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Key Features

Essentials of Diagnosis

  • Most human cases occur after exposure to infected poultry

  • Clinically indistinguishable from seasonal influenza

  • Epidemiologic factors assist in diagnosis

  • Rapid antigen assays confirm diagnosis but do not distinguish avian from seasonal influenza

General Considerations

  • Birds are the natural hosts

  • Avian influenza A

    • Outbreaks occur in poultry occasionally

    • Virus has become endemic in poultry in some countries, mostly in Southeast Asia and Egypt

  • Occasionally, avian influenza viruses may infect humans or other mammals, including domestic cats and dogs

  • Illness in humans ranges from mild disease to rapid progressive severe disease and death depending on the subtype

  • Risk factors for human infection

    • Direct or indirect exposure to infected live or dead poultry or contaminated environments, such as live bird markets

    • Slaughtering and handling carcasses of infected poultry

  • The emergence of H5, H7, and H9 avian influenza virus subtypes in humans raises concern that the virus may undergo genetic re-assortment or mutations in some of the genes and develop greater human-to-human transmissibility with the potential to produce a global pandemic


  • Human infections with H5N1 viruses have been reported to the World Health Organization from 16 countries; the first report in the Americas was in Canada in 2014, and approximately 60% of the cases have died

  • Average case fatality rate of 40%

  • Infections with other H7 avian influenza viruses (H7N2, H7N3, and H7N7) have occurred sporadically around the world

  • Rare human cases of influenza H9N2 are also reported

Clinical Findings

Symptoms and Signs

  • Fever

  • Lower respiratory symptoms (cough and dyspnea); upper respiratory tract symptoms are less common

  • Gastrointestinal symptoms are reported more frequently in H5N1 infections

  • Conjunctivitis is reported in influenza H7 infections

  • Other systems can also be involved leading to neurologic manifestations (encephalopathy, seizure) and liver impairment

  • Prolonged febrile states and generalized malaise are common

  • Bacterial superinfection is reported

Differential Diagnosis

  • Typical influenza (clinically indistinguishable)

  • Common cold

  • Primary bacterial pneumonia

  • Infectious mononucleosis

  • Mycoplasma infection

  • Early Legionnaires disease

  • Chlamydophila pneumoniae infection (TWAR)

  • Acute HIV infection

  • Meningitis

  • In returning tropical traveler: malaria, dengue, typhoid


Laboratory Tests

  • Commercial rapid antigen tests are not optimally sensitive or specific for detection of H5N1 influenza and should not be the definitive test for influenza

  • Diagnostic yield can be improved by early collection of samples, preferably within 7 days of illness onset

  • More sensitive RT-PCR assays are available through many hospitals and state health departments

  • An initial negative result in the right clinical setting warrants retesting

  • Throat swabs or lower respiratory specimens (such as tracheal aspirate or bronchoalveolar lavage fluid) may provide higher yield of detection than nasal swabs When highly pathogenic strains (eg, H5N1) are suspected, extreme care in the handling of these samples must be observed during ...

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