Upper Respiratory Tract Infections

Dr M. Kothalawela Infection 2 2009/10 batch

Burden of URI
Significant morbidity and direct health care costs Direct costs of $ 17 billion annually Occasionally leads to fatal illness Excessive use of antibiotics a major issue

Common URI terms are defined as follows:

Rhinitis - Inflammation of the nasal mucosa Rhinosinusitis or sinusitis - Inflammation of the nares and paranasal sinuses, including frontal, ethmoid, maxillary, and sphenoid Nasopharyngitis (rhinopharyngitis or the common cold) Inflammation of the nares, pharynx,hypopharynx, uvula, and tonsils Pharyngitis - Inflammation of the pharynx, hypopharynx, uvula, and tonsils Epiglottitis (supraglottitis) - Inflammation of the superior portion of the larynx and supraglottic area Laryngitis - Inflammation of the larynx Laryngotracheitis - Inflammation of the larynx, trachea, and subglottic area Tracheitis - Inflammation of the trachea and subglottic area

The Common Cold (Rhinitis)

Children average 8 per year, adults 3 Etiologies :
Rhinoviruses 30 to 35% Coronaviruses about 10% Miscellaneous known viruses about 20% Influenza and adenovirus-30% Presumed undiscovered viruses up to 35% Group A streptococci 5% to 10%

Parainfluenza was the first respiratory virus isolated (1955) Seasonal variation
Rhinovirus early fall Coronavirus- winter

Describe the scientific basis of

A person may have more than one episode of common cold while get only one episode of chickenpox for life

The common cold

Transmission of rhinoviruses
Direct contact is the most efficient means of transmission: 40% to 90% recovery from hands. Infectious droplet nuclei Brief exposure (e.g., handshake) transmits in less than 10% of instances Kissing does not seem to be a common mode of transmission.

Clinical characteristics
Incubation period 12-72 hours Nasal obstruction, drainage, sneezing, scratchy throat Median duration 1 week but 25% can last 2 weeks Pharyngeal erythema is commoner with adenovirus than with rhino or coronavirus

Acute bacterial sinusitis

Epidemiological studies suggest 1 billion cases of viral rhinosinusitis occur annually in the US Of these0.5-2% are complicated by bacterial sinusitis Viral infection--> obstruction of ducts and compromise of mucocilary blanket--> acute infection from virulent organisms (most often S. pneumoniae and H. influenzae)--> opportunistic pathogens Nose blowing generates high intranasal pressures that deposit bacteria into the sinus cavity More common in adults than in children

Paranasal sinuses

Sinusitis
Community acquired bacterial sinusitis
S.pneumoniae H. influenzae S. pyogenes

Nosocomial sinusitis
Seen in critically ill, mechanically ventilated
S. aureus Pseudomonas aeruginosa Serratia marcescens

fungal

Clinical features
Clinical features
Sneezing Nasal discharge Facial pressure Fever Purulent drainage Headache

Sinus imaging not routinely recommended

Acute sinusitis: complications

Maxillary: usually uncomplicated Ethmoid: cavernous sinus thrombosis-serious Frontal: osteomyelitis of frontal bone; cavernous sinus thrombosis; epidural, subdural, or intracerebral abscess; orbital extension Sphenoid: Rare; extension to internal carotid artery, cavernous sinuses, pituitary, optic nerves; common misdiagnoses include ophthalmic migraine, aseptic meningitis, trigeminal neuralgia, cavernous sinus thrombosis

Chronic sinusitis
The previous patient had an invasive aspergillus sinusitis as a result of chronic high dose steroid therapy, resulting in occlusion of carotid artery and invasion into the brain. She died in a month. Bacterial: Cultures show a variety of opportunistic pathogens including anaerobes but problem is mainly anatomic, not microbiologic Fungal: suspect especially when a single sinus is involved;

Spectrum of fungal sinusitis

Simple colonization Sinus mycetoma (fungus ball) Allergic fungal sinusitis Acute (fulminant) invasive sinusitis (notably, rhinocerebral mucormycosis) Chronic invasive fungal sinusitis

Acute pharyngitis
Inflammatory syndrome of the pharynx
Most cases are viral Most important bacterial cause is Streptococcus pyogenes (15-20%)

Presents with sore or scratchy throat In severe bacterial cases there may be odynophagia, fever, headache

Acute pharyngitis: physical exam

Viral: edema and hyperemia of tonsils and pharyngeal mucosa Streptococcal: exudate and hemorrhage involving tonsils and pharyngeal walls Epstein-Barr virus (infectious mono): may also cause exudate, with nasopharyngeal lymphoid hyperplasia

Pharyngoconjuntival fever
Adenoviral pharyngitis Pharyngeal erythema and exudate may mimic streptococcal pharyngitis Conjunctivitis (follicular) present in 1/3 to 1/2 of cases; commonly unilateral but bilateral in 1/4 of cases

Vincents angina and Quinsy

Vincents angina: anaerobic pharyngitis (exudate; foul odor to breath) Ludwigs angina- cellulitis of dental origin Quinsy: peritonsillitis/peritonsillar abscess. Medial displacement of the tonsil; often spread of infection to carotid sheath

Diphtheria
Classic diphtheria (Corynebacterium diphtheriae): slow onset, then marked toxicity Arcanobacterium hemolyticum (formerly Cornyebacterium hemolyticum): exudative pharyngitis in adolescents and young adults with diffuse, sometimes pruritic maculopapular rash on trunk and extremities

Diphtheria fibrous

pseudomembrane with necrotic epithelium and leukocytes

Miscellaneous causes of pharyngitis

Primary HIV infection Gonococcal infection Diphtheria Yersinia entercolitica (can have fulminant course) Mycoplasma pneumoniae Chlamydia pneumoniae

Treatment
Symptomatic Penicillin for Strep throat Macrolides for pen allergic patients Add an anti-anaerobic agent for Vincents and Ludwigs angina

Acute laryngotracheobronchitis (croup)

Children, most often in 2nd year Parainfluenza virus type 1 most often in U.S.A. but other agents are Mycoplasma pneumoniae, H. influenza Involvement of larynx and trachea: stridor, hoarseness, cough Subglottic involvement: high-pitched vibratory sounds Can lead to respiratory failure (2% get hospitalized)

Acute epiglottitis
A life-threatening cellulites of the epiglottis and adjacent structures Onset usually sudden (as opposed to gradual onset of croup); drooling, dysphagia, sore throat H. influenzae the usual pathogen both in children (the usual patients) and adults

Acute suppurative parotitis

Uncommon, but high morbidity and mortality Usually associated with some combination of dehydration, old age, malnutrition, and/or postoperative state S. aureus the usual pathogen

Deep fascial space infections of the head and neck

Several syndromes according to anatomic planes Can complicate odontogenic or oropharyngeal infection Ludwigs angina: bilateral involvement of submandibular and sublingual spaces (brawny cellulitis at floor of mouth)

Deep fascial space infections of the head and neck (2)

Lemierre syndrome: suppurative thrombophlebitis of internal jugular vein (Fusobacterium necrophorum) Retropharyngeal space infection: contiguous spread from lateral pharyngeal space or infected retropharyngeal lymph node; complications include rupture into airway, septic thrombosis of internal jugular vein

Severe acute respiratory distress syndrome (SARS)

Caused by a previously unrecognized coronavirus genome has now been sequenced. Clinical manifestations are similar to those of other acute respiratory illnessesnotably, influenza Cases in U.S.associated mainly with travel or as secondary contacts

SARS: Radiographic findings

Early: a peripheral/pleuralbased opacity (ground-glass or consolidative) may be the only abnormality. Look especially at retrocardiac area. Advanced: widespread opacification (ground-glass or consolidative) tending to affect the lower zones and often bilateral. Pleural effusions, lymphadenopathy, and cavitation are not seen.

Disease

Possible organisms

Preferred specimen

Disease

Possible organisms

Preferred specimen

Lower respiratory tract infections

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Respiratory tract

Anatomy of lower respiratory tractTrachea

Trachea 11-12cm tube, thickened by cartilage, which extends from the larynx into the thoracic cage. It is lined with pseudostratified epithelium, containing ciliated and mucous-secreting cells, and branches to form the left and right primary bronchi. It represents the change from upper to lower respiratory tract.

Bronchi
One primary bronchus supplies each lung. lined with pseudostratified, ciliated epithelium and, on entering the lungs, divide to form the secondary lobar bronchi, one for each lobe of the lungs. Each secondary bronchus divides to produce tertiary bronchi, which in turn produce the bronchioles

Bronchial tree
This successive branching produces a bronchial tree of ever decreasing diameter which is characterised by a gradual loss of cartilage, increase in smooth muscle within the wall and change from columnar to cuboidal epithelium.
16 divisions in neonates 23 divisions in adults

Lungs
Each lung is divided by fissures into lobes: 2 in the left (superior and inferior), 3 in the right (superior, middle and inferior). The lobes are further subdivided into lobules. The lungs are housed in a pleural membrane. Within the lobules, the bronchial tree is now at the level of the bronchioles and subsequently the alveoli. It is estimated that the adult human lung contains 300 million alveoli, which collectively offer a total surface area of 70m2 for gaseous exchange. The lungs therefore, are primarily composed of alveoli, the capillaries of the pulmonary circulation and connective tissue. Adequately perfused lungs may consist of 40% by weight of blood in the circulation.

Normal Host Defence Mechanisms

Mucocilliary escalator Phagocytosis Alveolar macrophages Lysozymes IgA Interferons

Bronchitis
Inflammation of the bronchial tubes Tissues become irritated More mucous then usual produced Results in cough

Acute bronchitis
Only lasts for a few weeks Generally viral in origin
Rhinovirus, parainfluenzae, RSV and Influenza

Can get secondary bacterial overgrowth

H. influenzae S. pneumoniae S.aureus Mycoplasma and Chlamidiya

Chronic respiratory diseases

Bronchiectasis Localised, irreversible dilation of part of the bronchial tree COPD This is a term used for a number of conditions including Emphysema Alveoli lose their elasticity resulting in shortness of breath Chronic bronchitis

COPD
Acute exacerbations generally caused by viruses (rhinoviruses, parainfluenza) Secondary bacterial invasion is extremely common (H.influenzae, Moraxella)

Pneumonia
Inflammation of the alveoli of the parenchyma of the lung with consolidation and exudation Cough Pleuritic pain Production of purulent sputum Fever

Pneumonia
Risk factors COPD Diabetes Cardiac / Renal failure Immunosuppression Reduced levels consciousness Anything that inhibits the gag / cough reflex

Community acquired pneumonia

S. pneumoniae H. influenzae Moraxella K. pneumoniae (Friedlanders bacillus)

Pasturella N. meningitidis

Hospital acquired pneumonia

Risk factors include mechanical ventilation Enterobactericiae Acinetobacter Pseudomonas apecies S.aureus (MRSA)

Atypical pneumonia
Mycoplasma pneumoniae (Eaton agent) Obligate human pathogen Epidemics occur at 4-6 year intervals Spread requires close contact Common in children <5 years mild illness Most common in 5-20 year age group walking pneumonia

Atypical pneumonias
Chlamydia pneumoniae Chlamydia psittaci Legionairres disease Q fever (Coxiella burnetti)

Hantavirus (ARDS)

Investigations for pneumonia

Blood culture Resp specimens/blood for viruses, chlamydia & mycoplasma Urine for legionella & pneumococcal antigen testing Sputum BAL Pleural fluid

Pneumocystis jiroveci- stains

Panel A shows typical pneumocystis cyst forms in a bronchoalveolar-lavage specimen stained with Gomori methenamine (x100). Thick cyst walls and some intracystic bodies are evident. WrightGiemsa staining can be used for rapid identification of trophic forms of the organisms within foamy exudates, as shown in Panel B (arrows), in bronchoalveolar-lavage fluid or induced sputum but usually requires a high organism burden and expertise in interpretation (x100). Calcofluor white is a fungal cyst-wall stain that can be used for rapid confirmation of the presence of cyst forms, as shown in Panel C (x400). Immunofluorescence staining, shown in Panel D, can sensitively and specifically identify both pneumocystis trophic forms (arrowheads) and cysts (arrows) (x400).

Overview
A. Basic Virology B. Flu, Seasonal flu, Avian flu, Swine flu and Pandemic Flu C. Transmission D. Specimen Collection and Transport E. Infection Control

A. Influenza viruses
Three main types
Influenza A Influenza B Influenza C

Influenza A Human, Mammals and Birds

Influenza B- Humans only, Only one sub type(But different strains)

The Agent A virus

Are Members of Ortho Myxo viridae family
Ortho Straight Myxo- Love mucus

Consists of Protein container covered with spikes & a 8 segmented genome

Two types of spikes

H type to attach the respiratory epithelium (Pathogencity) N type To break up the cell and spread further within host Infect more cells

H type is antigenic and antibodies formed against it, Only homo typic protection
17 H types and 9 M types (These are used to name the different viruses)

Influenza A subtypes
Different subtypes causes infections in different species Generally Avian Viruses cause infections in birds Human Strains cause infections in humans Inter species spread is minimal species barrier But occur @ Human animal interface

Sub types
Source Avian Influenza viruses Any type may be present but H5, H7 and H9 are common Influenza A ( H5) Influenza A (H7) Influenza A (H9) Swine origin H1, H2 and H3 Subtypes H5N1, H5N2, H5N3, H5N4, H5N5, H5N6, H5N7, H5N8, and H5N9 H7N1, H7N2, H7N3, H7N4, H7N5, H7N6, H7N7, H7N8, and H7N9. H9N1, H9N2, H9N3, H9N4, H9N5, H9N6, H9N7, H9N8, and H9N9 H1N1, H1N2, H2N1, H3N1, H3N2, and H2N3

Prominent Human

H1N1, and H3N2

Human and Avian subtypes are different

Difference @ Human subtype Avian Sub types

Overole Genetic differences PB2 RNA polymerase gene

Binding to Sialic acid receptors

52 key genetic differences exist between human and avian sub types Position 627 in RNA Same position codes for polymerase all human GLU subtypes- codes for LYS Until discovery of H5 N1 2-3 sialic acid 2-6 sialic acid receptors receptors Swine types binds to the both 2-3 and 2-6 sialic acid receptors

Man- Bird interface

Pig-Man Interface

B. 1. Flu
Common term used to describe clinical manifestation of infection caused by influenza viruses Influenza A, B, and C Clinical feature
Fever* or feeling feverish/chills Cough Sore throat Runny or stuffy nose Muscle or body aches Headaches Fatigue (tiredness) Some people may have vomiting and diarrhea, though this is more common in children than adults.

 Flu, which shows epidemic spread in certain Seasonal flu Usually due to human adapted sub types
Seasonal flu in northern hemisphere -October and as late as May Seasonal flu in southern hemisphere-

B 2. Seasonal Flu

In each flu season- 15% to 20% of population get flu during a season with average of 36,000 deaths (USA) Risk groups
Elderly, patients with chronic Respiratory infections, Diabetics, residents in Long term Care

These human adapted strains may change the antigenic structure in due to changes occur in genome antigenic drift

Seasonal Flu.
Every year, the public health officials of northern hemisphere look out for Virological Surveillance for Infkuenza A and B and Novel Viruses Outpatient Illness Surveillance (ILI) and SARI Mortality Surveillance - from influenza A like illnesses Influenza-Associated Pediatric Mortality Surveillance System Hospitalization Surveillance from SARI and ILI Summary of the Geographic Spread of Influenza In parallel, a surveillance is going on in southern hemisphere as well

We too, carry out them in smaller scale ILI, SARI, and Sentinel site surveillance too.

National Influenza Reference Centre in MRI

B 3 Avian Flu(Bird Flu)

Flu in birds May be due to two types of agents
HPAI LPAI

All are due to Influenza A viruses

LPAI virus- causes Milder disease HPAI severe disease and may cause death among large herds

If found to be positive in a herd- CULLING is advices in order to prevent further spread So far not reported in SL A rare possibility of transferring to humans at Human animal interface High Mortality

B 4. Swine Influenza
Also known as
pig influenza, swine flu, hog flu and pig flu

Infection by one of several types of swine influenza viruses SIV or S-OIV (Viruses endemic to pigs) H1N1, H1N2, H2N1, H3N1, H3N2, and H2N3.

Swine Flu

B 5. Pandemic Flu
When usually influenza illnesses spread across continents with huge mortality among humans Usually due to appearance of novel virus strain which is transmissible from person to person As the people lack immunity to Large numbers succumbed Cytokine Storm Due to major change of genome due to re-assortment

Pandemic Influenza Viruses

Are Novel viruses Due to re-assortment, Completely new virus where no one is immune Ex
1918 1919 (spanish flu) Killed 20 to 50 million H1N1 1957 1958(Asian flu) Killed 3 million- H2N2 1968 1969 (Hong Kong flu) Killed 1 million- H3N2 2009 2010 Killed 18,000 world wide H1N1

C.Transmission
Infected asymptomatic and Infected symptomatic
When Sneeze or talk
Direct spread Up to 6 feet through droplets Indirect spread- via surfaces and fomites through contact

Flu is contagious
Healthy adults with disease -infectious one day before symptoms to 5 to 7 d after become sick Children - infectious >>7 days

Some may get asymptomatic disease- but still spread the disease

D. Specimen collection and transportation

National Influenza Centre

Sample collection
Personal Protective Equipment N95 mask, gloves, gown Timing : Early as possible (<7 days), before starting antivirals Sample into sterile, externally screw capped container with VTM Stored and transported at +4oC (not more than 72 hours)

National Influenza Centre

National Influenza Centre

National Influenza Centre

E. Infection Control
Prevent Infection transmission