The World Health Organization (WHO) was notified about a laboratory-confirmed case of human infection with an influenza A(H5N1) virus on 1 April 2024 by the United States of America IHR National Focal Point (NFP). The patient developed symptoms on 27 March and had a history of exposure to dairy cattle (cows) presumed to be infected with influenza A (H5N1) virus. This is the first human infection with A(H5N1) acquired from contact with infected cattle and the second confirmed human case of influenza A(H5N1) detected in the country. No additional associated cases of human infection with influenza A(H5N1) have been identified. Since the virus has not acquired mutations that facilitate transmission among humans and based on available information, WHO assesses the public health risk to the general population posed by this virus to be low and for occupationally exposed persons, the risk of infection is considered low-to-moderate.

On 1 April 2024, the IHR NFP of the United States of America notified WHO of a laboratory-confirmed human case of avian influenza A(H5N1) detected in the state of Texas.

The case is aged over 18 years. On 27 March, the case developed conjunctivitis, was reported to be while working at a commercial dairy cattle farm and had a history of exposure to dairy cattle (cows) presumed to be infected with influenza A(H5N1) virus (1).

On 28 March, respiratory and conjunctival specimens were collected from the case and tested at the Texas Tech University Bioterrorism Response Laboratory. Reverse transcription-polymerase chain reaction (RT-PCR) analysis indicated that both specimens were presumptive positive for influenza A(H5) virus. The specimens were then sent to the United States Centers for Disease Control and Prevention (US CDC) for further testing. They were received and tested at the US CDC on 30 March and confirmed as high pathogenicity avian influenza (HPAI) A(H5N1) virus clade 2.3.4.4b by RT-PCR and sequencing (1) (2). Genome sequencing of the virus didn’t show new mutations possibly associated with increased transmission to humans.

On 28 March, the patient was advised to isolate and given antiviral treatment (oseltamivir) following US CDC guidance. The patient did not report symptoms other than conjunctivitis, was not hospitalized, and at the time of reporting, was recovering (1).

Household contacts of the patient have not reported illness and have been provided influenza antiviral prophylaxis as per US CDC recommendations. No additional cases of human infection with influenza A(H5N1) associated with this case have been identified (1).

In the United States, since January 2022, detections of HPAI A(H5N1) virus among wild birds have been reported in 50 states or territories. There have been reports of sporadic A-(H5) virus outbreaks among poultry and backyard flocks as well as sporadic detections in mammals and outdoor cats on the dairy facilities as reported by the United States Department of Agriculture (USDA) Animal Plant Health Inspection Service (APHIS).

Influenza A virus infection is exceptionally rare in bovine species (3). This human case had exposure to dairy cattle in Texas, presumed to be infected with HPAI A(H5N1) virus (4)(5). On 25 March, the USDA reported the first detection of HPAI A(H5N1) virus in dairy cattle and unpasteurized milk samples from cattle in Texas and Kansas in four dairy herds. On 29 March, USDA announced confirmation of additional detections in dairy cattle in Michigan dairy cattle that recently received cows from Texas. USDA has also announced additional confirmed detections in dairy cattle in Idaho, New Mexico, and Ohio. To date, USDA has announced confirmed detections on 15 farms across six states: Idaho (n=1), Kansas (n=3), Michigan (n=1), New Mexico (n=2), Ohio (n=1), and Texas (n=7) (5,6,7). USDA is continuing to monitor and test samples collected from other farms where cattle are displaying decreased lactation, low appetite, and other signs (1,5,6,7).

The USDA has publicly posted the genetic sequences of several recently detected HPAI A(H5N1) viruses found in US wild birds, poultry, wild mammals and cattle in Texas (8). The viruses are from clade 2.3.4.4b, which is the most common HPAI A(H5N1) virus circulating among birds worldwide currently. CDC has publicly posted the genome of the virus identified from the patient in Texas and identified only minor changes when compared to the animal viruses (2). Between 9 February 2022 to 29 March 2024, more than 8000 people were actively monitored in the United States following exposure to animals presumed to be infected with HPAI A(H5N1) viruses.

Animal influenza A viruses normally circulate in animals but can also infect humans. Infections in humans have primarily been acquired through direct contact with infected animals or contaminated environments. Depending on the original host, influenza A viruses can be classified as avian influenza, swine influenza, or other types of animal influenza viruses.

Avian influenza virus infections in humans may cause diseases ranging from mild upper respiratory tract infection to more severe diseases and can be fatal. Conjunctivitis, gastrointestinal symptoms, encephalitis and encephalopathy have also been reported in previous human infections with A (H5N1) viruses. There have also been a few detections of A(H5N1) virus in asymptomatic persons who had exposure to infected birds.

Laboratory tests are required to diagnose human infection with influenza. WHO periodically updates technical guidance protocols for the detection of zoonotic influenza using molecular methods, e.g. RT-PCR. Evidence suggests that some antiviral drugs, notably neuraminidase inhibitors (oseltamivir, zanamivir), can reduce the duration of viral replication and improve prospects of survival in some cases.

Avian influenza A(H5N1) virus belonging to Gs/GD lineage, clade 2.3.4.4b Eurasian-origin infections have been reported in birds in the United States since 2022. In late March 2024, HPAI A(H5N1) was also detected in dairy herds in Texas and Kansas (4,5).

This is the first human infection caused by avian influenza A(H5N1) virus in 2024 in the United States and the second confirmed detection in human in the country. This also appears to be the first human infection with A(H5N1) acquired from contact with an infected mammal although human infections with other influenza subtypes have been acquired from mammals. The first detection of influenza A(H5N1) in human in the United States was identified in April 2022, in a person involved in culling birds at a commercial poultry facility in Colorado (9).

In the past, small clusters of A(H5) virus infections were reported, including some involving health care workers, where limited human-to-human transmission could not be excluded; however, sustained human-to-human transmission has not been detected. In this event, the case had direct contact with cows presumed to be infected with A(H5N1) viruses and no further human cases have been detected associated with this event.

This human case was reportedly exposed to dairy cattle in Texas, where HPAI A (H5N1) has recently been confirmed in dairy herds.

From 2003 to 1 April 2024, a total of 889 cases and 463 deaths (CFR 52%) caused by influenza A(H5N1) virus have been reported worldwide from 23 countries. The most recently reported case in humans prior to the current case, was in March 2024 in Viet Nam (11). The human case in Texas is the fourth reported in the region of the Americas, the most recent prior case having been reported in Chile in March 2023 (12).

Whenever avian influenza viruses are circulating in birds, there is a risk for sporadic infections in mammals and humans due to exposure to infected animals (including livestock), or contaminated environments and thus, further human cases are not unexpected. Influenza A infection has been rarely reported in bovine species and spread among dairy cattle herds in four U.S. States is being assessed. Previously, there have been human infections with other avian influenza subtypes following exposure to infected mammals.

Since the virus has not acquired mutations that facilitate transmission among humans and based on available information, WHO assesses the public health risk to the general population posed by this virus to be low and for occupationally exposed persons the risk of infection is considered low-to-moderate.

There are no specific vaccines for preventing influenza A(H5N1) virus infection in humans. Candidate vaccines to prevent H5 infection in humans have been developed for pandemic preparedness purposes. Close analysis of the epidemiological situation, further characterization of the most recent viruses (from human cases and animal) and comprehensive investigations around human cases are critical to assess associated risk and to adjust risk management measures in a timely manner.

If needed, the risk assessment will be *reviewed* should further epidemiological or virological information become *available*.