Influenza

Question 1

Influenza - Epidemiology

Answer 1

15-20%
kid infected (miss school) -> parent infected (miss work) -> epidemic

Question 2

Influenza - Viral Structure

Keywords: Orthomyxovirus Family, Hemagglutinin (HA), Neuraminidase (NA)

Answer 2

Orthomyxovirus Family
- Spherical, enveloped, ssRNA(-) sense, segment genome (8pcs), replication in the nucleus of the infected cells

Hemagglutinin (HA)

• Bind with sialic acid receptors (viral entry)
• Agglutinates RBS
• Antigenic (neutralizing)

Neuraminidase (NA)

• Cleaves sialic (neuraminic) acid to release virus
• Degrades mucin
• Antigenic (non-neutralizing)

Question 3

Influenza - Serology

3 Subgroups

Answer 3

Influenza A - human and animals (pandemic)
Influenza B - human (epidemic)
Influenza C - human (mild RTI)

Differentiated by HA (16 subtype) and NA (9 subtype)
Named by specific combination (eg. H1N1)

Question 4

Antigenic Drift

Answer 4

Minor mutations in HA or NA (seasonal changes)

Occurs in Influenza A, B, and C

Question 5

Antigenic Shift

Answer 5

Complete change of HA, NA or both

Occurs in only Influenza A (need non-human intermediate)

Question 6

Influenza - Pathogenesis

Keywords: Spreading, Incubation time, Steps of Infection

Answer 6

Spread by large droplets, surfaces (hands!) and aersol
Incubation: 1-4 days from time of exposure

Steps:
1 - Neuraminidase degrades protective mucus
2 - Hemagglutinin binds cell surface receptors
3 - Virus enters the cell and uncoats
4 - Genome segments -> mRNA within the nucleus
5 - mRNA -> protein (cytoplasm) or mRNA -> progeny (nucleus)
6 - Viral particles assembled in cytoplasm
7- Virions released from cells by budding from cell membrane (NA)
8 - Viral replication kill host cells -> neucrosis

Question 7

Influenza - Clinical Manifestations

Answer 7

Abrupt with onset of fever, myalgias, headache, pharyngitis, rhinorrhea, cough, and fatigue

5-7 days of acute illness, full recover may be prolonged

Infectious period
Adult 3-5 days after symptom onset
Peds 10 days or more
Imunocompromised several weeks

Question 8

Influenza - Complications (2)

Answer 8

Pneumonia - Body ache and pain (I.D)

• Primary Influenza Pneumonia
• Secondary Bacterial Pneumonia (“improve” then worsen)

Reye’s Syndrome

• Rare life threatening syndrome: fever, rash encephalopathy, liver failure
• Pathogenesis unclear, aspirin implicated

Question 9

Influenza - Diagnosis

Keyword: Collection method, 4 dxg tests, False positive, False Negative

Answer 9

Collection Method (decreasing order of sensitivity)
Nasopharyngeal (NP) aspirate or swab
Nasal aspirate, wash, or swab
Throat swab

Viral culture (old gold standard) - 10 days
Immunoflorescene tests
- Direct Flourescene Antibody (DFA): 1 - 4 hrs (quick) + detect other viruses)
PCR* - most sensitive and specific, 1-6 hrs, detect other viruses, new gold standard
Rapid antigen detection - <30 min, wide range of sensitivity (30-70%), false negatives

Earlier testing is better (first 3-4 days of illness)
False positive - when prevalence for disease is low
False negative - when prevalence for disease is high

Question 10

Influenza - Treatment

Answer 10

Amandantases: Amantadine and Rimantadine

Neuraminidase inhibitors: Oseltamivir and Zanamavir

Question 11

Amantadine and Rimantadine

Answer 11

Type: Amandantases

MOA: M2 ion channel inhibitors -> block viral uncoating

Usage: Influenza A only, treatment or prophylaxis (alot of resistance -> usefulness unclear)

Side effects: CNS + anticholinergic effects, teratogenic

Question 12

Oseltamivir (oral), Zanamavir (inhale)

Answer 12

Type: Neuraminidase inhibitors

MOA: ?????

Usage: Influenza A + B, (effective within 48 hrs), osteltamivir (prohylaxis)

Side effects: N/V, relief symptoms <1 day, questionable performance in severe disease

Question 13

Influenza - Risk Factor

Answer 13

Geriatrics
- reduced immune functions + blunted vaccine response

Pediatrics:
- IgG (mother) depletion, weaning of breast milk -> IgA reduction, and immature immune system create an opportunity window for attack

Overweight:
- Adipose cell -> inflammatory stimuli dysregulation -> chemotoxin

Pregnancy:
- 3-4x increases, Treg suppress Th1 -> decrease immunity

Question 14

Influenza - Prevention

Answer 14

Vaccination Types:

• Inactivated vaccine: intramuscular, adult >65 yo need higher dose vaccine
• Live attenuated influenza vaccine (LAIV): intranasal, children 2-8 yo (healthy), contradictions (asthma, immunodeficiency, or pregnancy)

Vaccine Adverse Effects:
Common: pain, redness swelling, myalgia, malaise, headache, fever
Rare: Hypersentivity rxn, Guillain-Barre syndrome (host immune dmg nerve -> m. weakness -> paralysis), egg allergy (administer recombinant vaccine instead)

Vaccine Goal:
- Prevent severe complication

Post-exposure prophylaxis
Inffection control