Viral Infections of Respiratory Tract

Question 1

Influenza Virus: family, structure and glycoproteins, medically important types, nomenclature

Answer 1

Orthomyxoviridae (80-120 nm, pleomorphic, characteristic fringe)
- enveloped, -ve ssRNA

8 segments – each corresponds to a gene

• envelop glycoproteins –> neuraminidase (NA) and haemagglutinin (HA)
  - induces immune responses: 18 H and 11 N subtypes
• internal genes e.g. M2, PB1, PB2

Influenza A-D:
- A: affects humans, birds, pigs
- B: affects almost exclusively humans, slower mutation rates
(- C: affect humans, minor symptoms)
- D doesn't affect humans

Nomenclature
- type/origin/strain/year of isolation

Question 2

Mode of Transmission

Answer 2

Respiratory

• droplet (1m)
• airborne? for new flu

Direct contact

• fomites – direct contact with respiration contaminated items
• survive in env up to 48 hrs
• easily disinfected (because enveloped): >56 degrees, Hibiscrub, alcohol, soapy water

Question 3

Clinical Presentation: common features, younger children presentations, elderly presentations

Answer 3

Usually infectious one day prior to symptoms

More commonly as URTI - influenza-like illness
(LRTI in avian flu)

Abrupt sudden onset of fevers, chills, headache, myalgia, sore throat, dry cough

• indistinguishable from other viral or bacterial infections
• fever and dry cough more in flu/ rhinorrhea and nasal congestion in common cold

Younger children:

• non-specific febrile illness
• higher viral load (longer duration of symptoms)
• bronchiolitis, croup, otitis media, vomiting

Elderly:
- sputum production, dyspnea

Question 4

Pathogenesis of Antigenic drift: definition, which types, consequence (2)

Answer 4

= accumulation of MINOR antigenic changes due to replication error of RNA polymerase (are 1/10^4 bases)

Usually Influenza A and B

Consequence: EPIDEMIC

• type A H3N2, H1N1, B
• mild in healthy adults
• severe in high risk groups

Question 5

Pathogenesis of Antigenic shift: definition, which types, consequence (3)

Answer 5

= gene reassortment of segments of genome between 2 different strains, forming a new subtype with a mixture of surface antigens - MAJOR change

Due to co-infection of 2 subtypes in the same cell

Usually Influenza A
Aquatic birds as gene pool (prone to most subtypes of H and N) –> humans and pigs as intermediate host

Consequence: PANDEMIC

• production of novel subtype with no immunity in population
• high mortality in general population

Question 6

Diagnostic approach: specimen of choice, benefits, requirements, detection methods (3)

Answer 6

• **Nasopharyngeal Aspirate: BEST SPECIMEN
• NP>nasal, oral, oropharynx
• higher virus yield than swab
• requires negative pressure and PPE
• least contamination
• can do culture

Other options: nasal or throat swab

Detection method

• direct detection: IF (rapid POCT)
• reverse-transcriptase PCR: standard - 1st line method; real-time PCR
• cell culture: gold standard but rarely used as takes too long (use in vaccine development)

Question 7

Antiviral treatment: types of drugs, mechanism of action, examples of common drugs used and their dosage/ side effects

Answer 7

M2 channel blockers e.g. amantadine

• interfere with uncoating
• not used due to resistance
• ineffective for influenza B

NA inhibitors

• normal fx of NA is to cleave sialic acids on host cell surface allowing release of progeny viruses
• inhibitors are analogues of sialic acid –> block active site of NA –> uncleaved sialic acid residues bind to HA
• —> aggregation of progeny viruses on host surface
• —> decreased virion release through secretion
• —> decrease viral penetration into host
• also promotes pro-inflammatory cytokines

Zanamivir - inhaled powder BD, bronchospasm, no renal adjustment
Oseltamivir - oral capsule BD, GI symptoms, QD if Cr 10-30ml/min

Question 8

Newer antiviral drug

Answer 8

Cap dependent endonuclease inhibitor
Baloxavir
- interfere with RNA transcription and viral replication
- single oral dose
- GI upset, headache
- renal adjustment if Cr<50 ml/min

Question 9

Vaccination: types, components, duration of protection, efficacy, high risk groups (5)

Answer 9

Most inactivated vaccines

• trivalent or quadrivalent: 2 strains of A and 1-2 strains of B
• —> short duration of protection (6-9 months) - repeat every year
• —> WHO recommendations in Feb for northern hemisphere and Sep for southern
• —> efficacy depends on matching of strains (generally 70-90% prevention in healthy and reduce severe illness by 50% in high risk groups)

High risk groups = extreme ages (>65 or 6mths-12yrs), pregnant, chronic disease (CVS, lung, renal), healthcare workers, poultry workers

Live attenuated vaccine

• intranasal
• similar composition to trivalent
• for ages 2-49

Question 10

Seasonality of epidemics: temperate vs subtropical, implications

Answer 10

Temperate region: 1 peak - winter

Tropical/ Subtropical: 2 peaks - winter (Feb/Mar) and summer (Jun/Jul) for Type A, summer peak less consistent for Type B

Implications: timing of vaccine and vaccine efficacy (as strain determined much ahead of vaccine)

Question 11

Other viral causes of respiratory infection: Paramyxoviridae - recall structure, any subtypes for each virus, clinical presentations, seasonality

Answer 11

• 90-300 nm, pleomorphic, less obvious fringe
• enveloped, -ve ssRNA

Respiratory Syncytial Virus

• subgroups A and B
• more severe in CHILDREN AND ELDERLY
• Most common cause of severe LRTI in infants e.g. 50-90% BRONCHIOLITIS, bronchopneumonia, croup (10%)
• mild disease in adults e.g. bronchitis, coryza-like illness
• high risk infants given MONOCLONAL Ab FOR PROPHYLAXIS (congenital heart, underlying pul disease, immunocompromised)
• seasonality: winter in temperate regions, variable and longer in tropical regions

Parainfluenza virus

• 5 serotypes (closely related to mumps)
• Most common presentation as CROUP in infants (laryngotracheobronchitis): barking cough, stridor, hoarseness, SOB
• adults: barking cough, sub glottal swelling, pneumonia, bronchitis etc
• supportive treatment

Question 12

Other viral causes of respiratory infection: Adenoviridae - recall structure, any subtypes, clinical presentations

Answer 12

70-75 nm, hexagonal, monomorphic

• non- enveloped dsDNA
• 7 subgenera (A-G)
• > 60 serotypes (3,4,7 most common)

Pharyngitis as most common presentation
Others: pharyngoconjuntival fever, pneumonia, conjunctivitis

Question 13

Overall DDx (6)

Answer 13

Infuenza A, B, C
Parainfluenza virus
RSV
Adenovirus
Rhinovirus, Enterovirus
SAR-CoV