CDC Health Alert Network (HAN): DHS Guidance to Wisconsin Providers Regarding Accelerated Subtyping of Influenza A in Hospitalized Patients to Detect Influenza A(H5N1)

Wisconsin Department of Health Services

Bureau of Communicable Diseases Information Update

Accelerated Subtyping of Influenza A in Hospitalized Patients to Detect Influenza A(H5N1) 

This message is being sent to the health alert network, local public health officers, Tribal health directors, local public health department nurses, local public health department staff, and infection preventionists.

Note: This guidance varies from the CDC HAN of the same name due to state-specific policies and circumstances. This guidance is subject to change as the epidemiological and operational situation around influenza A subtyping changes. 

Key points

  • All influenza A positive specimens from severely ill, hospitalized patients should be subtyped for influenza A(H1) or influenza A(H3), either at your clinical laboratory, a commercial laboratory, or a public health laboratory.
  • All influenza A positive specimens from patients admitted to the ICU that cannot be subtyped for influenza A(H1) or influenza A(H3) at a clinical or commercial laboratory should be sent to the Wisconsin State Laboratory of Hygiene (WSLH) for subtyping without batching or delay. These specimens may be in addition to or in place of the below.
  • As an update to pre-existing surveillance guidance, please send the WSLH three influenza A positive specimens per week from each Wisconsin hospital. Please ensure that these surveillance specimens are from admitted patients and not outpatients.
  • Any patient suspected to be infected with influenza A(H5N1), including patients with exposure to potentially infected animals, should be reported to the Wisconsin Division of Public Health (DPH), Bureau of Communicable Diseases (BCD) immediately.

Background

On January 16, 2025, the Centers for Disease Control and Prevention (CDC) issued a Health Alert Network (HAN) Health Advisory due to sporadic human infections with avian influenza A(H5) amid high levels of seasonal influenza activity.  

Highly pathogenic avian influenza (HPAI) A (H5N1) is currently circulating among poultry, cattle, and other animals in the U.S., with 67 human cases identified since 2024. While most human cases have been clinically mild, several patients have been hospitalized with one fatality reported. Most influenza A(H5) cases have been reported among people with known contact to infected animals through unprotected workplace exposures, but several cases have occurred in individuals with no identified animal exposures and were identified through routine subtyping of surveillance specimens. 

To enhance identification of human infections with influenza A(H5), the Wisconsin Department of Health Services (DHS) and CDC recommend subtyping all influenza A virus-positive specimens from hospitalized patients, especially among patients in the intensive care unit (ICU). Early identification of influenza A-positive specimens that do not subtype as influenza A(H1) or influenza A(H3) can help identify specimens that might contain influenza A(H5) and ensure proper infection control for hospitalized patients and expedite public health investigation of severe cases to prevent future spread.  

Note on clinical influenza tests and influenza A subtyping:  

Most available clinical tests do not distinguish between influenza A and influenza A(H3N2), influenza A(H1N1) and influenza A(H5N1), or other subtypes of influenza A. Influenza A(H5N1) will result on these tests as influenza A. Laboratory tests that return subtyped results, such as influenza A(H3) or influenza A(H1) can be used to identify specimens that might contain influenza A(H5) virus, as they will return a positive influenza A result and negative A(H1) and A(H3) results. Frequently, the tests that include these subtyped results are called respiratory pathogen panel tests and also test for other viruses, such as rhinovirus or human metapneumovirus.

For this reason, subtyping of specimens of hospitalized patients is recommended, to identify influenza A specimens that are neither influenza A(H1N1) nor influenza A(H3N2) and therefore need further characterization. 

Recommendations for clinicians

  • Collect exposure history from all patients with respiratory illness and/or conjunctivitis: Collect a thorough exposure history from all patients with suspected or confirmed influenza, asking about potential exposure to wild and domestic animals, including pets (for example, cats), and animal products (for example, poultry, dairy cows, raw cow milk and raw cow milk products, raw meat-based pet food). If a patient reports these exposure histories and tests positive for influenza A, have their specimen subtyped (tested for A(H3) and A(H1), either at your clinical laboratory or at WSLH without batching or delay. If a patient reports exposure to ill or dying animals or their products, or recent close contact to a person with a probable or confirmed case of influenza A(H5), notify the Wisconsin DPH BCD immediately at 608-267-9003 to arrange for influenza A(H5N1) testing.
  • Test for influenza: Test for seasonal influenza A in hospitalized patients with suspected seasonal influenza using whatever diagnostic test is most readily available for initial diagnosis. 
    • All hospitalized patients with respiratory illness and/or conjunctivitis should be tested for influenza. 
    • If the initial diagnostic test does not allow determination of subtype (for example, identify A(H1) and A(H3)), order an influenza A(H1) and A(H3) subtyping diagnostic test within 24 hours of hospital admission for patients who tested positive for influenza A. Frequently, the tests that include these subtyped results are called respiratory pathogen panel tests and also test for other viruses, such as rhinovirus or human metapneumovirus.
    • Subtyping should be performed with assays available to the testing laboratory, as follows:
      • Ensure that ICU admission status is easily accessible to your clinical laboratory.
      • Influenza A(H1) and A(H3) subtyping tests should be performed in the hospital clinical laboratory, if available.
      • Alternatively, specimens should be sent to a commercial clinical laboratory for influenza A(H1) and A(H3) subtyping.
      • If the patient is admitted to the ICU and a specimen cannot be subtyped at your clinical laboratory or a commercial laboratory, this specimen should be immediately sent to WSLH for subtyping.
        • These specimens can be sent without approval of the Wisconsin DPH BCD using the normal WSLH respiratory surveillance requisition form. 
      • If the patient reports recent contact with animals susceptible to infection with a novel influenza A virus or international travel and a specimen cannot be subtyped at your clinical laboratory or a commercial laboratory, this specimen should be immediately sent to WSLH for subtyping.
  • Provide antiviral treatment: Any hospitalized patients, especially those in an ICU, with suspected seasonal influenza or avian influenza A(H5) should be started on antiviral treatment with oseltamivir as soon as possible without waiting for the results of influenza testing. 
  • Report suspected influenza A(H5N1): Notify Wisconsin DHS immediately at 608-267-9003 if avian influenza A(H5N1) virus infection is suspected, probable, or confirmed in a patient.
  • Use appropriate infection control measures: If avian influenza A(H5) virus infection is suspected, probable, or confirmed in a hospitalized patient, place the patient in an airborne infection isolation room with negative pressure with implementation by caregivers of standard, contact, and airborne precautions with eye protection (goggles or face shield).

Recommendations for clinical laboratories to use the WSLH, rather than commercial laboratories, for subtyping

  • Send the following specimens to WSLH for subtyping immediately, without batching specimens for consolidated shipment:
    • All influenza A-related hospitalizations for patients admitted to the ICU.
    • All positive influenza A specimens that are unsubtypeable (for example, positive for influenza A and negative for influenza A(H1) and A(H3), if subtyping was attempted).
    • All positive influenza A specimens for patients with international travel history or reported exposure to any animal susceptible to infection with a novel influenza A (for example, bovine, swine, or avian).
  • WSLH also requests submission of specimens from three influenza-related hospitalizations per week for each Wisconsin hospital. This is an increase from previous surveillance efforts when one specimen per week was requested. Please ensure that these specimens come from hospitalized patients.

It is critical that clinical laboratories ensure that requisition forms are filled out accurately and completely, including accurately indicating if a patient is hospitalized.

Hospitalized influenza A patients not meeting the above criteria should have specimens subtyped for influenza A(H1) and A(H3) by clinical or commercial laboratories as described above.

Specimens must be received at WSLH or frozen within 72 hours of collection to be acceptable for influenza A subtyping.

In addition to being available at WSLH, Influenza A subtyping is available at the City of Milwaukee Health Department Laboratory for City of Milwaukee residents.

Recommendations for infection preventionists and local and Tribal health department staff

  • Ensure prompt and accurate reporting of all influenza-related hospitalizations in accordance with published EpiNets.
  • Ensure that the laboratory information, including influenza type and any subtyping results, is accurately filled out in Wisconsin Electronic Disease Surveillance System (WEDSS) forms and is not only attached to the record via PDF.
  • Ensure that race, age, hospital admission date, and ICU admission information are promptly and accurately entered into a record. Accurate reports of ICU admission are critical for our influenza surveillance, including our influenza A(H5N1) surveillance.
  • Contact the DPH Bureau of Communicable Diseases at 608-267-9003 with questions about reporting.