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Clinical Guidance for highly pathogenic avian influenza (HPAI) A(H5N1)

Published December 04, 2024

Authored by: Tress Goodwin, MD (PPN and Region 3 RESPTC Pediatric Lead from Children’s National Hospital, Washington, DC.; Clayton Mowrer, DO, MBA. UNMC, Children’s Nebraska, Omaha, NE.; Doneen West, UCSF Benioff Children’s Hospital, Pediatric Pandemic Network, ID Domain Lead

This content is jointly provided by the Pediatric Pandemic Network (PPN) and the National Emerging Pathogens Training & Education Center (NETEC).

Highly pathogenic avian influenza (HPAI) can be caused by several different strain types. H5N1 was initially detected in 1996 and has primarily been found in wild birds. Although transmission directly from birds to humans is very unusual, transmission from birds to other mammals occurs more frequently. Sporadic outbreaks in several species of mammals (both terrestrial, including commercial poultry, and marine species) have occurred and are increasing in frequency. 

On March 25, 2024, an outbreak of HPAI A(H5N1) was reported in cows across multiple states.  As of November 18, 2024, there are 549 herds affected in 15 states (see image below). While cows are known to occasionally contract influenza viruses, this marks the first documented outbreak involving highly pathogenic strains in cattle. There is no evidence yet of infections in beef cattle, though expanded testing of livestock has not yet been pursued. Poultry has been similarly affected in 49 states. As of November 2024, there has been even more mammalian spread, most recently including pigs. 

As of November 21, 2024, 53 confirmed human cases of H5N1 have been reported across seven states.Human transmission from animals is rare and typically occurs in adults with close occupational contact with animals. These farm workers all described mild symptoms, many with eye redness or discharge (conjunctivitis). Some workers who tested positive in Washington reported some mild upper respiratory symptoms. None of the workers were hospitalized.  However, several recent cases have unclear exposure histories.

On November 9, 2024 a healthy teenager in British Columbia with no clear epidemiologic link was confirmed to have H5N1 infection and is currently in critical condition. The virus has been identified as the 2.3.4.4b clade and D.1.1 genotype, distinct from the strain circulating in U.S. dairy cattle. An additional pediatric patient in California presented with mild upper respiratory symptoms with a confirmed H5N1 infection. Investigations are ongoing. Notably, there have been no reports of human-to-human transmission in the United States or Canada to date.  More information about the case in Canada and ongoing epidemiological investigation is available in a statement from PHAC.

A recent CDC seroprevalence study of dairy workers exposed to H5N1-infected cows revealed that 7% had detectable antibodies, with 50% of seropositive individuals being asymptomatic, underscoring the potential for subclinical infections among those with occupational exposure. In light of these findings, the CDC has updated guidelines to recommend diagnostic testing and antiviral prophylaxis for exposed individuals, regardless of symptom presentation.  HPAI Confirmed Cases in Livestock | Animal and Plant Health Inspection Service.

Clinical Information

CDC has a summary of recommendations for patients with signs/symptoms compatible with avian influenza A infection who have had recent exposure to avian influenza virus. This includes isolating the patient, initiating empiric antivirals, notifying state and local health departments, and collecting respiratory specimens to be tested at the state health department.

The CDC has noted that circulating strains of H5N1 have retained susceptibility to current antivirals, and available vaccines for H5N1 remain effective.

Image source: Detections of Highly Pathogenic Avian Influenza in Mammals Obtained 12/6/24.

Clinical Information: Top 5 facts the pediatrician needs to know

1. Transmission to humans tends to occur in persons exposed to infected animals, and human-to-human transmission is very uncommon

As of November 21, 2024, a total of 53 cases have been reported in 7 States in the US. All of these cases resulted in mild illness and most reported cases had epidemiologic links to infected cattle and poultry.

Worldwide, since the beginning of 2024, there have been multiple new cases of HPAI A(H5N1) infection reported, with a wide spectrum of illness and outcomes. Most recently, 2 pediatric cases were reported in Cambodia (3 year old and 5 year old cousins), both with exposure to dead poultry. While one was hospitalized, both recovered. However, the clade is unknown and may be due to an older 2.3.2.1c clade that has been noted in parts of Southeast Asia previously, and is unrelated to the current world-wide outbreak. Similarly, a teenager with HPAI A(H5N1) in Canada has been hospitalized in critical condition, though no epidemiologic link has been elicited. This strain, however, (genotype D.1.1) is related to the predominant strain circulating in British Columbia and is different from  that circulating in the US. 

Those with direct contact with animals or animal feces (primarily occupational exposures) are at risk for H5N1, but there remains no evidence that humans can transmit the virus to another human. The CDC continues to monitor the situation, and has found no increase in overall influenza rates.

2. Milk and formula supply is safe

In late April 2024, tests of the pasteurized milk supply found one in five milk samples had fragments of the H5N1 virus, but additional testing did not identify live virus.  In November 2024, virus was detected in raw milk sold retailers in California on routine surveillance by California Department of Public Health, prompting recall of the product.  The FDA also tested several samples of both infant and toddler formula and found no viral fragments in any of the testing. At this time, the U.S. Food and Drug Administration considers commercial (pasteurized) milk and formula to be safe.

The pasteurization process should inactivate any H5N1 virus found in raw milk, and so far tests continue to confirm this. Raw milk or milk products are not recommended, as this milk is unpasteurized and carries a heightened risk of disease.

3. Testing for H5N1 requires specific subtyping typically limited to public health labs

If you have high suspicion for a patient with H5N1 with a high risk epidemiological link, contact your local health department or public health lab to discuss availability of subtyping.

WastwaterSCAN dashboard has been launched on 6/3/24 and is regularly monitoring H5 levels.

The CDC has been partnering with state health departments across the country to pursue seroprevalence studies in high-risk populations.

4. There is no H5N1 specific vaccine available for public use

Seasonal influenza vaccines do not provide protection against H5N1 strains, there are several licensed vaccines available for H5N1 through US Strategic National Stockpile. Vaccine candidates are stockpiled for emergency use, but it remains unclear what the efficacy may be with the current strain. Studies are ongoing for further vaccine candidates. No vaccines for H5N1 are currently available for public use.

There are further federally-funded efforts underway to produce new vaccines through several academic and pharmaceutical institutions, including one mRNA vaccine that has shown promising early immunogenicity animal studies.

5. Current antivirals are likely effective against H5N1

Antivirals used for typical influenza are effective, including oseltamivir, zanamivir, baloxavir, peramivir. The most widely used medication is oseltamivir (brand name: “Tamiflu.”).

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Resources for further reading

USDA with regular updates and links to biosecurity measures for producers and vets:

Center for Infectious Disease Research and Policy

Other Resources