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INFLUENZA

MICROBIOLOGY AND PATHOGENESIS

Influenza A, B, and C viruses are segmented, single-stranded, negative-sense RNA viruses that have on their outer surface prominent spikes formed by two surface glycoproteins, hemagglutinin (H) and neuraminidase (N). Influenza A and B viruses are major human pathogens, but influenza C virus causes only intermittent mild disease.

  • Influenza A viruses are subtyped by the H and N antigens.

    • – Virus attaches to sialic acid cell receptors via the hemagglutinin. Neuraminidase cleaves the virus from the cell membrane to facilitate its release from the cell.

    • – Influenza A viruses undergo antigenic drift (modification of immunogenic epitopes, particularly on the H antigen), which counteracts prevailing immunity, and antigenic shift (reassortment of genes among different isolates), which results in major changes in antigens). The viruses have extensive mammalian and avian reservoirs. These features give influenza A virus the ability to cause a worldwide epidemic (pandemic).

  • Influenza is transmitted by small- and large-particle droplets. Virus spread is facilitated by the coughing and sneezing that accompany the illness.

EPIDEMIOLOGY

Influenza outbreaks occur during cooler months. A typical outbreak begins in early winter and lasts 4–5 weeks in a given community, although its impact on the entire country lasts considerably longer.

  • All of the annual influenza A epidemics in the past 50 years have been caused by H1N1 and/or H3N2 strains. H2N2 strains circulated between 1957 and 1968, and H1N1 strains circulated prior to that.

  • Potentially pandemic viruses continue to emerge, mostly in Asia, with higher-number hemagglutinins (e.g., H5, H6, H7, H9). It is thought that swine serve as an important intermediary of pandemic strains: these animals can sustain simultaneous infection with swine, human, and avian influenza viruses, which facilitates reassortment of genetic segments of different viruses (enabling antigenic shift).

CLINICAL MANIFESTATIONS

Influenza is primarily a sudden-onset respiratory illness causing rhinorrhea, sore throat, conjunctivitis, and cough. Symptoms typically begin within 48–72 h of exposure.

  • Physical examination is often notable for nonlocalizing scattered rales, rhonchi, and wheezing. Localized pulmonary findings may suggest relatively complicated pneumonia with a bacterial component.

  • Influenza is distinguished from other respiratory illnesses by the greater degree of accompanying fever, fatigue, myalgia, and malaise.

  • Systemic symptoms generally resolve within 2–5 days, but respiratory symptoms (e.g., recurrent cough, decreased exercise performance) can persist for ≥1 month.

  • Complications of influenza (respiratory and extrapulmonary manifestations) are more common among pts <5 and >65 years old, pregnant women in the second or third trimester, and pts with chronic disorders (e.g., cardiopulmonary disease, immunosuppression).

    • – Respiratory complications: Pneumonia (progressive air hunger, localized pulmonary findings on physical or radiographic examination) is the most common complication of influenza. These cases can be due to primary influenza pneumonia and/or secondary bacterial pneumonia.

      • In secondary bacterial pneumonia or mixed viral and bacterial pneumonia, illness may be biphasic, with recrudescence of fever and ...

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