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Microbiology and Pathogenesis

Influenza A, B, and C viruses are RNA viruses and members of the family Orthomyxoviridae that have different nucleoprotein (NP) and matrix (M) protein antigens. Influenza A and B viruses are major human pathogens and are morphologically similar; influenza B infection is associated with less severe disease than influenza A infection, and influenza C virus causes subclinical disease.

  • Influenza A viruses are subtyped by surface hemagglutinin (H) and neuraminidase (N) antigens.

    • – Virus attaches to sialic acid cell receptors via the hemagglutinin. Neuraminidase degrades the receptor and plays a role in the release of virus from infected cells after replication.

    • – Antibodies to the H antigen are the major determinants of immunity, while antibodies to the N antigen limit viral spread and contribute to reduction of the infection.

  • Influenza is acquired from aerosolized respiratory secretions of acutely ill individuals and possibly by hand-to-hand contact or other personal or fomite contact. Viral shedding usually stops 2–5 days after disease onset.


Influenza outbreaks occur each year but vary in extent and severity. Influenza A epidemics occur almost exclusively during the winter months in temperate climates but take place year-round in the tropics. These epidemics begin abruptly, peak over 2–3 weeks, last 2–3 months, and then subside rapidly.

  • Global pandemics (the most recent of which took place in 2009 and was due to an A/H1N1 virus) occur, by definition, at multiple locations; they carry high attack rates (10–20% of the general population), extend beyond normal seasonality patterns, and are due in part to the propensity of the H and N antigens to undergo periodic antigenic variation.

    • – Major changes (which are restricted to influenza A viruses) are called antigenic shifts and are associated with pandemics.

    • – Minor variations are called antigenic drifts.

  • Avian influenza viruses (e.g., A/H5N1) cause sporadic human cases, but sustained human-to-human transmission has not been observed; infection is linked to direct contact with infected poultry.

  • Swine can sustain simultaneous infection with swine, human, and avian influenza viruses; these multiple-virus infections facilitate reassortment of genetic segments of different viruses. For example, the pandemic A/H1N1 virus of 2009–2010 represented a quadruple reassortment among swine, avian, and human influenza viruses.

  • Interpandemic outbreaks of influenza are associated with an average of 226,000 hospitalizations and 23,000 excess deaths per year in the United States. Chronic cardiopulmonary disease and old age are the most prominent risk factors for severe illness.

Clinical Manifestations

Influenza has a wide spectrum of clinical presentations, ranging from a mild illness resembling the common cold to severe prostration with relatively few respiratory symptoms. The classic description involves the abrupt onset of headache, fever, chills, myalgia, and malaise in the setting of respiratory symptoms (e.g., cough, sore throat).

  • Pts typically defervesce within 2–3 days, but respiratory symptoms accompanied by substernal pain can persist ...

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