Influenza

Virus

Enveloped, SEGMENTED negative-sense ssRNA, Orthomyxoviridae. 3 types: A, B, C (D not significant human disease). INFLUENZA A = most important — ONLY type causing PANDEMICS.

Antigenic Structure

H (Hemagglutinin) — attachment/fusion. N (Neuraminidase) — releases budding virions, prevents aggregation. H/N nomenclature (H1N1, H3N2). 18 HA subtypes, 11 NA subtypes across full host range (human, bird, pig).

TWO mechanisms of variability (COMMONLY TESTED, distinguish precisely):

ANTIGENIC DRIFT: small gradual point mutations, HA/NA genes, ALL 3 types, CONTINUOUS. Why vaccine reformulated ~yearly. Partial immune evasion.

ANTIGENIC SHIFT: sudden dramatic HA/NA change, REASSORTMENT (segmented genome, co-infection 2 strains same cell — classic: human+avian/swine strain in PIG, which supports both). ONLY INFLUENZA A (needs multi-species reservoir only A has — birds+pigs+humans). Produces PANDEMIC strains — no pre-existing population immunity to novel subtype.

Pathogenesis/Transmission

Respiratory droplets + fomites. Destroys ciliated respiratory epithelium → impairs mucociliary clearance → predisposes SECONDARY BACTERIAL PNEUMONIA (classically pneumococcal/staph) days-weeks post-infection — important distinct complication from viral illness itself.

Clinical Manifestations

Abrupt fever, chills, SEVERE myalgia, headache, dry cough. Systemic symptoms MORE pronounced than most other common respiratory viruses (imperfect distinguisher, needs lab confirmation). Self-limited ~1wk healthy individuals, cough/fatigue may persist longer. High-risk groups (severe disease/complications): extremes of age, pregnancy, chronic cardiopulmonary disease, immunosuppression — target for antiviral priority + vaccination.

Laboratory Diagnosis

Rapid antigen test: minutes, MEANINGFUL sensitivity limitation (negative doesn’t exclude). RT-PCR: HIGHER sensitivity, PREFERRED confirmatory, enables subtyping/surveillance. Viral culture: slow, reference/surveillance use only.

Treatment

Neuraminidase inhibitors (Oseltamivir main, Zanamivir inhaled alternative): blocks NA-mediated virion release. MOST effective if started <48hr symptom onset. Reserved for HIGH-RISK/severe cases, not routine uncomplicated flu in healthy patient (modest benefit there). Baloxavir: newer, single-dose, DIFFERENT mechanism (cap-dependent endonuclease inhibition, blocks viral mRNA transcription initiation). Secondary bacterial pneumonia: needs OWN antibacterial Rx, not expected to resolve with antiviral alone.

Prevention — Vaccination

Inactivated + live-attenuated vaccines, REFORMULATED ANNUALLY (WHO surveillance predictions) — UNIQUE among curriculum vaccines, driven by antigenic drift. Effectiveness varies year-to-year (prediction-match dependent) — CONTRAST fixed unchanging vaccines (measles, polio, HBV) whose antigens don’t drift. Annual vaccination recommended broadly, esp. high-risk groups + healthcare workers (own protection + reduce nosocomial transmission).

The Virus

Influenza viruses are enveloped, segmented negative-sense ssRNA orthomyxoviruses (see General Properties of Viruses for how negative-sense RNA replication specifically works, and why a genome split across segments enables reassortment) — three types exist, A, B, and C (a fourth, D, is not known to cause significant human disease), of which influenza A is by far the most clinically and epidemiologically important, being the only type capable of causing pandemics, reflecting a property unique to it among the three (below).

Antigenic Structure and the Basis of Its Genetic Variability

Influenza A is classified by its two major surface glycoproteins — haemagglutinin (HA), mediating attachment to host cell sialic acid receptors and membrane fusion, and neuraminidase (NA), cleaving sialic acid to release newly budded virions from the infected cell surface and prevent self-aggregation — giving the familiar H/N subtype nomenclature (e.g. H1N1, H3N2), with 18 known HA subtypes and 11 known NA subtypes circulating across influenza A’s full host range (humans, birds, pigs, and other species), though only a limited subset has ever established sustained human-to-human transmission.

Two genuinely distinct mechanisms drive influenza’s antigenic variability, and distinguishing them precisely is one of the most commonly tested points in this entire topic: antigenic drift — small, gradual point mutations accumulating in the HA/NA genes over time (the same accumulation-of-mutation process covered generally under General Properties of Viruses) — occurs continuously in all three influenza types and is responsible for the need for an updated vaccine formulation nearly every year, since drift is enough to erode existing population immunity gradually without requiring a wholesale new subtype. Antigenic shift — a sudden, dramatic, wholesale change in HA and/or NA, arising specifically from reassortment (the segmented-genome mechanism covered under General Properties of Viruses and Rotavirus, where co-infection of one host cell with two different influenza A strains — classically a human strain and an avian or swine strain infecting the same pig, which can support both — allows whole gene segments to be exchanged, generating a genuinely novel HA/NA combination) — occurs only in influenza A (never B or C, since shift requires antigenic diversity across a broad multi-species reservoir that only influenza A actually has, given its circulation in birds and pigs as well as humans) and is exactly what produces pandemic strains, since a population has no pre-existing immunity at all to a genuinely novel HA subtype, in sharp contrast to drift’s more gradual, partial immune-evasion.

Pathogenesis and Transmission

Transmission is by respiratory droplets and contact with contaminated surfaces/fomites; the virus infects and destroys ciliated respiratory epithelial cells directly, impairing mucociliary clearance (a genuinely important, if often underappreciated, mechanism behind influenza’s well-established tendency to predispose to secondary bacterial pneumonia — most classically pneumococcal or staphylococcal, since destroyed ciliated epithelium and impaired local clearance leave the lower respiratory tract genuinely more vulnerable to bacterial invasion in the days-to-weeks following acute influenza, a real, clinically important complication worth remembering as a distinct entity from the viral illness itself).

Clinical Manifestations

Abrupt-onset fever, chills, severe myalgia, headache, and a dry cough, with the degree of systemic constitutional symptoms (myalgia, headache, malaise) genuinely more pronounced than in most other common respiratory viral infections — a real clinical distinguishing feature, though imperfect enough that laboratory confirmation is needed for reliable diagnosis in most clinical contexts (see below). Most disease is self-limited in healthy individuals, resolving over about a week, though cough and fatigue can persist longer. Populations at genuinely elevated risk of severe disease/complications — extremes of age, pregnancy, chronic cardiopulmonary disease, immunosuppression — are the specific target groups for both antiviral treatment prioritization and annual vaccination (below).

Laboratory Diagnosis

Rapid antigen tests give results within minutes but have real, meaningful sensitivity limitations (a negative result does not reliably exclude infection in a clinically compatible case). RT-PCR offers substantially higher sensitivity and is now the preferred confirmatory method where available, also enabling subtype/strain determination relevant to surveillance and, during a pandemic, outbreak characterization. Viral culture remains available but is slow and used mainly for reference/surveillance purposes rather than routine clinical diagnosis.

Treatment

Neuraminidase inhibitors (oseltamivir, the most widely used; zanamivir as an inhaled alternative) block the NA-mediated release of newly formed virions from infected cells, genuinely most effective when started early (within 48 hours of symptom onset) and generally reserved for patients at high risk of complications or with severe/progressive disease, rather than used routinely for uncomplicated influenza in an otherwise healthy patient, given their modest effect on illness duration in that lower-risk population balanced against cost and side-effect considerations. Baloxavir (a newer, single-dose polymerase-inhibitor-class agent, acting via a different mechanism — cap-dependent endonuclease inhibition, blocking viral mRNA transcription initiation) offers an alternative with a more convenient dosing schedule. Secondary bacterial pneumonia, when it occurs, needs its own specific antibacterial treatment rather than being expected to resolve with antiviral therapy alone.

Prevention: Vaccination

Inactivated (killed) and live-attenuated influenza vaccines both exist, reformulated annually based on WHO surveillance predictions of which strains are likely to circulate in the coming season — a genuinely unique vaccine-programme feature among the diseases covered in this curriculum, driven directly by antigenic drift’s continuous erosion of prior-year immunity described above. Vaccine effectiveness varies year to year depending on how well the predicted strains actually match the strains that end up circulating — a real, inherent limitation of any prediction-based vaccine strategy, in contrast to the fixed, unchanging formulations used for most other vaccines covered in this curriculum (measles, polio, hepatitis B), whose target antigens don’t drift the way influenza’s do. Annual vaccination is recommended broadly, with particular emphasis on the high-risk groups named above and healthcare workers (both for their own protection and to reduce nosocomial transmission to vulnerable patients).

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