Q1 LONG ANSWER 10M ★ High-yield

Describe influenza virus with its structure, antigenic variation, complications and prevention.

Microbiology · 2nd Professional — Para-Clinical

Structure and Types

Orthomyxovirus — enveloped, with helical symmetry and a genome of single-stranded negative-sense RNA in eight separate segments
The segmented genome is the crucial structural fact — it allows two different influenza viruses infecting the same cell to reassort their segments, producing an entirely new virus in one step
Being negative-sense, it carries its own RNA polymerase within the virion, since the host has no enzyme able to read it

Surface glycoprotein	Function	Significance
Haemagglutinin (H)	Binds sialic acid receptors and mediates attachment and fusion; agglutinates red cells	The target of neutralising and protective antibody, and therefore the main vaccine antigen; 18 subtypes
Neuraminidase (N)	Cleaves sialic acid, releasing newly formed virions from the cell surface and preventing them clumping	The target of oseltamivir and zanamivir; 11 subtypes
M2 ion channel	Uncoating	The target of amantadine, now abandoned because of resistance

Type	Reservoir	Epidemiological behaviour
Influenza A	Man and animals — wild birds are the natural reservoir of all subtypes, with pigs and poultry as intermediaries	Undergoes both drift and shift; causes epidemics and pandemics; subtyped by H and N (H1N1, H3N2)
Influenza B	Man only (and seals)	Drift only, so NO pandemics; causes epidemics, often in children
Influenza C	Man and pigs	Mild sporadic illness

Antigenic Variation

Feature	Antigenic drift	Antigenic shift
Mechanism	Accumulation of point mutations in the H or N gene, since RNA polymerase has no proofreading	Reassortment of whole gene segments between a human and an animal virus infecting the same cell — or direct transfer of an animal virus
Extent of change	Minor and gradual	Major and abrupt — an entirely new subtype
Occurs in	Types A and B	Type A only, because only A has an animal reservoir
Population immunity	Partial — existing antibody gives some cross-protection	Absent — nobody has seen the new subtype
Consequence	Annual epidemics; the vaccine must be reformulated each year	Pandemics — 1918 H1N1, 1957 H2N2, 1968 H3N2, 2009 H1N1
Frequency	Continuous	Every few decades, unpredictably

CLINICAL PEARL

The pig is the classical "mixing vessel" because its cells carry both human and avian receptors. Human influenza binds alpha-2,6-linked sialic acid and avian influenza binds alpha-2,3 — and swine respiratory epithelium has both. A pig can therefore be infected by a human and a bird strain simultaneously, allowing the eight segments to reassort into a virus with avian surface proteins and human transmissibility. That is how a pandemic strain is made, and why influenza surveillance watches agriculture as closely as hospitals.

Clinical Features and Complications

Transmission by respiratory droplets and by contaminated hands and surfaces; incubation 1 to 4 days; infectious from about a day before symptoms
Abrupt onset of fever, chills, severe myalgia and headache, dry cough and prostration — the systemic symptoms are what distinguish it from a common cold
Primary viral pneumonia — rapidly progressive and often fatal, occurring particularly in pregnancy, cardiac disease and during pandemics
Secondary bacterial pneumonia — commoner, with a characteristic pattern of initial improvement then deterioration; caused by Streptococcus pneumoniae, staphylococcus aureus (which may be necrotising) and H. Influenzae. It accounts for most influenza deaths
REYE syndrome — encephalopathy with fatty liver in children given aspirin
Other complications — myocarditis, myositis with rhabdomyolysis, encephalitis, Guillain-Barré syndrome, and exacerbation of chronic lung and heart disease
Groups at risk — the elderly, infants, pregnant women, the obese, and those with chronic heart, lung, renal or immune disease

Diagnosis, Treatment and Prevention

RT-PCR of a nasopharyngeal swab is the test of choice — sensitive, specific and able to subtype; rapid antigen tests are quick but insensitive, so a negative result does not exclude influenza
Culture in the amniotic or allantoic cavity of an embryonated egg, or in cell culture with haemadsorption, which detects growth before any cytopathic effect; serology by haemagglutination inhibition on paired sera
Treatment — oseltamivir (oral) or zanamivir (inhaled), neuraminidase inhibitors that are most effective within 48 hours of onset; baloxavir is a newer agent. They shorten the illness modestly and reduce complications in high-risk patients
Vaccine — reformulated annually on WHO recommendation to match the circulating strains, because of drift. The inactivated quadrivalent vaccine is given intramuscularly; a live attenuated intranasal vaccine is available for children
Vaccination is recommended for health workers, the elderly, pregnant women, children and those with chronic disease
Non-pharmaceutical measures — hand hygiene, respiratory etiquette, masks, ventilation and isolation, which matter most before a vaccine exists

Avian and Pandemic Influenza

Subtype	Features
H5N1 (highly pathogenic avian influenza)	Acquired from infected poultry by direct contact; very high case fatality (around 50%) but poor person-to-person transmission, which is what has prevented a pandemic so far. Outbreaks in Indian poultry are controlled by culling
H7N9	From live bird markets in China; high mortality; birds may appear healthy, making surveillance harder
H1N1 pdm09 ("swine flu")	The 2009 pandemic strain, arising by reassortment of swine, avian and human viruses; now circulating as a seasonal strain
Requirements for a pandemic	A novel subtype to which the population has no immunity; ability to cause disease in man; and efficient person-to-person transmission. Avian strains satisfy the first two but not the third — which is precisely what surveillance is watching for

Pandemic preparedness — surveillance in animals and man, stockpiling of antivirals, capacity for rapid vaccine production, and non-pharmaceutical measures for the months before a vaccine can exist

Applied Aspects

Suspect secondary bacterial pneumonia when a patient deteriorates after apparent improvement; this biphasic pattern is characteristic and the organisms are predictable, so antibiotic cover should include S. Aureus
Vaccinate pregnant women; influenza in pregnancy carries a substantially higher risk of severe disease, and maternal antibody also protects the infant in the months before vaccination is possible
Do not give aspirin to a child with influenza or chickenpox
Start oseltamivir early in high-risk patients without waiting for confirmation; its benefit falls away sharply after 48 hours
Avian influenza in India is monitored through poultry surveillance; human infection with H5N1 is rare but carries high mortality, and any cluster of severe respiratory illness with poultry contact must be notified urgently
Annual vaccination is under-used in India, including among healthcare workers, who are both at risk and a source of transmission to vulnerable patients
Influenza and COVID-19 are clinically indistinguishable in many patients, so testing for both may be needed; and co-infection occurs
The 1918 pandemic killed a disproportionate number of young adults, probably through an excessive immune response, which is a reminder that virulence is not simply a property of the virus
Notify clusters of severe respiratory illness with poultry contact, and take an occupational and animal exposure history in any unusually severe influenza
The vaccine takes about two weeks to protect, so it must be given before the season rather than during an outbreak
Egg-based production explains the months of lead time for each season’s vaccine and the historical caution in egg allergy, which is now regarded as a contraindication only for severe anaphylaxis
Influenza in a pregnant woman warrants prompt oseltamivir regardless of severity at presentation, because deterioration can be rapid

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