OUTBREAK: H5N1

Background 

Highly Pathogenic Avian Influenza (HPAI) A (H5N1), is a virus belonging to the Orthomyxoviridae viral family. It was first detected in 1996 in poultry in China with the first human infection detected in Hong Kong in 1997. Since 2003, the virus has spread to at least 24 countries across all six World Health Organization (WHO) regions. In 2021, a genetically different H5N1 virus (clade 2.3.4.4b) was first seen in wild aquatic birds and domestic poultry and has since caused outbreaks in birds globally. This is now the dominant strain of H5N1 circulating. Though rare, cases of H5N1 clade 2.3.4.4b in humans have been reported, ranging from asymptomatic cases to mild illness, severe disease, and death. To date, nearly all human cases have had recent exposure to sick or dead poultry and no cases of sustained human-to-human transmission have been identified (as of 13 August 2024). Humans infected can be treated with antivirals such as oseltamivir and four antivirals have been recommended by the United States (US) for use against influenza A viruses. Vaccination with seasonal flu vaccines does not protect against H5N1.

Current Outbreak 

On 1 April 2024, the US reported a confirmed human case of HPAI A (H5N1) in an adult with a history of exposure to commercial dairy cattle in Texas. This is the first human infection believed to have contracted the virus via an infected mammal and only the second human case in the US. Since then, and as of 3 October 2024, HPAI A (H5) has been detected in five additional human cases exposed to dairy cattle, nine cases exposed to poultry, and one case with no known exposure to sick or infected animals across three additional states (Colorado, Michigan, California, and Missouri) bringing the total human cases in 2024 to 16. The most recent human cases were reported in California on 3 October 2024. Due to low viral RNA levels, the US has not been able to isolate the virus from all recent human cases and therefore unable to determine the neuraminidase subtype as N1 however it is likely that that all human cases have been infected with H5N1. 

In infected animals, veterinarians have observed lactating dairy cattle with reduced feed intake, decreased milk production, and thickened yellow milk. There has also been an increase in wild bird and domestic cat deaths near affected areas. As of 3 October 2024, there have been HPAI-confirmed cases in over 250 dairy cattle across 14/50 states. Poultry and wild birds infected with HPAI A (H5) have been detected in the US since 2022 and since then there have been over 100 million poultry and over 9,000 wild birds affected. Detection of the virus has also been documented in other animals and tests indicate that the virus detected in cows, wild birds, domestic cats, commercial poultry flocks, house mice, and alpacas is H5N1 clade 2.3.4.4b. 

The initial virus spillover is likely of wild bird origin, but current evidence suggests onward lateral transmission among cattle. The virus is shed in milk, and objects in contact with unpasteurized milk may transmit the virus. To date, viral sequences from cattle and workers have maintained avian genetic characteristics and lacked changes in the haemagglutinin gene affecting receptor binding specificity (α2-6-linked sialic acid receptors) where mutations can lead to increased transmission risk to humans. 

The CDC is supporting US states in monitoring people with exposure to cows, birds, and domestic or wild animals that are at risk of H5N1 exposure as well as detecting influenza A viruses in wastewater. Barriers that exist include a) the extent and adequacy of testing people at risk particularly as farm owners are reluctant to allow authorities into their farms to have access to their workers and animals, especially where workers may be undocumented migrants; and b) standard wastewater surveillance cannot distinguish the subtype or source of influenza A virus. 

The CDC’s assessment of the threat of the H5N1 clade 2.3.4.4b virus to public health is low, with the caveat that with the widespread geographical prevalence of infected birds and poultry, and sporadic infections of mammals and people, continued surveillance to detect genetic changes may change its risk assessment. Similar assessments have been made jointly by the Food and Agriculture Organization of the United Nations (FAO), the World Health Organization (WHO), and the World Organisation for Animal Health (WOAH).

For more information about the ongoing HPAI A(H5N1) outbreak in the United States, click here.

Key Public Health and Research Updates 

September 2024:

• The US CDC has reported a confirmed case of H5 infection in an individual with no known exposure to infected or sick animals. One household contact also became ill however, the CDC maintains that this does not support person-to-person transmission but a common exposure. Risk to the public remains low. 
• The Pandemic PACT team and GloPID-R shared a technical briefing detailing ongoing research activity, highlighting evidence gaps and outlining the funding landscape. 

August 2024:

• The FAO-WHO-WOAH published an updated assessment of the H5N1 situation and deemed the global public health risk as low. However, individuals exposed to infected birds, mammals, or contaminated environments are at a low to moderate risk depending on the nature of exposure. 

July 2024:

• A study by Eisfeld et al supported by the National Institute of Allergy and Infectious Diseases (NIAID) and others published findings from a study that indicated HPAI H5N1 in cows have features that suggest the virus can transmit to the upper respiratory tract of humans which could facilitate mammal-mammal (including human) transmission. 

May 2024:

• The National Institute of Allergy and Infectious Diseases (NIAID) released the ‘NIAID Research Agenda for 2024 H5N1 Influenza – May 2024’ which outlines a plan for H5N1 research and translation to public health interventions. 
• Preliminary findings from a study conducted by Guan et al supported by NIAID and others, suggest that consuming untreated raw milk from infected cattle could infect other animals however, the US Food and Drug Administration (FDA) maintains that the commercial milk supply is safe. 

April 2024

• The US notified the WHO of a laboratory-confirmed human case of H5N1 in an adult with exposure to commercial cows. 

February 2024:

• WHO publishes a ‘Summary status of development and availability of A(H5N1) candidate vaccine viruses and potency testing reagents’ for Northern Hemisphere influenza seasons. 

Outbreak-Specific Research Priorities 

The US CDC released a ‘Public Health Science Agenda for Highly Pathogenic Avian Influenza A(H5N1)’ (June 2024).  This is framed under three objectives:

1. Prevent infection and illness in people exposed to HPAI A(H5N1) viruses 

2. Understand human infection and illness with HPAI A(H5N1) virus (clinical, virologic, and epidemiologic characteristics) 

3. Prepare for and mitigate the possibility of an HPAI A(H5N1) virus pandemic 

Relevant Links

The US CDC surveillance of H5N1 is updated weekly 

The WHO Global Influenza Programme

The US CDC Public Health Science Agenda for Highly Pathogenic Avian Influenza A(H5N1)

Pandemic PACT Data

See below our data visualisations for H5N1, H5, and pandemic-prone Influenza research funding.