State of California—Health and Human Services Agency
California Department of Public Health

Health Advisory

To: Healthcare Providers and Laboratories

Subtyping of Influenza A in Hospitalized Patients

2/6/2025

Key Messages

Enhanced surveillance recommendations for humans with avian influenza A(H5N1) infections.

Healthcare providers should facilitate influenza A subtype testing for:
Hospitalized patients who are severely ill with influenza A infections, particularly those in intensive care units (ICUs).
Healthcare providers should report any suspected case of influenza A(H5N1) infection or any influenza A specimen for which subtyping is negative* to the patient’s local health department.

*If neither current seasonal influenza subtype (H1 or H3) is detected, the specimen is “unsubtypeable.”

Influenza A(H5N1) Background

This health advisory includes guidance on influenza A subtyping for healthcare providers and laboratories in California. This is in accordance with the January 16, 2025, CDC Health Advisory recommending accelerated subtyping of influenza A-positive specimens from hospitalized patients, particularly those in ICUs, as part of a comprehensive strategy to identify human infections with avian influenza A(H5N1).

The ongoing global outbreak of avian influenza A(H5N1) has caused the outbreak in domestic poultry on record. Dairy cows have been infected with avian influenza A(H5N1) for the first time ever, and cases have been detected in cows in 16 states. To date in California, there have been over 700 infected dairy cow herds and 38 confirmed human cases, all but two of whom were dairy workers working with infected herds.

No known human-to–human transmission of avian influenza A(H5N1) has been detected in the U.S. and the risk to the general population remains low. However, because of the possibility that this virus could gain the ability to spread between people or evolve to cause more severe disease, ongoing monitoring for human infection is important.

Recommendations

General recommendations for healthcare providers

Stay up to date on CDC and CDPH (PDF) guidance for influenza A(H5N1).

Guidance on evaluation, testing, and treatment of patients suspected to have influenza A(H5N1) infection is provided in the 12/6/2024 CDPH health alert.
Exposure risk factors for influenza A(H5N1) include exposure to animals or humans suspected or confirmed to have influenza A(H5N1) infection or consumption of raw milk in the last 10 days.

Continue to suspect and test for influenza A(H5N1) infection in outpatients or inpatients with symptoms or signs consistent with influenza A(H5N1) infection and the exposure risk factors described above.
Immediately notify the local health department of the patient’s residence if either are true:

Influenza A (H5N1) infection is suspected based on patient’s symptoms and exposure history; OR
Testing is positive for influenza A but subtyping is negative for seasonal influenza subtypes A(H1) and A(H3).

Manage patients suspected to have influenza A(H5N1) infection using standard, contact and airborne precautions with eye protection per CDC infection control recommendations for novel influenza.

Recommendations for healthcare providers caring for hospitalized patients with severe acute respiratory illness

The following activities are recommended to enhance influenza A(H5N1) surveillance in patients with severe influenza A infection without known exposure risk factors for influenza A(H5N1).

Test for influenza A.

Initial influenza testing can be done using whatever diagnostic test is available, but preferably by real-time RT-PCR.
If available, an initial diagnostic test that can provide influenza A subtyping results for A(H1) and A(H3) can be ordered.

If the initial testing is positive for influenza A but did not include testing for seasonal influenza subtypes A(H1) and A(H3), order subtyping as soon as possible for patients in the ICU (and, when resources allow, all hospitalized patients with influenza A infection).

If reimbursement for influenza A subtyping may be an issue, specimens can be referred to a local public health laboratory for subtype testing.

Patients without known influenza A(H5N1) exposure risk factors for whom influenza A subtyping is ordered can be managed using infection prevention and control precautions recommended for seasonal influenza (e.g. adhere to standard and droplet precautions and use caution when performing aerosol-generating procedures).

Recommendations for hospital laboratories

If influenza A virus subtyping is available: Specimens that are positive for influenza A, but negative for seasonal influenza A virus subtypes, i.e., negative for A(H1) and A(H3), require subtyping for A(H5).

Specimens that test negative for A(H1) and A(H3) should be sent to a public health laboratory or a commercial laboratory with influenza A(H5) testing capability as soon as possible and ideally within 24 hours of obtaining the results.
Do not batch specimens for consolidated or bulk shipment to the public health laboratory if that would result in shipping delays for specimens.

If influenza A virus subtyping is not available: Arrangements should be made for influenza A- positive specimens to be subtyped at a public health laboratory or a commercial laboratory that has subtyping capability as soon as possible.

Specimens should be clearly linked to clinical information from the patient to ensure that specimens from severely ill patients are prioritized for testing.

Recommendations for public health laboratories or other laboratories performing A(H5) subtyping

Complete influenza A virus H5 subtyping assays ideally within 24 hours of receipt and report results to CDPH and CDC, as required.
If a positive result for influenza A(H5) virus is obtained using a laboratory developed test or another A(H5) subtyping test, immediately contact the patient’s local health department so that important time-critical actions can be implemented.

Recommendations for local health departments

To enhance statewide surveillance, local health departments should assess subtyping capacity in their jurisdictions.
Local health departments should ensure that influenza A subtyping test results performed in their jurisdictions are reported to CDPH.