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Marburg Virus
Ebola virus
o Genome: (-) sense, nonsegmented, single-stranded RNA
o Size: 19kb
o 7 polypeptides
o Enveloped
o Replication: Cytoplasm
o Assembly: budding from plasma membrane
FLAVIVIRIDAE
Flavivirus (Japanese B Encephalitis)
o Shape: Spherical
o Diameter: 40-60nm
o Genome: (+) sense, single-stranded RNA (infectious)
o Size: 11kb
o 3 structural polypeptides; 2 glycosylated
o Enveloped
o Replication: Cytoplasm
o Assembly: within endoplasmic reticulum
Hepatitis C has NO ARTHROPOD VECTOR and is NOT AN ARBOVIRUS
TOGAVIRIDAE
Alphavirus (Chikungunya)
o Shape: Spherical
o Diameter: 70nm
o Nucleocapsid: 42 capsomeres
o Genome: (+) sense, single-stranded RNA
o Size: 11-12kb
o 3 or 4 major structural polypeptides; 2 glycosylated
o Enveloped
o Replication: Cytoplasm
o Assembly: budding through host cell membranes
Antigenically related
Inactivated by acid pH, heat, lipid solvents, detergents, bleach, phenol, 70% alcohol, and formaldehyde
MOST possess hemagglutinating ability
Rubella virus has NO ARTHROPOD VECTOR and is NOT AN ARBOVIRUS
Replicase & transcriptase – needed for viral RNA replication
CLINICAL FINDINGS (Encephalitides)
Incubation period: between 4-21 days
Sudden onset
Fever lasts 4-10 days
LABORATORY DIAGNOSIS
Appears in blood only in EARLY INFECTION (before onset of symptoms)
Can be found in CSF and tissue specimens
Alphaviruses and flaviviruses are usually unable to grow in common cell lines, such as:
o Vero
o BHK
o HeLa
o MBC
Mosquito cell lines are useful
Intracerebral inoculation of suckling mice or hamster may also be used
Antigen detection and PCR assays are used for direct detection of viral RNA
IMMUNITY
Believed to be permanent after a single infection
Humoral antibody and cellular immune responses are important
EPIDEMIOLOGY
Most infections are ASYMPTOMATIC
Most cases occur in summer months when arthropods are most active
ANTIGENIC PROPERTIES
HI, ELISA, and IMMUNOFLUORESCENCE TESTS define 8 antigenic complexes or serogroups of
alphaviruses
Neutralization test – identification of a specific virus
PATHOGENESIS AND PATHOLOGY
MYELOID and LYMPHOID CELLS or VASCULAR ENDOTHELIUM – where primary viral
multiplication occurs
Multiplication in the CNS depends on the ability of the virus to pass the blood-brain barrier to infect
nerve cells
Japanese B Encephalitis Virus
Leading cause of viral encephalitis in Asia
50,000 cases in China, Japan, Korea, and Indian subcontinent
10,000 deaths among children and elderly adults
30% mortality rate
50% survival rate but left with neurologic and psychiatric sequelae
300:1 – ratio of asymptomatic to symptomatic infections
Host: Swine (important)
o Mosquito-bird-mosquito cycle also occurs
o Mosquitos remain infected for life
o ONLY female mosquitoes feed on blood and can transmit the virus more than once
o Mosquito’s midgut: site of primary viral multiplication
Treatment: none
Vaccine: Available in Asia
o Inactivated Vero cell culture-derived vaccine (US, 2009)
Chikungunya Virus
Mosquito-borne alphavirus
Semliki Forest antigenic complex
Reemerged in Kenya in 2004 after an absence of several decades and subsequently caused massive
outbreaks of infection in India, southeastern Asia, and the Indian Ocean region
Outbreak in Italy 2007
Cases reported from returning travelers in US
Established in Carribean region in 2013 and spread rapidly
Resembles a dengue fever, rash, and severe joint pain
Asymptomatic infections are rare
Vaccine: not available
Dengue
Also known as breakbone fever
Caused by flavivirus
Characterized by:
o Fever
o Severe headache
o Muscle and joint pain
o Nausea
o Vomiting
o Eye pain
o Rash
Occur in severe forms:
o Dengue hemorrhagic fever
o Dengue shock syndrome
CLINICAL FINDINGS
Disease begins 4-7 days after an infective mosquito bite
Onset of fever may be sudden
Prodromal symptoms: malaise, chills, and headache
Back, joint, and muscle pain then develops
Fever lasts from 2 to 7 days (peak viral load)
Myalgia and deep bone pain (breakbone fever) are characteristic
Enlarged lymphnodes
Severe syndrome (DHF and DSS) may occur in children with passively acquired (maternal antibody)
infection
o Key pathological feature: increased vascular permeability with plasma leakage
LAB DIAGNOSIS
RT-PCR – rapid identification and serotyping of dengue virus in acute-phase serum
Isolation of virus is difficult
Serologic diagnosis: cross-reactivity of IgG antibodies to heterologous flavivirus antigen
o ELISA and HI
EPIDEMIOLOGY
Distributed worldwide in tropical regions where Aedes vectors exist
2008 – most important mosquito-borne viral disease affecting humans
A. aegypti - primary vector for dengue in the Western Hemisphere
WW2 was responsible for the spread of dengue from SE Asia throughout the Pacific region
Only type 2 dengue was present in America for years
1977 – dengue type 1 was detected in the Western Hemisphere
1981 – dengue type 4
1994 – dengue type 3
2005 – first case of dengue hemorrhagic fever in US 2005
A. albopictus – mosquito of Asian origin, was discovered in Texas (1985)
o Replaced A. aegypti which cannot overwinter in the northern states
TREATMENT AND CONTROL
No antiviral drug therapy
Fluid replacement therapy – DHF
No vaccine
Control: antimosquito measures
o Elimination of breeding places
o Use of insecticides
o Screened windows and doors
FILOVIRUSES
Pleomorphic particles
Appear as long filamentous threads or as an odd-shaped forms 80nm in diameter
Highly virulent and require maximum containment facilities (Biosafety level 4)
Destroyed by:
o heating for 30 minutes @ 60C
o ultraviolet and gamma-radiation
o lipid solvents
o bleach and phenolic disinfectants
Natural hosts and vectors are suspected to be African fruit bats
Marburg virus and Ebola virus
Incubation period: 3 to 9 days (Marburg); 2-21 days (Ebola)
Characterized by fever, headache, sore throat, and muscle plain followed by abdominal pain, vomiting,
diarrhea, and rash with external and internal bleeding
Tropism: cells in macrophage system, dendritic cells, interstitial fibroblasts, endothelial cells
Possess the highest mortality rates (25-90%) among all the viral hemorrhagic fevers
Reservoir host: fruit bats
Accidental host: humans
Natural reservoirs are still unknown
Marburg virus
Recognized in 1967
Laboratory workers exposed to tissues of African green monkeys (Cercopithecus aethiops)
Outbreaks documented in:
o Kenya
o South Africa
o Democratic Republic of Congo
o Angola
Can infect guinea pigs, mice, hamsters, monkeys
Ebola Virus
Discovered in 1976 when two severe epidemics of hemorrhagic fever occurred in Sudan and Zaire (now
Democratic Republic of Congo)
More than 500 cases and at least 400 deaths during outbreaks
Hospital staff became infected through close and prolonged contact with patients and their blood
Zaire and Sudan subtypes are highly virulent
Mean time to death (7-8 days)
Western Africa 2014 – largest known Ebola outbreak
September 30, 2014 – first confirmed case by CDC of travel-associated case of Ebola in US
Lab Diagnosis
Infections appear to be immunosuppressive
Fatal cases show impaired humoral immune responses
Filovirus antibodies are detectable by ELISA
Viral antigens in serum – ELISA (rapid screening test)
RT-PCR – clinical specimens
Culture: Vero and MA-104 monkey cell lines
Zika Virus
February 2017 (Philippines)
Asymptomatic
Characterized by
o Myalgia (muscle pain)
o Joint paint
o Retro orbital pain
Associated with Guillan-Barre syndrome
Ebola
Zaire and Sudan Ebola virus – responsible subtype for Africa Outbreak (2014-2016)
Reston Ebola virus – subtype found in Philippines (2015)
o From monkeys, does not cause disease to humans
First outbreak in US (1989) among laboratory monkeys
Chikungunya
Name came from Kimakonde language of Tanzania and Mozambique meaning “to become contorted”
Outbreak in Indang, Cavite (September 2016)
Vector may be A. aegypti or A. albopictus
Characterized by severe muscle and joint pain