission. Additionally it should not give a positive reading in the tuberculin test (or any other immunological-based test) since this would confuse the regular herd testing procedure and create serious regulatory problems. However an additional concern about the use of cattle vaccination in GB relates to the strong likelihood that a wildlife reservoir of TB infection would persist in the countryside environment and exposure of cattle, protected by a successful vaccine to this source of infection, would result in immunological responses which might compromise the skin test. 2.1.3 Any diagnostic test based upon detecting an immune response would need therefore to distinguish immune responses generated following infection from those elicited following challenge of a protected vaccinated animal. This would be difficult to achieve. In addition to being highly sensitive such a test
101
would have to have a high level of specificity for it to be acceptable, since false positive reactions would trigger a herd breakdown control response. 2.2 Are these aims realistic or are these too restrictive? We must consider: 2.2.1 Accepting that it might not be feasible to prevent infection becoming established in all cattle? 2.2.1.1 The apparent level of induced protection likely to depend on the level of challenge. 2.2.1.2 That some individuals may not be capable of effective immunity. 2.2.2 And that there are also other impacting factors. 2.2.2.1 The possible effect of prevaccine exposure to environmental mycobacteria. 2.2.2.2 There may be cattle with latent M. bovis. 2.3 Also, we need to explore whether the use of a vaccine to limit cattle to cattle spread of infection has any potential? 2.3.1 Could vaccination be of value if there was a change of policy which focussed on the protection of public health by managing zoonotic aspects of the disease by for example banning the sale or consumption of nonpasteurised milk, strict abattoir monitoring etc, and limiting the disease in cattle. It would be necessary to consider whether a vaccine capable of decreasing shedding could be of benefit - the impact that it would be likely to have on disease incidence, the limiting effect on pathology and visible lesions at post mortem, the reduction in the number of cattle sacrificed to control the disease and the possible limiting effect that cattle vaccination would have on the disease in badgers by reducing cattle to badger transmission. 2.3.2 The only vaccine candidate that could be considered at the moment would be BCG. 2.4 Does BCG have this potential? 2.4.1 Experimental use of BCG in cattle suggests a 50% to 75% efficacy and an average of 75% reduction in disease severity. Although vaccinated animals remain bacteriologically positive it might be expected that vaccination would reduce the opportunity for disease transmission. 2.4.1.1 Immunological tests could be developed to differentiate vaccinated from non vaccinated animals. 2.4.1.2 Naturally infected (from wildlife or cattle) but vaccinated and protected animals could not be distinguished on the basis of immunological tests.
102
2.5 Research requirements. 2.5.1 In addition to what is already in place, there is a need to consider: 2.5.1.1 The design of a field trial; is it conventional? 2.5.1.2 The effect on cattle TB breakdowns; is it measurable? 2.5.1.3 The diagnostic test on live animal, is it available (with limitations already identified)? 2.5.1.4 The size, time frame and cost to be considered? 3. WHAT IS AN EFFECTIVE BADGER VACCINE? 3.1 Introduction. 3.1.1 By contrast with cattle, vaccination of wildlife would require a less demanding vaccine, since although widespread coverage of the population would be the goal, the proportion of the population that would need to be protected to influence the disease in cattle is not known and protection of each individual badger would not be essential. The primary rle of a wildlife vaccine would be to reduce the severity of the disease in the target species and the consequent rate of transmission to cattle. However a wildlife vaccine would only be effective in controlling cattle TB if most infections derived from wildlife. 3.2 Aims of vaccination programme. 3.2.1 To eradicate TB from the badger population, to reduce disease severity and hence bacterial excretion. 3.2.1.1 This would be achieved by: immunising susceptible animals, increasing the pool of immune animals and hence reducing transmission below the level needed to sustain endemic infection. 3.2.1.2 This would require successful immunisation of a critical proportion of susceptible animals. 3.2.1.3 What are the barriers? 3.2.1.3.1 The proportion of the population to be vaccinated is not known; it might be high given the slow disease dynamics. 3.2.1.3.2 We would be likely to need a highly effective vaccine. 3.2.1.3.3 Vaccine delivery and uptake would need to highly effective. 3.2.1.3.4 Do we need to vaccinate cubs in the sett (vertical transmission)?
103
3.2.1.3.5 The influence of environmental Mycobacteria is unknown. 3.2.1.3.6 Coverage would need to be maintained for a long period to prevent reinfection of the badger population by cattle. 3.2.1.3.7 Some influence groups would argue that badgers dont need this. 3.2.2 To reduce exposure of cattle to TB by reducing bacterial shedding by badgers. 3.2.2.1 This would be achieved by vaccination of an unknown population of badgers. 3.2.2.2 What are the barriers? 3.2.2.2.1 The effect of vaccination on bacterial shedding is not known; what is the rle of super excretors? 3.2.2.2.2 The spatial relationship between infected badgers and cattle is not known. 3.2.2.2.3 There would be a need for vaccination to be continued in perpetuity since eradication would not be expected. 4. GENERAL ISSUES. 4.1 The proportion of cattle TB originating from badgers is not known. 4.2 Vaccination is likely to be less effective than culling, and thus detecting any effect on cattle TB would require a field trial of an extent and duration comparable with the culling trial but with a smaller expectation of success. 4.3 Coverage might have to be maintained in perpetuity if eradication is not achieved (or extremely unlikely to be achieved). 4.4 Live vaccine in the environment may expose cattle and lead to spurious breakdowns. 4.5 The effect of vaccine on already infected badgers is not known it could promote shedding or be lethal (but there is no evidence for this in other species). 4.6 Interest groups could be uncooperative. 4.7 Vaccinating badgers is not a quick fix that can be implemented outside trial areas with any expectation of effectiveness in the medium or short term. 4.8 With current policy for controlling cattle TB based on the tuberculin test vaccinating badgers has the potential for causing as many breakdowns as it prevents.
104
4.9 The outcome of the culling trial will have a profound influence on the expected success of any vaccination programme. Unless perturbation effects are massive, vaccination is likely to be less effective than culling. The trial will provide data that are essential if we are to provide informed scientific opinion. 5. NEXT STEPS. 5.1 Establishing the protective activity of candidate vaccines, including BCG. An immune effect and some protection has been demonstrated following intradermal vaccination of badgers with BCG, but the effects of bacterial excretion and transmission have not been studied in detail and duration of immunity has not been determined. 5.2 Protection studies are needed. Facilities in GB are not available; can we rely solely on studies that will take place in RoI which will encompass: 5.2.1 Establishing an experimental colony of badgers. 5.2.2 Establishing an experimental challenge model. 5.2.3 Using this model to reach point of proof principle of vaccine candidate. 5.3 If we are satisfied about the relevance of the RoI studies to the GB situation we could move on to consider field experimental trials and field validation. 5.4 If our advice is that further experimental studies should be conducted in GB, what additional information do we need? 5.4.1 Legal position. 5.4.2 Re-procurement and use of badgers as an experimental animal, given that, it will be argued, this work will provide little if any benefits to the badger population.
105
CHAPTER 14. VACCINATION OF CATTLE AGAINST TB Ivan Morrison Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Roslin, Scotland EH25 9RG 1. INTRODUCTION. 1.1 Vaccination of cattle against TB would require either a vaccine that is compatible with the diagnostic assay currently used for herd testing, or changes in the way surveillance for TB is conducted to permit the use of alternative vaccines. Any new control strategies incorporating vaccination would not only need to be cost-effective, with respect to control of the disease in cattle, but also would be required to maintain protection of human health. 2. PROSPECTS FOR VACCINATION IN THE SHORT TERM. 2.1 As discussed elsewhere, the only vaccine that is likely to be available for use in the field over the next few years is BCG. Although vaccination of cattle with BCG has been shown to reduce the severity of pathology following challenge with virulent M. bovis, a significant proportion of the vaccinated animals continue to harbour bacteria. Moreover, animals vaccinated with BCG give a positive reaction in the tuberculin skin test, and hence cannot be distinguished from infected animals. For these reasons, vaccination of cattle with BCG is not a viable option at present. 3. POTENTIAL USE OF VACCINATION IN THE LONGER TERM. 3.1 For the last 50 years control of bovine TB in the UK and the rest of Europe has relied on herd testing to identify and remove infected animals. This strategy was originally adopted with the aim of eradicating the disease. The only available vaccine, BCG, was not sufficiently effective for vaccination to be considered as a primary strategy to achieve eradication, and BCG could not be used in conjunction with herd testing because of interference with interpretation of the skin test. Looking to the future, development of new diagnostics and vaccines might allow alternative control strategies incorporating vaccination to be considered: 3.2 Vaccination in conjunction with an alternative diagnostic test. Leaving aside the issue of vaccination, there is a need to improve the sensitivity of the diagnostic assay used in herd testing. Substantial research effort (funded by DEFRA) is currently being devoted to development of TB-specific gamma interferon assays incorporating defined M. bovis antigens. In the short term, it is envisaged that such assays could be used in conjunction with the skin test 106
to improve the efficiency of herd testing. It is likely that a gamma interferon assay with similar or superior sensitivity to that of the skin test will be developed over the next few years. If sensitivity can be achieved along with a high level of specificity, serious consideration should be given to replacing the skin test with the gamma IFN assay as the primary diagnostic assay for herd testing. Such a laboratory-based assay would allow improved standardisation of TB testing and require only one farm visit per test (as compared to 2 at present). 3.3 A diagnostic assay based on the use of defined antigens would also potentially allow the use of vaccines that did not contain the antigens used in the diagnostic assay. Since many of the candidate diagnostic antigens are absent from BCG but present in wild-type M. bovis, either live attenuated or sub-unit vaccines could be considered. However, as discussed elsewhere (see Appendices 1 & 12), the diagnostic assay would not only need to distinguish infected from vaccinated animals but also infected from vaccinated immune animals that have been exposed to challenge with M. bovis. The latter may be difficult to achieve but is amenable to experimental investigation. 3.4 Vaccination without herd testing. Current resources for control of TB are focused on identification of animals once they have become infected with the causative organism. If wildlife are confirmed as a major source of infection and if measures to control infection in wildlife prove to be impractical, unacceptable or ineffective, this control strategy will have a limited impact on the problem and will continue to consume a large amount of resource. An alternative radical approach would be to use vaccination of cattle as the primary means of control in affected regions, dispense with routine herd testing and focus resources on detection of infected carcasses in slaughterhouses. Such a strategy would require a highly effective vaccine, which reliably prevented systemic infection and substantially reduced pathology and bacterial excretion. The principal aim would be to protect human health, by ensuring that vaccination prevented organisms reaching the mammary gland, reduced bacterial excretion to a level that posed negligible risk to humans in contact with the live animal and limited pathology to, at most, a few small lesions in tissues that are discarded following slaughter. This approach would probably require a vaccine with protective activity superior to that of BCG. 3.5 These strategies are dependent on advances in diagnostics and vaccine development and would require rigorous experimental and field testing of the candidate vaccines before they could be implemented. Legislative changes would also be required to allow the new TB control policies to be adopted. Nevertheless, in view of the uncertainty concerning the impact of other approaches to improving control of bovine TB, we consider that the options for vaccination of cattle need to be retained. In any event, much of the work on testing vaccine candidates is relevant to both badgers and cattle and the bovine experimental model allows studies of the properties of experimental vaccines that are difficult to undertake in badgers.
107
APPENDIX 15 1.1 The Terms of Reference for the Sub-Committee were: to assist the ISG in advising Defra Ministers on the feasibility for pursuing a TB vaccination strategy for either cattle or wildlife. This should also include consideration of future research requirements in addition to those already in place. 2.1 The Composition of the Sub-Committee was:
Meetings attended: no / max possible
Chairman: Professor F J Bourne Members: Dr C L Cheeseman Dr M J Colston Professor C A Donnelly Miss S M Eades Professor P Fine Dr B Grenfell Dr R G Hewinson Mr S Houghton Professor W I Morrison Dr J Pollock Mr A G Simmons
ISG Defra Central Science Laboratory, Woodchester Park National Institute of Medical Research, London ISG Defra Animal Disease Control Division London University, School of Hygiene & Tropical Medicine Cambridge University Defra Veterinary Laboratories Agency, Weybridge Hoechst Roussel Ltd., Milton Keynes ISG Queens University, Belfast Defra, Head, Veterinary Endemic Animal Diseases & Zoonoses Division ISG London University, Imperial College
7/7 6/7 7/7 5/7 6/7 1/7 1/7 7/7 4/7 6/7 4/7 6/7 4/7 6/7 6/7 1/1 1/1 1/1 7/7 6/7 2/2 4/5
Dr R Woodroffe Professor D B Young Adviser: Miss F A Stuart Defra Science Directorate Visiting Speakers: Dr L Corner Massey University, New Zealand Dr E Gormley University College, Dublin, Eire Mr W Nash Consultant Secretariat: Dr A L Patey Defra Animal Disease Control Division Mr J W Pitchford Defra Animal Disease Control Division Mr T K Matthewsa Defra Animal Disease Control Division Ms S Shahb Defra Animal Disease Control Division a = meetings 1 & 2; b = meetings 3-7
108
Equi-TB : The Tuberculosis Research Project

5 January 2006
Home | About the Project | Project Staff | News and Events | Resource Library | Site Map | Contact Us | Admin
Welcome
i) Diagnostics, access and direct smear microscopy ii) Observation, adherence and clinical care Welcome to the EQUI-TB Knowledge Programme Website. The purpose of the programme is to promote the implementation of pro-poor strategies, which enhance care and support for TB among the poorest. This year, more people will die of tuberculosis than in any other year in history and it disproportionately affects the poor. Tuberculosis kills around 2 million people each year, mostly in Developing Countries.
EQUI-TB Team Structure Mandela urges action to fight TB Year 3 Partners Meeting Report EQUI-TB Work Plan 21st October 2005 Symposium - Scaling up TB Control to Meet the Needs of the Poor Vacancy - Maternity Leave Cover for Research Coordinator Meeting Millennium Development Goals 3 and 5 Reach Trust Policy Paper How much of Chinas success in tuberculosis control is really due to DOTS? Vulnerability to malaria, tb, and HIV/AIDS infection and disease. Part II: Environmental and institutional level Vulnerability to malaria, tb, and HIV/AIDS infection and disease. Part 1: individual and household level Systematic Review of TB and Poverty Liverpool School of Tropical Medicine STOP TB TB Fact Sheet
iii) Therapeutic Monitoring, The purpose of this website is to provide information on the programme and a set of management, evaluation and quality resources for programme partners and third parties interested in the work of EQUI-TB. The EQUI-TB core funding is from the UK's Department for International Development iv) Short Course and the Programme is co-ordinated from the Liverpool School of Tropical Medicine, chemotherapy, affiliated to the University of Liverpool. uninterrupted supplies and administration v) ! Government and stakeholder Commitment vi) About EQUI-TB vii) TB POVERTY viii) REACH TRUST, Lilongwe x) Fudan School of Public Health, Shanghai xi) Centre for Infectious Diseases and International Health, University College of London xii) College of Medicine, Lusaka
EQUI-TB Knowledge Programme, Liverpool School of Tropical Medicine 2004
Web Design: WestWindMoves, Liverpool
http://www.equi-tb.org.uk/ (1 of 2) [04/01/06 22:37:31]
Equi-TB : The Tuberculosis Research Project
http://www.equi-tb.org.uk/ (2 of 2) [04/01/06 22:37:31]
Tuberculosis - eMedicine Health
Search
Go!
January 5, 2006
Registration You are in: Bacterial and Viral Infections > Tuberculosis
Healthcare Professionals
Tuberculosis
Sections
Tuberculosis Overview
Tuberculosis (TB) describes an infectious disease that has plagued humans since the Neolithic times. Two organisms cause tuberculosisMycobacterium tuberculosis and Mycobacterium bovis. Physicians in ancient Greece called this illness "phthisis" to reflect its wasting character. During the 17th and 18th centuries, TB caused up to 25% of all deaths in Europe. In more recent times, tuberculosis has been called "consumption."
q
Are you sad, bored, fatigued, irritable, unable to concentrate, pessimistic? If you've been feeling this way for at least 2 weeks, you may have clinical depression. Learn what can help. Dementia is not something that happens only to older people. Learn about causes and treatment options. Wheezing, breathlessness, chest tightness, coughingall symptoms of asthma. Find out more. Stress, fear, or worries can lead to severe anxiety, which can have a serious impact on your life. Do you need to seek help?
-Tuberculosis Overview -Tuberculosis Causes -Tuberculosis Symptoms -When to Seek Medical Care -Exams and Tests -Tuberculosis Treatment -Next Steps -Multimedia -Synonyms and Keywords -Authors and Editors
Robert Koch isolated the tubercle bacillus in 1882 and established TB as an infectious disease.
r
In the 19th century, patients were isolated in sanatoria and given treatments such as injecting air into the chest cavity. Attempts were made to decrease lung size by surgery called thoracoplasty. During the first half of the 20th century, no effective treatment was available. Streptomycin, the first antibiotic to fight TB, was introduced in 1946, and isoniazid (Laniazid, Nydrazid) became available in 1952.
M tuberculosis is a rod-shaped, slow-growing bacterium.

r
M tuberculosis' cell wall has high acid content, which makes it hydrophobic, resistant to oral fluids. The cell wall absorbs a certain dye and maintains a red color despite attempts at decolorization, hence the name acid-fast bacilli.
M tuberculosis continues to kill millions of people yearly worldwide. In 1995, 3 million deaths from TB occurred.
r
Up to 8 million new cases of TB develop each year. More than 90% of these cases occur in developing nations that have poor resources and
http://www.emedicinehealth.com/articles/17621-1.asp (1 of 2) [04/01/06 22:39:23]
Tuberculosis - eMedicine Health
Anxiety Arthritis Bone, Joint, Muscle Cholesterol Dementia Depression Headache Mental Health Women's Health
high numbers of people infected with HIV.

q
In the United States, incidence of TB began to decline around 1900, because of improved living conditions.
r
TB cases have increased since 1985, most likely due to the increase in HIV.
Tuberculosis continues to be a major health problem worldwide. In 1997, the World Health Organization (WHO) estimated that 32% of the global population was infected with TB bacteria.
r
7.9 million new cases of TB developed. 1.87 million people died of this disease.
With the spread of AIDS, tuberculosis continues to lay waste to large populations. The emergence of drugresistant organisms threatens to make this disease once again incurable. In 1993, the WHO declared tuberculosis a global emergency.
Last updated: Nov 23, 2004 Tuberculosis Causes > About Us | Privacy | Code of Ethics | Terms of Use | Contact Us | Advertise | Healthcare Professionals
We subscribe to the HONcode principles. Verify here. 2003-2005 eMedicine.com, Inc.
All Rights Reserved.
Medicine is a constantly changing science, and clearly established therapies are not always available for every condition. New research findings necessitate continual changes in drug and treatment therapies. The authors, editors, and publisher of this journal have used reasonable efforts to provide up-to-date, accurate information that is within generally accepted medical standards at the time of publication. However, as medical science is ever evolving, and human error is always possible, the authors, editors, and publisher (or any other involved party) do not guarantee total accuracy or comprehensiveness of the information in this article, nor are they responsible for omissions, errors, or the results of using this information. The reader should confirm the accuracy of the information in this article from other sources. In particular, all drug doses, indications, and contraindications should be confirmed in package inserts.
FULL
DISCLAIMER
http://www.emedicinehealth.com/articles/17621-1.asp (2 of 2) [04/01/06 22:39:23]
www.euroTB.org : EuroTB, Surveillance of tuberculosis in Europe
EuroTB Homepage About EuroTB Annual reports Slide sets Recommendations Data collection materials Country profiles Other publications Newsletter Data queries Participants Advisory committee Staff
Surveillance of tuberculosis in Europe WHO Collaborating Centre Annual reports Recent publications Falzon D, Le Strat Y, Belghiti F, Infuso A. Exploring the determinants of treatment success for tuberculosis cases in Europe. Int J Tuberc Lung Dis 2005 ; 9: 12241229 Other publications Congress communications
2003 2002 | 2001 | 2000 | 1999 1998 | 1997 | 1996 | 1995 Slides Recommendations Data collection materials
: : EuroTB Newsletter No 2 : : September - December 2005
MDR-TB surveillance
About EuroTB EuroTB started in 1996 with the objective to improve the contribution of public health surveillance to tuberculosis control in Europe and the standardisation of tuberculosis surveillance methods. More about EuroTB ...
Country profiles Country-specific, updated information and trends on tuberculosis case notification, anti-TB drug resistance and treatment outcomes in the countries of WHO European Region. ------- Country profile in PDF -------
In memoriam Andrea Infuso 1961-2005
http://www.eurotb.org/ (1 of 2) [04/01/06 23:18:27]
www.euroTB.org : EuroTB, Surveillance of tuberculosis in Europe
This project receives funding from the European Commission (DG SANCO). Neither the European Commission, nor any person acting on its behalf is liable for any use made of the information published here. This website www.eurotb.org is hosted and updated by InVS
http://www.eurotb.org/ (2 of 2) [04/01/06 23:18:27]
FAQ about BCG
Frequently Asked Questions about BCG

P D O Davies, Director, Tuberculosis Research Unit, Cardiothoracic Centre, Liverpool. UK
Does it work?
Trials of the vaccine have been undertaken since it was first developed in the 1920s. The results have been variable. About a third of the total trials have shown no protective effect. The remainders have shown protection of up to 80%* at best lasting a maximum of 15 years. No trials on second or subsequent vaccinations have shown any protective effect. (*Protective efficacy is a measure of the proportion of people who would have got the disease had they not had the vaccination. 80% protection means that 4 out of 5 individuals are protected. Efficacy for most vaccines exceeds 95%. BCG is therefore a relatively weak protective vaccine.) In summary
50% randomised control trials show it to be effective.70% Case-Control studies show it to be effective. Why is the effectiveness is variable? The reasons for variability are not fully understood. There have been a number of theories put forward, none of which seem to provide a total explanation
1.Methodological. All studies varied slightly in the way they were designed 2.Different vaccines. The development of BCG has meant that strains vary according to the time at which each has been developed. Different vaccine strains were used in the trials and are in use across the world today. 3.Tuberculin status of subjects. Within trials some individuals in both control or vaccinated group may have been tuberculin positive and therefore had natural protection. This may not have been accounted for in some of the trials.
http://www.priory.com/cmol/bcg.htm (1 of 8) [04/01/06 23:21:44]
FAQ about BCG
4.Different strains of M.tuberculosis. New molecular techniques have demonstrated that there are a large number of different strains of the bacterium. It is possible that different areas of the world have different strains, which may vary in virulence. 5.Genetic differences in population. There is variation in individual susceptibility to tuberculosis. This could have caused disparity in results. 6.Intensity of infecting dose. Infection and susceptibility to disease may be affected by the quantity of bacteria inhaled. 7.Nutritional differences. It is known that different nutritional states can vary susceptibility to disease. The poorly fed individual is more susceptible. 8.Protection of controls by environmental mycobacteria. These free living mycobacteria which resemble M.tuberculosis sometimes cause disease. They may be responsible for infecting individuals therefore providing partial immunity to M.tuberculosis.
How is BCG used in the UK?

Studies carried out by the British Medical Research Council in the 1950s showed that BCG, when given to teenage school children gave about 75% protection for 15 years.(1). Since 1953 it has been national policy to vaccinate all children aged 12-13. Thus in theory the entire population receives protection from early teenage years through to about the age of 30. The reason for choosing that age range was because in the 1950s cases rates were highest in young adults. The limited length of time for which BCG appeared to be protective would therefore be maximal at the age when most people suffered from the disease. Secondly the form of tuberculosis which pre-teenage children suffer from (primary) is not usually infectious, whereas the form suffered by adults is infectious. Providing protection during early adult life therefore reduced transmission.
In addition to the national policy for all teenagers, BCG is given at birth to those at high risk of disease; those with a family history of tuberculosis and those from minority ethnic groups.(see below) Is the policy of BCG vaccination the same throughout the world?
FAQ about BCG
No, mainly because of variation in trial results. Most countries give BCG at birth to provide protection in the early years when infection can often lead to devastating widespread disease such as miliary tuberculosis or tuberculous meningitis. This is particularly important in high prevalence countries where the chance of being infected in very early life is high. Some countries such as the USA have chosen not to use it because most trials there have not shown any protective effect. Why is there not international agreement on how to use BCG?
Again because of variation in trial results across the world. In 1994 a metanalysis of all the trials was published. (2)This looked at a total of 1264 articles, 70 in depth, 14 prospective trials and 12 case-control studies. The authors found that seven trials show a protective effect from death of 71%, five trials showed protection from meningitis of 64%, three, protection from disseminated disease of 78% and three, protection from laboratory-confirmed disease of 83%.
The authors concluded that geographical site of study explained 66% of variability. They also found that on average BCG reduces risk of infection leading to disease by 50%.
This is probably an erroneous conclusion, as the efficacy of BCG cannot be averaged. Trials show it to be 80% protective in one place and 20% in another. Average efficacy should not be taken.
Is the efficacy of BCG waning?

Some workers believe that it is(3). This is because the BCG vaccine is continually being reproduced as part of the manufacturing process and in common with other live organisms, which undergo this process, may be becoming less virulent and therefore less able to provide immunity to those who are vaccinated.
In contrast sequential studies form the UK show that the 75% efficacy has been
FAQ about BCG
maintained (4,5) Does giving BCG prevent the use of the tuberculin test in determining the presence of infection with M. tuberculosis? This is another area of controversy . BCG converts the tuberculin test from negative to positive. Workers are split as to whether it is possible to tell the difference between a positive test due to BCG alone and a positive test due to infection with M.tuberculosis whether the individual has had previous BCG or not. In the UK we believe it is possible to do this on the basis of the degree of positivity.(6) The USA do not use BCG partly for the reason that they do not believe it is possible to make the distinction.
The importance of this is the decision to give preventive therapy for Latent Tuberculosis Infection (LTBI). The USA has relied on prevention by determining whether infection (without disease) is present on the basis of regular tuberculin testing for those at risk of infection such as health workers. BCG is not given as it is believed to interfere with the interpretation of the tuberculin test. Other countries, such as the UK, do
give BCG but in cases where infection has occurred in addition to BCG and where the risk of disease is appreciable, such as in co-householders of Sputum Smear positive patients, preventive therapy can be given if the tuberculin test is strongly positive.(7) Doea BCG protect against drug resistant tuberculosis The probable answer to this is yes though evidence for this is necessarily sketchy. It is probably more effective in preventing disease than providing preventive therapy to those infected; a procedure for which there is no evidence of any efficacy at all. For health care workers who may be exposed to drug resistant tuberculosis, even a low protective efficacy of BCG would make vaccination worthwhile. In a recent study of a mathematical model, BCG was preferred by small margin over post-infection chemoprophylaxis. Threshold for protective efficacy was 26%. BCG should be considered for health care workers with risk of MDRTB exposure.(8,9)
FAQ about BCG
Should BCG still be used in low prevalence countries? As rates of tuberculosis have declined the argument for continuing routine BCG to the whole population becomes weaker. (10)For example if rates of disease are 5/100,00 and even if it is assumed that BCG gives 80% protection for 15 years then vaccinating 100,000 people would prevent (0.8x5)x15=60 cases over 15 years.
A number of countries with very low rates of disease have stopped BCG vaccination, but due to the increase of cases that has resulted at least one; the Check republic has restarted a routine BCG programme.
Conditions necessary to stop giving BCG include a good control programme, good reporting especially of TB meningitis and the prevalence HIV and its possible impact on TB increase must be evaluated.(11) For example in 1975 mass vaccination in Sweden was replaced by selective vaccination. As a result BCG coverage fell from95% to 1.8%. It then increased to 13.7% (12) The result on TB cases is shown in the table below which shows rates of disease in the Swedish and foreign born children at different percentage BCG cover.
BCG coverage % Swedish Foreign 95 13 1.8
Incidence per 100,000 according to BCG Coverage: 0.8 2.6 2.9 13.2 3.9 39.4
FAQ about BCG
From these figures it can be calculated that the protective effect was 82%. In the present climate of rapidly increasing cases of disease world wide and mass travel, the decision is probably not whether to stop BCG but whether to increase its use.(13)
Arguments against use of BCG vaccine in a mass programme are not about efficacy but cost effectiveness. (14)
Can BCG be harmful?

Abscesses at the site of BCG injection are frequently reported. It is often assumed that this is due to bad technique, as the injection should be given intra-cutaneaously and an accidental intramuscular injection may result. Proximal lymph node swelling and abscess formation may rarely occur. If the injection is given at the correct site, over insertion of Deltoid in the upper arm, the swelling will develop in the axillary lymph nodes.
Very rarely indeed, disseminated BCG disease may result in the immunocompromised infant. This is usually fatal. For this reason BCG should not be given to symptomatic HIV positive individuals.
In conclusion Im glad I had my BCG

PDODavies. References 1.Hart PD. Efficacy and applicability of mass BCG vaccination in tuberculosis control BMJ 19677;1:587-592.
2.Colditz GA et al.Efficacy of BCG Vaccine in the prevention of TuberculosisJAMA
1994;271:698-
702.Newborns and infants.Paediatrics 1995;96:29-35.

FAQ about BCG
3.Behr MA, Small PM Has BCG attenuated impotence?Nature 1997;389:133-134. Casts doubt on continued efficacy 4.Sutherland I, Springett VH Effectiveness of BCG vaccination in England and Wales in 1983.Tubercle 1987;68:81-92.5.Capewell S. et al.The current value of tuberculin testing and BCG vaccination in school children Br. J. Dis. Chest 1986;80:254-264. and prevention of tuberculosis in the United Kingdom:Code of practice 2000 Thorax Thorax 2000;55:887-901. 7.Rathus EM. The Heaf multiple puncture test compared with the Mantoux test in epidemiological surveys.Med J. Aust 1956;1:696-8. 8.Greenberg PD et al.Tuberculosis in House StaffA decision analysis comparing the Tuberculin Screening Strategy with the BCG vaccination.Am Rev Respir Dis 1991;143:490495. 9.Stevens JP Daniel TMBCG immunization of health care workers exposed to MDRTB: a decision analysisTubercle & Lung Dis. 1996;77:293-4. 6.Joint Tuberculosis Committee of the British Thoracic SocietyControl
10.Tala EO et al. Pros and Cons of BCG Vaccination in Countries with Low Incidence of Tuberculosis.Infection Control and Hospital Epidemiology 1994;15:497499. 11.Trnka L Dankova D Svandova E.Six years experience with the discontinuation of BCG vaccinationTubercle & Lung Disease 1993;74:167-72. 12.Romanus et al.The impact of changing BCG coverage on tuberculosis incidence in Swedish-born childrenn between 1969 and 1989.Tubercle and Lung disease 1992;73:150-161.
13.Cobelens GJ, van Deutekom H, Draayer-Jansen WE et al: Risk of infection with M.tuberculosis in travellers to areas of high tuberculosis endemicity. Lancet 2000;356:461-65.
14.Watson JM BCG - mass or selective vaccination?J. Hosp. Infect. 1995;30:508513.

Further reading.
FAQ about BCG
PGSmith and PEMFine BCG vaccination in Clinical Tuberculosis 2nd Editn Edit PDODavies, Chapman and Hall, London 1998 pp417-434.
Click on these buttons to visit our journals
Psychiatry On-Line
Dentistry On-Line
Vet On-Line
Chest Medicine On-Line
GP On-Line
Pharmacy On-Line
Anaesthesia On-Line
Medicine On-Line
Family Medical Practice On-Line
All pages copyright Priory Lodge Education Ltd 1994-2004.
FREE Internet Encyclopedia - MacroReference
MacroReference
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z Free Dictionary INDEX T
Television Tobacco and Smoking
q
National Smokers Alliance Americans for Nonsmokers' Rights Smokers Rights Groups Laws Protecting Nonsmokers Federal Judge Overturns EPA Report Mistaken Ruling by Federal Judge Model Ordinance to Ban Smoking in Public Places Cigar.com Tobacco Control Resource Center
http://www.cam-info.net/enc/macro.t.html (1 of 4) [04/01/06 23:24:32]

q
Cigarette Packs Collector Tobacco Timeline Smoking From All Sides The Tobacco BBS Center for Disease Control's Tobacco Information and Prevention Sourcepage Tobacco Companies World-Wide Cigarete Health Warnings Tobacco and Alcohol Industries in Cyberspace
Travel and Tourism

q
TravelWeb Tourism Virtual Tourist Bed and Breakfast Inns of North America Bed and Breakfast on the WWW Airlines of the WEB Travel Weekly's Home Page Rental Cars 'n' Cruises Skiing Adventure Low-Cost Airfares & Tours to Europe U.S. State Department Travel Warnings

q
International Travelers Clinic Tourism Canada TheWorld(TM) Guide to Travel World Health Organization: Internationl Travel and Health Weather/Travel Forecasts Other Weather/Travel Information Travel Resource Where to get Worldwide Tourist Information Tourism Offices Worldwide Directory Travelers' Center World Travel Watch
Trains Tuberculosis
q
Centers for Disease Control: TB FAQ American Lung Association: TB FAQ People's Plague: Tuberculosis in America (PBS special)(c. 1995) Centers for Disease Control: TB American Lung Assn. TB .pdf files (Adobe Acrobat) Drug-Resistant Tuberculosis (1997) Test for Drug-Resistant Tuberculosis Facts & Figures: Tuberculosis Today (c. 1995)

q
Interferon Gamma Protocol Multi-Drug Resistant Tuberculosis (1992)
Free Internet Encyclopedia

Top of Page Next Page
q
MicroReference - Home Page
Copyright 2004 by Clifton Davis. Reproduction in whole or part of this arrangement of links only with permission. It is intended that this document be viewed with a browser and permission for such usage is granted including the making of temporary copies as part of the normal operation of such browsers. Free Internet Encyclopedia is sponsored in part by another Free Encyclopedia.. Thanks to the University of Houston Department of Computer Science For providing part of the web space used for the Encyclopedia
Global Alliance for TB Drug Development
http://www.tballiance.org/ (1 of 3) [04/01/06 23:29:45]
Copyright 2005 The Global Alliance for TB Drug Development +1 212 227 7540 info@tballiance.org
site by darby communications
Read the December 2005
newsletter!
View our 2005 Animated
Holiday Card
Opportunities for
overcoming tuberculosis: new treatment regimens
TB Alliance and Bayer
Launch Historic TB Trials
Abbott Provides Freedom
to Operate
Read the 2004/05 Annual
Report
Hardin MD : Tuberculosis
Tuberculosis
A service of the University of Iowa
Site Map Diseases | Home
AIDS +Pictures Anemia +Pictures Blood Diseases +Pictures Crohns Disease +Pictures Digestive System +Pictures
Headaches +Pictures Immune System +Pictures Infectious Diseases +Pictures Kidney Diseases +Pictures Lung Pictures Lupus +Pictures
Medical Pictures Meningitis +Pictures Parasitic Diseases +Pictures Pneumonia +Pictures Respiratory System
Free journals Diseases

Search Hardin MD
q
[ Tuberculosis Pictures | Tuberculosis Symptoms ] LookSmart : Tuberculosis or TB TB-Related Links Division of Tuberculosis Elimination, US Center for Disease Control (CDC) MEDLINEplus : Tuberculosis National Library of Medicine Links to TB related sites Tuberculosis strategy & operations, World Health Organization Links to related resources National Tuberculosis Center, New Jersey Medical School Open Directory Project : Health : ... : Infectious diseases : Tuberculosis (Other versions: Google) Tuberculosis Mary K. Taylor, Southern Illinois Univ Library healthfinder : Tuberculosis US Government Yahoo : Tuberculosis ClinicalTrials.gov : Tuberculosis National Library of Medicine, National Institutes of Health
Search
See also:
q
q q
Popular
q q
Tuberculosis Pictures
q
MEDLINEplus Health Encyclopedia : Pulmonary tuberculosis Disseminated tuberculosis A.D.A.M. / National Library of Medicine Tuberculosis (Scroll down for picture links) Edward C. Klatt, WebPath, Univ Utah Mycobacterium tuberculosis (Picture of tuberculosis bacteria) Donna Duckworth., Richard Crandall, Richard Rathe, Univ Florida
Tuberculosis Symptoms
q
MEDLINEplus Health Encyclopedia : Pulmonary tuberculosis : Symptoms Disseminated tuberculosis : Symptoms A.D.A.M. / National Library of Medicine MEDLINEplus : Tuberculosis : Symptoms / Diagnosis [Directory] National Library of Medicine Tuberculosis : Signs & symptoms
http://www.lib.uiowa.edu/hardin\md/tuberculosis.html (1 of 2) [04/01/06 23:31:20]
Hardin MD : Tuberculosis
Mayo clinic, Rochester, Minnesota
Hardin Library for the Health Sciences, University of Iowa Please send comments to hardin-webmaster@uiowa.edu The URL for this page is http://www.lib.uiowa.edu/hardin/md/tuberculosis.html Last updated Tuesday, Nov 29, 2005 [pictures of tuberculosis, tuberculosis symptoms, pictures of lungs with tuberculosis, tuberculosis lung pictures, tuberculosis pictures, tuburculosis, TB, tb, tuberculosis symtoms, tubercolosis symptons, mycobacterium tuberculosis] [132932]
http://www.lib.uiowa.edu/hardin\md/tuberculosis.html (2 of 2) [04/01/06 23:31:20]
Journal of Occupational and Environmental Medicine - home
LWWOnline | LOGIN | eALERTS | REGISTER | CUSTOMER SUPPORT
Home Search Current Issue Archive
Important Message: Easily submit and review manuscripts online with LWW's Prompt/Editorial Manager. This automated, web-based tool simplifies the manuscript submission and review processes and enables users to electronically submit, review and track manuscripts and artwork online in a few easy steps. We invite contributors and reviewers to begin using the Prompt/Editorial Manager interface today at http://joem.edmgr.com.
LINKS & RESOURCES q Author & Reviewer Info q Journal Information q Advertising Information q Classified Ads q Society Information q ePrints/Reprints SUBSCRIPTION SERVICES q New Subscriptions q Renewal Information q Trial Issue Request q Special Sales
ACOEM MEMBERS - American College of Occupational and Environmental Medicine Members can access content published in Journal of Occupational and Environmental Medicine by completing login at the ACOEM website using the journal link to come back to this site and view content. Once back, you will see "American College of Occupational and Environmental Medicine" in the top right corner of this site. Proceed to the Current Issue or Archive page and select an issue to view full-text article content. If you do not have your membership credentials, please contact the ACOEM Membership Department directly by phone at 847-818-1800 ext. 375.
ISSN: 1076-2752 Online ISSN: 1536-5948 Frequency: 12 issues per year
Editor Paul W. Brandt-Rauf, MD, ScD, DrPH Columbia University New York, NY
Official Journal of the American College of Occupational and Environmental Medicine
The Journal of Occupational and Environmental Medicine is the official journal of the American College of Occupational and Environmental Medicine. Edited to serve as a guide for physicians, nurses, and researchers, the clinically oriented research articles are an excellent source for new ideas, concepts, techniques, and procedures that can be readily applied in the industrial or commercial employment setting. Now offering CME credits! ************ Journal Subscribers - you may activate your subscription online via the REGISTER button on the top menu bar. You will need your 12-digit subscriber number (which can be found on your journal mailing label) or membership ID to complete activation. Guests - simply create a new account via the REGISTER button on the top menu bar. Once you have established an account you will be able to purchase articles via our pay-per-view service and sign up for additional online services.
Copyright 2006, Lippincott Williams & Wilkins. All rights reserved. Published by Lippincott Williams & Wilkins. Copyright/Disclaimer Notice Privacy Policy Subscribe to RSS feed utrdc-pt02 Release 4.1
http://www.joem.org/pt/re/joem;jsessionid=D9DgF5wpjN...NJ2WTJ6IBBtHQtNUWJTJ1!-1094538453!-949856144!9001!-1 [05/01/06 0:02:51]
Portal Toolkit Invalid Site URL
Sorry, the URL specified, http://www.thoracicimaging.com:80/pt/re/ jti/, is invalid.

q
To go to site for "Journal of Thoracic Imaging" please click here http://www.thoracicimaging.com The site code " jti" specified in the URL is invalid To go to the LWW Online site, please click here http://www.lwwonline.com
Thank you
http://www.thoracicimaging.com/pt/re/%20jti/;jsessioni...dkeG1MApJ6NY1FNXtvK22S0!-1094538453!-949856144!9001!-1 [05/01/06 0:04:32]
2005 ... 11 - ... 2005 3... 11 - ... () 2005 2005 ... 11 - ... 2005 3... 11 - ... () 2005
[2006/01/02] [2005/12/27]
[2005/12/02] [2005/11/30] [2005/11/16] [2005/10/13] [2005/09/05] [2006/01/02] [2005/12/27] [2005/12/02] [2005/11/30] [2005/11/16] [2005/10/13] [2005/09/05] [2005/09/06] [2005/09/06]
http://www.knta.or.kr/korea/index.asp (1 of 2) [05/01/06 0:06:53]

: 128806 : 15 - 10 93 ... ] 7 1 ... [] , 200 342 32... -- ! ... - 10 93 ... ] 7 1 ... [] , 200 342 32... -- ! ... , ... , ... [2005/10/10] [2005/07/01] [2005/06/13] [2005/06/09] [2005/06/07] [2005/04/18] [2005/04/15] [2005/04/11] [2005/10/10] [2005/07/01] [2005/06/13] [2005/06/09] [2005/06/07] [2005/04/18] [2005/04/15] [2005/04/11]
2006 / 01
1 8 2 3 4 5 6 7
9 10 11 12 13 14
15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31
http://www.knta.or.kr/korea/index.asp (2 of 2) [05/01/06 0:06:53]
Links
Links
Other Mycobacteria Web Sites:
Johne's Information Center National Milk Producers Federation (NMPF) Information on Animal Health: Johne's Disease United States Animal Health Association, 1999 Committee on Johne's Disease University of Nebraska, Johne's Disease
http://www.mycosresearch.com/links.htm (1 of 3) [05/01/06 0:10:49]
Links
University of California Davis, Johne's Disease in Dairy Cattle and UCD Vet Views California Cattleman, February 1997: Johne's Disease, Part II Case Western Reserve University, Tuberculosis Research Unit Colorado State University, TB Research Materials and Vaccine Testing WHO Tuberculosis Control Programme Mycobacterium tuberculosis genome sequencing program (Sanger) CDC National Center for HIV, STD, and TB Prevention NIAID: Focus on Tuberculosis -TB research attains new heights in Colorado -Closing in: The long road to a TB vaccine
Links
Copyright 1999, Mycos Research, LLC.
Web Site mycosresearch.com by Kenton Solutions
L.R.S. Institute of Tubercolisis & Respiratory Diseases
DNB Course
World TB Day Director's Message AIMS & Objectives Visions Departments CT Scan DOTS Centers Patient Care Services Training (RNTCP) Teaching & Training I.E.C. Material Research Institute Publications Annual Statistics Citizen's Charter Ethical Guidelines FAQ on TB Related Links About the Site Contact Us
Conference Vacancy Interview Tender VCTC Indian Journal of Tuberculosis RNTCP DOTS Directory (Delhi)
TB Unit Directory - India
http://lrsitbrd.nic.in/ (1 of 2) [05/01/06 0:14:41]
L.R.S. Institute of Tubercolisis & Respiratory Diseases
Disclaimer : All rights reserved to Director, L.R.S. Institute of TB & Respiratory Diseases Designed,Developed & Maintained by : Computer Section, L.R.S. Institute of TB & Respiratory Diseases.
visitors Since 24.03.2003 Updated on 13.10.2005
Last
http://lrsitbrd.nic.in/ (2 of 2) [05/01/06 0:14:41]
MedlinePlus: Tuberculosis
Skip navigation
Other health topics: A B C D E F G H I J K L M N O P Q R S T U V W XYZ List of All Topics
Tuberculosis
q q
Contents of this page: News From the NIH Overviews Diagnosis/Symptoms Treatment Prevention/Screening Specific Conditions Related Issues Clinical Trials Research Organizations Statistics
q q
Latest News NIAID Researchers Show How Promising TB Drug Works (12/26/2005, National Institute of Allergy and Infectious Diseases) From the National Institutes of Health Learn about Tuberculosis (National Institute of Allergy and Infectious Diseases) - Links to PDF Also available in: Spanish Learn about Tuberculosis Infection (National Institute of Allergy and Infectious Diseases) - Links to PDF Also available in: Spanish Tuberculosis Overview (National Institute of Allergy and Infectious Diseases) Overviews Questions and Answers about TB (Centers for Disease Control and Prevention) Tuberculosis (Mayo Foundation for Medical Education and Research) Tuberculosis (Patient Education Institute) Requires Flash Player Also available in: Spanish Tuberculosis (TB) (American Lung Association) Diagnosis/Symptoms AFB Culture (American Association for Clinical Chemistry) Diagnosis of Tuberculosis Disease (Centers for Disease Control and Prevention) QuantiFERON-TB (Food and Drug Administration) - Links to PDF Radiography (X-Ray): Chest (American College of Radiology, Radiological Society of North
Select services and providers for Tuberculosis in your area.

Select Location
Select from map
View slideshow on: Tuberculosis
Children Women Other Languages Information from the Medical Encyclopedia
The primary NIH organization for research on Tuberculosis is the National Institute of Allergy and Infectious Diseases
Search MEDLINE/PubMed for recent research articles on Tuberculosis: General Diagnosis Multidrug Resistant Prognosis Therapy Latent Tuberculosis You may also be interested in these MedlinePlus related pages: Infections Lungs and Breathing
q q
http://www.nlm.nih.gov/medlineplus/tuberculosis.html (1 of 3) [05/01/06 0:16:54]
America)
q q
Treatment TB Can Be Cured (Centers for Disease Control and Prevention) Prevention/Screening TB Skin Test (American Association for Clinical Chemistry) Tuberculosis: The Meaning of a Positive Test (American Academy of Family Physicians) You Can Prevent TB (Centers for Disease Control and Prevention) Specific Conditions Multidrug-Resistant Tuberculosis (American Lung Association) Related Issues Exposure to TB (Centers for Disease Control and Prevention) Living with Tuberculosis (TB) (National Jewish Medical and Research Center) Nontuberculous Mycobacteria (NTM) (National Jewish Medical and Research Center) Tuberculosis: Health Information for International Travel (Centers for Disease Control and Prevention) Tuberculosis: The Connection between TB and HIV (the AIDS Virus) (Centers for Disease Control and Prevention) Also available in: Spanish Clinical Trials ClinicalTrials.gov: Tuberculosis (National Institutes of Health) Research First U.S. Tuberculosis Vaccine Trial in 60 Years Begins (01/26/2004, National Institute of Allergy and Infectious Diseases) Organizations American Lung Association National Institute of Allergy and Infectious Diseases Statistics TB Elimination: Now Is the Time! (National Center for HIV, STD, and TB Prevention) Also available in: Spanish Tuberculosis in the United States, 2004 (Centers for Disease Control and Prevention)
q q
q q
q q
q q
q q
q q q
q q
q q
Children Pediatric Tuberculosis (American Lung Association) TB (Tuberculosis) (Virtual Hospital) Women Tuberculosis (National Women's Health Information Center) Other Languages Tuberculosis Information - Albanian: Informacion Per Tuberkulozin (1) (Centers for Disease Control and Prevention) - In Albanian Tuberculosis Information - Albanian: Informacion Per Tuberkulozin (2) (Centers for Disease Control and Prevention) - In Albanian Information from the Medical Encyclopedia Tuberculosis
q q
Home | Health Topics | Drugs & Supplements | Encyclopedia | Dictionary | News | Directories | Other Resources Copyright | Privacy | Accessibility | Quality Guidelines U.S. National Library of Medicine, 8600 Rockville Pike, Bethesda, MD 20894 Date last updated: 29 December 2005 National Institutes of Health | Department of Health & Human Services Topic last reviewed: 29 December 2005
Mycobacterium tuberculosis information Diseases Database
Diseases Database | Index | Disclaimer | Sponsors | Contact | Previous Page
Mycobacterium tuberculosis information
| Search |
3 synonyms or equivalents were found. Mycobacterium tuberculosis

aka/or
TB
aka/or
Tuberculosis
q
may cause or feature + (Follow link for list.) risk factors may include + (Follow link for list.) may be a risk factor for + (Follow link for list.) belong(s) to the category of + (Follow link for list.)
Mycobacterium tuberculosis: Definition(s) via UMLS.....Code translations and terms via UMLS.
Mycobacterium tuberculosis: specific web sites.
Send Mycobacterium tuberculosis to medical search engines.
We subscribe to the HONcode
principles of the Health On the Net Foundation.
Valid XHTML 1.0

Served 2006-01-05 16:17:10 CPU <1s. View metadata
MOOSe Technology.
Last major update 2006-01-01.
The medical information here is presented for education, background reading and general interest. The Diseases Database is not a diagnostic or clinical decision-making tool. Please consult your own licensed physician regarding diagnosis and treatment of any medical condition! Content is not asserted complete or error free, please see also our disclaimer.
http://www.diseasesdatabase.com/ddb8515.htm [05/01/06 0:17:58]
National Institutes of Health (NIH)
Ovarian Cancer Treatment NCI issues clinical announcement for preferred method of treatment for advanced ovarian cancer Ovarian cancer What you need to know More information More Press Releases... Health Issues Menopausal Hormone Therapy Medical Research Issues Public Access NIH Roadmap HIPAA Privacy Rule Stem Cell Information Conflict of Interest Information
A-Z index of NIH health resources, clinical trials, MedlinePlus, health hotlines
Grants news, applications, grants policy, NIH Guide, award data, eRA Commons, research training, research contracts, loan repayment programs, Small Business Research Programs
News releases, RSS, media center, calendars, radio & video, media contacts, News in Health newsletter
Intramural research, Human Embryonic Stem Cell Registry, scientific interest groups, library catalogs, journals, training, labs, scientific computing
The individual organizations that make up the NIH
Visitor info, employee directory, jobs, science education, mission, Director's Page, public involvement, research planning, organization, budget, history, doing business with NIH, FOIA
[ Q&A About NIH | Jobs at NIH | Visitor Information | FOIA ] [ Telephone & Service Directory | Employee Information | Informacin en espaol ] [ Contact Us | Privacy Notice | Disclaimer | Accessibility | Site Map | Search ] National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892 Department of Health and Human Services
http://www.nih.gov/ [05/01/06 0:21:22]
New Jersey Medical School National Tuberculosis Center
http://www.umdnj.edu/ntbcweb/tbsplash.html [05/01/06 1:51:23]
NJMS National TB Center - Links Page
Links to Related Resources
Tuberculosis Sites
q
q q q q q q q q q q q
q q
q q q q
q q q q q q q q q q
q
Action TB Brown University's TB/HIV Lab CDC's Division of TB Elimination Charles P. Felton National Tuberculosis Center at Harlem Hospital Ending Neglect: The Elimination of Tuberculosis in the United States - IOM Report Francis J. Curry National Tuberculosis Center Global Fund to Fight AIDS, TB, & Malaria Global TB Drug Facility Health Canada: Preventing the Transmission of Tuberculosis International Union Against Tuberculosis and Lung Disease Japan Anti-Tuberculosis Association Multidrug-resistant Tuberculosis (MDR-TB) - Annotated Bibliography from the University of Chicago NHBLI TB Academic Award National Center for Infectious Diseases, Division of AIDS, STD, and TB Laboratory Research National Jewish Center for Immunology and Respiratory Medicine New Jersey Department of Health and Senior Services, TB Program Northeast Regional RFLP Lab for DNA Typing OSHA Directive CPL 2.106 Enforcement Procedures and Scheduling for Occupational Exposure to TB PHRI/Soros Russian Infectious Disease Program RESULTS World Health/Diseases of Poverty Initiative Sanger Sequencing Center Information about TB genetics Sequella Incorporated - Moving Infectious Disease Technology from Promise to Product Stanford University Center for Tuberculosis Research STOP TB Initiative Website TB Timebomb - The Global Epidemic of Multi-Drug Resistant Tuberculosis TB in the Workplace - IOM Report Tuberculosis and HIV Infection from the VA AIDS Information Newsletter The Global Alliance for TB Drug Development World Bank - Tuberculosis Control
http://www.umdnj.edu/ntbcweb/links_frm.html (1 of 2) [05/01/06 1:53:13]
NJMS National TB Center - Links Page
AIDS Related Sites

q q
The Body: A Multimedia AIDS and HIV Information Resource UNAIDS
Other Health Related Sites

q
Academy of Medicine of New Jersey
q q q q q q q q q q q q q q q q q q q
q
American College of Chest Physicians American Lung Association American Public Health Association American Thoracic Society Health on the Net Foundation Institute of Medicine The Lancet Medical Education Information Center at UT Houston Medical School Merck Manual On-line National Center for Minority Health and Health Disparities National Heart, Lung, and Blood Institute National Library of Medicine: Hyperdoc Resources New England Journal Of Medicine NJ MED: Health Care Providers Nova Southeastern University's Health Resources Links Pan American Health Organization Partners in Health U.S. Food and Drug Administration U.S. Immigration and Naturalization Service
U.S. Census Bureau
Revised: Thursday, September 13, 2001 All contents copyright 1996 NJMS National Tuberculosis Center. All rights reserved.
http://www.umdnj.edu/ntbcweb/links_frm.html (2 of 2) [05/01/06 1:53:13]
http://www.paho.org/English/HCP/HCT/TUB/tuberculosis.htm
Surveillance Prevention and Control PAHO Activities Other PAHO Materials General Info/Links
Surveillance
Featured Surveillance Items
No. cases, regional %...
1998-2001
Guidelines for HIV Surveillance among Tuberculosis Patients (2nd ed.)
What's New
The main objective of these guidelines is to provide a framework for the methods to be used for measuring HIV prevalence among tuberculosis patients and to encourage implementation of HIV surveillance. The guidelines are aimed at managers of national tuberculosis programs (NTPs) and Workshop national AIDS programs (NAPs), those responsible for HIV surveillance, and on public-health decision-makers at national and subnational level. They form part of the TB/HIV series on "Second-Generation Surveillance" (SGS). This page offers a summary, lists the recommendations, and links to the e-book on the WHO website. tb-hiv-surv-who.htm
Planning Communication for Tuberculosis Control in the Americas: Summary Report : Informe resumido (Cochabamba, Bolivia, 67 October 2005; prepared by Silvio Waisbord, Academy for Educational Development / AED)
This expert meeting in communication provided a venue not only for bringing together specialized consultants but also for forming a regional working group to continuously advise PAHO on the use of communication for tuberculosis control. Objectives were to form a group of consultants to provide technical assistance in planning communication for the National Tuberculosis Programs (NTPs), reach agreements on the terms and principles of mass communication, and define criteria and work operations. tb-taller-cochabamba-oct05.htm tb-tallercochabamba-oct-05.pdf
Regional Meeting of the Tuberculosis Laboratory Network (Mexico City, 68 September 2004)
The PAHO TB Program has just published (in Spanish) the final report for this meeting, the objectives of which were (1) to analyze and discuss aspects related to the areas of quality control, National Tuberculosis Programs (NTPs) using current and new techniques, and TB Laboratory Networks managing information; (2) become acquainted with the experiences of selected countries that have successfully dealt with these areas; (3) get to know the work of the laboratories currently carrying out reference functions in the Region; (4) distribute and discuss regional proposals; and (5) promote collaboration and communication networks among those in charge of TB Laboratories and the Heads of National TB Programs. tb-labs-2004.htm
Epidemiological Status of TB (Region of the Americas, 2004)

This presentation of 19 slidesincluding tables, figures, and mapsillustrates and summarizes the epidemiological situation of tuberculosis in the Region up to 2004. It includes data on multidrugresistant TB (MDR-TB), TB/HIV, the extension of the DOTS/TAES strategy up to now as well as its achievements and challenges. PowerPoint ... more Surveillance Features.
Situation Reports
Epidemiological Status of TB (Region of the Americas, 2004)
Incidence/Mortality/Case Fatality
SIEPI Epidemiological Information System Public Health Agency of Canada's Tuberculosis Prevention and Control Site Statistical Tables, TB in the Americas: Incidence, National Programs, DOTS Coverage
Guidelines and Manuals

Tuberculosis: A Manual for Medical Students
Epidemiological Surveillance Systems (ESS)

Second Meeting of a Surveillance Network for Emerging Infectious Diseases (EID) in the Southern Cone Region (Brasilia, Brazil, 11-13 May 1999)
Country Profiles
Tuberculosis: Number of Cases and AFB (+), Reduction Rate (Region of the Americas, by country and year, 20012002)
Statistical Databases
SIEPI Epidemiological Information System
http://www.paho.org/English/HCP/HCT/TUB/tuberculosis.htm (1 of 2) [05/01/06 1:55:18]
http://www.paho.org/English/HCP/HCT/TUB/tuberculosis.htm
... more items. Regional Core Health Data System - Table Generator 2004
Product Types and/or Keywords: Product Types (register under only one): Situation Reports, Country Profiles, Forms, Guidelines and Manuals, Health Profiles and Data, Statistical Databases, Other Databases Keywords (no limit, or key in Product type/s in keyword field for crossreferencing): Surveillance features TUBERCULOSIS, Annual status reports, Incidence/Mortality/Fatality, Incidence and disease registries, Resistance surveillance, Epidemiological surveillance systems, Geographic information systems, Groups affected, Risk factors/behaviors, Outbreaks
Back
Top
Comments/Questions?
http://www.paho.org/English/HCP/HCT/TUB/tuberculosis.htm (2 of 2) [05/01/06 1:55:18]
Philippine Tuberculosis Society Inc. Website
PTSI is a non-profit charitable organization founded on July 29, 1910, to combat the spread of tuberculosis and kindred diseases in the Philippines. It has been in the forefront in the fight against TB ever since.
Quezon Institute Hospital Field Operation Division National Research & Training Center Central Laboratory
Burden of Illness PTSI Critical Role and Continuing Needs How to Help Fight the Lung Diseases
News Archive: Pulmonary Medicine Specialty Training World TB Day Controlling TB The Manila Manifesto
Click here for your donation
We want to hear from you: For more information email us at: ptsi@vasia.com Or contact us at: Tel. Nos.: (+) (632) 781-3761 to 65 Fax No.: (+) (632) 740-8164 Best viewed at 800x600 display resolution using Netscape 4.0 or IE 4.0 and higher Copyright 2001 Philippine Tuberculosis Society, Inc. All rights reserved. Designed and Maintained by: web dot com website development phils., inc.
http://www.ptsi.org.ph/ [05/01/06 1:57:46]
Rapid Blood Tests: Infectious Diseases, Tuberculosis, HIV, AIDS, STD

WHAT WE OFFER HOW THEY WORK HIV TESTING HEMA DIAGNOSTIC INSERT PAGES NEW DEVELOPMENTS TRADE FAIRS AND EVENTS CONTACT HDS HOME PAGE SPANISH(ESPAOL) FRENCH(FRANAIS) PORTUGUESE(PORTUGUS) RUSSIAN
Rapid blood test sampler and housing
CALL USA 305.535.6123 FOR MORE INFORMATION
Contact Hema Diagnostics for more ...
RAPID 1-2-3 BLOOD TESTS incorporate the latest . . . HEMA DIAGNOSTIC SYSTEMS makes testing devices for . . .
RAPID MEDICAL DIAGNOSTICS are now as simple as . . . MEDICAL LAB PROFESSIONALS worldwide are invited to . . .
FOR EXPORT ONLY: NOT YET FDA APPROVED FOR SALE OR USE IN USA WHAT HOW HIV ABOUT PDFs LINK RESOURCES CONTACT HOME TOP
HemaDiagnostics.com: Copyright 2004 Hema Diagnostic Systems, LLC: Rapid Blood Tests for Infectious Diseases, Tuberculosis, HIV, AIDS, STD
HEMA DIAGNOSTICS SYSTEMS: RAPID BLOOD TESTS FOR HIV/AIDS, WEST NILE VIRUS ET AL GENERAL OFFICES: Hema Diagnostic Systems Panama, S.A. World Trade Center, 1st Floor Area Comercial Calle 53 Marbella, Apartado 0832-0588 Panama City, Republic of Panama 507-205-1955 (tel) 507-205-1802 (fax) Email: Info@RapidBloodTests.com USA OFFICES: Hema Diagnostic Systems, LLC 650 West Avenue, Suite 2507 Miami Beach, Florida 33139 USA 305-535-6123 (tel) 305-535-0019 (fax)
http://www.rapidbloodtests.com/index.html (1 of 2) [05/01/06 2:06:20]
Rapid Blood Tests: Infectious Diseases, Tuberculosis, HIV, AIDS, STD

Email: Info@RapidBloodTests.com HemaDiagnostics.com Rapid Blood Tests: Infectious Diseases, Tuberculosis, HIV, AIDS, STD CONTEXT INDEX: West Nile Virus . abnormalities abnormality abo abuse accredited acid adenovirus administration adult adults afghanistan afp africa african agar age aids albania alcohol alert algeria allergen allergic allergy alpha america american amex aminex amp amphetamine amplification analysis andorra anemia angola anguilla animal antarctica anti-human antibody anticoagulant antidepressant antigen antigens antigua antilles antioxidant approval approved arab arabia argentina armenia aruba australia austria autoimmune automation availability azerbaijan . bag bahamas bahrain bandage bangladesh bank bar barbados barbiturate barbuda based basic batch bca belarus belgium belize benin benzo benzodiazepine benzodiazepines bermuda bhd bhutan bio biochemical biochemicals bioinformatics biointact biology biomolecule biotechnology blood bloodtest bloodtests blot bnp bolivia bosnia botswana bouvet brain brazil breast british brunei bse bulgaria burkina burundi bzd bzo . caga caicos caledonia cambodia cameroon canada cancer cancerthyroid canine cannabis cape carcinoembryonic cardiac cardio cardiovascular care carpal causes cayman cbc cea cell cells centers central ceramic cervical cha chad chagas chain chamber characterization check chemistry children chile china chlamydia cholera cholerae cholesterol cholestorol christmas chromatography chronic cjd clinical clinically clostridium coc cocain cocaine cocos code coli collect collection colombia colon comoros comparison compliance condition conditions congo container cook costa cote cotinine croatia crp css cuba culture cure cyprus cystic czech . d'ivoire darussalam deaths deficiency delcon democratic denmark detectable detection device devices dgx diabetes diagnose diagnosis diagnostic diagnostics dipstick discovery disease diseases disorders distributes distribution distributors djibouti dna doa dominica dominican dosing draw drawing draws drug drugs . ea early east ebv ecuador egypt el electronic electrophoresis elisa eliza emirates encephalopathy endocrinology environmental enzymes epidemic equatorial equipment eritrea esoteric estonia ethiopia evidence exchange exporters express expression . falkland faroe faso fda fda-approved febrile fecal federal federated federation feiv feline felv female ferritin fertility fetoprotein fibrosis fiji finland fiocchetti fiv flake flow fluid france french fsh ftc fusion futuna . gabon gambia gastrointestinal gauze gca gel gene genebased genetic genomics germany ghana gibraltar global globulin glucose glycerol glycohemoglobin gonorrhea greece greenland grenada grenadines guadeloupe guam guarantee guaranteed guarantees guatemala guiana guinea guinea-bissau guyana . h-p-t haccp haemoglobin hair haiti hbsab hbsag hcg hcv hds heal health healthcare heart heartworm helena helicobacter hema-strip hematology hemo hemoglobin hemomix-plus hemophiliacs hemostasis hemotek hemoweld hepatitis heptimax heroin herpes herzegovina heterophile hipaa hiv hiv-1 holy homocysteine honduras hong hormone hospital hospitals hs human hungary hydridization hydroxyapatite hygiene . ice iceland iga ige igg igm illness immune immunoassay immunocap immunodeficiency immunodiagnostic immunofluorescence immunology in-vitro incubator india indian individuals indonesia industrial industry infected infections infectious insert instant institute instruments insurance international ion iran iraq ireland islamic island islands israel italy jamahiriya jamaica jan japan jordan . kazakstan keeling kenya kidney kingdom kiribati kit kits kitts kong korea kuwait kyrgyzstan lab laboratories laboratory labs laminar lancet lancets lanka lao latvia lebanon leone lesotho leukaemia leukemia level levels lh liberia libyan liechtenstein lifesign lipid listeria lithuania live lives living lucia luxembourg lyme . macau macedonia madagascar maker malaria malawi malaysia maldives male mali malta malvinas man manage managed manufacture manufacturer manufacturers manufactures manufacturing mariana marijuana marino marshall martinique mathdon mauritania mauritius mayen mayotte measles medical medically medicine men metabolic methadone methamphetamine mexico micro-albumin microbiological microbiology micronesia microplate microscopy miquelon mlc moldova molecular monaco mongolia monitoring mono mononucleosis montserrat mop morocco morphine mortuary mozambique mtd mumps myanmar myo myoglobin myosin . nam namibia natriuretic nauru nausea nepal netherlands nevis newborn nicaragua nichols nicotine niger nigeria niue nmr non-treponemal norfolk northern norway nucleic . oca offer offering oman one-step onestep opi opiate opiates oral orbital order ovarian oven ovulation pad pain pakistan palau palestinian panama pap papua paraguay pathogen patient patients pcp pcr pediatric pending people pepsinogen peptic peptide peru pglo pharmacy phencyclidine philippines physically physician physicians pierre pitcairn plasma plasmathor platelet poland polynesia portugal potentiators pouch practice predictor pregnancy premarket preparation prevent prevented principe process product products professionals profile prolactin prostate protein proteomics prothrombin provide provided provider provides providing psa pth puerto purification pylori . qatar quick range rapid rapidtest rapidtests reactive reagent reagents reagin records refrigerated refrigerator rehab rep replace replacement republic required research respiratory result results rhesus rica rico romania rotary rotavirus routine rpr rsv rubella russian rwanda . safe safety sahara saint saliva salmonella salvador samoa sample san sandwich sao saudi scientific scrapie screen screening screens sdn secure sedimentation select selected self-exam self-use senegal separation sero-strip serodiagnosis serum service services severe sexually seychelles shaker shakers sierra signal simplex simultaneous singapore single skin slovakia slovenia smear solomon solution solutions somalia sores south southern spain special specialize specialized specialty specific specimen specimens spectra spectrometry spectroscopy sperm spongiform sri staining stains standard state states std step steps sterilising sterility steroids stick stomach streams strep streptococcus strip strips substance sudan sulfamethazine suppliers supply support surface suriname susceptibility svalbard swaziland sweden switzerland symptoms syphilis syrian . taiwan tajikistan tanzania technical technician technology technologies territories territory tested tester testing testosterone tests thailand thawing therapeutic therapy thermal thermostatic thyroid tibc timor tobago togo tokelau tonga toxin trachomatic trachomatis transduction transfection transformation transformed transfusion transmissible transmitted treatment treatments tricyclic trinidad tropical troponin tse tsh tuberculosis tumor tumour tunisia turkey turkmenistan turks tuvalu types typing . uganda ukraine ulcer united urinalysis urine uruguay usa usda users uzbekistan vaccination vaccine vaccines vacuum vanuatu variety vatican venezuela verde victim viet vincent virgin virus visit vitro volume . wallis warn warnings weight wellness western wet woman women yemen yugoslav yugoslavia zambia zealand zimbabwe . Other Resources
http://www.rapidbloodtests.com/index.html (2 of 2) [05/01/06 2:06:20]
Registre de Tuberculosi
CONJUNT MNIM DE DADES PER A LA VIGILNCIA DE LA TUBERCULOSI A EUROPA.

Recomanacions del grup de treball de l'Organitzaci Mundial de la Salut (OMS) i de la Regi Europea de la Uni Internacional contra la Tuberculosi i les Malalties Pulmonars (IUATLD) per a la uniformitzaci de la recollida de dades dels casos de tuberculosi.
Guia per al compliment del full de declaraci de cas de tuberculosi, Programa de prevenci i control de la tuberculosi a Andorra (PPCT) (15 de mar del 2000)
Fer click per veure el full
Definici del cas

q
Cas "definit" de tuberculosi
1. cas amb malaltia confirmada per cultiu provocada pel complex M. tuberculosis. 2. cas amb frotis positiu per bacils acidoresistents (AFP) si no es disposa de
laboratoris de nivell II (que puguin processar mostres per al cultiu) o quan no es pot esperar el cultiu rutinari d'espcies extretes de tots els casos.
q
Tamb s'han de notificar els casos "no definits", els quals han de complir les dues condicions segents:
1. quan un clnic cregui que els signes i/o els smptomes clnics i/o radiolgics del
pacient sn compatibles amb la tuberculosi, i
2. quan un clnic decideixi tractar el pacient amb una terpia completa contra la
tuberculosi. Els casos "definits" (i, quan sigui aplicable, els "no definits") de tuberculosi pulmonar s'han de dividir en funci del resultat del frotis provocat o espontani en:
r r r
casos de frotis positiu casos de frotis negatiu casos "demostrats" o "no demostrats" : noms els casos que donen positiu en el microscopi de material de rentada broncoalveolar o gstrica no haurien de considerar-se frotis positiu d'esput. Aquests casos es poden qualificar de "demostrats" o "no demostrats" tenint en compte els resultats del cultiu i altres criteris.
http://www.col-legidemetges.ad/docs/fulltb.html (1 of 5) [05/01/06 2:08:03]
Variables essencials Les variables essencials sn: informaci que descrigui el cas, incloent-hi el temps, el lloc i la persona, com tamb els detalls de la localitzaci de la malaltia, l'estat bacteriolgic i el fet si el pacient ha estat tractat anteriorment. 1. Persona afectada Edat i sexe: La data de naixement, que permet calcular l'edat en el moment en qu es va iniciar el tractament, i el sexe sn variables que s'han de saber de cada pacient. Pas de naixement. A les societats de cultura heterognia, la incidncia de la tuberculosi pot variar d'una manera important en diferents grups tnics. En vista de la importncia creixent de la tuberculosi als pasos europeus entre els immigrants i altres estrangers, el Grup de Treball sobre el Control de la Tuberculosi i Migraci Internacional va identificar el pas de naixement com una variable addicional que s'hauria de recollir rutinriament [5]. En alguns pasos, l'origen tnic, la ciutadania o la ciutadania dels pares pot ser ms important que el pas de naixement a l'hora de descriure la demografia dels pacients de tuberculosi. El lloc de residncia. El lloc de residncia d'un pacient de tuberculosi s essencial per a l'acci de la salut pblica. El lloc de residncia ha de ser el lloc on el pacient estava vivint en el moment en qu es va iniciar el tractament. En el cas de persones sense llar, migrants, detinguts.., es pot donar el lloc de residncia dins del pas durant els 3 mesos anteriors, o es pot buscar qualsevol altra soluci que els pasos individualment considerin apropiada. Localitzaci de la malaltia. 2. Localitzaci principal 3. Localitzaci menor La localitzaci de la malaltia s'ha de recollir en tots els pacients. Ats que els pacients poden tenir diverses localitzacions de malaltia, es recomana que es recullin com a mnim dues localitzacions, una de principal i una de secundria (o menor), quan sigui aplicable. Ja que la classificaci de la localitzaci de la malaltia pot variar a diferents pasos, es recomana que es facin servir les localitzacions segents, perqu permetran fer les agregacions que siguin necessries en un pas concret: Tuberculosi pulmonar: tuberculosi del parnquima del pulm i de l'arbre trqueobronquial. La tuberculosi pulmonar, si hi s present, sempre s'ha d'inscriure com a localitzaci principal, sigui quin sigui l'altre lloc que pugui estar afectat. Tuberculosi extrapulmonar: Tuberculosi que afecta qualsevol altre lloc diferent dels que afecta la pulmonar. - Tuberculosi pleural. Tuberculosi extrapulmonar que noms s una pleuresia tuberculosa, amb efusi o sense.
- Tuberculosi limftica. s la que afecta el sistema limftic. A causa de les manifestacions intratorciques de la tuberculosi en els infants i pacients infectats amb el virus de la immunodeficincia humana (VIH), la tuberculosi limftica es divideix en:
1. Intratorcica - tuberculosi limftica intratorcica 2. Extratorcica - tuberculosi limftica que no sigui la tuberculosi limftica
intratorcica. Quan la tuberculosi en infants afecta tant el parnquima del pulm com un component limftic, s'ha de classificar com a localitzaci principal, la pulmonar, i com a localitzaci secundria, la tuberculosi limftica intratorcica. - Tuberculosi osteoarticular. Tuberculosi que afecta els ossos i/o les articulacions; es subdivideix en:
1. tuberculosi espinal i 2. altres tuberculosis osteoarticulars que no siguin l'espinal.

- Tuberculosi del sistema nervis central (CNS). La tuberculosi del sistema nervis central se subdivideix en:
1. meningitis tuberculosa i 2. una altra tuberculosi del sistema nervis central que no sigui la meningitis.
- Tuberculosi genitourinria. La tuberculosi del sistema gnitourinari, inclou la tuberculosi renal, ureteral, de la bufeta i del tracte genital mascul i femen. - Tuberculosi del tracte peritoneal/digestiu. Aquesta tuberculosi inclou la tuberculosi del peritoneu, amb ascitis o sense, i la tuberculosi del tracte digestiu. - Altres. Altres localitzacions extrapulmonars, incloent-hi la tuberculosi larngia, i per a l'anlisi de pasos concrets es poden anomenar especficament. - Tuberculosi disseminada. La tuberculosi disseminada inclou tuberculosis en ms de dos rgans o la tuberculosi miliar. Si un d'aquests llocs afectat s el parnquima del pulm, el cas s'hauria de classificar com a tuberculosi pulmonar o com a tuberculosi disseminada. Per tant, la tuberculosi miliar, per exemple, es pot classificar com a pulmonar i com a disseminada. Quan el complex M. tuberculosis ha estat allat de la sang, la localitzaci de la malaltia s'ha de designar com a "disseminada". 4. Estat bacteriolgic La informaci sobre l'estat bacteriolgic s'ha d'incloure sempre. El metge ha d'enregistrar: - La mostra i data de recollida de la localitzaci principal o, si s negativa o sense
resposta, la de la localitzaci secundria que hagi donat un resultat positiu (ex.: frotis d'esput positiu, tuberculosi pulmonar confirmada per cultiu o frotis de bipsia negatiu, tuberculosi limftica confirmada per cultiu). - el resultat i la data: - de l'examen microscpic directe (negatiu o positiu respecte dels bacils acidoresistents, o examen no realitzat). - del cultiu (negatiu o positiu respecte del complex M. tuberculosis, o examen no realitzat). - l'espcia identificada: M. Tuberculosis (MT), Mycobacterium bovis (MB), o Mycobacterium africanum (MA),. - L'examen histolgic amb evidncia de bacils acidoresistents hauria de considerar-se com un examen microscpic positiu i, per tant, s'hauria de registrar tamb aix. 5. Cas recurrent o nou cas Abans de comenar el tractament per a la tuberculosi, s important establir el segent: 1) que el pacient t tuberculosi activa; 2) si el pacient ha patit de tuberculosi anteriorment; i, si s aix, 3) quin tractament se li va donar anteriorment. Les dues primeres preguntes sn de carcter tant epidemiolgic com clnic, i la tercera t una importncia clnica ja que la resposta determinar el tractament ms apropiat per a l'episodi de tuberculosi en qesti. Per als efectes de la salut pblica s essencial informar sobre tots els casos de tuberculosi que hagin estat diagnosticats per metges. Per a l'epidemiologia, on les tendncies en la incidncia sn d'especial inters, s molt important conixer si un cas notificat ha tingut o no tuberculosi prviament. S'ha d'anar amb compte a l'hora d'assegurar-se que no es repeteixen els informes dels casos crnics i dels pacients que van i vnen de forma intermitent. La resposta a les preguntes d'aquest apartat hauria d'aclarir aquestes qestions: - la primera pregunta demana si al pacient se li havia diagnosticat tuberculosi anteriorment. Si la resposta s afirmativa, la segona pregunta respon l'any de l'episodi anterior i, si pot ser, el mes. La tercera pregunta estableix si al pacient se li va fer un tractament amb quimioterpia i, si la resposta s afirmativa, si es va considerar satisfactori o no. Aix permetr classificar aquests casos en recaiguda i recurrncia amb quimioterpia prvia o sense i, per tant, millorar la definici dels casos. 6. El temps La data d'inici del tractament: L'ideal, per obtenir estimacions acurades de la incidncia de la malaltia, seria conixer la data del seu comenament, per aix no acostuma a ser factible; tamb la data del diagnstic pot ser difcil de fixar en el temps, per aix es recomana que la "data d'inici del tractament" , considerada una dada proxy se registri en tots els casos. La data d'inici del tractament es defineix com la data en la qual el metge est prou segur de la seva diagnosi i inicia el tractament adequat per a la tuberculosi. Per a la tuberculosi pulmonar, aquesta acostuma a ser quan s'obt del laboratori un resultat de
frotis d'esput positiu o, en els casos de frotis d'esput negatiu, quan el metge ha reunit proves clniques i/o radiolgiques suficients per a la diagnosi que justifiquen l'inici del tractament. Quan no es pot disposar de la data d'inici del tractament, aquesta es pot substituir per la data de notificaci del cas. I per als casos que no han rebut mai cap tractament, com ara la diagnosi postmortem, aquesta ha de substituir la data del diagnstic.
Darrera modificaci 26/1/01
RIT/JATA Home Page in English
RIT: Organization & Activities Research Trends TB Statistics Maps WHO Stop TB Partnership IUATLD Links Comments to
TB Publications
@ Annual Report of RIT 2001-2003 (PDF file) (updated 05.12.20) Newsletter from Kiyose No.21 (updated 05.12.07) Organization & Activities (updated 05.10.24)
Department of Program Support, Department of Research, Mycobacterium Reference Center
TB Statistics Monthly reportAnnual report Quality Smear Preparation for AFB
WHO Regional Committee for WP declares a "TB crisis" Declaration! State of Emergency Concerning Tuberculosis ! NEWS! TB patients increase for 1st time in 38 yrs !
Annual Report of RIT 20012003 (PDF file)
E Database : Abstracts of
http://www.jata.or.jp/eindex.htm (1 of 2) [05/01/06 2:22:12]
RIT/JATA Home Page in English
(Journal of the Japanese Society for Tuberculosis)
@@@@@@
World TB Day
@@@@ Cured TB patient stories
Updated 05/12/07
http://www.jata.or.jp/eindex.htm (2 of 2) [05/01/06 2:22:12]
Stanford Center for Tuberculosis Research Guestbook

Thank you for visiting our pages. We invite those with research interests to Add to this email address list we are keeping! We request that you include your email address and only a few lines for contact information and keywords or phrases characterizing your research interests. This page is provided for those interested in identifying research-related contacts. Please note multiple entries, or any inappropriate entries, including questions, will be edited or erased at the sole discretion of the Stanford Center for Tuberculosis Research. Use the Message Board for a more free discussion format and for questions. If you have questions regarding personal treatment, follow the links provided from our home page; there are many sources for general information on tuberculosis disease. Don't neglect to talk to your health care provider!
Indentification and Cure of side effects of Isoniazide & Rifamipicin Sundip <harshsun@hotmail.com> New Delhi, Delhi India - Wed Jan 10 09:04:24 2001 send me information regarding my thesis topic that is: immunodiagnosis of intrathoracic tb in children by elisa for igg antibodies. dr ps varma <varma1986@yahoomail.co.in> gulbarga, karnataka india - Mon Jan 1 16:00:39 2001 Dear Sir, I am an experienced researcher on Applied Environmental Microbiology and Microbial Technology. Is it possible to apply for a postdoc position in your group to do the genetic research of environmental microbiology? In last year, I just got a Ph.D. in Microbiology in Shandong University. During recent two years, I am mainly looking for special microbes for organic desulfurization and denitrification. I have got about more than 20 bacteria desulfurizing DBT, benzothiophene, nonbenzo-thiophene, alkylated benzothiophene and methyl-benzothiophene and methyl-DBT with 4S pathways or other pathways. One of the bacteria is thermophilic (under 45-60 centridegrees)to desulfurizing petroleum very well. I am also screening the solvent tolerant strain. I am trying to study on the genomic genes and oxido-reductases of the interesting bacteria. I would also join in your group on Environmental Research to contribute my experience on the enviroment. John P. XU, Ph.D. The State Key Lab of Microbial Technolgy Shandong Universtiy Jinan 250100, PR China Email: pingxu@sdu.edu.cn, 2000/12/31 John Ping XU <pingxu@sdu.edu.cn> Jinan, Shandong PR China - Sun Dec 31 11:58:46 2000 My research interests are human tuberculosis, bovine tuberculosis, siderophores of mycobacteria
http://www.stanford.edu/group/molepi/guestbook.html (1 of 58) [05/01/06 2:27:09]
and pcr diagnosis of mycobacteria Mallikarjuna reddy.M <m.reddy@lycos.com> Hyderabad, Andhrapradesh India - Thu Dec 21 15:46:45 2000 Hi! I am yasir. I am intersted to do some thing for T.B patients, thats why I am keenly interested to my Doc in this research. I have done Mphil(biotechnology).I have experienced all the molecular biology techniques,PCR diagnostics, sequencing,Southern, Northern and westren analysis.Gel documentation and cloning. yasir-ul-Musawar <yasirawan@yahoo.com> faisalabad, punjab Pakistan - Tue Dec 19 16:52:52 2000 Sarcoidosis mycobacterial DNA Gen Probe Ahmet <dr.erbaycu@superonline.com> Izmir, Turkey - Sun Dec 10 21:42:49 2000 working as general manager in a bulk drug manufacturing company. products being manufactured are RIFAMPICIN, ETHAMBUTOL,PYRACINAMIDE,ISONIACIN HYDRAZIDE,. would be interested in new molucules based on anti TB drugs. qualified as M.Sc (research) PhD (by research).looking for assistanceship in development of new molucules.25 years of industrial experience in product identification, development in lab , scaling up to pilot plant and finally to the production stage. waiting for early reply. DR RAJNIKANT VYAS <leenavyas@hotmail.com> mumbai, maharashtrs india - Fri Dec 8 16:13:09 2000 working as a professional librarian in an engineering college. looking for some projects in field of library and information science.qualified masters degree in library and information science.would like to takeup some research projects with academic structures. waiting for the early reply. LEENA R VYAS <leenavyas@hotmail.com> MUMBAI, MAHARASHTRA india - Thu Dec 7 15:43:43 2000 working as a professional librarian in an engineering college. looking for some projects in field of library and information science.qualified masters degree in library and information science.would like to takeup some research projects with academic structures. waiting for the early reply. LEENA R VYAS <leenavyas@hotmail.com> MUMBAI, MAHARASHTRA india - Thu Dec 7 15:42:38 2000 I am Head of Laboratory of Molecular Biology, St.Petersburg Pasteur Institute. I will be happy to be on you mail list. We are providing research in molecular epidemiology of TB by fingerprinting (IS6110-RFLP, spoligotyping and RLBH for searching for the nutations to drug resistance etc.). We have a computer data bank derived by GelCompar including more than 70 RFLPs and many spoligotypes of Russian strains. I am interested to make contacts in the same field with any interested researcher. Olga Narvskaya Olga Narvskaya <onarvskaya@mail.ru>
St.Petersburg, Russia - Mon Dec 4 10:09:27 2000 I am trying to locate the final records of my grandmother who suppose -dly died of Tuberculosis in 1940, somewhere in Northern Illinois. Probably in Adams County, Illinois. I don't know where to look for her records. Her name was Jennie Sue Cookson, nee Bushman, born in 1883. Joseph A. Braun <jbraun636@msn.com> Farmington, Missouri USA - Sun Dec 3 22:53:56 2000 TUBERCULOSIS DIAGNOSIS, tuberculosis serology, epidemiology URSZULA DEMKOW <u.demkow@igichp.edu.pl> WARSAW, POLAND - Fri Dec 1 15:08:10 2000 i have just submitted my thesis. i am interested in the field of tuberculosis immunology especially in the CMI response induce by proteins of M.tuberculosis. and how the macrophages of the contacts of tb patients process antigens differently. i would like information of labs working on this aspect. i amm also interested in proteomic analysis of such proteins which elicited a protective immune rseponse in contacts as compared to the pateints shobhita johari <joharishobhita@hotmail.com> delhi, delhi India - Thu Nov 30 07:36:52 2000 Available schollarships for foreign students in Germany, France, Spain, Portugal, England, Irland, Scotland, and all Southern America. Ekaterina Belotsvetova <M.Kate@g23.relcom.ru> Moscow, Russia - Tue Nov 21 21:09:29 2000 Schollarships for foreign students in Germany, France, Spain, Portugal, England, Irland, Scotland, and all Southern America. Ekaterina Belotsvetova <M.Kate@g23.relcom.ru> Moscow, Russia - Tue Nov 21 21:07:53 2000 Curriculum Vitae Dear Sir/Madam, In reference to the position, I would like to be considered for this position and have provided a CV and a brief list of the techniques I have used during the course of my research. 1- Personal details, TITLE Holding PhD degree in Molecular Microbiology From U.K NAME JAMSHID SURNAME RAHEB DATE OF BIRTH 17 / 3 /1962 PERMANENT ADDRESS 19, Saviz, Ghiasvand, Dampezeshki, (Contact address) Tehran 13416, IRAN WORKE ADDRESS National Research Center for Genetic Engineering and Biotechnology, P. O. Box: 141556343 Tehran, IRAN TEL (HOME) (0098) 21 6039344 (Dr Jamshid Raheb) TEL (WORKE) (0098) 21 6413626 (Dr Jamshid Raheb) FAX (0098) 21 6419834 E-MAIL jamshid@nrcgeb.ac.ir HEALTH no disability ENGLISH LANGUAGE Speaking fluently Listening fluently Reading fluently Writing fluently NATIVE LANGUAGE Azeri & Persian 2- Higher education, Subject Degree From To University Country Molecular PhD 1994 1998 The University U.K. ENGLAND Microbiology of Warwick Bacteriology Ms.C 1987 1991 Tarbiat Modarres IRAN University Microbiology Bs.C 1983 1987 Tehran University IRAN 3-Ph.D thesis For many years physiological,
morphological and particularly molecular studies on gliding bacteria were impossible due to the lack of a suitable technique for the genetic manipulation of this group of bacteria including Flexibacter chinensis. Our study has focused on the physiological and morphological changes in molecular level in this organism during the transition from the exponential to stationary phase of growth, and during long -term stress condition. Our data demonstrate that there is a dramatic change in respiration activity and enzymes during the stationary phase which can not be seen in the exponential phase. Parallel to this bacterial morphology changes with a particularly noticeable size reduction in this usually filamentous bacterium. With the collaboration of Wisconsin University in USA we have developed a method for the molecular study of this group of bacteria. We have constructed two mutants for the genes which produce two novel sigma factors, KatF(sS) and RpoH(s32), and have investigated the effect of these mutants with respect to cell size changes during the transition from growth to starvation conditions and under heat stress. The mutants were unable to change from the filamentous to coccoidal form and consequently were unable to survive stress as effectively as the parental strain which could undergo morphological changes. Our data have demonstrated the importance of cell division in Flexibacter chinensis for the survival of this bacterium under stress conditions. 4- Research work. The Microbial sulfur-specific transformation which selectively desulfurize organic sulfur compounds in fossil fuels, has been identified. We have cloned a 4kb gene locus from Rhodococcus erytheropolis IGTS8 (4S pathway) on a broad host range plasmid with integration ability in chromosome of gram negative bacteria. This organized as one operon with three genes (dszA, dszB and dszC)under the control of single promoter. The dsz gene has been cloned under control of tac promoter in different pseudomonas solvent tolerant species. We have applied an industrial microorganism , with the ability in biological desulfurization. In this way, using molecular and microbiological techniques we successfully constructed a manipulated bacterium with two relevant industrial application, that is biosurfactant production and desulfurization of fossil fuel. Further researches is in progress to find out the influence of the biosurfactants on DBT desulfurization. This is the new alternatives to commercialize the biodesulfurization of crude oil processes. 5- Work experiences I have at least four years experiences in laboratory work in microbiology and molecular microbiology in full time basis. I have learnt many techniques in this time including molecular cloning, DNA sequencing, southern hybridisation, northern hybridisation, two dimentional gel electrophoresis, DNA separation techniques, DNA cloning methods using different vectors including several suicide and other vectors, general microbiology and relevant computer skills. 6- Skills I have had more than four years laboratory experience and have used various techniques involved in the detection, isolation and manipulation of nucleic acids and feel that I could make a significant contribution to your program. I have made contributions to the field of molecular biology of bacteria, due to working with a particularly difficult bacterial strain, Flexibacter, to manipulate using conventional molecular biology techniques. I have learned many techniques in Warwick University in United Kingdom and National Research Center for Genetic Engineering and Biotechnology, including molecular cloning, polymerase chain reaction, DNA sequencing, southern hybridization, northern hybridization, western blots, DNA separation techniques, two-dimensional gel electrophoresis, general microbiology, DNA library, Over-expression of proteins, and computer skills. 7-Resarch interests. Molecular Biology and Microbiology Research. 8- Publication and record Currently three works for publication on the molecular biology and physiology of Flexibacter are being prepared
for publication. 9- Referees 1- Dr S Mahmoud A Najafi ( Ph.D, Assistant Professor). National Research Centre for Genetics Engineering and Biotechnology, P.O. Box 14155-6343 Tehran-IRAN. Tel 00 98-21-4316643. Fax 00 98- 21-6419834 Email najafi@nrcgeb.ac.ir 2- Dr Seyed A Ghorashi ( Ph.D, Assistant Professor). National Research Centre for Genetics Engineering and Biotechnology, P.O. Box 14155-6343 Tehran-IRAN. Tel 00 98-21-7891692. Fax 00 98- 21-7891692 Email alig@nrcgeb.ac.ir 3- Dr Alireza Zomorodipoor ( Ph.D, Assistant Professor). National Research Centre for Genetics Engineering and Biotechnology, P.O. Box 14155-6343 Tehran-IRAN. Tel 00 9821-4429018. Fax 00 98- 21-6419834 Email zomorodi@nrcgeb.ac.ir 4- Dr Bagher Yakhchali ( Ph.D, Assistant Professor). National Research Centre for Genetics Engineering and Biotechnology, P.O. Box 14155-6343 Tehran-IRAN. Tel 00 98-21-3347512. Fax 00 98- 21-6419834 Email byakhcha@nrcgeb.ac.ir 10- Hobbies Sports, music, cinema, and arts. Dr Jamshid Raheb <jamshid@nrcgeb.ac.ir> Tehran, Tehran IRAN - Fri Nov 10 13:00:05 2000 SOS FROM CHINA! My mother was burned by pulmonary tuberculosis, which was controlled goodly for some time. Unfortunetely, the illness rebaddened recently, the tuberculosis ball has formed, said by the doctor, but there is not effective medicine in China that can enter into the tuberculosis ball to kill the bacteria. The only choice it operation, but it may bring some danger to the patient. I am here to ask for a favor that whether there are some effective medicine in US. Your assistance and advice is appreciated. Yong Luo <luoqiyun@hotmail.com> Chongqing, China - Wed Nov 8 23:11:50 2000 I would appreciate any information about collaboration in the field of BCG phylogeny and comparative genomic studies of BCG Vaccines. Thank you in advance! Tzvetelina Stefanova <tzvetelina_dimkova@hotmail.com> Sofia, Bulgaria - Tue Oct 31 07:57:34 2000 I'm a market analyst. My interest is to keep informed of the latest medical research on TB. Ms. Homa Christensen <homac@vhinc.com> Valencia, CA U.S.A. - Mon Oct 30 22:36:39 2000 THIS SITE ROTTS! I DON'T LIKE IT MAN!!!!! BUILD A NEW ONE YOU FESTY POO!!! Sorry, It's actually quite good!!!!@@@@ Man! Nar CHo <lilgodfatherau@yahoo.com> With only 2 people, This One Jamaica - Mon Oct 16 23:12:52 2000 Information on Mycobacteria Fortuitum Nancy Wagoner Watsonville, CA US - Sun Oct 15 19:57:47 2000 i am a fresh post-graduate , done my M.Sc.(microbiology). i am interested in doing research in my field & especially medical or applied microbiology.so please , do contact me at my e-mail if you
have any information. At present i'm working with a reputed pharmaceutical co. in my own city as a sr. microbiologist.my future plans are to go for research. PINKAL DIWAN <pinnacle@netwala.com> ahmedabad, gujarat india - Sun Oct 15 13:47:20 2000 information on Muti-drug resistant Tuberculosis.(Especially India,and to be more specific Karnataka,India) vidya <vidyasundareshan@yahoo.com> - Sun Oct 15 01:45:15 2000 I am interested in speaking with anyone who has information about the former Mt. Kipp sanitorium located in Glen Gardner, New Jersey. I am writing a research paper on the institution and how its role has changed. Karin Gruss <nirakg@yahoo.com> - Sat Oct 14 21:37:43 2000 Film research: writer needs accounts of patients, doctors, nurses, admin. workers associated with tb sanitoriums in 1940s-50s. Also those involved with tb screening of US public schools. Many thanks, patriciaroberts@home.com patricia roberts <patriciaroberts@home.com> toronto, ontario canada - Wed Oct 11 15:45:55 2000 Interested in it 2 much ! savita chauhan <chausavi@rediffmail.com> Indore, MP INDIA - Tue Oct 10 17:42:14 2000 My department is advising the Swiss government on various international health issues. A recent topic of concern and interest is the tuberculosis in penitentiary centers in countries of the former Eastern Block and possibilities to control it. Nicolaus Lorenz MD, MSc Head of Department Swiss Tropical Institute Swiss Centre for International Health Socinstrasse 57 P.O. Box CH-4002 Basel/Switzerland Tel. +41 61 284 8 125 Fax + 41 61 271 86 54 http://www.sti.unibas.ch/scih/scih.htm Dr. Nicolaus Lorenz <nicolaus.lorenz@unibas.ch> Basel, Switzerland - Wed Oct 4 12:23:00 2000 My theory is proven correct. One of my relatives complained of back pain. We thought maybe it was muscle strain. We went to the doctor for a check up. After the check up she was given a medicine which is for TB. Aha! So I asked my relative. Have you been lacking sleep. She said yes. She said she was working a lot. Could not get much sleep because of a lot of worries. She does get enough rest and sleep she says. But there is a difference between a genuine rest and sleep and just closing your eyes and pretending to be asleep. When you worry don't do it while you are resting. Start worrying once you wake up. When you rest, just free your mind of worries. And just concentrate on sleeping. They said she was coughing and her back really hurts.She even skipped
one day of work because of it. So I told her that her lungs are strained. And that she should let it expand. I told her about the "Ulcer Theory". And the next day she was working already. Had I not told her about the "Ulcer Theory" she would be in a hospital coughing blood already. And now she's fine. Norman Greg <Pehpot@yahoo.com> CA U.S.A. - Wed Sep 27 23:20:04 2000 Hello everybody, I shall highly appreciate if you send me detailed information on PCR based diagnosis of TB and MDR-TB.I shall be happy to receive the details about the PCR protocols, primer designs and information regarding detection kits and their reference. Thank you Dr Nilanjan Das <dasnilanjan@hotmail.com> Calcutta, West Bengal India - Wed Sep 27 18:47:45 2000 I have been working in the medical research center in Russia (Novosibirsk State medical University).We are developing the project about dependence with hypertermia (temperature increase) and pulmonary tuberculosis. I would highly appreciate if somebody could provide me the information about it.(do you have an experience to treat a people with this type of treatment, what kind of results were achieved) Or may be you know where can i find this information. I hope that there is the possibility of fruitful cooperation. seeler@mail.ru Elena <seeler@mail.ru> Novosibirsk, RU Russia - Sat Sep 16 13:44:28 2000 I am presently researching on the history and statistics of tuberculosis. Hope you'll help me to accomlish this research through giving addresss that are relevant to my research. Thanks bernard <blue_svo@yahoo.com> manila, philippines - Wed Sep 13 02:18:44 2000 Mycobacterium bovis ADN isolation in milk. PCR Cristian Leiva <mfleiva@yahoo.com> Santa Fe, Santa Fe Argentina - Fri Sep 8 21:07:03 2000 Tuberculosis-Diagnosis-serology Tsigeweini Asgedom <Tsigeweini.Asgedom@cih.uib.no> Bergen, Bergen Norway - Fri Sep 8 13:46:20 2000 Seeking for Co-operation and Support -----a specific remedy for tuberculosis Now, a specific tuberculosis remedy, which belongs to Traditional Chinese Medicine has been discovered. It's named " Jiupin Baoling Pellet". According to the results of observation from more than 1,000 cases, this remedy has outstanding result in treating pulmonary tuberculosis, tuberculosis of lymph nodes and bone tuberculosis. The curative rate may reach over 85%. This completely natural remedy is adapted to pharmacopeia compatibility clo9sely. The intranasal usage enables the effectiveconstituents exchange with qi and blood in lungs. According to Traditional Chinese Medicine theory, tuberculosis is caused by infection of " certain worm ". People are attacked by
this worm at the state of deficiency of vital- qi and blood. Pulmonary tuberculosis occurred when the worm existed in lungs. If the worm reached bone marrow from the blood circulation, bone tuberculosis and tuberculosis of lymph node would form. Among the constituents of this pellet, secretio bufonis has the functions of detoxification, analgesis, inducing insuscitationa and treating the toxifying disease with poisonous agents: Unbelliferae can promote blood circulation to stop pain and tonify the blood. If the course lasted too long, this chronic disease may demage qi and blood, even cause stagnancy of qi and blood stasis. Deficiency of qi may prevent the folw of blood, and deficiency of blood may do harm to channedl and collaterals. The symptoms of blood stasis and stagnation of qi can be relieved by the use of umbelliferae in the remedy. Another component --horner nest can be used for eliminating wind and toxic material, stopping pain and even killing the worm. Because of the cause of disease mentioned above, the use of hornet nest can achieve expected results. With the rich clinical practice and hard research, the use of the components is efficient, and the results are satisfied. According to outside body experience, the tuberculomyces which have drug resistance to anti- tuberculosis drugs are sensitive to the remedy. In clinical use obvilus results of treatment have been achieved especially for the patients with long lasting tuberculosis. All right reserved by ZhaoDong. Any co-operations in research, development, investment and sale are welcome. ZhaoDong <dhc0@21cn.com> - Fri Sep 8 13:08:53 2000 i'm reserching for the case of ashtma it's a disease that can kill and no one has found a cure for it yet i have ben reserchen about it for over 18 years and still have not found the closes to it i have the disease my self and believe me i have allmost died of it alot of times i would like to find something that is close to it so i my self can have a good life to just like other people too. so if any one out there can give me some pointers i would sped it where everyone will know that you have gave me infor. and you will be in that book that i write about this killer disease and god will thatnk you too. i know i would; thank you again; ms. june;; june lopez <lopezjune@hotmail.com> houston, tex. 77020 usa - Fri Sep 1 17:26:32 2000 Dine in or take out? Shang-hai Chef <shrmpflavor@mailcity.net> - Tue Aug 29 08:11:09 2000 lady doctors are invited to have sex with andhra doctor suresh <mysexmail@rediffmail.com> - Thu Aug 17 19:23:09 2000 Hi there!. I would like to know about tuberculosis diagnosis and antigen immunogenicity evaluation, collaboration programs between institutions and MSc and PhD schollarships. Jorge Luis Gonzalez Quintana <jlgonzalez@finlay.edu.cu> Havana, Cuba - Thu Aug 17 18:45:44 2000
Deteriorating liver. Tom Crowley <TomCrowley13@aol.com> Shelby Twerp, MI USA - Wed Aug 16 04:56:44 2000 i am originally from bangladesh.i,Dr.md.nazmul haque, doing ph.d in microbiology from dhaka university.i have strong interest in doing reseach in microbiology.for that iwantjoin in ph.d programme in usa.are there any scholorship or assistanceship for me.pleasesend me the response as soon as possible. dr.md nazmul haque <rokeya@technohaven.com> dhaka, bangladesh bangladesh - Sun Aug 13 06:45:50 2000 I am interested in the application of bioinformatics on studying the virulence genes of M. tuberculosis. My mailing address: School of Graduate Studies Mapua Institute of Technology Intramuros, Manila 1002 Philippines Bonifacio T. Doma,Jr. <bonidoma@hotmail.com> - Sat Aug 12 16:20:14 2000 cool! Jango <Jango@office.com> - Fri Aug 11 10:49:52 2000 am a respiratory therapist..i have a case study report this tuesday about pleural effusion and pulmonary edema and am having a hard time finding patient data,history etc.. please HELP! JAE RRT jae <jae718@yahoo.com> manila, manila phillipnes - Sat Aug 5 06:27:36 2000 I have a sister who is a doctor, in her practice with patients with Tuberculosis she got the Potts disease; I want to known a Medical Center in the Conus of U.S. which can help us to treat her as aid for foreign patient with this disease; any help is welcome. Enrique A. Posada <fam.posada@navegante.com.sv> N.Cuscatlan, La Libertad El Salavdor - Tue Aug 1 04:32:09 2000 I am doing research in production and quatitative techniques in india and Looking for any additional scholarships/sponserships by organisations to carry out studies.If U know any of the organisations pls inform me.Thanks jha T.K <tarun_kumar_jha@hotmail.com> Ahmedabad, Gujrat india - Mon Jul 31 18:41:34 2000 I am doing research in production and quatitative techniques in india and Looking for any additional scholarships/sponserships by organisations to carry out studies.If U know any of the organisations pls inform me.Thanks jha T.K <tarun_kumar_jha>
ahmedabad, gujrat india - Mon Jul 31 18:36:07 2000 genome project is my intrest,reply if any contacts.thank you! gokul <grtosh123@rediffmail.com> mysore, karnataka india - Thu Jul 27 16:00:56 2000 Great Site! PageCrafters.net <sbt2@sendfree.com> - Wed Jul 26 22:15:19 2000 AFLP/cDNA AFLP, mycobacterial functional genomics Dr Niyaz Ahmed <niyaz@www.cdfd.org.in> Hyderabad, AP India - Tue Jul 25 12:25:11 2000 Dear Sir, I am director of PPD providing in IRAN.I would be very pleased if I be in your mailling list and have an opportunity to take higher education. Bye. With Best Wishes. Dr. Nader Mosavari Nader Mosavari <nmosavari@rvsri.com> Karaj, Tehran Iran - Tue Jul 25 06:41:07 2000 I am a medical graduate,presently working as a medical officer in a Govt. hospital in Pakistan.I have also done post graduate training in Tuberculosis.Iwant to do post graduate diploma/ degree in EPIDIMIOLOGY from Australia.Iwill be thankful if any body can guide me about this.I am also interested in any information regarding financial assistance/scholarships offered by the Australian universities/institutions.I have IMMIGRATION VISA for Australia. Dr.Shazia Shaukat <crunchy_chocolate@yahoo.co.uk> Karachi, Sindh Pakistan - Mon Jul 24 13:31:51 2000 analyzing, designing, installment and teaching of the analog circuit and the digital circuit; Digital imaging processingpattern recognition for developing the software in C, assemble language Bao Susu <baosusu@scnu.edu.cn> Guangzhou, Guangdong P.R.China - Mon Jul 24 13:24:09 2000 Healthy nutrition is important also. Ryan Mills - Mon Jul 17 07:16:44 2000 As I have read in one web page as a result of my web search. I can only wonder why it would need a person to spend eight hours a day for six months or 24 hours a day for 2 months before he or she gets infected with TB. I call it duplicating habits. It's when u acquire a persons habits. "TB is an ulcer". An ulcer of the lungs. If u think u have TB, get plenty of rest and sleep. And relax ur body. The less movement the better. Until you recover. "Getting enough rest and sleep expands the lungs". Preventing it from shrinking or tightening up due to fatigue or lack of sleep. Shrinking or tightening up of the lungs could cause one to spew blood. It's like twisting a wet towelette. Let ur
lungs expand. Don't stress ur lungs out. Mark Polido <markpolido@yahoo.com> Manila, Philippines - Wed Jul 12 08:38:47 2000 I'm looking for a current phylogenetic tree of Mycobacteria, as complete as possible, as well as a bit of information on each species- whether or not it is free-living, and whether or not it has any horizontal gene transfer. Any leads would be most appreciated. Thanks. Hunter Fraser <hunter@mit.edu> - Tue Jul 11 17:56:22 2000 Please check also my message on the message board. And don't forget to e-mail me. Thanks. Ryan Mills <ten_f0ur@email.com> Los Angeles, CA USA - Sun Jul 9 08:14:17 2000 Good air ventilation, a quiet surrounding and plenty of rest and sleep could cure TB. Pressures of day to day life, not getting enough sleep and getting up early in the morning combined with an over fatigued and tired body could lead to TB. Our lungs like our muscles could get over worked. To the point that it's grinding itself. That it wants to spew blood. Children who lack sleep because of the pressures of school could get TB. That is why the virue can't be cured by madicine. Because it is not a virus and you don't need medicine to cure it. Maybe a drug or medicine to make the patient calm and relaxed to have plenty of rest and sleep might help. E-mail me and let me know if I have a point or not. The name I use is not my real name. Thanks Ryan Mills <ten_f0ur@email.com> Los Angeles, CA USA - Sun Jul 9 08:00:17 2000 Fixed dose combinations of antitubercular drugs, Bioequivalence of FDCs Pavankumar M. Sancheti <pavansancheti@usa.net> Chandigarh, Punjab India - Fri Jul 7 13:45:21 2000 In my research, I try to indentify the Mycobacterium Tuberculosis species by using phagemediated antibody library technology. At this moment, I got trouble to coat M.TB( fixed by Formalin) to the ployabsorb ELISA plates. When I got M.TB. samples from my patron, the cells clamped together very tightly and the sonication was useless to the clamps. Expert said that the glass surface was better that plastics. Can I get some information about people do ELISA with M.TB.? Thank you! Kezhi Dai <dkz2000@excite.com> Hull, East Yorkshire U.K. - Wed Jul 5 11:00:08 2000 I am looking for accounts/stories from people who spent time in tb sanitariums during the 1940 and early 1950's. Any ideas on where to look? missgreer2u@yahoo.com Julie Greer <missgreer2u@yahoo.com> - Thu Jun 29 02:12:51 2000
What is the % composition of mycobacteria in the environment? Is it essential to obtain LICENCE for working in TB BACILLI ? Working in ecology of MYCOBACTERIUM in aquaculture ponds. chandrika senior scientist,CMFRI, COCHIN INDIA DR .V. Chandrika <anu73@md4.vsnl.net.in> Cochin ,682014, Kerala INDIA - Tue Jun 20 18:53:54 2000 I need information about History of Tuberculosisi in India . Web addresses will be helpful. Dr. Irene Churruca <irenechu@teleline.es> Barcelona , Barcelona Spain - Tue Jun 20 14:17:13 2000 hi! i am reshma. i am studing in mithibai collage. i am in 2nd year of microbiology. i want to do genetic. actually, i don't know that it is possible after TYBsc or after postgraduation. please tell me university in maharastra, other requirements for genetics. please help me . reshma <reshma104@yahoo.com> bombay, maharastra india - Thu Jun 15 15:48:47 2000 I'm doing a paper on Tuberculosis, the history and how it began the "1health century" at the beginning of the 21st century. If you have any information regarding any of these please send it to me. Rebecca <s.spears@usa.com> New Hampshire United States - Wed Jun 14 17:39:54 2000 I'm doing a paper on Tuberculosis being the beginning of the health century, any information I can get would be very helpful. Rebecca <s.spears@usa.com> Wilton, New Hampshire United States - Wed Jun 14 17:31:57 2000 i am doing a paper on Tuberculosis especially in the bones and articulations. Any information would be helpful alex s. <enemeno@hotmail.com> Cali, Valle del Cauca Colombia - Tue Jun 6 22:27:00 2000 i am doing a paper on Tuberculosis especially in the bones and articulations. Any information would be helpful alex s. Cali, Valle del Cauca Colombia - Tue Jun 6 22:26:35 2000 I am a student at UCLA and I was infected with TB about a year ago. I am now trying to do a reseach paper on TB and I would really appreciate it if you could send me some information about how TB started, what it is , and how to prevent and cure it. Meital Amir <OOgigi> santa monica , California - Sat May 20 17:47:52 2000
Mycobacteria culture and sensitivity DR. SATADAL DAS <drsatdas@hotmail.com> - Sat May 20 14:08:48 2000 DNA microarrays in TB research, Proteomics in TB research, Malaria Research. Susmith Mukund <susmith@icgeb.res.in> New Delhi, New Delhi India - Fri May 19 17:37:22 2000 As an internist I am interested in the incidence of atypical mycobacterium as the causal agent of multiorgan extrapulmonary manifestation such peripheral lymphadenitis or pleural effusion, which is difficult to differentiate from mycobacterium tuberculosis complex. I hope some of you could share your experience on using current method to diagnose it such as molecular analysis (PCR and sequensing) or immunologic method. Thank you. Zul Dahlan <zuldhln@bdg.centrin.net.id> Bandung, Indonesia - Wed May 17 03:42:19 2000 As an internist I am interested in the report of atypical mycobacterium as the causal agent for extrapulmonary manifestation such as peripheral lymphadenitis or pleural effusion, which is difficult to differentiate from mycobacterium tuberculosis complex. I hope some of you can share your experience on how to diagnose in by current method such as molecular analysis or immunologic method. Thanks. Zuldahlan <zuldhln@bdg.centrin.net.id> Bandung, Indonesia - Wed May 17 03:29:34 2000 Hey can you please send some names of some hospitals that help only in the healing of TB, I need a list of hospitals for my Health class. Thank you very much, if you can email me back by April 27th. luv to all. Holly <Rbros@sigecom.NET> Evansville, Indiana USA - Thu Apr 27 04:04:50 2000 Just passing through...very interesting site - I'll be back. Best wishes, Sheila Digital-Price - Furniture Boston, MA United States - Tue Apr 25 18:45:59 2000 This is a very nice place ! Protector 1uno <spavle@nightmail.com> Gospic, Li Croatia - Thu Apr 20 07:35:12 2000 I would like to be on your mailing list. I am head of TB Research,BLUE PETER RESEARCH CENTER,Cherlapally,Hyd,501 301,A.P.,INDIA. My areas of research are Drug Resistance in M.tuberculosis,By culture and molecular techniques. Dr.Suhail Naser. <lepind@hd1.vsnl.net.in> HYDERABAD, A.P. INDIA. - Sat Apr 15 07:06:15 2000
I have just got into my internship(S.N.Medical College,agra).please send me information regarding miliary tuberculosis. Nupur Pruthi <nupurpruthi@yahoo.com> agra, U.P INDIA - Fri Apr 14 09:21:15 2000 I am originally from Turkey and very much interested to do any kind of research related with tbc. I am an M.D. and prefer clinical or epidemiological researches. Sukran Timbil <sukranti@yahoo.com> Athens, GA USA - Mon Apr 10 22:20:33 2000 diagnosis multidrug resistence fingerprintings Maria Noel Cortinas <manoel@fcien.edu.uy> Montevideo, Uruguay - Mon Apr 10 21:12:18 2000 Pseudomonas aeruginosa , Imipenem and Ceftazidime(solvent,diluent,storage,...), MIC(minimum inhibitory concentration) , M. A. Rezai <ahanga_m@net1cs.modares.ac.ir> Tehran, Tehran Iran - Mon Apr 10 09:02:03 2000 A recent breakout, this week, of TB has just happened in our community Jr. High. With a possible infection of 200 - 250 kids I want to know in laymen's terms what TB is about, how it starts, it's infectious rate, symptoms and incubation periods. This is a prime concern in our community right now. Has a lot of parents scared, their children are being tested by school. Is this typically a good thing to test so many students in such a short amount of time? Are the tests effective and what treatments are available in the US? Thank you. Mrs.Melanie Davis <melanie_davis@yahoo.com> Hillsboro , OR USA - Tue Mar 28 08:34:17 2000 I have been looking for information on my paper due this Tuesday... This webpage was a great place to look for info. I am a 6th grade student and Science is a great intrest of mine. Thanks alot this webpage helped so much Clay Dallas <HAWKSCTC140@Home.com> Dallas, Texas USA - Thu Mar 23 02:10:18 2000 I'm looking for a sanitorium in Franklin County or somewhere around there called "Savilisville Sanitorium" in the 1940's. Of course, it has been closed down for years. I'm loking for ANY information what so ever. Thanks, Vicki G. Vicki Gladfelter <Vickigladfelter@yahoo.com> - Tue Mar 21 14:37:40 2000 send me addresses of women's/girls of South Delhi(India) based who are interested having sex at any time. Thanks, Jassi
Arvind Jassi <jassi_110066@yahoo.com> New Delhi(South), Delhi India - Wed Mar 15 08:30:48 2000 send me addresses of women's/girls who are interested having sex at any time. Thanks, Jassi Arvind Jassi <jassi_110066@yahoo.com> New Delhi(South), Delhi India - Wed Mar 15 08:29:16 2000 I am highly interested on the research been done on M. bovis. Molecular biology, gene expression adn diagnosis. ana maria zarraga <azarraga@uach.cl> valdivia, chile - Tue Mar 14 01:11:26 2000 Please send me info on tb asap, thanks. scotty mcdonald <autofinders@msn.com> lincoln, NE USA - Tue Mar 14 00:17:29 2000 please place me on the mailing list, thanks. Todd Weisse <tweisse@bhc.org> New York, NY USA - Thu Mar 9 18:49:13 2000 Mycabacteria-macrophage interaction Signal Transduction Dormancy in mycobacteria Sadhana Majumdar <sadhana_77054@yahoo.com> Houston, Texas USA - Mon Mar 6 19:39:27 2000 Can some one please tell me of a good web site where i can find out about Teberculosis. I am from Scotland and a family member of my boy friend here has it. PLease suggest a web site for me! Thank you Clara <heeps_2000@yahoo.com> Amsterdam, Netherlands Holland - Wed Feb 23 12:35:35 2000 Yeah! Tuberculosis is fucking cool! Yeah! Yeah! Elan Gerzon <assdoctor69@aol.com> california, usa globe - Mon Feb 14 18:32:09 2000 I'm a high school student doing some reasearch on antibiotic resistance for my senior Bio class. Any suggestions? Andi G <shambala@maytheforcebewithyou.co.uk> - Fri Feb 11 22:26:51 2000 Hi, biological research has always been of great interest to me. I am especially interested in how bilogical pathogens effect cultural patterns. I have a B.A. from Binghamton University (S.U.N.Y) in theAnthropological Sciences... I am currently pursuing a second B.A. in Biology...Please contact me if you have any research availability in the New York City area. Thank You, Ian C. Lord
Ian C Lord <Ianclord@hotmail.com> Queens, NY US - Sun Feb 6 01:11:25 2000 clinical aspects sandeep saluja <drsaluja@hotmail.com> new delhi, DELHI india - Sat Feb 5 23:46:10 2000 I'm a graduate of B.S. Medical Technology of Far Eastern Unversity-NRMF, working at De La Salle Medical Center HSC-A. King Research Center-TB Reseach Laboratory Level II. I'm a Tubercologist, my work is purely concentrated on TB identification, culture and sensitivity, and we are working out procedures in preventing the spread of it.PTB is not a JOKE!. Eric Matthew S. J. Dela Cruz, B.S.MT, RMT <ericmatthew@usa.net> Imus, Cavite Philippines - Fri Feb 4 10:31:47 2000 A research about serum A.D.Alevel in pulmonary T.B.If you have iny interest or idea please contact. Dr.HAKIM <anooshi@whatmail.com> TEHRAN, IRAN - Wed Feb 2 22:06:17 2000 vaccines against tuberculosis, improved Mycobacterium bovis BCG, Salmonella spp. as recombinant antigen delivery device Juergen Hess <hess@mpiib-berlin.mpg.de> Berlin, Germany - Tue Feb 1 13:09:39 2000 I am a highschool student interested in holistic medical research and development for a future profession and I am looking for any suggestions to any colleges dealing with this field, Suggestions?? Lindsey Nero <Kacey26@Worldnet.Att.net> Mt.Holly, NJ USA - Fri Jan 28 21:27:35 2000 I'm a graduate student and would like to obtain new full text articles on Mycobacteriophage. Wendell O. Junia <wenesis@hotmail.com> Manila, Philippines - Fri Jan 28 11:08:47 2000 Email me with info about Tuberculosis. Shauna <Stargirl_8@yahoo.com> Texas USA - Tue Jan 25 22:31:58 2000 I'm a Medical Resident and I'm making a paper on the Incidence of Lung Ca in patients presenting as PTB. I've seen a # of patients who have been treated as PTB but on biopsy or pleural fluid studies showed CA. Joseph E. Poblacion, MD <jopobsmd1@hotmail.com> Cebu City, Philippines - Sun Jan 9 06:18:54 2000
We are interested in molecular characterization and drug sensitivity of Mtb strains. Also, serodiagnosis of infection by Mtb is of our interest. Angel Gustavo GUEVARA PhD <labinves@hcjb.org.ec> Quito, Pichincha Ecuador - Wed Dec 22 16:05:23 1999 TB.Microbiology $ Epidemiology Mir.Mohammad Ziaei <mmziaei@hotmail.com> Tabriz, East Azerbaijan Iran - Mon Dec 13 19:54:18 1999 HIV-TB, cytokines in TB, controlled clinical trials in tuberculosis Soumya Swaminathan <mahadevi90@yahoo.com> Chennai, Tamilnadu India - Sun Dec 12 16:30:30 1999 effects on body, treatments, symptoms Rachel Wilford <peaches31484@yahoo.com> Millsboro, DE USA - Tue Dec 7 22:59:35 1999 effects on body, treatments, symptoms Rachel Wilford <peaches31484@yahoo.com> Millsboro, DE USA - Tue Dec 7 22:59:21 1999 effects on body treatments symptoms Rachel Wilford <peaches31484@yahoo.com> Millsboro, DE USA - Tue Dec 7 22:58:06 1999 Too big of words. I don't understand it. Please use smaller words, or maybe hyperlinks to the definations of big words. Thank you. tammi Tammy <sporkypunk@aol.com> Bremerton, WA USA - Sat Nov 27 21:44:55 1999 I am a student completely fascinated with molecular biology and genetics. I have performed research on transgenic mice in embryonic develpoment at the EIB/NCI/NIH, the most incredible experience I have gained yet. My interests mainly include the following: the human genome research project, cancer research, and anything affiliated with genetics. Leana Movsessian <HyeLeana@aol.com> Germantown, Maryland USA - Mon Nov 22 20:26:03 1999 I am a student completely fascinated with molecular biology and genetics. I have performed research on transgenic mice to decode all genes coding for embryonic develpoment and the EIB/NCI/NIH. My interests mainly include the following: the human genome research project, cancer research, and anything affiliated with genetics. Leana Movsessian <HyeLeana@aol.com>
Germantown, Maryland USA - Mon Nov 22 20:25:06 1999 Genetics, Molecular biology, research in cancer cells, human genome project, etc Leana Movsessian <HyeLeana@aol.com> Germantown, Marylan USA - Mon Nov 22 20:22:18 1999 I'm italian. I'm going to finish my PhD at the end of 1999. The subject of my thesis is: Tuberculosis in human fetal brain: microglia infection with M. tuberculosis and different strains of M. avium. I studied mycobacterial effects on microglia cell cultures (cytokines expression and production, chemokines expression) I'm looking for a post-doc in California to study tuberculosis. I have a strong background in immunocytochemistry, human fetal neurons cell cultures. If you have any ongoing projects in this area please contact me. Monica Curto <curto@vaxca1.unica.it> - Mon Nov 1 08:14:14 1999 I am a Masters student (history) at San Diego State researching the social effects of Tuberculosis in Mexico and the border region. Any help is appreciated. Christine Moore <cmoore@aznet.net> Oceanside, Ca USA - Thu Oct 28 16:08:46 1999 i am carrying my research studies at masters level in computer assisted molecular modelling.my main topic is tuberculosis and isoniazed..i will be thankful to any of my friend who give information to me. khawaja sohail qamar <sohailqamar@yahoo.com> penang, penang malaysia - Tue Oct 26 01:36:56 1999 i am carrying my research studies at masters level in computer assisted molecular modelling.my main topic is tuberculosis and isoniazed.. khawaja sohail qamar <sohailqamar@yahoo.com> penang, penang malaysia - Tue Oct 26 01:25:17 1999 Elisa in diagnosis of primary tuberculosis in children Sero Diagnosis of primary tuberculosis in Children using 38KDA and 16 KDA Pathozyme TB complex in diagnosis of tuberculosis in children Fred Castro <fredcastro@vasia.com> Makati, Philippines - Sun Oct 24 14:02:20 1999 Databases Statistics Data Mining Meta Data Epidemiology Geography Don Van Dyke <merdvd@meridian-software.com> Raleigh, NC USA - Wed Oct 20 18:08:50 1999 Another TB positive person. Have been told never, repeat never, to get another TB test again. As far as I know, I have no symptoms. Have been positive for 30+ years. Just sharing this with you.
Agnes Truske <atruske@salud.unm.edu> Albuquerque , NM USA - Wed Oct 13 19:54:00 1999 I am doing a cell projest on Tuberculosis Rebecca Galloway <g127@alltel.net> Sanford, North Carolina Lee - Mon Oct 11 21:55:21 1999 secreted proteins from M.tb for vaccination mao huaxong <mbx@pub.sdnet.gd.cn> Guangzhou, Guangdong china - Sun Oct 10 08:05:13 1999 I am a Medical doctor with a Master's degree in Biostatistics. I'm interested in current research on multidrug resistance and current evaluation of the DOTS programme. Dr Alexander Quarshie <quarshiea@hotmail.com> - Thu Oct 7 22:39:44 1999 I am a Medica doctor with a Master's degree in Biostatistics. I'm interested in current research on multidrug resistance and current evaluation of the DOTS programme. Dr Alexander Quarshie <qurshiea@hotmail.com> - Thu Oct 7 22:38:43 1999 I am doing this for a science extra credit project. Connie Gillaspie <bball84@hotmail.com> Midland, SD USA - Wed Oct 6 13:35:13 1999 I am a student conducting research on the controlling of TB. Although I have only begun my research, I will be conducting and submitting information regarding the testing of a particular drug and its derivatives. Any information about TB research is greatly appreciated as I am just getting started. Amber Garcia <a_garcia@po.bethanywv.edu> Bethany, WV USA - Tue Oct 5 00:32:22 1999 I hold Ph.D. degree in Vet.Public Hlth from U.K. I am an assiss.Prof. at dep. Microbiol., Col. Vet. Med. Baghdad previousely, now am looking for a job in Jordan. I used to supervise many M.Sc. and Ph.D. research projects and I worked on many types of Bacteria, mainly Campylobacter, Salmonella, Moraxella, S.aureus, Streptococci ( esp. Enterococci), Pasteurella, E.coli, Klebsiella and I was always interested to work on T.B. because it is widely distributed in our country and in many other countries, and more important, my wife was suffering from bone T.B. and is being treated since February 1999, until and her condition improved quite well on an intensive course of INH-Ethambutol-Rifampicin. I used to work in a private human clinical lab. and I was extremely efficient in preparing acid-fast smears and I did some improvements on the routine methods under use by most laboratories. I shall be very glad to keep in continuous touch with you. Thank you. Dr. Amir S. Rahim Al-Obaidi <wave-gang@usa.net>
Amman none, none Jordan - Sun Oct 3 17:29:59 1999 I am a pulmonary physician working in the Centre for Tuberculosis &Chest Diseases since 1990.I hold two diplomas in Tubercular &Chest Diseases from Pakistan.My spheres of interest are MULTIDRUG RESISTANCE IN TB,SERODIAGNOSIS OF TB AND REVIEWING THE EFFICACY OF BCG VACCINE.Iam particularly distressed at the re emergence of this great killer disease and needs a global effort to combat this trend.Iwould be indebted if I am in anyway able to contribute towards the research in TB.Iwelcome anyone with similiar concern to get in touch with me. DR. SYED FASIHUDDIN <sfasih@awalnet.net.sa> MAKKAH, SAUDI ARABIA - Sun Oct 3 10:24:22 1999 I am a pulmonary physician working in the Centre for Tuberculosis &Chest Diseases since 1990.I hold two diplomas in Tubercular &Chest Diseases from Pakistan.My spheres of interest are MULTIDRUG RESISTANCE IN TB,SERODIAGNOSIS OF TB AND REVIEWING THE EFFICACY OF BCG VACCINE.Iam particularly distressed at the re emergence of this great killer disease and needs a global effort to combat this trend.Iwould be indebted if I am in anyway able to contribute towards the research in TB.Iwelcome anyone with similiar cocern to get in touch with me. DR. SYED FASIHUDDIN <sfasih@awalnet.net.sa> MAKKAH, SAUDI ARABIA - Sun Oct 3 10:19:04 1999 What is tuberculosis. Lori Palmer <lp3acres@earthlink.net> Doswell, VA USA - Fri Oct 1 13:20:42 1999 Epidemiology Jill Mengel <JL_Mengel@acad.fandm.edu> Lancaster, PA Lancaster - Thu Sep 30 01:24:08 1999 know someone with tb Melissa <sycodream@aol.com> Pa 17011 - Wed Sep 29 22:44:39 1999 Sanatoria in Davos, Switzerland, c. 1930-1945; the work of Dr Gustav Maurer William Lee <wlee77@aol.com> Vancouver, Washington USA - Wed Sep 22 06:28:49 1999 I would like if I can receive some posters I can use for Health education. Boubker Naouri <Boubker_Naouri@doh.state.fl.us> Kissimmee, Fl USA - Fri Sep 17 19:15:57 1999 mycobacteria, membrane proteins, detergent soluble and water soluble ones, molecular biology
Anjana Gupta <mrinku@hotmail.com> New Delhi India - Fri Sep 17 04:17:48 1999 Mycobacteria, BCG , membrane proteins, detergent soluble ones, molecular biology Anjana Gupta <rinkum@hotmail.com> new delhi india - Thu Sep 16 04:25:41 1999 iam doing my MS in Computer Science.and iam very much interested in Medicine. naveenkota <naveenkota@hotmail.com> MORGANTOWN, WV USA - Thu Sep 9 13:38:40 1999 test test - Mon Aug 30 19:11:37 1999 Dear sir, Here I attached a personal resume to apply for a post doctor research in new drug research and development.I hope you will read it carefully and reply me. your sincerely, Jie Yang JIe Yang <tbrg@public.km.yn.cn> kunming, yunnan P. R. China - Mon Jul 26 02:38:13 PDT 1999 I am a graduate student working on " Synthesis of cell wall fragments of Mycobacterium tuberculosis" at National Chemical Laboratory, PUNE. I would appreciate any information regarding the synthesis of cell wall fragments or developement of new drugs based on the inhibition of arabinan biosynthesis. My contact addresss: Srinivas Hotha, Senior Research Fellow, Organic Chemistry:Technology, Pune - 411 008, India; e-mail:shotha@hotmail.com Srinivas <shotha@hotmail.com> PUNE, Maharashtra INDIA - Fri Jul 23 08:13:13 PDT 1999 Drugs Resistance. Guillermo A. Paredes <gapmd@ix.netcom.com> Martinez, CA USA - Tue Jul 20 21:30:12 PDT 1999 Interest: Social History of Tuberculosis in Australia; specifics re people who came to colonial Australia 'for their health', i,.e. the cure for 'consumption'. Lois Baglin <baglin@alphalink.com.au> East Brighton, Victoria Australia - Mon Jul 19 22:08:36 PDT 1999 Extrapulmonary tuberculosis Anna Marie G. Pato <docanna@cebu.pw.net.ph> Cebu, Cebu Philippines - Fri Jul 16 06:19:17 PDT 1999 I'm a surgical resident and is interested in the management of extrapulmonary tuberculosis, since we still have a high incidence of tb in our country we still see and treat patients with
extrapulmonary tb. Jose Roy Z. Gregorio, M.D. <joeygmaninistis@yahoo.com> Quezon City, Philippines - Sat Jul 3 01:00:28 PDT 1999 I have a bachelor's degree (honors) in Molecular, Cellular, and Developmental Biology and will be studying infectious diseases as a graduate student. I would like to volunteer either in clinical or laboratory environments - I have experience in both areas. Please contact me if you would like assistance and are located in the SF area. Kiersten Israel-Ballard <kiersten_ballard@hotmail.com> Santa Cruz, CA USA - Tue Jun 29 21:28:37 PDT 1999 I want to volunteer in your research project. I am a medical doctor and already had one year clinical experience (internship in Internal medicine at New York Hospital ).Want to volunteer while waiting for residency.I hope to hear from you soon. Roeliza Ebbah-Pascua <roelizapascua@hotmail.com> San Jose, California - Tue Jun 29 09:58:07 PDT 1999 Tuberculosis and Patient's Compliance/Treatment Partners (DOTS) DR. DOMILYN VILLARREIZ <domz@main.dmsf.edu.ph> Davao, Philippines - Tue Jun 15 03:32:34 PDT 1999 Spatial epidemiology of TB Phil Atkinson <p.atkinson@cdsc.nthames.nhs.uk> London, UK - Tue Jun 8 09:10:42 PDT 1999 Bovine TB, molecular epidemiology, RFLP, spoligotyping, PFGE, VNTR, AFLP, virulence, transmissibility, stability, genomics, direct detection, PCR Robin Skuce <skucer@dani.gov.uk> Belfast, Northern Ireland - Tue Jun 8 06:42:57 PDT 1999 tuberculosis diagnosis, prevention, treatment We will be interested to know whether a case where M.tb. has been isolated twice on two different days by Bactec and confirmed by use of TMA of Gene Probe should be treated or not. General consesus is not people who are infected as the above case should not be treated. Why. Are they not in danger to themselved in future ? How does one get extrapulmonary tuberculosis such as renal, bone or meningitis, or lymphadenitis. Are these infected people also dangerous to other. Would appreciate to form and be part of discussion group on this type of matter. I am new web learner and would appreciate reply by e-mail. Dr.Suresh Amin <suamin@pi.zaverchand.com> Baroda, Gujarat India - Sun Jun 6 19:02:22 PDT 1999 RFC and ELISA in Paratuberculosis Dr. Valeriu Crangus <vally@k.ro> Bucharest, Romania - Thu Jun 3 07:01:57 PDT 1999
I am interested to conduct an evaluation study on the TB Program of our local government. Are there available research literature in this area? Dr. Jocelyn C. Kintanar, <joycorki@iname.com> Cebu, Cebu Philippines - Mon May 31 05:56:10 PDT 1999 I am researching the effects and damage caused by bacterial infections following surgical procedures within major hospitals. I am interested in hearing from anyone who following infection has tested positive for Tuberculosis, Mycomplasma, Toxomplasma, Luekemia, Cytomegolivirus. My research interest is in particular to women who have had caesarian section. Liani Simpson <liani@powerup.com.au> Brisbane, Queensland Australia - Thu May 20 21:07:49 PDT 1999 I'm a graphic designer and i've been assigned a project to create a stamp collection related to Tuberculosis and its history. I need all the visual information i can get about subjects, people linked to this disease and pictures of the bacteria itself. Websites with good pictures related with TB will help very much. This work will help ANTDR (Associacao Nacional de Tuberculose e Doencas Respiratorias) in its fight against this plague. Any help i could get would be very important. Thanks in advance. Antonio Manuel Silva <antonio@mrnet.pt> Lisbon, Portugal - Thu May 20 13:31:50 PDT 1999 DNA based methods for diagnosis of tubersulosis and molecular epidemiology. Interested in collaborations. Dr Madhu Goyal <m.goyal@herts.ac.uk> Hatfield, U.K - Mon May 17 06:13:41 PDT 1999 I'm doing a science report on tuberculosis and I really, Really,REALLY need pictures of the tuberculosis microbe. Katrina Katrina Howe <thowe@ideafamilies.org> Fairbanks, AK USA - Fri Apr 30 13:22:55 PDT 1999 I am currently conducting some research on the increasing occurance of antibiotic immunity of TB and would appreciate any info. that could be given. Thank you. Matt Nelson <Wolfrton@aol.com> Tacoma, WA USA - Tue Apr 20 23:28:50 PDT 1999 interested in vaccine development for tuberculosis. by using molecular techniques and bacteriophage. M.S.Ranjith mehendarkar <msranjith@hotmail.com> chennai, tamil nadu india - Fri Apr 9 10:46:26 PDT 1999 i am a post graduate student doing my thesis work on mycodot LAM test efficacy in diagnosing TB
cases,please send me any information regading this s satish madhav <ssakhamuri@hotmail.com> visakhapatnam, andhrapradesh india - Fri Apr 9 00:13:07 PDT 1999 Gene expression regulation in stationary-phase of bacterial growth cycle. Molecular mechanism underlying to adaptive mutation process in stationary-phase. Molecular mechanism of antibiotic resistance. Jos Mara Gmez Gmez <chemaseg@datalogic.es> Madrid, Madrid Spain - Mon Mar 29 10:49:06 PST 1999 Vibrio cholerae, Population Genetics, Molecular Evolutionary Genetics, Pulsed Field Gel Electrophoresis, Bacterial Diversity. Diego Riao <mao9823@usa.net> Santaf de Bogot D. C., Cundinamarca Colombia - Sun Mar 28 18:58:55 PST 1999 TB and STDs in Migrant Farmworkers. David Much, Ph.D. <much@muhlenberg.edu> - Tue Mar 23 14:30:24 PST 1999 I am a Ph.D in applied Biology with specialisation in Immunodiagnosis of tuberculosis. I am at present looking for a postdoc position in any of the following fields-- Mol.Biology/ Immunology. Dr Mythili Kameswaran <kmythili@hotmail.com> Mumbai, Maharastra INDIA - Tue Mar 23 00:44:38 PST 1999 Multidrug resistant tuberculosis Tuberculosis in AIDS patients Effect of Tb prophylaxis in drugresistant isolates Jos Luis Fuentes Allen <jlfuentes@compuserve.com.mx> Mexico, D.F. MEXICO - Sun Mar 21 17:21:24 PST 1999 I would like to know more about the diagnostic aspect of tb. especiallly the modern methods. Is there any association for tuberculosis? Elizabeth Anne Scicluna <elizabet@mail.global.net.mt> Malta - Sat Mar 20 12:38:44 PST 1999 Hi, We would like to inform you that our Singapore Anti-Tuberculosis Association (SATA) website has changed its homepage address from Http://rs.nic.net.sg/virtuoucity/sata to Http://home2.pacific.net.sg/~satakat/index.html but our Email address remains the same as Satakat@pacific.net.sg. Please update or help to link our new webpage address to your site. Thank you. Regards SATA Henry <satakat@pacific.net.sg> - Fri Mar 12 19:50:17 PST 1999 Susceptibility of man to bovine tuberculosis - Koch stated, most medical men believed the intestins
would suffer first. "I myself," he wrote, "have seen primary tuberculosis of the intestines only twice. ...at Charity Hospital in Berline, only ten cases in five years. Primary TB of intestine w/o lungs and bronchia never occured, in 933 cases. Biedart found only 16 cases in 3104 postmortems on tubercuar children. So how then can we accunt for the inter-transmissibility of human and bovine tuberculosis?" (Koch) The solution? The very tiny dark particles within each of the diseased cells are actually plasmids. They are far too small to be clearly identified with an ordinary microscope. Note also, plasmids are the microorganisms that transfer genes between various stains of bacteria. it is not only tuberculosis that produces plasmids. The same microorganism(s) also transfer genes, DNA, or drug resistant modlues between drug resistant bacteria. Hence, the very dark, tiny particles within each cancer cell, turn out to be the same thing - plasmids. The plasmid transfers into a weakened cell, and it resets the genes. Some plasmid are self-transferable. All are self replicating. Hence, this well-hidden genetic altering mechanism is what produces tuberculosis, as well as all kinds of cancers and tumors. Onces the new gene(s) are transplanted, the newly completed genetic material functions completely FROM INSIDE THE IMMUNE SURVEILLANCE SYSTEM OF THE HOST. Hence, this explains the subtle inheritance patterns found in many disease, such as TB, MS, MD, Diabetes, Leprosy - and any of these, as well as cancers and tumors are only PSEUDO-GENETIC in the orgin. Would you agree with these statements, or not? Please let me know. Bruce D McKay, Bio Epistemologist <jeferson@gte.net> Tampa, FL USA - Fri Mar 5 00:23:09 PST 1999 Studying Mycobacterium paratuberculosis. Interested in tuberculosis virulence factors, antibiotic resistance mechanisms, cell wall components, identification/location of these genes(plasmid?). Jason Azat <azat@mindspring.com> Santa Barbara, CA USA - Sat Feb 27 22:52:39 PST 1999 I am conducting a study on the toxic elements in hair analysis of both patients diagnosed with TB and family members that don't have the disease. I need information or research done on the effects or lack of of nutrients and toxic elements in TB. I work in Hospital Santa Clara, the most important hospital for TB in South America and we are in great need for help and support. John E. Bastidas M.D. <fmoser@cable.net.co> Bogot, Colombia - Fri Feb 12 04:16:37 PST 1999 I am a PhD student and my research involves in vitro screening of antimycobacterial (both sensitive and MDR strains) activity by South African medicinal plants. Any relevant information in this respect will be greatly appreciated. Namrita Lall <mailto:Namrita@scientia.up.ac.za> Pretoria, Gauteng South Africa - Thu Feb 11 00:09:20 PST 1999 I have an interesting case on tuberculosis of gall bladder. I need some references regarding the tuberculosis of Gall Bladder Dr. O. P. Sudrania <opsudrania@usa.net> Siliguri, West Bengal India - Wed Feb 10 03:28:40 PST 1999
I'm doing and investigation about tuberculosis, Immunology, Genetics, diagnostic in LCR I would like to have some information about this, if you please by able to send me these information victor Minera <oscargal@mail.concyt.gob.gt> Guatemala, Guatemala Guatemala - Tue Feb 9 10:16:03 PST 1999 radiology tuberculosis diagnostic Olga Malyscheva <ok_mal@usa.net> Moscow, mo Russia - Sun Feb 7 23:59:28 PST 1999 tuberculosis Olga Malyscheva <ok_mal@usa.net> moscow, mo RF - Sun Feb 7 07:33:12 PST 1999 I am the student of medicine faculty of Cerrahpaa and 1 year left to be a doctor.I just want to learn more about every patience and especially about tuberculosis because of the fact that tuberculosis is a very important patience in my country. Ozan Karata <okaratag@hotmail.com> stanbul, Trkiye - Sat Feb 6 08:00:34 PST 1999 Me: TB epidemiologist at the World Health Organization (but applying to medical school, hoping to be able to go back to California!). In the meantime, my research interests include TB and gender, particularly gender-based differences in the delivery of TB care (a common problem in the developing world), among other things... Suzanne K. Scheele <ScheeleS@who.ch> Geneva, Switzerland - Tue Feb 2 07:00:02 PST 1999 Ihave a 5 month old patient with tuberculous meningitis&cavitary lesions.How frequent we see cavitary tuberculosis in children? Soner Sarmask <mehmetsoner@.superonline.com> Istanbul, Turkiye - Wed Jan 27 11:51:43 PST 1999 Doing some research work related to tuberculosis, Immunology, Genetics MengZhang <meng.zhang@263.net> Beijing, PRChina - Tue Jan 26 03:14:00 PST 1999 Looking for more info about the guidelines on testing positive on the Manatoux test when the BCG was given over 22 years ago. Shelagh Taylor <Oscaig@aol.com> Great Lakes, IL USA - Fri Jan 22 07:28:41 PST 1999 I am a doctor specializing in the spheres of immunology, allergies, infectious diseases, pediatrics, gastro-intestinology, endocrinology and also cancer diseases in the recent past. In 1985 I started to
develop this method of diagnosis for different diseases, the foundation being in immunological reactions, registered with the help of the immuno-bio-chemo-luminescence naturally present in the body, and stimulated in the acidic agent hydrogen peroxide. With the use of standard methods of testing as a control I compared them for many years with this method of analysis and it has proved extremely accurate. Yakuba Nataliya <frolke@ibm.net> Toronto, Ontario Canada - Thu Jan 21 02:43:01 PST 1999 Any research findings on TB in immigrants to developing countries. Are they responsible for transmission to the indeginous peoples or is the reverse true? Kenneth <kennethm@epid.lan.mcgill.ca> Montreal, Quebec Canada - Mon Jan 18 15:07:02 PST 1999 Any research findings on TB in immigrants in developing countries. Are they responsible for transmission to the indeginous peoples or is the reverse true? Kenneth <kennethm@epid.lan.mcgill.ca> Montreal, Quebec Canada - Mon Jan 18 15:05:23 PST 1999 I want to know about multiresistant tuberculosis, any information or link will be useful. Thank Katherine Hernandez <bartleyjames@hotmail.com> Lima, Lima Per - Mon Jan 18 14:51:49 PST 1999 Research on Active TB in adults who have had no sympotoms, negative skin tests and negative chest Xrays negative smears, but does have positive culture of liquid from a washing of the lungs due to a broncochope as result of a chronic non-productive cough for years.. Kay <kdddalga@ocsonline.com> Dalton, GA USA - Sun Jan 10 22:54:04 PST 1999 Genetics, MHC, T cell receptors, thymic education. PITCHAPPAN <immunology@vsnl.com> MADURAI, Tamil Nadu INDIA - Thu Jan 7 07:54:56 PST 1999 Tuberculosis in children and adolescent, profilaxis, epidemiology, treatment. Datchev <datchev@rousse.bitex.com> Rousse, Bulgaria - Wed Jan 6 14:12:51 PST 1999 Portable TB Isolation Systems For Healthcare and other needs eliminates most respirator use Ted Arts <isosys@localnet.com> Buffalo, NY USA - Wed Jan 6 06:48:34 PST 1999 We want to express several recombinant proteins from M.tuberculosis. Where can we get the corrseponding DNA or cDNA? Werner Schmitz <wschmitz@biozentrum.uni-wuerzburg.de>
Wuerzburg, Germany - Tue Dec 15 01:36:05 PST 1998 I am a school nurse, our District TB policy was to conduct mass PPD skin testing on the 7th grade students. I have found a 30% conversion rate with a 2nd PPD test, in those students that had only redness (no induration) with the 1st PPD test. I would be interested in any research or information regarding the signifecance of redness only reaction to a PPD skin test and its correlation to TB infection in this or any age group. please contact me at Lannalyn@aol.com thank you L. Lee RN,BSN Lynn Lee <Lannalyn@aol.com> Brownsville, Texas USA - Thu Nov 26 19:02:35 PST 1998 I am a 3 rd year Bsc student and my final year project is a kit review of Gen Probe MTB kit. I am intrested to hear from any one else who has used this kit so that we can share useful information or anyone who can provide useful links. THANKS Latham Yates <latham_yates@yahoo.com> Weymouth , Dorset England - Wed Nov 25 10:28:05 PST 1998 I am in my final year (BSc hons applied biological sciences), my final project involves Heminested inverse PCR for rapid identification of M.tb strains. I would be grateful for any information or links to information you can provide. Thanks Elaine Connor <elaine.connor@iki.fi> Manchester, England - Wed Nov 25 07:10:19 PST 1998 I am a medical Doctor.Iwas a researcher in my country(Epidemiology of TB and execution of DOT's).I got to canada recently and I'd like to continue epidemiological study of TB here too. Would you please introduce me organizations or research centers of TB anywhere in Canada.Thank you. Nooshin Ahmadi pour <nahmadipour@sprint.ca> Montreal, Quebec Canada - Thu Nov 19 20:21:00 PST 1998 MDR TB MARCIA SEISCENTO <600@apm,.org.br> so paulo, so paulo brazil - Tue Nov 17 12:41:31 PST 1998 Tuberculosis,Fibreoptic Bronchoscopy,treatment of TB DR BHARAT GOPAL;MD <engee@nda.vsnl.net.in> delhi, delhi india - Sat Nov 7 01:06:06 PST 1998 Was there any Clinincal trials done in using morhine or heroin in treating Tuberculous or any lung diseases? Helena Bonner <Helena@physio.unr.edu> coleraine, N.Ireland - Thu Nov 5 04:39:52 PST 1998
I am interested in all aspects related to molecular drug resistant mechanisms employed by TB. Eric T. Y. Leung <eric@hkusua.hku.hk> - Wed Nov 4 21:58:54 PST 1998 I am interested in any reported case dealing with Mycobacterium tuberculosis infection leading to Interstitial lung disease or pulmonary fibrosis or any new treatment modalities for tuberculosis infection or disease. Emilina Montero-Luz <vinlyn@compass.com.ph> Manila , Philippines - Mon Nov 2 21:47:43 PST 1998 I need information about resistance to Tuberculosis in Per HENRI PEREA <henriperea@hotmail> AREQUIPA, AREQUIPA PERU - Sun Nov 1 21:00:11 PST 1998 I am interested in research about susceptibility genetic and TB or others topics about Molecular Genetic in this disease Paula Andrea Granda Carvajal <agranda@mailexcite.com> Medelln, Antioquia Colombia - Wed Oct 14 14:42:59 PDT 1998 I'd really apreciate if anyone could send me any file rellated with tuberculosis treatment. Chemical aspects of the drugs, farmacology, etc. Any kind of information would be usefull. Thanks! Julian Catalan <julian@crb.org.br> Blumenau, SC Brasil - Tue Oct 13 15:52:29 PDT 1998 Please include infor regarding epidimiology of TB within the Asian population in America. Christine Nguyen <christine112.hotmail.com> san jose, california U.S.A - Tue Oct 13 12:54:44 PDT 1998 I'm a biologist working at the hygiene institut in Morocco I'm unteresting in huomoral response to mycobateium tuberculosis,SDS PAGE. LARBI BAASSI <baassilarbi@mailcity.com> Rabat, Morocco - Fri Oct 9 08:57:21 PDT 1998 Please forward all information/latest research papers on TUBERCULOSIS regarding D.O.T. [direct observation treatment]. Khalid <jt3d@super.net.pk> Karachi, Karachi Pakistan - Tue Oct 6 07:54:09 PDT 1998 Interest in PCR of gene probe. The local distributer claims that we can do sensitivity by PCR. Is it true ? Dr Suresh Amin <suamin@pi.zaverchand.com> Baroda, Gujarat india - Sun Oct 4 17:09:13 PDT 1998
slide culture of M.tuberculosis Dr.N.Selvakumar <vana@md3.vsnl.net.in> Chennai 600 031, TamilNadu India - Fri Oct 2 19:19:32 PDT 1998 Diagnosis of tuberculosis, Culture methods Bactec, PCR , Nontubercular mycobacteria , their pathogenicity, treatment if any. Envirommental mycobacteria, Rifampin resistant gene band in MTb. Dr Suresh Amin <suamin@pi.zaverchand.com> Baroda, Gujarat India - Wed Sep 23 08:21:07 PDT 1998 Adenocarcinoma Plueral effusion in females Treatment available in India Monali Jain <g086mj@bomplant3.appl.ge.com> Mumbai, Maharashtra India - Mon Sep 21 05:46:32 PDT 1998 So nice a site. I would like to continue studying on TB. I am looking for some hard workers to do research. The world is my country. It does not matter to me where to work. Waiting for you! Babak Shokouhi <Mesri@me.ut.ac.ir> Tehran, Iran - Sat Sep 19 14:24:56 PDT 1998 I'm a medicine student from Brasil and I need some information in order to apply in my research :epidemiology of pleural tuberculosis and diagnosis statistics of ADA and citological analysis of pleural effusion. Juliana Ferreira de Oliva <Oliva@iron.com.br> Santos, So Paulo Brasil - Wed Sep 16 10:54:20 PDT 1998 New Diagnostic techniques for Tuberculosis Anjul Shrivastava <anjul@cyberspace.org> Bangalore, Karnataka India - Wed Aug 19 09:31:34 PDT 1998 I am a 5th year medicine student in Colombia. The incidence of TBC is very high down here since this is a third world nation. I am planning on doing my thesis about the efficiency of the ADA (Adenosine Deaminase) test in patients with pleural effusion due to TBC. I would be interested in any information or previous studies that have been done about this theme. My mailing address is: Federico Castellanos Arango Calle 80 No. 55-22 Apto. 7A Barranquilla, COLOMBIA I am very thankful for all the information you can provide me. Federico castellanos Arango <fedecaste@hotmail.com> Barranquilla, Atlantico Colombia - Thu Aug 13 20:24:52 PDT 1998 Dear colleagues I am very interesting to develop relations with researchers and organisations involved in study of immunology and genetics of tuberculosis. I am representing the group of azerbaijanian scientists from the Institute of Lung Diseases and TB. We are also very interesting in investigation of efficacy of BCG vaccination and new forms of prevention of tuberculosis. We'll appreciate any interest and suggestions to us. Looking forward to hearing from you.
Professor Alexandr UMNYASHKIN <moh@alexd.baku.az> Baku, Azerbaijan - Wed Aug 12 01:23:57 PDT 1998 epidemiology of tuberculosis in Volgograd Russia multiple drug resistance in Volgograd Russia sexually transmitted infections in Volgograd Russia public health or population programs for tuberculosis control in Russia therapy for tuberculosis in Russia Jim Wohlleb <wohllebjamesc@exchange.uams.edu> Little Rock, AR USA - Thu Aug 6 03:45:15 PDT 1998 In February of this year, my 6-year-old son was diagnosed with TB meningitis. This in turn caused hydrocephalus, which caused several strokes to his mid- brain. We were told he had 1 week--1 month to live. If by some chance he did live he would be a vegetable. Right now he is at Methodist Hospital in Indianapolis and is learning how to talk and walk all over again. What I'm looking for is statistics on the survival of children who have been diagnosed with this disease and the possibility of more strokes (what are the odds of him having more). I would also like to know if there is a chance for him to recover completely. Please e-mail to me any information on TB Meningitis so I can know what would be reasonable expectations for me to have. Thank you for your time and efforts. Holly M. Gimenez <miracleboy@hotmail.com> Muncie, IN USA - Fri Jul 31 12:35:56 PDT 1998 I am interested in information on the spread of TB in Russia since the fall of the Soviet Union. Thank you. genise ghee Genise O. Ghee <gheego@mcmail1.marshall.adsn.int> - Wed Jul 29 06:10:11 PDT 1998 Iam a professor of Biochemistry of the school of medicine, our proyect is is RFLP of multiresistant strain of Mycobacterium Tuberculosis here in the valley of Mexicali the incidence of tb is around 49 per 100,000 we have around 650 new cases of tb per year reported by the Helth department the number or multiresistant strains (2 or more antifimic drugs) is almost 30%. Multidrug resistant strain,RFLP,IS6110,Inmunological response anti-tb DNA probes Acosta-Valle Hector <acosta@csiam1.mxl.uabc.mx> Mexicali, Baja California Mexico - Mon Jul 27 13:53:09 PDT 1998 kindly send me updates on pott's disease (journals, etc..) thru e-mail. i will highly appreciate it if you could send it by tuesday next week because i have a case presentation re: pott's disease on friday, thanks in advance. more power! dr. abner m. hornedo department of pediatrics de los santos medical center quezon city, philippines abner m. hornedo, m.d. <hornedomd@hotmail.com> quezon city, philippines - Fri Jul 24 21:37:32 PDT 1998 What kind of fish are in the picture of Peter Small? Did he really catch them?? How many are there?? What did they weigh??
Lizzie - Sun Jul 19 07:15:16 PDT 1998 I would appreciate any information about all forms of TB throughout history in New York state especially sanitoriums>Thank-you Rebecca Guthrie <Beks1@aol.com> - Wed Jul 1 20:56:10 PDT 1998 Clinical Tuberculosis, Chapman and Hall London, 1998. Why is the AIDS conference in Geneva not telling the world that the commonest cause of death in AIDS patients is tuberculosis? Peter Davies <p.d.o.davies@liverpool.ac.uk> Liverpool, UK - Mon Jun 29 04:01:49 PDT 1998 I am in need of information about TB to be used as a teaching tool for children and parents in a pediatric hospital in Boston Ed Gilbert <ejg51@yahoo.com> Evertt , MA. U.S.A. - Wed Jun 24 16:34:26 PDT 1998 Rapid mycobacterial identification by PCR-Restriction Enzme Analysis (hsp65 gene) How to make it more practical for use in heavy burden clinical laboratories? O. Kaya Koksalan <koksalan@escortnet.com> Istanbul, Turkey - Mon Jun 22 11:35:22 PDT 1998 MDR tuberculosis,molecular methods of rapid identification of drug resistance,molecular mechanisms drug resistance Edward Generozov <Edward.Generozov@ripcm.org.ru> Moscow, Moscow Russian Federation - Fri Jun 19 04:47:14 PDT 1998 Medical Air Technology Corporation provides leading edge Air Purification systems for hospital, correctional and long term care facilities. We work closely with infection control personnel,facility management,safety officers, engineers and architects to provide individually designed rooms that are GUARANTEED and CERTIFIED in writing to meet or exceed all present CDC guidelines and OSHA regulations. For more information on TUBERCULOSIS / AIRBORNE INFECTION CONTROL for the 21st century visit our website www.medair.com Thank you Jeff Olarte <medairjeff@aol.com> mission viejo, ca usa - Thu May 28 09:32:11 PDT 1998 Medical Air Technology Corporation provides leading edge Air Purification systems for hospital, correctional and long term care facilities. We work closely with infection control personnel,facility management,safety officers, engineers and architects to provide individually designed rooms that are GUARANTEED and CERTIFIED in writing to meet or exceed all present CDC guidelines and OSHA regulations. For more information on TUBERCULOSIS / AIRBORNE INFECTION CONTROL for the 21st century visit our website www.medair.com Thank you
Jeff Olarte <medairjeff@aol.com> mission viejo, ca usa - Thu May 28 09:26:03 PDT 1998 I am a student of medice at the UIA in Costa Rica, I am working about multidrug resistant tuberculosis and management. I would appreciate any input in this matter. Andres Obando Valverde <aobando@hotmail.com> Cartago, Costa Rica - Mon May 25 23:03:46 PDT 1998 I am working at mycobacterial laboratory which is a top national referral center for the country. We examined about 100 samples per day, almost one third of them got MDR. I would like to share the data and learn more from TB experts in Stanford as well as other institute in USA Dr. Tjandra Yoga Aditama SpP(K) DTM&H DTCE <doctjand@link.net.id> Jakarta, Jakarta Indonesia - Wed May 20 07:11:27 PDT 1998 Differentiate between MOTT and M.TB in extra pulmonary specimens. regards, Bela Oza Bela Oza <fabritex.haho@medusa.sprintrpg.ems.vsnl.net.in> Vadadora, Gujarat India - Tue May 19 19:49:25 PDT 1998 diagnostic mycobacteriology; molecular typing of MTB; drug resistance surveillance programmes; epidemiology of atypical mycobacterioses; Mycobacterium haemophilum David Dawson <dawsond@health.qld.gov.au> Brisbane, Queensland Australia - Tue May 19 15:25:27 PDT 1998 Multidrug resistant tuberculosis,surveillance and management Tulay Torun <torun@ibm.net> Istanbul, Turkey - Tue May 19 14:32:37 PDT 1998 Mycobacterium Avian Intracellular Complex, Pan Sinisitus, Pneumonia > 3 + Fx. Ribs < coughing since 10/97 -- 4/15/98. Associated with Herpes Simplex I and systemic yeast--infections recently diagnosed--Possible Occupational Exposure ?? HIV possible. Pet dog uthanized & checked for above. Mother & friend also spent time w/ me checked for TB. What experience or info do you have on this subject ? Thank You, jrstutts@sprynet.com J. Stutts <jrstutts@sprynet.com> White Plains, NY USA - Sun May 10 14:34:43 PDT 1998 I am working at Mycobacterial Laboratory which is also a WHO Collaborating Center in Jakarta Indonesia and a national top referral laboratory for our 200 million people country. We examined about 100 TB samples every day, mostly using conventional method. I would like to share our result and learn more about TB from the expert in UK and other European countries. Dr Tjandra Y Aditama SpP(K) DTM&H DTCE <doctjand@link.net.id> Jakarta, Jakarta Indonesia - Fri May 8 23:15:05 PDT 1998 I am a graduate student working on " Novel immunodominant antigens of BCG-Tuberculosis
complex " interested molecular mechanisms granuloma formation, mycobacterial virulence and impaired macrophage function. other interest include Rheumatoid arthriris, Stroke and cancer. Dr Vinayak D Kanade, Dept of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, Karnataka State, INDIA. Dr Vinayak D Kanade <vinay@mcbl.iisc.ernet.in> Bangalore , Karnataka INDIA - Sun May 3 09:57:15 PDT 1998 tb anything Jeff Bauer <jeff_bauer1@hotmail.com> New york, New york U.S.A - Fri May 1 18:18:36 PDT 1998 I am doing a term paper for Anatomy. I am a junior in high school. I am very interested in the study of this disease. if applicable, please send me any info. Thanks. H. Khan <h-man@thegrid.net> - Tue Apr 28 19:15:15 PDT 1998 Isoniazid, Serodiagnosis, Newer drugs, Culture methods, Slow release preparations of antiTB drugs Dr.Rajesh M.Ballal <clintech@mailexcite.com> Nagpur, Maharashtra India - Tue Apr 28 04:01:16 PDT 1998 This is a really helpful web page. Jasmine Lopez Bellevue, IA U.S.A - Fri Apr 24 12:40:35 PDT 1998 (M. bovis)Tuberculin production, quality assurance, potency assay Animal (domestic and exotic)tuberculosis diagnosis Dr. Elizabeth Rohonczy <Rohonczyl@em.agr.ca> Nepean, Ontario Canada - Fri Apr 24 09:53:44 PDT 1998 Found the web-site very useful in researching a project on TB Trends in Dudley, UK. Keep up the good work everybody. Simon Round Wolverhampton, UK - Wed Apr 22 01:25:05 PDT 1998 Found the web-site very useful in researching a project on TB Trends in Dudley, UK. Keep up the good work everybody. Simon Round Wolverhampton, UK - Wed Apr 22 01:24:34 PDT 1998 Found the web-site very useful in researching a project on TB Trends in Dudley, UK. Keep up the good work everybody. Simon Round
Wolverhampton, UK - Wed Apr 22 01:24:22 PDT 1998 Rapidly Growing Mycobacteria, SDS-PAGE of whole cell proteins of nontuberculous mycobacteria, GLC for identification of mycobacteria, other molecular methods for identification of mycobacteria. Jaime Esteban <jesteban@uni.fjd.es> Madrid, Madrid Spain - Tue Apr 21 05:53:50 PDT 1998 I'm a senior at Richard Stockton College of New Jersey. I'm working on a research paper for my Molecular Genetics class I found MDR-TB to be a very interesting topic. I would appreciate any input in this matter. Anything to do with Molecular Bio will be an asset. Sunil Daniel <stk2846@loki.stockton.edu> Absecon, NJ USA - Sun Apr 19 19:40:09 PDT 1998 userdata 128.249.49.110 mo <mg690770@bcm.tmc.edu> - Thu Apr 16 21:38:08 PDT 1998 Mycobacteria, multi-drug resistance, NAD biosynthesis, isoniazid catalase Riccardi Giovanna <Riccardi@ipvgen.unipv.it> Pavia, Italy - Thu Apr 16 07:21:31 PDT 1998 Occupational Medicine/Industrial Hygiene/Environmental Health especially related to health care workers Nicola Magnavita <n.magnavita@oasi.it> Rome, Italy - Sun Apr 12 08:05:48 PDT 1998 miliary: diagnosis, treatment Is imipenem ussefull in tb? Jakob, Ernest <ejacov@roche.com.ar> Crdoba, Crdoba Argentina - Thu Apr 9 13:06:35 PDT 1998 Occupational Medicine / Industrial Hygiene / Environmental health - especially related to remote, industrial construction locations. Dennis J. Allen, CIH <DAllenCIH@aol.com> Birmingham, AL USA - Mon Apr 6 06:06:02 PDT 1998 Bacteria Viruses Infectous Disease Adam Peteson <GORfBOY@Juno.com> CA USA - Sun Apr 5 11:41:41 PDT 1998 I am a doctor working at the National Research Hematological center. We are interested whether you had got clinical cases of association of tuberculosis with pure red cell aplasia. We have just had a patient who had been suffering for a long time of chronic lymphocytic leukemia ( T-cell origin).
She died of disseminated tuberculosis which was diagnosed only at autopsy. Romanova Larisa <larisa@blood.ru> Moscow, Russia - Fri Apr 3 01:01:10 PST 1998 I am a student at Monash University, Australia, keenly interested in the tuberculosis epidemic which has re-emerged even in a drug resistant strain. I would be interested to maintain contact with Stanford's development in TB research, as your commitment is well known. Daniel Jontof-Hutter <djon5@student.monash.edu.au> Melbourne, Victoria Australia - Thu Apr 2 20:02:21 PST 1998 research on: 1. new drugs 2. new vaccines (for primary disease and adult disease) 3. treatment failures Dr. Gina S. Itchon <jprcm@xu.edu.ph> Cagayan de Oro, Philippines - Thu Apr 2 17:56:25 PST 1998 I want to have information about IgA determination by ELISA test ,usefull for diagnosis in children tuberculosis.Also I can provide some results of research in Extrapulmonary tuberculosis, and trends of bacteriological resistance in pacients from all the cities in Bolivia. mirtha camacho <inlasa@caoba.entelnet.bo> La Paz, La Paz. Bolivia - Thu Apr 2 15:18:09 PST 1998 Hi... I'm writing a paper on paleopathology (New World) concerning tuberculosis from a zoonotic perspective. Do you have any information concerning mammoth/elephant, bison, etc (pleistocene) tb-man transmission? Thank you...Tammy Tammy Grady <tegrady@acs.ucalgary.ca> Calgary, Alberta Canada - Wed Mar 25 12:06:24 PST 1998 tuberculosis; Surveillance; quintessential public health service; public health informatics; Epidemiology Sunitha V. Narayanan <drsunitha@glasnet.ru> Moscow, Russia Russia - Tue Mar 24 08:57:19 PST 1998 I am a high school student I'd like some information about TB i can use in my research paper can you help me?please? Carrie Childers but its my dad's comp name <kf4owd@naxs.com> gray, tn usa - Mon Mar 23 18:55:25 PST 1998 lawsuits regarding contracting t.b. @ employment. contracting @ correctional facilities. statute of limitations. any other related topics or ideas. roland gray <roro@ite.net> Yigo, GU (guam) - Mon Mar 23 03:46:47 PST 1998 Need information on engineering and environmental controls for airborne infection isolation rooms
in health care facilities looking for research regarding anterooms scott carroll <scarroll@mail.doh.state.ar.us> little rock, ar usa - Thu Mar 19 14:48:09 PST 1998 nefrotoxicity of antituberculos drugs Munteanu Mircea <mmircea@online.ro> timisoara, timis Romania - Fri Mar 13 14:51:23 PST 1998 Serology culture resistant strains Srinivasan P Dr <jeevan@giasmd01.vsnl.net.in> Chennai, Tamilnadu India - Fri Mar 13 03:05:57 PST 1998 incidence and statistics on tb cases in the US and the world mdr tb statistics jonel p. saludes <sotera.g@ustcc.ust.edu.ph> manila, philippines - Thu Mar 12 02:46:10 PST 1998 I'm doing a research paper on Native American Health Services, I understand American Indians have a history with the disease 'Tuberculosis'. Please write to me if there is any further information. Sincerely, Lucynda Gorman Lucynda Gorman <lcgorman@rocketmail.com> Tempe, AZ US - Tue Mar 10 05:24:00 PST 1998 information on extrapulmonary tuberculosis especially the female reproductive system bone joints Eroica Chmura <mailto:eroica.chmura@marymount.edu> - Mon Mar 9 10:28:49 PST 1998 i am a 8th grade student doing a report on tb and i would be glad if you would help me out and send me info whenever it is possible. thank you very much billy Billy Stewart <c3e@hotmail.com> dearborn hts., michigan united states - Sun Mar 8 20:02:26 PST 1998 I'm giving a speech on Tuberculosis on 3-11-98 and would like any information you might have on case studies or any statistics regarding TB. JoKasta McMillen <mpayne@remc.11.k12.mi.us> Bridgman, MI USA - Fri Mar 6 11:23:56 PST 1998 I am doing a GNVQ and need research on TB and the people it effects.ASAP please. Hannah Aylward <tony.aylward@MCmail.com> London, England - Thu Mar 5 04:50:41 PST 1998 Public Health Lab Border Health MDR TB Mexicali, Mexico Bob Freeman <icphlab@icoe.k12.ca.us> El Centro, CA USA - Tue Feb 24 08:23:44 PST 1998
Molecular interactions between MTB and human macrophage. MTB gene expression pattern Francesca Mariani <mariani@utovrm.it> Rome, Italy - Thu Feb 19 01:58:30 PST 1998 I went to the gulf in 90/91. In March of 1997, I found out I was TB Positive after a positive skin test. I completed the regimen of six months isoniazid. If you need someone for post treatment study, I'd like to volunteer, and I'm in the area. Jonathan L. Hopwood Jonathan L. Hopwood <hopwood@hoover.stanford.edu> Menlo Park, CA US - Sat Feb 14 14:54:14 PST 1998 TUBERCULOSIS CUTANEAS PRESEDO JULIO <JULPRE@CIUDAD.COM.AR> BUENOS AIRES, ARGENTINA - Sun Feb 8 20:50:28 PST 1998 I am a graduate student at the University of Georgia. I am currently working on an intervention proposal for a Strategies of Health Promotion course. My interest is in examining TB in the South African children population. Preston Clark <pclarkjr@coe.uga.edu> Athens , GA United States - Thu Feb 5 18:17:06 PST 1998 I am a graduate student at the University of Georgia. I am working on an intervention proposal for a Strategies of Health Promotion course. My interest in examining TB in the South African children population. Preston Clark <pclarkjr@coe.uga.edu> Athens , GA United States - Thu Feb 5 18:14:25 PST 1998 Tratamiento de Tuberculosis drogoresistente. Drugresistant Tuberculosis Treatment Felix Canal <fcanal@acer.com.pe> Lima, Peru - Wed Feb 4 13:52:39 PST 1998 Data concerning incidence of suspect/confirmed infectious Tb in the long-term health care setting (e.g. skilled nursing and assited living facilities). Chris Davis <chris_davis@manorcare.com> Gaithersburg, MD - Wed Feb 4 08:53:19 PST 1998 TB clinic Follow-up of patients on anti-TB medication Treatment of MRTB Dr. Gilles Blanchette <blanchg@ere.umontreal.ca> Montreal, Quebec Canada - Tue Feb 3 18:48:53 PST 1998 I'm in the 8th grade and doing a Science Fair Prject on TB. Please provide me with any information possible by the end of the week.
William Kipp <Whplash227@aol.com> Springfield, Illinois USA - Mon Feb 2 19:54:42 PST 1998 I am undertaking a Masters Degree in Health Economics and have chosen Tuberculosis as my subject in order to cost new drugs against predicted benefits to the health service. David H Higgins <d.higgins@mrc.ucl.ac.uk> London, England - Mon Jan 26 06:27:23 PST 1998 FL Department of Corrections Office of Health Services, Environmetal Health 2601 Blair Stone RD Tallahassee, FL 32399-2500 Gregory S. Redmon <redmon.gregory@mail.dc.state.fl.us> Tallahassee, FL US - Fri Jan 23 06:43:38 PST 1998 molecular typing methods, rapid identification of drug resistance Beate Heym <beate.heym@apr.ap-hop-paris.fr> Paris, France - Thu Jan 22 02:34:48 PST 1998 molecular typing methods, rapid identification of drug resistance Beate Heym <beate.heym@apr.ap-hop-paris.fr> Paris, France - Thu Jan 22 02:27:30 PST 1998 molecular typing methods, rapid identification of drug resistance Beate Heym <beate.heym@apr.ap-hop-paris.fr> Paris, France - Thu Jan 22 02:26:58 PST 1998 Immunopathology of TB Efficicy of Anti-TB Vaccine Feng Pei Zhong <wangg@public.bta.net.cn> Beijing, China - Wed Jan 21 19:16:15 PST 1998 Recurrence How would TB be identified if it were to recure? Ten years post can TB re-appear, the patient followed the TB drug program and no further problems related to TB. Currently there appears to be a small spot on the lung. Not able to preform biopsy. Could it be TB? Eliot Bernstein <alps1@pacbell.net> CDM, CA usa - Wed Jan 21 08:24:15 PST 1998 TB infection control public health issues worker exposures conversion rates in general population Teresa A. Caruthers <tcaruthers@afscme.org> Washington, DC US - Wed Jan 21 08:05:36 PST 1998 Diagnostic Tests for Tuberculosis Gavin Horrigan, CSL Biosciences <ghorrigan@csl.com.au> Melbourne, Victoria Australia - Mon Jan 19 05:02:15 PST 1998
Diagnostic Tests for Tuberculosis Gavin Horrigan, CSL Biosciences <ghorrigan@csl.com.au> Melbourne, Victoria Australia - Mon Jan 19 05:01:07 PST 1998 I'm innterested in "Tuberculosis" and I would like to have more inforamtion on it. If it's possible plese send a couple of pages I don't mind Martin Ronnig Martin Ronning <Faconnable@usa.net> Brussels, Belgium - Mon Jan 19 01:57:36 PST 1998 Patient education, college health issues, promotion of skin testing, skin testing results and medications used. Jo Buczko <jabuczko@paccd.cc.ca.us> Pasadena, CA USA - Sun Jan 18 11:34:40 PST 1998 Patient education, college health issues, promotion of skin testing, skin testing results and medications used. Jo Buczko <jabuczko@paccd.cc.ca.us> Pasadena, CA USA - Sun Jan 18 11:34:22 PST 1998 Epidemiology of tuberculosis Prikazsky Vladimir, M.D. <prikjr@mbox.vol.cz> Prague 10, Czech Republic - Sun Jan 18 08:40:58 PST 1998 Tuberculosis of the fpine Tuberculosis of the potts Jess dela Merced <jessbud@webquest.com> Pasig, Philippines - Thu Jan 15 21:23:08 PST 1998 Interested in finding a position as a research assistant for Summer 98 in San Francisco area. I am currently attending Bryn Mawr College' s postbaccalaureate pre-medical program and have some additional reasearch/lab experience. I graduated from Princeton University in 1996, and I am entering Jefferson Medical College in the fall. Would love suggestions from those already immersed in research as to how they found their wonderful positions. Thanks. Laurie Gustafson <lgustafs@brynmawr.edu> - Mon Jan 12 12:36:37 PST 1998 international opportunities- I am a 2nd year veterinary student who would like to help with research abroad (preferably epidemics in impoverished countries) during the summer months of 1998 Lena Gutberlet <lgutberl@mail.vt.edu> Blacksburg, VA usa - Mon Jan 12 09:18:16 PST 1998 international opportunities- I am a 2nd year veterinary student who would like to help with research abroad (preferably epidemics in impoverished countries) during the summer months of
1998 Lena Gutberlet <lgutberl@mail.vt.edu> Blacksburg, VA usa - Mon Jan 12 09:17:46 PST 1998 international opportunities- I would like to help with research abroad during the summer months of 1998 Lena Gutberlet <lgutberl@mail.vt.edu> Blacksburg, VA usa - Mon Jan 12 09:05:57 PST 1998 I would be grateful for any information relating to the instance of TB in Ireland, past and present, general information on TB would be likewise valuable. Thanking you, in anticipation.... Edel <Ge94323861@ailm.may.ie> Co.Kildare, Ireland - Mon Jan 12 05:31:13 PST 1998 Hey, cool page here. Yah, well THAT'S ALL hahahahahahaha yelling's DUMB!!! Ben Jones <banjones@hotmail.com> Pitwomen, New Jersey USA - Sun Jan 11 14:55:46 PST 1998 social impact of tuberculosis in urban areas Amy Harrington <aharrin1@swarthmore.edu> - Sat Jan 10 22:56:34 PST 1998 MDR Tuberculosis Dr. S. Martnez-Selmo <martnez.selmo@codetel.net.do> Santo Domingo, Distrito Nacional Dominican Republic - Sat Jan 10 18:47:49 PST 1998 Interests: Tuberculosis in Colorado throughout history We need some information, please!!!! jessica Perino <perino_jim@fortlewis.edu> Durango, Co USA - Sat Jan 10 15:02:46 PST 1998 Antimocrobial Susceptibility Testing Ron Dudek <ron_dudek@bio-rad.com> Hercules, CA USA - Thu Jan 8 18:56:13 PST 1998 TB in other organs than lungs. Loriane Frewing <Loriane_Frewing@bc.sympatico.ca> Langley, B.C. Canada - Thu Jan 8 13:30:29 PST 1998 Dear Sirs: Be very pleased of directing me you with motive of requesting informacion on the disease called granuloma tuberculosis or tumor endumedular, the request is due to that I have to a relative with that disease and wanted to know of the fact that is tried and which isyour cure. From already I thank your time, and I wait prompt response.
Ariel Pola <apola@raiz.uncu.edu.ar> Godoy Cruz, Mendoza argentina - Thu Jan 8 05:14:58 PST 1998 I don't have a comment at this point, but ask me later. MMMMM....I Forgot <blah31@aol.com> Crazyville, Calafornia (DUH!!!) - Mon Jan 5 20:18:58 PST 1998 Please inform me if my newborn is at risk of contracting TB. My uncle has TB that recently became active again after being dormant for a number of years. If my baby comes in contact with him, is it likely, or possible, that it will infect my son? Please reply as I am very concerned and will keep my son away from my uncle if I have to. Thank-you. Traci Lizotte <lizotte@uniserve.com> Chilliwack, BC Canada - Mon Jan 5 20:11:41 PST 1998 Environmental Health & Safety Joe Rizkallah <jrizk@csulb.edu> Long Beach, California USA - Mon Jan 5 17:53:53 PST 1998 Drug resistance tuberculosis serveilance and management Dr.Md.Rabiul Hossain <rabiul@bangla.net> Dhaka, Bangladesh - Fri Jan 2 17:09:46 PST 1998 I would like to know about tuberculosis on the skin, because two years ago I had that problem. I need to know if I'm going to have more problems when Ill decide to become mother.I finish my treatment, but sometimes I have some little samples of Tb. Lucia Diaz <lucy@fenix.ifisicacu.unam.mx> Mexico, D.F Mexico - Fri Jan 2 14:00:57 PST 1998 Alternative approaches to TB control (esp. MDR) Sudeep Rao, M.D. <srao@jhsph.edu> Baltimore, MD U.S.A - Fri Jan 2 13:16:07 PST 1998 tuberculosis of urogenital tract the evolution prognosis and treatment i am doing research on these topics and would be thankful if you can guide me to obtain some information thank you and a happy new year bafiq nizar <bafiq@gmb.ro> constanta, constanta romania - Fri Jan 2 04:51:04 PST 1998 Drug resistant strainsof TB currently in proliferation, research, discoveries, etc... James McMurray <smplygrn@aol.com> Venice, CA. U.S.A. - Wed Dec 31 19:58:18 PST 1997 I need informations about the transmission of TB.Ihad some cases in my family and i would like to
know how to stop the transmission thanks. francis <francis.ottou@camnet.cm> yaounde, cameroun - Wed Dec 31 08:38:20 PST 1997 i like your web page it was very helping to me in my TB reort thanks a lot . keep trying to find a cure and update this site asap . thank you so much , dominkue dominikue whitehaven , pa usa - Mon Dec 29 15:58:36 PST 1997 tuberculosis, cyclopropyl mycolic acids, treatment, mode of action, dormant bacilli, d taylor <dtaylor@chemistry.adelaide.edu.au> adelaide, south australia australia - Mon Dec 29 15:42:32 PST 1997 Diagnosis; Diagnosis by Polimerase Chain Reaction Claudia Morais <CMORAIS@CYGNUS.CI.UC.PT> Coimbra, Portugal - Fri Dec 26 11:52:31 PST 1997 tuberculosis mdr and dr tuberculosis JACINTA GRACE-PARKER <jgracepa@phls.co.uk> london, United kingdom - Tue Dec 23 09:03:52 PST 1997 I'm interested in contacts study of tbc patients. Do you have any protocol? QP of contacts in tbc resistant cases (INH,...) Neus Camps Cura <fcodina@grn.es> Girona, catalonia spain - Mon Dec 22 11:51:43 PST 1997 I'm very interesting in coinfection HIV-M.tuberculosis in penitentiary population. I'm working in temporal trend of coinfection HIV-M.tuberculosis in penitentiary pooulation of Spain. Vicente Martin Sanchez <vmartin@telprof.eurociber.es> 24005 LEON, SPAIN - Mon Dec 22 09:31:54 PST 1997 I am very intersted in the system regerding the care of TB patients especially highly infectious Pts. in USA. Do most of hospitals have isolation wards or how to isolate these pts from other immunocompromised pts? Shuji kurane, M.D. <skurane@nms.ac.jp> Tokyo, JAPAN - Sun Dec 21 10:01:21 PST 1997 Tuberculosis, mycobacteria, BCG vaccination Victoria Romanus <victoria.romanus@smi.ki.se> Stockholm, Sweden - Thu Dec 18 05:58:21 PST 1997 I need info. Andrew Rosenthal <jarosen@chicago.avenew.com>
Wilmette, Illinois USA - Tue Dec 16 17:31:51 PST 1997 Necesito informacin sobre tuberculosis y brucella en bovinos para titulacin de medicos Veterinarios mvz. mercedes guillermina nuez gutierrez <guille@cusur.udg.mx> guzmn, jalisco mexico - Tue Dec 16 13:25:32 PST 1997 Am interested in TB pathology and prevention particularly pertaining to prisons in developing countries. Adrienne Acomb <aacomb@usa.net> Washington, DC USA - Thu Dec 11 12:35:10 PST 1997 TB and homelessness Theresa Butler <theresa.butler@metrokc.gov> - Wed Dec 10 12:24:51 PST 1997 Diagnostics Maria Scully <mktg@feiltd.com> Buffalo, NY USA - Wed Dec 10 05:44:15 PST 1997 I would appreciate any information on TB possible. Especially pictures dealing with the bacteria and patients Abigail Nickel <atn6037@acs.tamu.edu> College Station, Texas USA - Wed Dec 10 02:08:43 PST 1997 State Tuberculosis Program Manager - All areas Kim Field <KWF0303@hub.doh.wa.gov> Olympia, Washington USA - Tue Dec 9 14:43:42 PST 1997 Encapsulated TB Melody Becker <chloe@bellsouth.net> Whitehouse, TN USA - Mon Dec 8 12:08:26 PST 1997 I am pregnant and I saw that having lupus could affect my pregnancy. I don't know of having lupus and I don't know much about it. I was trying to find out how you get tested for it. Brandi Donley <jfoerch@remc8.k12.mi.us> Grand Rapids, Michigan U.S.A. - Mon Dec 8 09:39:00 PST 1997 Any expert information pertaining to the residual effects of pneumo-throax treatments on the heart muscle. Please respond. This information would be very important to me and my family. Forrest Stephanian <Woodmannn@AOL.com> - Sun Dec 7 19:07:01 PST 1997
I am a ninth grader conducting a research project pertaining to drug-resistand TB. I am in need of primary research and secondary research. If you can help, thank you. James Waters <jsh2os@aol.com> New York, New York USA - Sun Dec 7 15:38:55 PST 1997 Molecular Genetics of Tuberculosis Manu Deeudom <manu@lamar.colostate.edu> Fort Collins, Colorado USA - Thu Dec 4 14:06:35 PST 1997 I like your homepage! Good design! If you have time, come to our german homepage. Hallo, herzlichen Glckwunsch zur gelungenen Homepage. Ausgesprochen gutes Design. Auf jeden Fall eine Bereicherung frs Netz. Hoffentlich kommen noch viele Besucher vorbei. Mit einem freundlichen Gru aus Deutschland! Erich Berlin, DDR - Wed Dec 3 17:46:39 PST 1997 Hi I am a child from I.E Weldon I am doing a project on Tuberculosis My Grandma has the disease I was wondering if any of you could e-mail me with some websites or information on the disease at Jo.Frost@sympatico.ca Thank you Brad Frost <Jo.frost@sympatico.ca> Norwood, Ontario Canada - Mon Dec 1 10:25:41 PST 1997 I am doing a report on tuberculosis and would like to find some more information. especially primary sources, like people that had the disease or that live with it today. Lmeister <Lmeister@ix.netcom.com> Minneapolis, Minnesota USA - Thu Nov 27 11:51:44 PST 1997 tuberculosis in general atypical mycobacteria and treatment H.P.J. Daemen <hpjd@iaehv.nl> Eindhoven, The Netherlands - Tue Nov 25 05:44:00 PST 1997 -We are interested in pharmacokinnetics of tuberculostatic drugs in AIDS patients. -Also, we are researching in DOT prophylaxis in drug users with isoniazid twice weekly. j. portilla <portilla@san.gva.es> alicante, spain - Mon Nov 24 16:52:18 PST 1997 TB fascinates me!!!! I am a second year medical student at Mayo Medical School. I am currently seeking a position with a team researching TB in an endemic area. I am a hard worker and very committed. Please contact me if you are aware of any potential projects. Thank you!!! Sue Susan Kearney <Kearney.Susan@mayo.edu> - Sun Nov 23 14:32:00 PST 1997 We've reported three of the first short course tratment reports of TB/HIV in Peru, case control
study. We need more information about local experiencies with 6 months/four drugs/short course TB treatment Oswaldo Jave Castillo <gjave@rcp.net.pe> Lima, Lima Peru - Tue Nov 18 13:33:25 PST 1997 HIV/TB Multidrug-resistant TB Short course treatment Molecular epidemiology Third World TB/HIV research Oswaldo Jave Castillo <gjave@rcp.net.pe> Lima, Lima Peru - Tue Nov 18 12:35:57 PST 1997 Looking for info about how M.Tuberculosis escapes the immune system and develops into TB disease Margarida Monteiro <mmam@students.si.fct..unl.pt> Almada, Portugal - Sat Nov 15 11:09:02 PST 1997 I don't have any comments at this time. Corey Zadlo <Vike00@hotmail.com> Chicago, IL USA - Fri Nov 14 12:38:05 PST 1997 Personal experience of having TB Diane Morris <dmorris@e-tex.com> Mt. Vernon, Tx USA - Wed Nov 12 08:14:55 PST 1997 tuberculosis, drug resistance, transmission, and treatment. Scott Richardson <sorrento@eatel.net> sorrento, la usa - Sat Nov 8 09:33:13 PST 1997 I am interested in any materials on tuberculosis. Jill Sanders <jsand019@uwsp.edu> Stevens Point, WI USA - Tue Nov 4 12:10:36 PST 1997 INFORMATION REGARDING TUBERCULOSIS RESEARCH Dr.V.VISHWANATH <FRD@IFEUNIV.UNIFE.IT> FERRARA, ITALY - Tue Nov 4 07:01:12 PST 1997 I'm doing my BSc Genetics and biochemistry at the university of Wales, Aberystwyth. I am interested in the treatment to TB and in its future research into new treatments for MDR-TB. Karen Barker <kab5@aber.ac.uk> Ceredigion, Wales UK - Fri Oct 31 08:42:37 PST 1997 I have an uncle who is diabetic and was diagnosed lately to have potts disease. Is potts disease curable in this case? Or is it more likely to spread through the rest of the body? Thanks in advance. Mostafa Afifi <the_afifis@hotmail.com>
Helioplis, Cairo Egypt - Fri Oct 31 01:59:12 PST 1997 I'm spanish from Barcelona. I'm working in Tuberculosis recombinant vaccine. I'm very interested to work in New york city the next year 1998, due to my wife's work. I 've got a grant, then the economic source is already solved for next year 1998. Please contact with me if you are interested in my collaboration. Thank you very much. All together will fight against tuberculosis. Dr. Juan Joseph Munne MD PhD in Medicine <mil-garc@uniandes.edu.co> Barcelona, Catalunya Spain - Thu Oct 30 16:03:23 PST 1997 I'm spanish from Barcelona. I'm working in Tuberculosis recombinant vaccine. I'm very interested to work in New york city the next year 1998, due to my wife's work. I 've got a grant, then the economic source is already solved for next year 1998. Please contact with me if you are interest in my collaboration. Thank you very much. All together will fight against tuberculosis. Dr. Juan Joseph Munne MD PhD in Medicine <mil-garc@uniandes.edu.co> Barcelona, Catalunya Spain - Thu Oct 30 15:57:02 PST 1997 I've recently started my Ph.D. at McGill University in genetic susceptibility of tuberculosis in humans. I'm interested in becoming a part of the TB network of researchers. Suneil (Neil) Malik <Neil@igloo.epi.mcgill.ca> - Sat Oct 25 11:42:15 PDT 1997 M. avium complex drug therapy...My aunt has developed complications from miliary TB and M.avium complex, and cannot tolerate the current drug therapy...please send any information on any and all options for treating this terrible disease. Connie Koch <Sillyme@aol.com> Arden, NC USA - Wed Oct 22 07:29:21 PDT 1997 M. avium complex drug therapy Connie Koch <Sillyme@aol.com> Arden, NC USA - Wed Oct 22 07:24:58 PDT 1997 Looking for Global statistics on TB in 1997 Dr. Shagufta Iram <softlabs@brain.net.pk> Lahore, Pakistan - Sun Oct 19 01:43:28 PDT 1997 Latent infections, interaction with HIV Gale W. Newman, Ph.D. <newmang@link.msm.edu> Atlanta, GA US - Fri Oct 17 11:43:03 PDT 1997 I am in need of information about diagnostics for hydatidosis and statistics about hydatidosis in Peru. And some epidemiology, please. Thank you. Alfonso Barnechea <gasbarn@telematic.edu.pe> Lima, Lima Peru - Wed Oct 15 15:47:34 PDT 1997
On the queries, the replys are not there.... Joanna McGinn <LessonText@aol.com> - Fri Oct 10 12:54:48 PDT 1997 DNA fingerprinting (by RAPD) of Mycobacterium tuberculosis strains to determine if MTB strains corelate with epidemiological groups in patients which would assist in successfully seeking TB contacts. Cynthia B Fisher <Fisher.Cynthia@bay_pines.va.gov> Bay Pines, FLorida USA - Fri Oct 10 09:28:56 PDT 1997 RFLP, virulence, resistance. Molecular Mecanisms of Mtb resistance. Methods for detection Jose C. Palomares <folia@cica.es> Seville, Spain - Sat Oct 4 14:01:03 PDT 1997 ANY INFORMATION ABOUT SOLVENT OR VOLATILE ORGANIC COMPUND AND PULMONARY TUBERCULOSIS, WORK EXPOSURE DR. JOSE LUIS ROBLES L. <jlrobles@riogrande.net.mx> matamoros, tamaulipas mexico - Mon Sep 29 20:14:50 PDT 1997 immunology of TB secreted proteins vaccines Dr.S.Vijaya <vijaya@cge.iisc.ernet.in> Bangalore, Karnataka INDIA - Fri Sep 26 08:51:19 PDT 1997 Molecular mechanisms of intracellular survival Molecular mechanisms of resistance to ethambutol Vincent Escuyer <escuyer@citi2.fr> Paris, France - Wed Sep 24 01:33:03 PDT 1997 Thanx for helping me with my informative speech on TB! Kari Nygaard <mackruth@mail.dakota.net> Sioux Falls, South Dakota USA - Tue Sep 23 11:37:05 PDT 1997 Veterinarian with canine patient with avian tuberulosis. Interested in any information on canine tuberculosis. Kirsten Leach <kirsten@reap.org.nz> Taupo, New Zealand - Sat Sep 20 16:12:11 PDT 1997 I am a nursing student who is concerned with 2 fellow class mates that have tested positive on a PPD test several years ago, one was tested twice and had a severe reaction. They were told various things form they cannot take meds, to the meds will make their hair fall out, to they are healthy enough they should be okay. Each is in mid 20s early 30s. Any information would be helpful. Sarah Lieberenz <GROUCHOMAES@msn.com> Midland, Texas USA - Thu Sep 11 22:20:38 PDT 1997
Tuberculosis in Native Americans Miles Rudd, MD <mrudd@justicenet.net> Warm Springs, OR USA - Wed Sep 10 23:18:06 PDT 1997 VIRULENCE/PATHOGENECITY, ELICIT PROTECTIVE IMMUNE RESPONSE, ZHUQING LI <ZLI@OPUS.MCO.EDU> TOLEDO, OHIO, 43699 U.S.A. - Tue Sep 9 08:48:47 PDT 1997 Doctoral research Research Hypothesis: A culturally-sensitive health education intervention will have an effect upon knowledge of tuberculosis and behaviors related to the incidence of tuberculosis among the Bemba of sub-Saharan Africa. Date to begin research: January 1999. Estimated length: Six months. Funding needed: $20,000 (inclusive of round-trip transportation and cost of living in Zambia). Does anyone know of a funding source? Thank You. Marie G. Heithmar <heithmar@soleil.acomp.usf.edu> Valrico (near Tampa), Florida U.S.A. - Tue Sep 9 08:41:20 PDT 1997 We are interested to start a pilot study concerning the treatment of tuberculosis in the county of Iasi (Romania). We have already obtained the support of the WHO. Dr Traian Mihaescu Clinic of Pulmonary Diseases 30 Dr I Cihac St Iasi 6600 Romania tel:+40.32.214406 fax:+40.32.213532 Traian Mihaescu <mihaescu@sigma.tuiasi.ro> Iasi, Romania - Sun Sep 7 03:58:45 PDT 1997 tuberculoma flora samwel <killpests@raha.com> dar es salaam, tanzania - Sun Aug 31 05:48:23 PDT 1997 HIV Methadone maintenance programs Heroin on prescription AIDS Society of Kamloops /Methadone Advocacy & Advisory Group John Anderson <mr_anderson@bc.sympatico.ca> Kamloops, British Columbia Canada - Tue Aug 26 15:45:27 PDT 1997 pathophysiology of tb. how to diagnose(symptoms) Tseliso Nkuebe <Nkuebet@med.ac.za> Durban, South Africa - Sat Aug 23 09:52:31 PDT 1997 -all aspects of TB, currrently invloved in Community Health program at the Ubniversity of Natal as a medical Student Naeem Sader <sadern@med.und.ac.za> Durban, KwaZulu/Natal South Africa - Sat Aug 23 09:48:19 PDT 1997 I am interested in communicating with anyone who has treated TB-meningitis or has suffered from it. Please contact me at jgelfand@uci.edu or 714-824-4971
Julia Gelfand <jgelfand@uci.edu> Irvine, CALIF USA - Mon Aug 11 10:48:36 PDT 1997 I am involved in a project which deals with the effect of UV light on the nosocomial transmission of MTB and would like information related to the topic. Tracey <Kestingt@med.und.ac.za> Durban, Natal South Africa - Mon Aug 11 06:18:09 PDT 1997 I work in the area of image processing/rcognition and I am very interested in acquiring a large dataset of slides or digitised images from slides of both ZN-stained and auramine-stained TB bacilli in sputum. Colin Campbell <C.Campbell@bris.ac.uk> Bristol, Avon England - Mon Aug 11 02:43:26 PDT 1997 Interested in collaborating on TB research projects. Diagnosis, novel therapies Dr. Alexander D. Simidchiev <lungdis@sun.medun.acad.bg> Sofia, Bulgaria - Fri Aug 1 14:51:41 PDT 1997 I might have TB and need to knnow more info about the disease. Debbie Taillon <cnightmare@ibm.net> Stittsville, Ontario Canada - Fri Aug 1 09:17:59 PDT 1997 I need information about : molecular biology mycobacterium thuberculosis VIVIANA DADOR M.D. <dacas@ibm.net> lima, peru - Mon Jul 28 10:46:22 PDT 1997 I am looking for a suitable post-doc position. Have extensive experience in the field of tuberculosis for the past 10 years. Have experience in Immmunology, Microbiology, Mol. Biology & Biochemistry. Have developed Immunodiagnostic tests for tuberculosis. Dr. Mythili Kameswaran <rmc@rmc.ernet.in> Bombay, Maharastra India - Mon Jul 28 00:16:08 PDT 1997 I major in clinical pathology, especially microbiology. In korea, patients with active tuberculosis are about 1% of all population. So, I have a great interest in tuberculosis. I have studied the usefulness of TB PCR for the diagnosis of tuberculous meningitis. I would like to exchange opinions on molecular diagnosis and epidemiologic studies. Jae-Seok Kim, M.D. <SNUKJS@hitel.net> Seoul, Korea - Sun Jul 27 05:26:34 PDT 1997 Diagnosis, prevention and treatment of tuberculosis. Identification of species and strain specific DNA sequences. Methods for isolation of mycobacteria from clinical samples. Lakshmi Kantham <lkantham@amrad.com.au> Hawthorn East, Vic 3123 Australia - Thu Jul 24 22:39:15 PDT 1997
tuberculosis vaccines and cytokine responses Robert G. Townley M.D. <RTownley@Creighton.edu> Omaha, NE USA - Tue Jul 22 16:26:37 PDT 1997 I am currently doing research on therapy for MDR-TB resistant to the usual triple Anti-Koch's. Any form of help is highly appreciated. Thanks! Dr. Leonard Lao <lllao@aimonline.org> Caloocan, Philippines - Tue Jul 22 05:44:51 PDT 1997 This is a Very Nice Site!...Come visit us at World Association of Persons with Disabilities [WAPD]The Sleeping Giant is waking up! HELP you give TODAY is HELP you get Tomorrow..... BE A PARTNER! George Kerford, President/CEO [WAPD] <thehub@wapd.org> San Antonio, Texas USA - Sat Jul 19 13:59:00 PDT 1997 I am from Pakistan and working with tuberculosis for last four years. Ihave worked both with immunology and molecular pathology of mycobacteria. I have optimized the diagnosis of extrapulmonary tuberculosis from blood and have successfully applied the techniqu to the diagnosis of 120 clinical isolates (paper in preparation) Besides this I have also done molecular epidemiology of tuberculosis using both Is6110 and Is 1081 for the differentiation of organism within tuberculosis compelex and for the differentiation between M.bovis and Mtuberculosis. Currently Iam working with the Mtp40 gene. Iam intrested in doing my Phd and persuing my work in the same field. I am intrested in looking at the intracellular signalling followed by phagocytosis of tubercel bacillie. If you have any ongoing projects in the related areas please contact me. Shaper Mirza <Mirza_Shaper@micro.microbio.uab.edu> birmingham, Alabama united States - Fri Jul 18 14:39:07 PDT 1997 Mechanism of phagocytosis of Mycobacteria by macrophages Gallium as Treatment Aniva Orava <ak11054@cedarnet.org> - Tue Jul 15 19:38:37 PDT 1997 I am working in the field of paleopathology at the department of anatomy (University of Gttingen). I am interested in bone alterations of the internal surface of the skull caused by tuberculosis. At the moment I am investigating a medieval skeletal population from Germany. Many skulls show signs of meningeal tuberculosis. I would like to have more information about recent cases of meningitis caused by tuberculosis, because we would like to compare our histological specimens with specimens from recent cases. Thorsten Schlomm <tschlomm@mdv.gwdg.de> Gttingen, Niedersachsen Germany - Mon Jul 14 13:43:27 PDT 1997 especially multiresistant tuberculosis strains in Balkans I'm from the European part of Turkey
Metin Otkun <otkunadali@superonline.com> Edirne, Turkey - Mon Jul 14 10:33:14 PDT 1997 I am working in epidemiology of tuberculosis in Cajamarca Peru, with PPD inmunoreaccion research in all this area also with Hystoplasmin an Paracoccidioidin, .My research also involve Intestinal Parasites and anothers as Cysticercosis, Fasciolasis, Hydatidosis etc.I need information of the last foundings in this subjects in Peru. Zoila Villavicencio de Muck <Zoila@unc.edu.pe> Cajamarca, Cajamarca Peru - Sat Jul 12 17:31:14 PDT 1997 I would like to receive information on BCG revaccination and protection against tuberculosis BCG revaccination tuberculosis immunity tuberculosis and vaccines Reinaldo de Menezes Martins <reinaldo@unikey.com.br> Rio de Janeiro, RJ Brazil - Tue Jul 8 19:18:36 PDT 1997 Actually I am researching in multiresistent patients with TB treatment. I would like to receive any information about this. Carlos Manuel Young <balanya@c.net.gt> Guatemala, Guatemala Guatemala - Tue Jul 8 14:35:39 PDT 1997 Estoy interesado en la epidmiooga de la tuberculosis. Saludos Santiago Rubio <srubiofelix@mx2.redestb.es> Zaragoza, Spain - Mon Jul 7 10:21:24 PDT 1997 I am interested on TB molecular diagnosis Dr.Khalid M. Bindayna <bindayna@batelco.com.bh> Bahrain - Wed Jul 2 08:17:13 PDT 1997 Im a student of medicine, I have to make a paper of TBC, epidemiolgy, drug resistance, and terapy of TBC (PAHO protocol ) Juan Gallegos Flores <hugoga@mail.cosapidata.com.pe> Arequipa, Per - Sat Jun 28 11:25:16 PDT 1997 I am a physician at the childrens infectious hospital in St. Petersburg, Russia. I specialize in TB & minengitis. I would like to discuss surgery applications for the treatment of TB. I am in San Francisco, CA from July 7-16th and from July 30 to Aug 9, 1997. I would like to discuss surgical treatment of TB with you. I have had several succesful cases and I would like to discuss & share this information with you. In CA my telephone number is 415-592-1397. I would like very much to visit Stanford and view your facility. Best regards Lioudmila Klotchkova Lioudmila klotchkova <lexas@russiamail.com> Belmont, CA USA - Fri Jun 27 15:19:24 PDT 1997 Diagnostic mycobacteriology. Microcolonies detection on Middlebrook 7H11 agar. Rapidly
growing mycobacteria Jaime Esteban <fjdmicro@microb.net> Madrid, Spain - Thu Jun 26 05:45:13 PDT 1997 I am a MS student and want to pursue a PhD degree in TB research. My research interests.(1)RFLP analysis of M.tuberculosis.(2)Multi-drug resistance of M.tuberculosis.(3)Detection of M.tuberculosis by PCR (4)Molecular epidemiology of TB. ***The email user's name is not Chuntao Wu,but Qi-lun Sun. Thank you. Chuntao Wu <qsqq@bltda.com.bta.net.cn> Beijing, P.R.China - Sun Jun 22 03:57:03 PDT 1997 Diagnosis and treatment Maria Luigia Lamona <m1970@telcel.net.ve> Caracas, Distrito Federal Venezuela - Mon Jun 16 18:24:23 PDT 1997 tuberculosis:resistance BK (primary and secondary) cancer bronchopulmonary (brachytherapy) dr. Ciobanu Doru Traian <ciobanut@unitbv.ro> Brasov, ROMANIA - Sat Jun 14 01:31:29 PDT 1997 BCG; Tuberculosis innoculations; Gerri Hynes <ghynes@ican.net> Burlington, Ontario Canada - Fri Jun 6 20:27:01 PDT 1997 Sensitivity of tuberculosis agent to UV-A exposure. Derek Griffith <dgriffit@csir.co.za> Pretoria, Gauteng South Africa - Wed Jun 4 14:04:33 PDT 1997 More zero band strains of M.tb exists in South India. DR probe has been found to be the ideal probe for molecular typing of M.tb. Key words: Mycobacterial virulence genes, promoters, intracellular survival. Dr. R. Sahadevan <sahadevan@hotmail.com> Madras, Tamil Nadu India - Sat May 31 04:43:56 PDT 1997 Study Results of UV Light Technologies, Management of DOT & DOPT, Community Healthcare Epidemiology Issues Kevin A. Gritzke <jjmce@ixnetcom.com> St. Louis, MO USA - Tue May 27 17:35:25 PDT 1997 EthnoBios S.R.L. is a small biotech company located in Bolivia working with medicinal plants that have a history of traditional usage. At this time we are working with the sap of a plant that has a history in treating TB, rheumatoid arthritis annd verruges. Studies have suggest that this product induces differnt effects on sveral phases of the immune response which may be compatible with the reported capacity to resolve the TB process. In addition, these effects (stimulation of splenocytes
and modulation of the marcrophages activity) lead to consider this substance as a promising candidate to further studies and application as an immunomodulatory product. We have another that is just as interesting but I have already writen more than a "few lines." Sorry. If anyone is interested please contact me at lipena@wara.bolnet.bo We lack funding to continue our studies so any info. would be apprecialted. Thanks, Joseph C. Traini Lic. Joseph C. Traini <lipena@wara.bolnet.bo> La Paz, La Paz Bolivia - Tue May 27 12:10:02 PDT 1997 38-kDa antigen, 16-kDa antigen, Diagnosis, Vaccine, TB molecular bilogy Zengyi Chang, Ph.D. <changzy@mail.tsinghua.edu.cn> Beijing, P.R.China - Thu May 22 16:05:41 PDT 1997 Louisiana Office of Public Health employee in Tuberculosis Control Program interested in learning more about TB diagnosis and treatment. Richard Adams <RWadams@msn.con> New Orleans, LA USA - Sun May 18 20:35:21 PDT 1997 INH therapy and longivity further testing once treated Dawn Bisenius Peoria, Illinois USA - Sun May 18 20:05:57 PDT 1997 I'm a graduate student who is prepareing a paper on the resurgence of TB and it's effects on the community. Any information that can be obtained would be very much appreciated Leslie F. Dowers <Sansouci22> Rosedale, New York U.S.A. - Sun May 18 19:19:33 PDT 1997 Synthetic organic chemistry. Preparation of tuberculostatic agents having enhanced lipophilicity. Preparation of antimicrobials having multiple tuberculostatic moieties in one chemical structure. Near infrared spectroscopy for the analysis of tuberculosis antimicrobials. M. J. Hearn <MHearn@Lucy.Wellesley.edu> Wellesley, MA USA - Sun May 18 07:22:01 PDT 1997 I would like to receive the lattest news about tuberculosis and the co-infection with AIDS. Im a brasilian pulmonologist that work with TB/AIDS. Thank you for your help Enio Pires Studart <enio@openlink.com.br> rio de janeiro, RJ Brasil - Sat May 17 15:33:18 PDT 1997 Mycobacterial genetics and pathogenesis Ed Swords <wds0@cdc.gov> Atlanta, GA USA - Fri May 16 11:42:53 PDT 1997 Use of HPLC for species identification of mycobacteria, susceptibility testing and epidemiology. David Fett <keon@prof.slh.wisc.edu>
madison, wi wi - Thu May 15 13:00:37 PDT 1997 Gene expression of Mycobacteria. analysis of limiting amounts of RNA using novel techniques. Microarray hybridization to study gene expression patterns. Joe Mangan <jmangan@sghms.ac.uk> London, England - Wed May 14 08:22:48 PDT 1997 I am a PhD student in Economics at the University of York. analysis of the spread and control of tuberculosis in developing countries (case study: South - Africa), mathematical models of population dynamics, rural-urban migration (** edited for length **) Doriana Delfino <dd109@york.ac.uk> York, UK Europe - Mon May 12 11:32:32 PDT 1997 Protein Crystallography, Structure-based drug design, Identification of Novel drug targets in M.tuberculosis, Understanding the molecular mechanisms of drug resistance in tuberculosis, evolution of TB as well as that of drug resistant species. Shekhar C. Mande <shekhar@bragg.imtech.ernet.in> Chandigarh, INDIA - Sun May 11 02:12:51 PDT 1997 I work as Lecturer in Preventive and Social Medicine in Government Medical College, Nagpur, INDIA. My interests are DOTS and epidemiologic models of tuberculosis. Hemant Kulkarni <h-kulkarni@usa.net> Chapel Hill, North Carolina USA - Sat May 10 13:20:44 PDT 1997 My academic unit has a growing program of TB research (Adult and pediatric) both in London and in Central Africa. The work encompasses immunology, epidemiology, immunotherapy and pathology. Keywords: TB, Adult, Pediatric, Central Africa, London, Epidemiology, immunology, microbiology Dr.Alimuddin Zumla PhD.MD.FRCP <a.zumla@ucl.ac.uk> London W1P 6DB, United Kingdom - Sat May 10 06:04:35 PDT 1997 TB-HIV; TB prevention and control in Latin America Kathy DeRiemer <kathyd@ax.apc.org> Brasil - Fri May 9 21:52:39 PDT 1997 Access to TB care / control programmes in developing countries Dr Bertie Squire <sbsquire@liv.ac.uk> Liverpool, U.K. - Fri May 9 01:46:48 PDT 1997 Pathology of T.B, Fingerprinting, PCR for diagnosis of T.B from PBMC. Shaper Mirza <Mirza_Shaper@microbio.micro.uab.edu> Birmingham, AL USA - Wed May 7 14:51:20 PDT 1997
I am a respiratory care student interested in information about TB. I am especially interested in the connection between AIDS and TB. Heather Hall <hhall@shelbynet.net> Indianapolis, Indiana USA - Tue May 6 20:42:20 PDT 1997 I am a 16 year-old high school student from Denver who is interested in learning about TB and the reasons for its resurgence in the past ten years, as well as multi-drug resistant tuberculosis. If anyone has information on this topic, it would be much appreciated. Merrill Abrams <abramsjl@texaco.com> Denver, CO USA - Mon May 5 13:34:05 PDT 1997 I am particularly interested in multi-drug resistant TB, DNA based assay for rapid detection of multidrug-resistant TB or rifampin resistant strains, molecular aspects of TB also ,,,and possibly virulence Ma. Sheila Mangalonzo-de Jesus <enteng@pusit.admu.edu.ph> Cupang, Muntinlupa City, 1771 Philippines - Mon May 5 07:43:34 PDT 1997 My interest is Epidemiology of tuberculosis control. TB DNA fingerprinting is one of the most fascinating new technologies for us. Toru Mori <tmori@jata.or.jp> Kiyose, Tokyo 204 Japan - Sat May 3 04:54:11 PDT 1997 I AM A PHYSICIAN FROM INDIA AND AM INTERESTED IN RESEARCH IN T.B. WHICH IS VERY RAMPANT IN INDIA HAVING SEEN A LOT OF TB AND WORKED VERY CLOSELY WITH THESE PATIENTS ,I WOULD BE VERY HAPPY IF YOU COULD HAVE ANY OPPORTUNITIES FOR THE SAME. murtuza bahrainwala h. <MUNDAVIA@aol.com> kew-gardens, ny-11415 U.S.A - Fri May 2 16:21:19 PDT 1997 diagnostic tests PCR-based molecular epidemiology Caterina Mammina, MD <diptigmi@mbox.unipa.it> Palermo, Italy - Fri May 2 08:03:46 PDT 1997 Direct detection of Mycobacterium species. Speciation by HPLC. Quantitative analysis of clinical specimens. Sher-Hwin Chiu <schiu@laba.tdh.state.tx.us> Austin, Texas USA - Thu May 1 19:09:58 PDT 1997 High-output UV for HVAC air disinfection Tom Schaefer <8009250440> Cincinnati, OH United States - Thu May 1 16:34:32 PDT 1997 Main interests: National TB Programmes, DOTS, TB and NGOs, training health workers. Visit the
tbNET website at http://www.south-asia.com/ngo-tb Ian Smith <iansmith@mos.com.np> Kathmandu, Nepal - Wed Apr 30 09:29:53 PDT 1997 New treatment methods for Pulmonary Tuberculosis Han Yu-ling <aking@public.jn.sd.cn> Jinan, Shandong P.R.China - Wed Apr 30 09:00:54 PDT 1997 Developing appropriate diagnostic tests for TB Dr. Leslie A. Stringfellow <leslies@gen-probe.com> San Diego, CA USA - Tue Apr 29 11:48:15 PDT 1997 Areas of interest: Molecular Biology, Pathogenesis, Drug development Juan A. Ayala <jayala@trasto.cbm.uam.es> Madrid, Madrid Spain - Tue Apr 29 10:21:41 PDT 1997 Bacterial lipoglycans (eg. mycobacterial LAMs) and lipoproteins Iain Sutcliffe <iain.sutcliffe@sunderland.ac.uk> - Tue Apr 29 08:40:38 PDT 1997 DOTS,TB/HIV-AIDS,TB researches, Petchawan Pungrassami ,M.D. <petch@t-rex.hatyai.inet.co.th> Hatyai District, Songkla Province THAILAND - Tue Apr 29 08:36:21 PDT 1997 Looking for info on the recovery time from TB in insulin dependent diabetes. Nancy Conner <nanna@mindspring.com> Birmingham, AL US - Tue Apr 29 08:23:27 PDT 1997 Dept. of Biochem., Baylor college of Medicine. Interests: pathogenesis, virulence. Have isolated and characterized the oligomeric state and chaperone activity of the 16 kDa antigen from M. tb. Todd P. Primm <tp034588@bcm.tmc.edu> Houston, Texas USA - Mon Apr 28 11:07:36 PDT 1997 Gerard Cangelosi, Ph.D. Seattle Biomedical Research Institute Department of Pathobiology University of Washington cangelos@u.washington.edu Interests: molecular diagnosis, pathogenesis, drug development Gerard Cangelosi <cangelos@u.washington.edu> Seattle, WA USA - Mon Apr 28 10:51:50 PDT 1997 automated fragment-based DNA genotype matching, computational methods, IS6110 fingerprint clustering methods, Please visit my web pages by following the link from my name. Hugh Salamon <hugh@molepi.stanford.edu> Stanford, California USA http://www.stanford.edu/group/molepi/guestbook.html (57 of 58) [05/01/06 2:27:11]
You may email me regarding this website! Hugh Salamon, Ph.D. <hugh@molepi.stanford.edu> Stanford, California USA -
q q
Stanford Center for Tuberculosis Research Scripts and Guestbook created by Matt Wright and can be found at Matt's Script Archive
Stanford University and individuals maintaining this page are not to be held responsible for any consequences whatsoever resulting from any and all words or other information on this page, or any actions taken as a result of contacting individuals listed herein.
Click on this icon to return to the top of the home page.
Stop TB Partnership
Links
Videos
News & Announcements World TB Day 2006 is coming! 23 December 2005 In end-January 2006, the Stop TB Partnership will release The Global Plan to Stop TB 2006-2015. In setting out the resources needed for action, the Plan will serve as a powerful advocacy tool that outlines regional and global scenarios for impact and costs of planned activities, and strategic plans for the Partnerships seven Working Groups for the next decade. The thematic focus for World TB Day 2006 is built on the Global Plan advocacy strategy, key messages and action points around the theme Actions for Life: towards a world free of tuberculosis as a basis for campaign development. Field testing the revised TB recording and reporting forms 20 December 2005 The Stop TB Department of WHO, in collaboration with partners, convened three informal expert consultations in Geneva, Switzerland in April, May and September, 2005. The expert group has issued revised TB recording and reporting forms and registers to facilitate building consensus at national level on a minimum standardized monitoring tool that complies with the Stop TB Strategy. The main changes in the information system forms are the inclusion of TB/HIV collaborative activities; culture for diagnosis and drug resistance testing; and the management of patient drug kits. The revision also aims to strengthen links with all care providers, civil society and the national health management information system (HMIS). New tuberculosis therapy offers
The Human Face of TB
Global Drug Facility
Fight AIDS, FightTB, Fight Now
Partners' Directory
Archbishop Desmond Tutu Speaks on TB Listen to his statement on TB in Africa
Calendar of Events Subscribe to the Stop TB Mailing List
Nelson Mandela Speaks on TB/HIV More Videos ...
Partner Highlight
http://www.stoptb.org/ (1 of 6) [05/01/06 2:29:28]
Stop TB Partnership
Destination Sant We are a multimedia press agency in French, Arabic, Dutch and English, devoted to health information for mass audiences. Destination Sant feeds over 130 newspapers in Europe, Africa and the Middle East. Prominent portals (Yahoo, Google, Algrie Presse Service, Menara) rely on Destination Sant material on a daily basis. We are an exclusive producer of the WHO radio programs in French (700 stations, 45 countries) and Arabic (125 stations, 11 countries). As of 1 January 2006, these programs are broadcast by Destination Sant as an independent press agency, keeping a strong connection with WHO program units. Services related to TB - In close cooperation with the WHO TB Strategy & Operations Unit, Destination Sant designed a special 10 minute feature in French and Arabic dedicated to World TB Day: over 100 hours of educational information were broadcast worldwide on this occasion. - Since Destination Sant joined the Stop TB Partnership (2003), over 60 news items related to TB diagnosis, treatment and prevention have been disseminated.
View the text in French View the text in Arabic View their partner profile
potential shorter treatment 17 December 2005 Clinical results on a new combination treatment that could dramatically shorten the length of tuberculosis (TB) treatment were presented today at the 45 th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy in Washington, D.C. Printable Version The Special Programme for Research and Training in Tropical Diseases (TDR) L'institut de recherche pour le dveloppement Stop TB Partnership Indonesia launches web site, and successfully holds first-ever National TB Congress attended by over 1000. 6 December 2005 The Stop TB Partnership Indonesia web site will serve as a comprehensive public information tool for tuberculosis in Indonesia. The web site was launched in coordination with the first-ever Indonesian National TB Congress, that took place in Jakarta, Indonesia, 18-19 November 2005. The TB Congress drew over 1000 health professionals, politicians, healthcare providers, NGO activists, and TB staff from throughout the country. The participants reviewed the national TB partnership movement, Gerdunas. Meeting agenda items included new mechanisms for supporting the 5-year national TB plan 2006-2010, progress and opportunities in clinical aspects of TB, community involvement, and the International Standards of TB Care. Indonesia launched Gerdunas in 1999. Indonesia was the first country in the world to establish a national Stop TB partnership.
Stop TB Partnership
World AIDS Day 1 December 2005 The TB community is committed to the theme of this World AIDS Day by collaborating with the HIV community to provide universal access to comprehensive TB and HIV prevention, treatment and care services. In highly HIV endemic countries TB programmes can raise awareness about TB/HIV co-infection, provide HIV counselling and testing and provide HIV prevention methods as well as antiretroviral therapy for TB patients who are also HIV positive. TB programmes can help keep the promise and Stop AIDS! UNAIDS web site TB/HIV Working Group November 2005 Information Circular Stop TB Partnership Executive Secretary addresses World Summit of Nobel Peace Laureates 24-25 November 2005 The Executive Secretary of the Stop TB Partnership, Dr. Marcos Espinal, was invited to make a special presentation on the global TB epidemic and regional TB emergency in Africa at the 2005 World Summit of Nobel Peace Laureates in Rome, Italy on 24-25 November. The summit was organized by the Gorbachev Foundation and sponsored by the Municipality of Rome, this year's theme being "Africa Emergency: From Attention to Action." The gathering attracted a number of Nobel Peace laureates including Mikhail Gorbachev, Frederik Willem De Klerk, Adolfo Perez Esquivel, John Hume, Mairead Corrigan Maguire, Betty Williams, Rigoberta Mench Tum, and Lech Walesa, as well as special guests Bob Geldolf, Robert F. Kennedy Jr., Carla Del Ponte and others. Italy urges tuberculosis to become a
Stop TB Partnership
priority for the G8 in 2006 (AGI) - Rome, Italy, Nov 10 2005 The Italian Government is to call on G8 countries to intensify global efforts on TB control and ensure it is included as a priority in the 2006 summit agenda. In a statement distributed by the Prime Minister's Office, Giuseppe Drago warned that "TB risks being forgotten" despite two million people dying from the disease every year. He also warned of the challenges of addressing TB in Africa where rates continue to rise, the threat of drug resistance, especially in the former Soviet Union, and the urgent need to find effective vaccines. Addressing delegates at the Stop TB Partnership's Coordinating Board meeting at Assisi in November, Mr Drago confirmed Italy's commitment to TB by announcing that his government will "take up the duty of informing other members of the G8 so that the fight against TB, in particular in Africa, becomes one of the priorities of the next summit at Saint Petersburg". More News ...
Highlighted Projects Panos and Stop TB Partnership journalism fellowships The Panos Global AIDS Programme and the Stop TB Partnership awarded fellowships for print and photo journalists in the South to raise local debate and understanding of TB and, in particular, its link with poverty and HIV/AIDS. The fellowships were awarded to local journalists in India, Bangladesh, Pakistan, the Philippines, Indonesia, Zambia, Malawi, Ethiopia and Haiti. Articles and photos will be published in the Fellow's local newspapers, and a best practice
Stop TB Partnership
reporting guide on TB and photo exhibition based on the Fellows' work will be subsequently published by Panos. TB Emergency in Africa In August 2005, TB was declared to be an emergency in the African region by The World Health Organization (WHO) Regional Committee for Africa - a response to an epidemic that has more than quadrupled the annual number of new TB cases in most African countries since 1990 and is continuing to rise across the continent, killing more than half a million people every year.
Recent Publications Communiqu, Issue No.43 December 2005 Italy urges tuberculosis to become a priority for the G8 in 2006
Sustaining the Gains October 2005 National Self-Sufficiency for TB Drug Access A Global Drug Facility Strategy
Stop TB Partnership Annual Report 2004 - Introductory page May 2005 Our Annual Report 2004 looks at the Stop TB Partnership's major achievements in core areas of work, including governance, advocacy and communication, partnership building, access to lifesaving TB drug treatments and resource mobilization.
Stop TB Partnership
Privacy Policy | Site Search | Site Map | Contact Us | Link to our site | Compatibility | Jump to top of page
TB Alert: Home page
TB Alert - the UK's National

Tuberculosis Charity
Welcome to TB Alert About us Why TB Alert Our mission Our people TB Alert India Newsletters Annual reports About Tuberculosis Common symptoms Other forms Diagnosis Treatment Your family Vaccination TB dictionary TB in Animals Worldwide issues A global emergency MDR TB TB and AIDS TB and children TB and women TB and poverty TB and stigma TB in the workplace DOTS fighting TB Our work Worried? Health worker? Press?
What's new ...
News
TB Alert Christmas Appeal - donate on- 22/12/05Carols line in Trafalgar To make a donation on-line, please click here. Square Thanks to If you haven't received the appeal which everyone who came from Winstone Zulu, TB Alert's helped us raise representative in Africa, click here over 400 in less Tuberculosis - A Global Emergency 9 million people develop active TB each year than one hour at Trafalgar square. and 2 million die - yet TB is curable. Read more... more 20/12/05New TB Therapy TB Alert 2006 diary/organiser available offers potential now shorter Pocket size, week to view, address and phone treatment times number section, plus many other features A new combination including 50 page refillable jotter pad. Order therapy for now....more tuberculosis might Multi-Drug Resistant TB reduce treatment Drug resistant forms of TB take longer to time for the cure, require more and more expensive drugs disease from six to treat, cure rates are low and fatality rates months to four are high. Read more months.... more 05/12/05TB Alert chosen as Lilly Charity of the year TB Alert is delighted to have been chosen by Lilly UK to receive donations from their employee activities during 2006. More info soon. 30/11/05Ratting out TB
http://www.tbalert.org/ (1 of 4) [05/01/06 2:30:55]
TB Alert: Home page
India Calcutta GMLF Krishna Nav Jivan VHAD Bangladesh LAMB Malawi QECH Mzimba Small projects UK Awareness Treatment support Clinical leaflets Hardship fund Zambia Bwafano ZAMBART Awareness Zimbabwe Murambinda Advocacy Help/Get involved Individuals Volunteer Donation Fundraise Sponsored Events Give for Free A gift in your will Cards and gifts Organisations Companies Trusts Schools/Unis Faith groups Rotary/Inner Wheel
Researchers with the Belgian organization Apopo are training rats in Tanzania to distinguish the smell of the TB bacterium in human sputum or breath samples ....more 16/11/2005MPs express concern over Tuberculosis emergency and HIV/AIDS Nick Herbert MP today tabled an Early Day Motion regarding the Tuberculosis Emergency and HIV/ AIDS... more
TB Alert: Home page
WI Clubs, groups, choirs Resources Awareness materials Clinical leaflets Treatment support Hardship fund World TB day Training resources Publications Links News Links Contact us Donate now FAQ Press Search A-Z Adjust text size
Update: 0401-2006
2005 TB Alert, Reg. charity 1071886 This site is not intended for diagnosis or self treatment. Link to: details, website terms and conditions & Privacy Statement. Design by LeanWeb
TB Alert: Home page
Johns Hopkins Division of Infectious Diseases Antibiotic Guide

click here..
by diagnosis... by pathogen... by antibiotic... (search term)
Visit the new Johns Hopkins Center for Clinical Global Health Education (CCGHE) Register Here!!! -- This service is FREE and available to all!
For technical questions or to send us feedback, please send email to abxfeedback@hopkinsabxguide.org.
Occupational deaths among healthcare workers By John G. Bartlett M.D. posted 12/21/2005 The authors estimated the annual death rate for health care workers from occupational events based on data from federal sources and estimates based on prevalence and natural history. The most recent major relevant event was SARS. There were 8,098 cases and 774 (9.6%) died; health care workers accounted for 1,707 (21%) of cases, but the number of deaths in this group is not known. The resource expected to provide substantial data is the National Institute for Occupational Safety and Health (NIOSH) which is a branch of the CDC and responsible for research on prevention of work place injury and illness. However, infectious diseases are not included in the illness report. Other conditions which are included are hypersensitivity pneumonitis, mesothelioma and occupational pneumoconiosis...more Novel, single-dose microsphere formulation of azithromycin versus 7-day levofloxacin therapy for treatment of mild to moderate community-acquired pneumonia in adults By John G. Bartlett M.D. posted 12/21/2005 The authors report the results of a randomized, doubleblind, comparative trial of single dose azithromycin (2 gm microsphere in an oral slurry) compared to levofloxacin (500 mg po/day times 7 days) in patients with "mild-tomoderate CAP." Eligibility criteria included x-ray evidence of pneumonia, and a PSI score of less than 90 (category IIII in the Fine PSI mortality risk scale). Microbiology assessment included sputum cultures, urine antigen assay for S. pneumoniae, blood cultures and serology plus PCR for M. pneumoniae and C. pneumoniae. The results show equivalence in the two drugs with no statistically significant difference in clinical cure rates of 94% in the 214 patients treated with levofloxacin vs. 90% in the 213 patients given azithromycin...more
Literature Review
s
Occupational Deaths among Healthcare Workers posted 12/21/2005 S aureus, Panton-Valentine Leukocidin, and Necrotizing Pneumonia posted 12/21/2005 Single-Dose Microsphere Azithromycin vs 7-Day Levofloxacin for Mild to Moderate CommunityAcquired Pneumonia posted 12/21/2005 archive
The Antibiotic Guide:

s
s s s
How do I move my ABX Guide (Palm version) to a memory card? Why do I have to register to use this site? Who is this site designed for? Why should I trust the material presented in the ABX Guide? Recent Press Releases
http://hopkins-abxguide.org/ (1 of 2) [05/01/06 2:33:23]
Johns Hopkins Division of Infectious Diseases Antibiotic Guide
We subscribe to the HONcode principles. Verify here.
Copyright 2000 - 2004 The Johns Hopkins University on behalf of its Division of Infectious Diseases. All rights reserved. Any work produced by Noreen A. Hynes, M.D., M.P.H., and so designated on this site is not copyrighted and remains in the public domain. Please contact us at abxfeedback@hopkins-abxguide.org with any comments, questions or concerns about this site. This site is advertising free. This web site is provided as an information resource only, and not as a guide for recommendation of treatment, for physicians and other health care professionals who are concerned with the appropriate treatment of infectious diseases, and who are knowledgeable in the selection of antibiotics, as part of the care and treatment of patients. Recommendations for care and treatment change rapidly and opinions can be controversial; therefore, physicians and other health care professionals are encouraged to consult other sources and confirm the information contained within this site. This site is for informational purposes only, and should not be relied upon for final treatment decisions. Johns Hopkins University makes no representations or warranties concerning the accuracy or reliability of information contained within this site, and the Johns Hopkins University, and the contributing authors, editors, production, and programming staff shall not be liable for errors, omissions or inaccuracies in information or for any perceived harm to users of this site or their patients. By referring to this site you agree and understand that the individual physician or other health care professional should use his/her best medical judgement in determining appropriate patient care or treatment. Full Disclaimer >>
http://hopkins-abxguide.org/ (2 of 2) [05/01/06 2:33:23]
- f |
- W J Z j D F 266
q X : (852) 2572 3466 u X : (852) 2834 0711 q l l : antitb@ha.org.hk U O H X
http://www.ha.org.hk/org/antitb/default.htm [05/01/06 2:38:17]
The Indian Journal of Chest Diseases and Allied Sciences
Current Issue Past Issue About the Journal VPCI NCCP Editorial Board Information for Authors Subscription Information Advertisement Tariff Contact Us Current Issue Jul - Sept 2002 Past Issues Oct - Dec 2000 Onwards
http://www.indegene.com/ijcd/indIJCDHome.html [05/01/06 2:40:31]
The Vaccine Fund
1/5/2006 GMT The Campaign for Child Immunization About The Vaccine Fund The Global Need The Vaccine Fund's Mission The Progress Media Center Events Support The Vaccine Fund
Highlights 9 September 2005 Key European Nations Join UK and France to Commit Nearly US$4 Billion to Expand Child Immunisation in Developing Countries Events 7-9 December 2005 3rd GAVI Partners' Meeting, New Delhi, India, Taj Palace Hotel. For more information click here. Franais | English
http://www.vaccinefund.org/ (1 of 2) [05/01/06 2:48:10]
The Vaccine Fund
Text Version | Site Map | Terms of Use | Privacy
http://www.vaccinefund.org/ (2 of 2) [05/01/06 2:48:10]
Tinplate Hospital (BCG Vaccine)
Vaccine
BCG Vaccine - for prevention of TUBERCULOSIS
Background and General Guidelines BCG, or bacille Calmette-Gurin, is a vaccine for tuberculosis (TB) disease. BCG is used in many countries, but it is not generally recommended in the United States because of the low risk of infection with M. tuberculosis, the variable effectiveness of the BCG vaccine against pulmonary TB, and the vaccines interference with tuberculin reactivity. BCG vaccines are live vaccines derived from a strain of Mycobacterium bovis that was attenuated by Calmette and Guerin at the Pasteur Institute in Lille, France (29). BCG was first administered to humans in 1921. Many different BCG vaccines are available worldwide. Although all currently used vaccines were derived from the original M. bovis strain, they differ in their characteristics when grown in culture and in their ability to induce an immune response to tuberculin. These variations may be caused by genetic changes that occurred in the bacterial strains during the passage of time and by differences in production techniques. The vaccine currently available for immunization in the United States, the Tice strain, was developed at the University of Illinois (Chicago, Illinois) from a strain originated at the Pasteur Institute. The Food and Drug Administration is considering another vaccine, which is produced by Connaught Laboratories, Inc., for licensure in the United States. This vaccine was transferred from a strain that was maintained at the University of Montreal (Montreal, Canada). BCG vaccination does appear to lower the risk of serious complications of primary TB in children. But in the United States, the consideration of BCG vaccination is recommended only for children BCG DPT
Home Vaccine
Oral Polio Varicella Measles Hepatitis-A Hepatitis-B Typhoid Fever MMR Haemo Influenza-B TT (Tetanus) Surgeries/Procedures Obstestrics and Gyneac Orthopeadic General Surgeries Urological Gastrointestinal Other Operations ENT Eye Pathology Dental Laparoscopic/Endoscopic News/Articles Incinerator for TPH New Facility for Sr.Citizen
http://www.tinplatehospital.com/bcg.asp (1 of 3) [05/01/06 2:50:28]
who have negative tuberculin skin test results, and who cannot be given treatment for latent TB infection but are at high risk for continuous exposure to infectious TB or to TB that is resistant to isoniazid and rifampin. BCG is no longer recommended for health care workers or other adults who are likely to be exposed to TB. However, vaccination of health care workers should be considered on an individual basis in settings in which (1) a high percentage of TB patients are infected with M. tuberculosis strains resistant to both isoniazid and rifampin, (2) transmission of such drug-resistant M. tuberculosis strains to health care workers and subsequent infection are likely, and (3) comprehensive TB infection-control precautions have been implemented and have not been successful. Furthermore, BCG should not be given to persons who are immunosuppressed, such as persons who are infected with HIV. It should not be given to pregnant women, even though no harmful effects of BCG vaccination on the fetus have been observed. Interpreting Tuberculin Skin Test Results in BCG-Vaccinated Persons In persons vaccinated with BCG, sensitivity to tuberculin is highly variable, depending upon the strain of BCG used and the group vaccinated. The presence or size of a postvaccination tuberculin skintest reaction does not predict whether BCG will provide any protection against TB disease. Furthermore, the size of a tuberculin skin-test reaction in a BCGvaccinated person is not a factor in determining whether the reaction is caused by M. tuberculosis infection or the prior BCG vaccination. Tuberculin skin testing is not contraindicated for persons who have been vaccinated with BCG, and the skin-test results of such persons are used to support or exclude the diagnosis of M. tuberculosis infection. A diagnosis of M. tuberculosis infection and the use of treatment of latent TB infection should be considered for any BCG-vaccinated person who has a tuberculin skin-test reaction of >=10 mm of induration, especially if any of the following circumstances are present: The vaccinated person is a contact of another person who has infectious TB, particularly if the infectious person has transmitted M. tuberculosis to others; The vaccinated person was born or has resided in a country in which the prevalence of TB is high; or The vaccinated person (e.g., some health care workers, employees and volunteers at homeless shelters, and workers at drug-treatment centers) is exposed continually to populations in which the prevalence of TB is high. Treatment of latent TB infection should be considered for BCG-
A New lease of life TPH rises from Ashes ETech. in eye surgery New Annexe for TPH Case Studies Gynaec tumor surgery A typical delivery case Remedy from Squint Other Links Best Indian Hospitals Jamshedpur hospitals Dhanbad hospitals Ranchi hospitals Ranchi Nursing homes Community/Health Family Welfare Bagbera Dispensary Lafarge OHC Tariffs Bed charges Operations charges Working Hours General working hours Clinical working hours Immunizational clinics ICU/Trauma center ICU Trauma center T C John center Health Care Patient's Feedback
vaccinated persons who are infected with HIV and who are at risk for M. tuberculosis infection if they have a tuberculin skin-test reaction of >= 5 mm induration. BCG-vaccinated persons who have a positive reaction to the tuberculin skin test, but who do not have TB disease, should be evaluated for treatment of latent TB infection. The possibility of TB disease should be considered for BCG-vaccinated persons who have symptoms suggestive of TB.
Tinplate Hospital P.O.Golmuri, Jamshedpur Phone: +91-0657-2340512, EPABX: 2340713-720 Site Developed by MSD(TCIL)
OI: Turberculosis -- GIS
Turberculosis
"TB" "MDR-TB" (multi-drug resistant TB)
This is part of a series on Opportunistic Infections ("OIs"). Please note that -1. This Page Is Just A Starting Point: GIS is a great place for you to find overview information about HIV and opportunistic infections, but it is not a substitute for getting medical advice from a doctor who specializes in treating HIV. 2. Finding The Latest Information: Advances in treating opportunistic infections can happen at any time, so the material on this page may be outdated. Some links in the see also section at the bottom of this page are actually special database links. They may contain information published after this page was written.
Tuberculosis (TB) is a dangerous -- often deadly -- disease. Testing, preventative measures, and aggressive treatment are important. TB is the most common opportunistic infection.
Classification
Infection with Mycobacterium tuburculosis
Description
q
Infection: TB is transmitted when a person with active TB coughs or sneezes, releasing microscopic particles into the air. These particles, also called droplet nuclei, contain live tubercle bacteria, and may result in infection when inhaled by another person. Once infected by TB, most people, remain healthy and develop only latent infection. People with latent infection are neither sick nor infectious. However, they do have the potential to become sick and infectious with active TB. (GMHC) An earli OI: Active TB often occurs early in the course of HIV infection, often months or years before other OIs. In fact, TB may be the first indication that a person is HIV-infected. TB also causes disease outside the lungs of HIV-infected people, particularly in the later stages of AIDS. (NIH)
http://www.aegis.com/topics/oi/oi-tb.html (1 of 3) [05/01/06 2:52:55]

q
Multi-drug Resistant TB: Of particular concern for people with AIDS is multi-drugresistant TB (MDR-TB). MDR-TB occurs when patients fail to take their TB medicine for the prolonged periods necessary to destroy all parts of the TB organism and it becomes resistant to the drugs. These resistant organisms can be spread to other people. Even with treatment, for individuals coinfected with HIV and MDR-TB, the death rate may be as high as 80 percent, as opposed to 40 to 60 percent for people with MDR-TB alone. The time from diagnosis to death for some patients with HIV and MDR-TB may be only months as they are sometimes left with no treatment options. (NIH) In about half of the HIV+ people with TB, the infection involves more than just the lungs. Other targets include the lymphatic system. Symptoms include: cough, fever, night sweats, weight loss, fatigue. Diagnosis is usually made with a skin test. The US Centers For Disease Control considers TB an AIDS-defining condition.
q q q
Danger Zone
q
TB is more frequent for those with CD4+ cells less than 200/mm but can occur at any CD4+ count.
NOTE: If you are undergoing treatment that has increased your CD4+ levels, see the important note on Naive T-Cells. There is some evidence that you should use the lowest CD4+ level you ever had when considering your risk for some opportunistic infections.
Prevention
q
q q
The US CDC recommends treatment for any HIV+ person with latent (inactive, no symptoms) M. tuberculosis. That diagnosis is made using skin tests. Prophylaxis (prevention) is usually isoniazid. Outside the US, BCG vaccination has been used for the prevention of TB.
NOTE: Many HIV experts stress that it is important that anyone newly diagnosed as being HIVpositive be given a "TB with anergy" test. That is a test for TB, mumps, and candida. Those with severely damaged immune systems can show false negative results on the TB test. 1. If you test positive for TB, you are infected with TB. 2. If you test negative for TB but positive for mumps or candida, you do not have TB. This is the result you want! Those with functioning immune systems will test positive for mumps, candida, or both ... so a positive result on these tests means the negative TB test can be
trusted. 3. If you test negative for all three, then you have anergy, which means your immune system is to damaged to respond to common antigens.
Treatment
s
Treatment usually includes multiple drugs: isoniazid, rifampin, pyrazinamide, ethambutol (or streptomycin). Some mutations of TB are resistant to some of the common drugs. There are susceptibility tests that can show which drugs will work on a particular strain. The US CDC recommends DOT (directly observed therapy) -- where a nurse watches each drug dose being taken. The biggest reason for TB treatment failure is a failure to take the medicines. Some with late-stage AIDS have trouble absorbing the drugs. Doctors can sometimes run tests to see if malabsorption is a problem.
See Also...
s s s
GIS Knowledgebase: TB Drugs GIS Knowledgebase: TB Clinical Trials GIS Knowledgebase: AIDSline TB Articles Being Alive newsletter: TB Screening NIAID Alert: TB and HIV Replication GMHC: What TB Is (1993) Yahoo! Tuberculosis web sites
s s s s
This information is designed to support, not replace, the relationship that exists between you and your doctor.
1998. AEGIS.
Tuberculosis Association of Ohio County
Tuberculosis Association of Ohio County

HOME HOLIDAY SEALS PROGRAMS HISTORY TB FACTS LOCATION CONTACT LINKS
TB is at the lowest rate of increase since it's emergence in the 1980's according to the CDC.
The Tuberculosis Association of Ohio County is a nonprofit organization located in Wheeling, West Virginia. The association has been providing programs and services for the residents of Ohio County since 1909.
q
Our mission is to combat tuberculosis and other primary lung diseases in the Ohio county area through prevention, treatment, and education.
Unlike many organizations which funnel contributions to a national headquarters, we use our funds locally, to benefit Ohio County residents. The money is not used for high administrative salaries and bureaucratic costs; it is used almost exclusively to fund preventive medical programs, scholarships and community service projects in Ohio County. Generous local donors can see the good things their contributions accomplish.
http://www.tboc.org/ [05/01/06 2:54:46]
Home Page
TB All Time Low in Chicago in 2001

Click on the dancing drug on bug icon to enter Web site for TB Chicago is hosted as a service to the public and is not an agency of any governmental organization Sponsors: Drs. Bapu P. and Vijaya L. Arekapudi Lake Shore Medical Associates, Ltd. Webmaster & Hostmaster: Bapu P. Arekapudi, M.D Disclaimer
http://www.tbchicago.org/ [05/01/06 3:14:43]
TBC India
Procurement Info | Method of Calculation
TUBERCULOSIS CONTROL - INDIA

In terms of population coverage, India now has the second largest DOTS (Directly Observed Treatment, Short course) programme in the world. However, India's DOTS programme is the fastest expanding programme, and the largest in the world in terms of patients initiated on treatment, placing more than 100,000 patients on treatment every month. This site provides information about tuberculosis and its control in India. Click here to see RNTCP implementation in India
WHO-recommended Directly Observed Treatment, Short Course (DOTS) strategy was launched formally as Revised National TB Control programme in India in 1997 after pilot testing from 1993-1996. Since then DOTS has been widely advocated and successfully applied. DOTS is the most effective strategy available for controlling TB The five key components More..
In India today, like any other day this year, more than 1,000 people will die from tuberculosis (TB) But these deaths can be prevented. With proper care and treatment, TB patients can be cured and the battle against TB can be won... More...
Indian TB Programme officers
Strategic Vision Document of the RNTCP
http://www.tbcindia.org/ [05/01/06 3:16:46]

Book Tuber

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Book Tuber

Uploaded by

Copyright:

Available Formats

TUBERCULOSIS

Selected Internet Resources

Mara Elena Sarmiento Garca-San Miguel

Vicepresidency of Research Finlay Institute, La Habana, Cuba

Havana City, December, 2005

Sobre la presente edicin: Finlay Ediciones, 2005

Finlay Ediciones Ave. 212 No. 3112 e/ 31 y 37, La Coronela, La Lisa,

Ciudad de La Habana, Cuba

THE UN SECRETARY-GENERAL KOFI A. ANNAN

THE AUTHORS La Habana, Cuba, May 2005.

TUBERCULOSIS SELECTED WEB SITES AND LINKS

International Union Against Tuberculosis and Lung Disease ... www.hcpartnership.org/Topics/tuberculosis.php

List of Noted Tuberculosis Victims

SOME CUBAN MASTER PAINTERS VICTIMS OF TB...

Carlos Enrquez (1900 - 1957)

Arstides Fernndez (1904-1934)

All WHO This site only

A partnership housed by WHO Global Drug Facility

TB PUBLICATIONS WHO publications on tuberculosis Most recent

Damien Foundation Bangladesh

WHO Report 2005: Global Tuberculosis Control Read online

http://www.who.int/tb/en/ (1 of 2) [23/08/05 16:42:20]

HIV/AIDS, Tuberculosis and Malaria (HTM) Newsletter View most recent

http://www.who.int/tb/en/ (2 of 2) [23/08/05 16:42:20]

Canada's Role in Fighting Tuberculosis, Yesterday, Today, and Tomorrow.

CANADA's ROLE in FIGHTING TUBERCULOSIS

Tuberculosis History in Canada Tuberculosis

Tuberculosis in Canada Today A "cure" was found

http://www.lung.ca/tb/ [23/08/05 17:08:30]

Aeras Global TB Vaccine Foundation

Denmark Becomes First European Country to Support Aeras

http://www.aeras.org/ (1 of 2) [23/08/05 17:10:36]

Aeras Global TB Vaccine Foundation

http://www.aeras.org/ (2 of 2) [23/08/05 17:10:36]

AMEDEO, The Medical Literature Guide - Scientific Information in Medicine

Free Medical Information: Doctor = Publisher

In addition, AMEDEO presents

http://amedeo.com/index.htm (1 of 2) [23/08/05 17:12:42]

AMEDEO, The Medical Literature Guide - Scientific Information in Medicine

http://amedeo.com/index.htm (2 of 2) [23/08/05 17:12:42]

Global Drug Facility

Calendar of Events Subscribe to the Stop TB Mailing List

http://www.stoptb.org/errorpages/404.asp (2 of 2) [05/12/05 22:15:20]

All WHO This site only

http://www.who.int/tb/publications/advocacy_report_2003/en/index.html [05/12/05 22:16:01]

All WHO This site only

TB cases and deaths linked to HIV now at alarming levels in Africa

http://www.who.int/tb/features_archive/wtbd2005/en/index.html (1 of 2) [05/12/05 22:21:30]

For more information, please contact:

http://www.who.int/tb/features_archive/wtbd2005/en/index.html (2 of 2) [05/12/05 22:21:30]

: The AMEDEO Literature Guide

2.1. Account Information E-mail:

http://amedeo.com/medicine/hep.htm (1 of 4) [05/12/05 22:22:12]

: The AMEDEO Literature Guide

2.2. Location Country:

2.3.1. Medical/Clinical Profession:

Phone number: (optional)

2.3.3. Student 2.3.4. Pharmaceutical Company 2.3.5. Press/Media 2.3.6. Consumer/Other

2.4. We welcome your comments

http://amedeo.com/medicine/hep.htm (2 of 4) [05/12/05 22:22:12]

: The AMEDEO Literature Guide

How did you hear about us?

Comments and suggestions:

Thank you for your interest in scientific medicine.