Criteria

Centers for Disease Control and Prevention (CDC): interim guidance on case definitions for investigations of human infection with highly pathogenic avian influenza A (H5N1) virus in the US[85]

Confirmed case:

  • Highly pathogenic avian influenza (HPAI) H5N1 virus infection in a patient that is confirmed by the CDC’s Influenza Laboratory or a CDC-certified public health laboratory using methods agreed upon by the CDC and the Council of State and Territorial Epidemiologists (CSTE).

  • Confirmation of infection with avian influenza A (H5N1) viruses may be made by public health laboratories following CDC-approved protocols for detection of avian influenza A (H5N1) virus, or by laboratories using a US Food and Drug Administration (FDA)-authorized test specific for detection of avian influenza A (H5N1) virus.

Probable case:

  • Illness compatible with influenza in a patient meeting the exposure criteria (below) and for whom laboratory diagnostic testing is positive for influenza A, negative for H1, negative for H1pdm09, and negative for H3 by real-time reverse transcription-polymerase chain reaction (RT-PCR) and therefore unable to be subtyped.

Case under investigation:

  • Illness compatible with influenza in a patient meeting any of the exposure criteria (below) and for whom confirmatory laboratory test results are not known or pending.

Exposure criteria:

  • Patients with recent travel (within <10 days of illness onset) to areas where human cases of HPAI H5N1 virus infection have become infected or to areas where HPAI H5N1 viruses are known to be circulating in animals; OR

  • Patients who have had recent close contact (within <10 days of illness onset) with confirmed or suspected cases of human infection with avian influenza A (H5N1) virus. Close contact may be regarded as coming within about 6 feet (2 meters) of a confirmed or suspected case while the case was ill (beginning 1 day prior to illness onset and continuing until resolution of illness). This includes healthcare personnel providing care for a confirmed or suspected case, family members of a confirmed or suspected case, persons who lived with or stayed overnight with a confirmed or suspected case, and others who have had similar close physical contact; OR

  • Unprotected exposure to live HPAI H5N1 virus in a laboratory.

World Health Organization (WHO): case definitions for human infections with influenza A (H5N1) virus[86]

Person under investigation:

  • A person whom public health authorities have decided to investigate for possible H5N1 infection.

Suspected H5N1 case:

  • A person presenting with unexplained acute lower respiratory illness with fever >100.4ºF (>38ºC) and cough, shortness of breath, or difficulty breathing AND one or more of the following exposures in the 7 days prior to symptom onset:

    • Close contact (within 3.2 feet [1 meter]) with a person (e.g., caring for, speaking with, or touching) who is a suspected, probable, or confirmed H5N1 case

    • Exposure (e.g., handling, slaughtering, defeathering, butchering, preparation for consumption) to poultry or wild birds or their remains or to environments contaminated by their feces in an area where H5N1 infections in animals or humans have been suspected or confirmed in the last month

    • Consumption of raw or undercooked poultry products in an area where H5N1 infections in animals or humans have been suspected or confirmed in the last month

    • Close contact with a confirmed H5N1-infected animal other than poultry or wild birds (e.g., cat or pig)

    • Handling samples (animal or human) suspected of containing H5N1 virus in a laboratory or other setting.

Probable H5N1 case (notify WHO):

  • Probable definition 1: a person meeting the criteria for a suspected case AND one of the following additional criteria:

    • Infiltrates or evidence of an acute pneumonia on chest radiograph plus evidence of respiratory failure (hypoxemia, severe tachypnea); or

    • Positive laboratory confirmation of an influenza A infection but insufficient laboratory evidence for H5N1 infection.

  • Probable definition 2: a person dying of an unexplained acute respiratory illness who is considered to be epidemiologically linked by time, place, and exposure to a probable or confirmed H5N1 case.

Confirmed H5N1 case (notify WHO):

  • A person meeting the criteria for a suspected or probable case AND one of the following positive results conducted in a national, regional, or international influenza laboratory whose H5N1 test results are accepted by WHO as confirmatory:

    • Isolation of an H5N1 virus

    • Positive H5 PCR results from tests using two different PCR targets (e.g., primers specific for influenza A and H5 hemagglutinin)

    • A fourfold or greater rise in neutralization antibody titer for H5N1 based on testing of an acute serum specimen (collected 7 days or less after symptom onset) and a convalescent serum specimen. The convalescent neutralizing antibody titer must also be 1:80 or higher

    • A microneutralization antibody titer for H5N1 of 1:80 or greater in a single serum specimen collected at day 14 or later after symptom onset and a positive result using a different serologic assay: for example, a horse red blood cell hemagglutination inhibition titer of 1:160 or greater or an H5-specific western blot positive result.

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