Laboratory Resources for Highly Pathogenic Avian Influenza (HPAI) – Update 2024

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NETEC experts in safe laboratory practices for high-consequence infectious diseases have developed a resource on laboratory testing, specimen handling, and shipping for Highly Pathogen Avian Influenza (HPAI). This is a part of a series of one-page resource guides for laboratorians.

Avian Influenza in Birds and Humans

Avian influenza, also known as bird flu, is a disease in birds caused by infection with avian influenza Type A viruses. There are two sub categories of the virus—low and highly pathogenic avian influenza—and the latter can cause severe disease and mortality upwards of 90-100 percent in infected poultry. Highly pathogenic avian influenza (HPAI) virus infections in poultry  can spill back into wild birds, resulting in further geographic spread of the virus as those birds migrate. 

Learn more about avian influenza in birds. (CDC, https://www.cdc.gov/bird-flu/, 4/25/24)

The severity of HPAI is defined as the disease relates to birds, and does not refer to the severity of illness in humans. However, human infection with HPAI can range in severity from no symptoms or mild illness to severe disease and death. The majority of human cases of bird flu are due to infection with influenza A (H5N1) and A(H7N9) viruses and have been associated with direct or indirect contact with infected live or dead poultry. Limited, non-sustained human-to-human transmission has been reported in cases of prolonged, very close, unprotected contact between infected individuals and family members. There have not been any reports of human-to-human transmission of avian influenza A viruses in the United States.

Learn more about avian influenza in humans. (CDC, https://www.cdc.gov/bird-flu/situation-summary/inhumans.html, 4/25/24)

When to Test for HPAI

People with job-related or recreational exposure to infected birds, other animals, or their contaminated environments are at the greatest risk of infection with HPAI. Exposure may include direct contact with potentially infected sick or dead birds, livestock, or other animals within the week before symptom onset, e.g., handling, slaughtering, de-feathering, butchering, or preparation for consumption or consuming uncooked or undercooked food or related uncooked food products, including unpasteurized (raw) milk or other unpasteurized dairy products, direct contact with surfaces contaminated with feces, unpasteurized (raw) milk or unpasteurized dairy products, or parts (including carcasses, internal organs, etc.); or prolonged close exposure to potentially infected birds or other animals in a confined space.

If infection with HPAI is suspected, laboratory testing is necessary to diagnose the disease in humans.

CDC Interim guidance: https://www.cdc.gov/bird-flu/prevention/hpai-interim-recommendations.html (CDC, https://www.cdc.gov/bird-flu/prevention/hpai-interim-recommendations.html, 4/25/24)

Diagnostic Testing for HPAI

Commercially available diagnostic tests for detecting seasonal influenza in respiratory specimens (rapid influenza tests) cannot distinguish between infection with seasonal influenza A and novel influenza A viruses, including HPAI. Furthermore,  respiratory panels that distinguish influenza subtypes may fail to detect novel influenza A viruses or may indicate a test result of “influenza A positive,” but without identifying the subtype. These tests may come back with an influenza A “unsubtypeable” result.

Clinicians and laboratorians using diagnostics that can detect all currently circulating influenza A virus subtypes (i.e., “seasonal influenza” subtypes) who get an “unsubtypeable” result should contact the Centers for Disease Control and Prevention (CDC) and their state or local public health laboratory for additional testing. Some public health laboratories can detect HPAIs from the H5 and H7 lineages. Check with your state or public health laboratory on their capabilities, and for help submitting specimens to the CDC if needed. (CDC, https://www.cdc.gov/infrastructure/contact/index.html, 4/25/24)

The CDC should be notified immediately (CDC, https://www.cdc.gov/flu/avianflu/severe-potential.htm#shipping-to-cdc, Accessed 4/25/2024) in the event that any clinical specimens from suspected patients test positive for novel influenza A virus or if the testing of clinical specimens from suspected cases are inconclusive. Human infection with a novel influenza A virus is a nationally notifiable condition.

Collecting Specimens for Testing

Specimens should be collected within seven days of illness onset to test for HPAI. Check with your local public health laboratory for accepted specimen types and requirements. Swabs should be placed in a viral transport media or other acceptable media as designated by your public health laboratory. See the NETEC video on specimen collection using NP swabs (NETEC, https://repository.netecweb.org/items/show/840, Accessed 2024).

Swab specimens should be collected using only swabs with a synthetic tip, such as nylon or Dacron®, and an aluminum or plastic shaft. Calcium alginate swabs are unacceptable, and cotton swabs with wooden shafts are not recommended because they can cause false-negative results.

When collecting specimens from patients with suspected HPAI, adhere to standard, contact, and airborne precautions.

See NETEC’s specimen collection tips for health care workers (NETEC, https://repository.netecweb.org/items/show/1415, Accessed 2024).

Packaging and Shipping HPAI Specimens

Clinical specimens of HPAI are considered a UN3373, Biological Substance, Category B (IATA Division 6.2 Infectious Substances). When sending clinical specimens to state public health laboratories, follow the APHL Category B Packaging & Shipping Guide. (APHL, https://aphl.org/docs/default-source/technical/PHPR-2021-Packaging-Shipping-Evaluation-Tool.pdf, 4/25/24)

Viral cultures are discouraged because they are considered a Category A, Dangerous Goods substance. Find training on packaging and shipping dangerous goods. (TRAIN, https://www.train.org/main/welcome, 4/25/24)

It is important to check regulations often, as designations can change for new and emerging pathogens.

See the CDC’s guidance on testing, specimen collection, packaging, and shipping of novel influenza A viruses (CDC, https://www.cdc.gov/flu/avianflu/severe-potential.htm, Accessed 4/25/2024).

Managing and Testing Routine Clinical Specimens

Most clinical specimens for clinical care may be managed as routine specimens in your facility’s core laboratory using standard safety precautions and PPE. Respiratory specimens should be handled with enhanced precautions and PPE based on your facility’s risk assessment. Additionally, aerosol-generating procedures should be avoided with respiratory specimens.

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