MicrobiologyTier 2Medical Sciences concept

Influenza antigenic drift vs shift - mechanism and epidemiological consequence

Core concept

	Antigenic DRIFT	Antigenic SHIFT
Mechanism	Point mutations in HA/NA genes; RNA polymerase has no proofreading	REASSORTMENT of the 8 genome segments when two strains co-infect one cell
Change	Gradual, incremental	Abrupt - a completely new HA and/or NA
Viruses	Influenza A and B	Influenza A ONLY (B and C have no animal reservoir of consequence)
Consequence	Seasonal EPIDEMICS; annual vaccine reformulation	PANDEMICS - little or no population immunity
Population immunity	Partial, from prior exposure	Essentially absent

Shift requires a segmented genome and an animal reservoir
- Aquatic birds are the reservoir of all influenza A subtypes; the pig is the classic "mixing vessel" (bearing both avian alpha-2,3 and human alpha-2,6 sialic acid receptors)
"Reassortment, segments, animal reservoir, pandemic" is one chain; "point mutation, gradual, epidemic" is the other. Do not use "mutation" for shift.

Nomenclature: type / host / place / strain number / year (H subtype N subtype) - e.g. A/California/07/2009 (H1N1)
HA (haemagglutinin, 18 subtypes) - binds sialic acid, mediates entry; the dominant protective antibody target
NA (neuraminidase, 11 subtypes) - cleaves sialic acid to release progeny; the target of oseltamivir and zanamivir
M2 ion channel - target of amantadine (now universally resistant, obsolete)
Pandemics: 1918 H1N1 (~50 million deaths), 1957 H2N2, 1968 H3N2, 2009 H1N1pdm09 (a quadruple reassortant of swine, avian and human genes)
Avian H5N1 and H7N9 cause severe human disease but have not acquired efficient human-to-human transmission - the feared shift event is exactly that acquisition
Antigenic drift is why the vaccine is reformulated annually by WHO in February (northern) and September (southern hemisphere); mismatch years give lower effectiveness
- Egg-adaptation mutations during manufacture further reduce match - the reason for cell-based and recombinant vaccines
Original antigenic sin (imprinting) - the first influenza strain encountered shapes the response to all later ones, and partly explains age-specific attack rates in pandemics (the 2009 pandemic spared older adults)

Annual vaccination is the core intervention; inactivated, so safe in immunosuppression and pregnancy
- NIP-funded in Australia: >=65 (adjuvanted or high-dose), Aboriginal and Torres Strait Islander people >=6 months, pregnancy (any trimester - protects the infant), children 6 months to <5 years, and medical risk groups
- Maternal vaccination is the only way to protect an infant under 6 months
Neuraminidase inhibitors - oseltamivir 75 mg bd for 5 days, best within 48 h of symptom onset; treat regardless of timing in severe or hospitalised disease and in high-risk groups
- Baloxavir (cap-dependent endonuclease inhibitor) is a single-dose alternative
Suspect novel influenza in severe respiratory illness with exposure to poultry, pigs or a returning traveller from an outbreak area -> notify public health, isolate, take specific PCR
Complications: secondary bacterial pneumonia (Staph aureus, pneumococcus), myocarditis, myositis, encephalitis, decompensated cardiac and respiratory disease

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