Editorial: Rapid Testing for the Avian Influenza A(H5N1) Virus is Urgently Required as Infections in Poultry and Dairy Cows are on the Rise, and so is Transmission to Humans

In the past century, avian influenza A strains have resulted in multiple epidemics and four major human pandemics [1,2]. The highly pathogenic avian influenza A(H5N1) virus was first reported in 1997 and has spread globally by migratory birds, resulting in infection in animals [1]. Avian influenza A(H5N1) clade 2.3.4.4b emerged in 2021 to cause fatal infections in poultry and mammals [1,3]. In March 2024, cases of avian influenza A(H5N1) virus, clade 2.3.4.4b, were reported in dairy cows in the US, resulting in the implementation of control measures by the US Department of Agriculture (USDA) [4]. In March 2024, the first case of avian influenza A(H5N1) was reported in cattle, and on April 1, 2024, the first confirmed case of human infection was reported in a dairy worker in Texas [5,6].

There is concern that infections in birds, poultry, cattle, and humans are increasing, particularly in the US, due to inadequate control measures [5]. In the past year, the A(H5N1) virus has spread to dairy farms in states across the US [5]. However, only in December 2024 did the US Department of Agriculture (USDA) announce a federal order to test milk nationwide [5,7]. A further concern is that the lack of control of influenza A(H5N1) virus in cattle in the US has revealed deficiencies in the health security system that could allow other new pathogens to spread [5].

On March 17, 2025, the Deputy Director-General of the United Nations Food and Agricultural Organization (FAO), with input from the International Poultry Council, the World Egg Organization, and Health for Animals, issued a directive to member countries regarding the spread of highly pathogenic avian influenza A(H5N1) virus [8]. Worldwide, poultry are becoming infected, and culling measures in poultry farms are impacting the supply of eggs and chicken [8]. Also, the increased transmission of avian influenza A(H5N1) virus infection to mammals highlights an urgent need for strengthened biosecurity, infection surveillance, risk assessments, and the development of rapid-response mechanisms to safeguard the poultry sector and protect economies [8]. The safe trade of poultry and animal products requires a globally coordinated response from a strong veterinary and animal health system in every country [8]. The FAO has advised every country to initiate measures, including enhanced surveillance and reporting, laboratory capacity improvements, and preparedness plans for avian influenza A(H5N1) virus infection [8]. The FAO also recommends promoting risk management through biosecurity and that poultry and livestock vaccination should be part of risk mitigation [8]. There is also an urgent need to strengthen the global outbreak response, improve regional and international cooperation, and raise awareness of the spread of H5N1 highly pathogenic avian influenza [8]. There is also a call for funding proposals for initiatives by the Pandemic Fund, hosted by the World Bank, to improve disease surveillance, including virus testing, and develop early warning systems to control infection outbreaks in poultry and livestock [8,9].

Recently, Garg and colleagues published an analysis of 46 human cases of laboratory-confirmed avian influenza A(H5N1) virus infection identified between March and October 2024 in the United States (US) [10]. Laboratory tests were done using a Centers for Disease Control and Prevention (CDC) influenza A/H5 subtyping kit [10]. Of the 46 confirmed cases, 20 patients were exposed to infected poultry and 25 to infected dairy cows, but one patient had no identified source of infection [10]. In the 45 patients with animal exposure, the median patient age was 34 years, which reflects the average age of US farm workers [10]. All patients had mild symptoms, none were admitted to a hospital, and none died [10]. Symptoms included conjunctivitis in 93% (42 patients), fever in 49% (22 patients), and respiratory symptoms in 36% (16 patients) [10]. Conjunctivitis was the only presenting symptom in 33% (15 patients) [10]. The median duration of symptoms in 16 patients was 4 days (range, 1–8 days) [10]. Most patients (87%) were quickly treated with antiviral agents, including oseltamivir, which was given at a median of 2 days after the onset of symptoms [10]. This study did not identify any other cases of infection in the patients’ households [10]. In this recent US study, A(H5N1) virus infection in adults could be traced to poultry or cattle, caused a mild illness of short duration, mainly associated with conjunctivitis, and most patients were rapidly tested and treated, and there was no evidence of human-to-human transmission [10].

However, a recent case report from Canada has described a 13-year-old girl with obesity and mild asthma with symptoms of conjunctivitis and fever who rapidly progressed to respiratory failure, requiring ventilation and antiviral treatment [11]. Isolates of influenza A(H5N1) virus from this patient identified three mutations that could indicate enhanced virulence and human transmissibility, including E627K in the polymerase basic 2 (PB2) gene and E186D and Q222H in the H5 hemagglutinin (HA) gene [11].

Global reports from infection surveillance by the World Health Organization (WHO) show different outcomes for human avian influenza A(H5N1) virus infection [12]. In January 2025, the WHO published data on the cumulative number of reported and confirmed human cases of avian influenza A(H5N1) in 24 countries [12]. Worldwide, the reported cases of avian influenza A(H5N1) in January 2025 were 964, with deaths reported in 466 patients, which gives a mortality rate of 48% [12]. Therefore, mortality from human infection with avian influenza A(H5N1) far exceeds that of infection with SARS-CoV-2, which caused the COVID-19 pandemic, where mortality rates were between 10–20% before vaccines were developed [13]. Therefore, it is clear that urgent and improved measures are required for surveillance, prevention, and control of avian influenza A(H5N1) in wild birds, mammals, poultry, cattle, other reservoirs of infection, and in humans [10,14].

In emergency departments and primary care centers in the US, point-of-care testing is available for the main viral pathogens of concern, including SARS-CoV-2, influenza A, influenza B, and, less commonly, for respiratory syncytial virus (RSV) [14]. In the US, there is currently a two-stage process to identify avian influenza viruses [15]. Samples from patients who test negative for seasonal influenza A virus subtypes are then sent to major virology units to be genetically identified, meaning the current surveillance and testing system takes several days [15]. Therefore, if human-to-human transmission of influenza A(H5N1) virus does occur, more rapid point-of-care testing should be available to contain outbreaks and prevent future epidemics and possible pandemics [10,16]. A lesson learned from the COVID-19 pandemic was that rapid antigen tests have an unacceptably high false negative rate, particularly in the early phase of infection when viral loads have not peaked [17].

In January 2025, the US CDC issued a Health Alert Network (HAN) Health Advisory to physicians and diagnostic laboratories in the US in response to high levels of seasonal influenza and reports of human infections with avian influenza A(H5N1) viruses [18]. The CDC has recommended more rapid subtyping of all influenza A specimens in hospitalized patients and possible cases of avian influenza A(H5N1) virus infection [18]. The CDC has confirmed that most influenza tests ordered in clinical settings do not distinguish between avian influenza A(H5) viruses and seasonal influenza A viruses, as a positive laboratory result usually confirms influenza A virus infection [18]. However, the CDC also recommends that when specimens are collected, a thorough exposure history is obtained from the patient, including exposure to wild and domestic animals, including pets, and certain animal products, including poultry and raw cow’s milk products [18]. The 2025 CDC HAN Health Advisory recommends that respiratory specimens that are positive for influenza A but negative for current seasonal influenza A virus subtypes, including A(H1) and A(H3), should be sent to a US public health laboratory as soon as possible [18]. Until safe and effective vaccines are developed, infection surveillance depends on more rapid testing for avian influenza A(H5N1) virus [10,14].

Conclusions

Until rapid and accurate testing for highly pathogenic avian influenza A(H5N1) virus is available and widely used, infection surveillance and control in poultry, cattle, and humans will not be possible. Should human-to-human transmission of this virus occur, then lack of available rapid testing will increase the likelihood of epidemic or pandemic human avian influenza A(H5N1) infection, with health outcomes that could be worse than those seen during the COVID-19 pandemic.