Dealing With Avian and Variant Influenza A Infections

While seasonal influenza activity is low during the summer months, clinicians should remain vigilant for potential cases of novel influenza A virus infection. Avian influenza A(H5N1) virus is circulating among wild birds and has caused outbreaks in commercial poultry and backyard flocks, with spillover to some mammals, and rare, sporadic human infections worldwide. Clinicians should also be aware of the potential for other novel influenza A infections (eg, other avian influenza A viruses or swine-origin variant viruses) associated with mild to severe acute respiratory illness.

Human infections with various subtypes of avian influenza A viruses, both low pathogenic and highly pathogenic, have been reported sporadically worldwide. These infections can lead to a wide range of disease severity, such as conjunctivitis, mild upper respiratory tract illness, pneumonia, respiratory and multiorgan failure, and even death. Pathogenicity in infected poultry does not necessarily translate to the same disease severity in infected humans. Both low pathogenic and highly pathogenic avian influenza A viruses have caused mild illness, as well as severe and fatal outcomes, in infected people.

While highly pathogenic avian influenza (HPAI) A(H5N1) viruses have spread widely among wild birds and poultry in many countries, including the United States, since 2022, and sporadic infections have been identified in many different mammals, only a small number of human cases have been reported. These cases are mostly associated with recent exposure to infected poultry, without human-to-human transmission. HPAI A(H5N1) viruses circulating in birds and poultry, causing sporadic human infections, do not easily bind to receptors in the human upper respiratory tract. Therefore, the risk to the public from HPAI A(H5N1) viruses remains low. However, because HPAI A(H5N1) viruses are circulating among wild birds and causing poultry outbreaks in many countries, sporadic human infections in exposed persons are expected to continue. It is crucial to continue comprehensive surveillance of these viruses in wild birds, poultry, mammals, and humans worldwide, and to regularly reassess the public health risk while maintaining preparedness efforts.

Overview – Human Infection With Variant Influenza A Viruses (Swine-Origin)

Swine influenza A viruses circulate among pigs worldwide. Swine influenza A viruses that have infected humans are referred to as variant influenza A viruses (denoted with "v" after the subtype). Variant influenza A viruses include:

A(H1): A(H1N1)v, A(H1N2)v
A(H3): A(H3N2)v

Most variant influenza A virus infections have been reported in children, and most illnesses have been mild. Since 2010, there have been more than 400 sporadic human A(H3N2)v infections reported in the United States. During the largest outbreak in 2012, the median age of reported cases was 7 years, and most cases were associated with swine exposure at agricultural fairs. Clinicians should consider the possibility of variant influenza A virus infection when managing patients with influenza-like illness who had recent exposure to pigs, including at country and state agricultural fairs.

Variant Influenza A Virus Infection, United States, 2010-To Date

Diagnostic Testing and Specimen Collection – Novel Influenza A

Commercial influenza tests in clinical settings can identify influenza A viruses in respiratory specimens but cannot differentiate between seasonal influenza A viruses and influenza A viruses of animal origin.

If a patient is influenza A positive, and novel influenza A virus infection is suspected because of animal exposures, subtyping should be performed.

In patients with mild disease, clinicians should:

Collect a nasopharyngeal (NP) swab, and combined nasal and throat swabs for rRT-PCR testing for influenza A and B viruses at public health laboratories (eg, using the CDC Flu rRT-PCR Dx Panel).
- Influenza A positives are subtyped for H1, H3 at public health laboratories.
  - If influenza A positive and not subtypeable (H1 negative, H3 negative), send specimens to CDC for testing.
  - If H5 is suspected, test by CDC H5 primer/probe set; send presumptive positive specimens to CDC for testing.
    - Throat swabs have higher sensitivity to detect H5N1 virus than nasal or NP specimens.
- If recent swine exposure and H1 or H3 is positive, and subtyping is presumptive positive for a variant influenza A virus, send specimens to CDC for testing.

In patients with lower respiratory tract disease:

If influenza A positive on a commercial influenza test, collect respiratory specimens for influenza A virus subtyping at a public health laboratory.
Collect NP swab, combined nasal and throat swabs, and sputum for rRT-PCR testing for influenza A virus subtypes H1, H3, at public health laboratories.
- For intubated patients, also collect endotracheal aspirate specimens (or BAL fluid).
  - If A positive, H1 negative, H3 negative: perform H5 subtyping (or other subtypes: H7).
  - Send presumptive positives or A non-subtypeable specimens to CDC.
Collect multiple respiratory tract specimens from different sites on multiple days for patients with suspected avian influenza A virus infection to maximize potential for diagnosis.

Clinical Management – Antiviral Treatment and Chemoprophylaxis

Treatment

If there is suspicion based on recent animal exposure or confirmation of infection with a novel influenza A virus known to cause severe illness in humans (such as H5N1 virus), patients should be started promptly on antiviral treatment with oseltamivir or another neuraminidase inhibitor (eg, inhaled zanamivir or intravenous peramivir).

Oseltamivir is recommended for patients who are hospitalized or outpatients with progressive or severe disease. The CDC recommends standard oseltamivir dosing (twice daily for 5 days) for outpatients and longer treatment for severe disease; however, the optimal duration is unknown. While there have been no clinical trials, observational studies have reported that starting oseltamivir treatment soon after illness onset is associated with greater survival vs later initiation of antiviral treatment.

Oseltamivir or baloxavir treatment is recommended for outpatients with mild illness who are at increased risk for influenza complications and have suspected or confirmed variant influenza A virus infection.

Postexposure antiviral chemoprophylaxis can also be considered on the basis of clinical judgment.

Infection Prevention and Control Recommendations – Novel Influenza A

Novel influenza A virus infections associated with severe disease and high mortality have the potential for large droplet and small-particle (aerosol) spread. In addition to standard contact and airborne precautions, patients should be placed in an airborne infection isolation room (AIIR). If not available, isolate the patient in a single-patient room, place a facemask on the patient, keep the door closed, and arrange transfer to a facility with an AIIR that includes negative pressure and HEPA filtration.

For novel influenza A virus infections not associated with severe disease, standard contact and droplet precautions should be followed.

More information on these recommendations are available here: Interim Guidance for Infection Control Within Healthcare Settings When Caring for Confirmed Cases, Probable Cases, and Cases Under Investigation for Infection with Novel Influenza A Viruses Associated with Severe Disease