Research and analysis

HAIRS risk statement: Avian influenza A(H5N1) in livestock

Updated 24 October 2024

Summary

Risk statement

This risk statement provides a qualitative description of the zoonotic risk avian influenza (AI) A(H5N1) clade 2.3.4.4b genotype B3.13 would present to people in contact with animals in the UK, and highlights evidence gaps and recommendations for mitigating the risk of zoonotic transmission.

Although new detections have been reported in dairy cattle, cats, alpacas and humans in the USA, and additional information has become available since the last risk statement (published in May 2024), the HAIRS group determined that this remains at most a very low risk. This is because there is no evidence to suggest AI A(H5N1) clade 2.3.4.4b genotype B3.13 is present in the UK. The HAIRS group will continue to monitor the situation and update this risk statement if any substantial developments arise.

Overview

Detections of highly pathogenic avian influenza (AI) A(H5N1) in dairy cattle from the United States of America (USA) are likely the result of one or more initial incursions, followed by within and between herd spread of AI A(H5N1), clade 2.3.4.4b genotype B3.13; a reassortant virus from Eurasian/North American origins. This genotype has only been detected in the USA, with the first wild bird cases being reported in November 2023. It is unknown exactly how or when the virus was introduced into the implicated dairy farms or how long the virus has been circulating undetected, but sequence dating suggests November 2023 would be the time of emergence of this strain.

There are several possible routes of introduction into the dairy cattle, including contact with wild bird cases, infected mammals or from undetected infected poultry. Clinical signs in infected dairy cows include reduced feed intake, a reduction in milk yield, thick discoloured milk, fever, slow rumination and dry and tacky faeces. No mortality in the affected dairy herds directly attributed to infection has been reported, with infected dairy cattle recovering within approximately 2 weeks of clinical onset. The United States Department of Agriculture have stated that cow-to-cow transmission is believed to be occurring through mechanical transmission (for example, contact with poorly disinfected milking equipment) and farm-to-farm transmission through the movement of animals, shared equipment or people.

There have been incidents of cats with respiratory and neurological signs reported from affected dairy farms in:

• Colorado
• Michigan
• Minnesota
• New Mexico
• Ohio
• Oklahoma
• Texas

These incidents are as of 31 July 2024 and associated with the consumption of raw milk or colostrum. Wild bird detections with the same genotype have also been reported on many affected premises, mostly of peridomestic birds. There have been cases of the same genotype in poultry, either a result of new incursions or as spill-back from infected dairy cattle, through fomite transmission via shared workers, equipment or transport.

Four confirmed human cases with on-farm exposure to dairy cattle infected with, or presumed to be infected with, AI A(H5N1) have been reported from Michigan (2 cases), Texas (one case) and Colorado (one case). The cases reported conjunctivitis like symptoms, whilst one also had mild respiratory illness. All were treated with antivirals and have recovered. There have also been 10 human cases in Colorado having been exposed to the same strain, but through contact with poultry during culling operations on two very large (around 1.8 million and 1.2 million) layer farms.  

Background

On 25 March 2024, the United States Department of Agriculture (USDA) reported that they were investigating illness among older dairy cows in Kansas, Texas and New Mexico states causing reduced milk yield, thickened milk resembling colostrum and reduced feed intake (1, 2). The USDA also reported positive detections of highly pathogenic avian influenza (AI) virus A(H5N1) clade 2.3.4.4b in milk samples and an oropharyngeal swab from sick dairy cattle on farms in:

• Texas (n=2)
• Kansas (n=2).

As of 31 July 2024, 178  farms across 13 states have reported confirmed cases in livestock, including:

• Colorado (n=52)
• Idaho (n=29, plus 1 case in alpacas)
• Michigan (n=27)
• Texas (n=23)
• Iowa (n=13) -  Minnesota (n=9)
• New Mexico (n=8)
• South Dakota (n=7)
• Kansas (n=4)
• Oklahoma (n=2)
• North Carolina (n=1)
• Ohio (n=1)
• Wyoming (n=1)

For up-to-date figures, including a map of affected states, see (3). An epidemiological brief published by the USDA on 8 June 2024 (35), based on a questionnaire completed by around 50 farms, stated that over 20% of farms received cattle within 30 days of animals developing clinical signs, and over 60% of farms moved animals off their premises after clinical signs were observed in cattle. Poultry were present on 20% of the farms, and cats on 80% of the farms while less than a third of farms noticed dead or dying wild birds within 30 days prior to onset of clinical signs in the cattle. The movement of infected animals, contaminated vehicles and equipment, and of people, including shared workers between poultry and dairy premises, are considered the main drivers of between-farm transmission.  

The prevalence of cattle with clinical signs on farms is 10 to 20% of the lactating cows, with very little observed in non-lactating cattle, heifers, calves or bulls. Over 80% of affected farms reported abnormal lactation and reduced feed intake in cattle, whilst 90% of farms reported thickened and/or discoloured milk. Other signs included fever, slow rumination, and dry and tacky faeces (35). No neurological signs have been observed, and cows typically recover within 2 weeks. Additionally, no explicit mortality attributable to infection has been reported, although some animals in a poor condition have been euthanised. It is too early to ascertain the duration of viral persistence in naturally infected cattle; longitudinal studies are expected. However, experimental infection of lactating cattle in one experiment suggested live virus could no longer be obtained from stripped milk (which means the first milking fraction), more than 2 weeks post infection (36).

Unpasteurised milk, and samples from various organs taken from naturally infected cattle from Texas and Kansas and from 2 cats from one of the Texas farms were tested by PCR and viral isolation (37). The reverse transcription-polymerase chain reaction (RT-PCR) signal was particularly strong for the milk samples (cycle threshold (Ct) value of around 10 to 20) and the mammary gland but barely detectable in lung, spleen, rumen or ocular samples from the cattle.

For the cats, the Ct values were highest in the brain and the lung. This may indicate some tissue tropism for mammary tissue or mammary gland epithelial cells, as the Ct values (greater than 25 when a positive result was returned) for other samples suggests there is not widespread infection of other tissues or the respiratory tract. Indeed, there is some evidence that both the human-(SA-α2,6) and the duck sialic acid receptors (SA-α2,3-Gal-β1,3) for the influenza haemagglutinin (HA) gene are highly expressed in bovine mammary glands which may be indicative of tropism (4), while other authors find it is the glycan backbone of the receptors which is bound more readily by this virus than others (38).

Experimental infections of lactating cattle have shown that if virus is directly injected up the teat into the mammary gland, infection occurs, and clinical disease was consistent with field reports (36). This is for both the B3.13 genotype in two separate labs, but also a recently isolated Eurasian AIV48 strain (36, 39). It should be noted that high viral titres were used. Respiratory infections of heifers resulted in mild clinical signs and no virus was detected in mammary glands (36). No evidence of respiratory or fomite transmission was observed during challenge infections in ferrets using the 2.3.4.4b viral clade. Transmission did occur through nose-to-nose contact (40) and direct ocular infection (41), which resulted in fatal disease.

The USA has continued to report outbreaks in commercial and backyard poultry, spill-over events in mammals and wild bird cases due to the Eurasian strain of the virus and other reassortants. Between January and 31 July 2024, there have been 111 outbreaks in either commercial or backyard poultry, 1,054 wild or captive bird cases and 138 detections in mammals (not including cattle). The B3.13 genotype which was detected on dairy farms had also been detected, albeit rarely, in wild birds, poultry, cats, alpacas and one skunk since November 2023 in the USA. Of the poultry outbreaks, 13 are attributed to the B3.13 genotype (2 of which are large layer farms in Colorado with associated human cases).

According to a technical assessment summarising genetic analysis of sequences from cattle and an associated human case in Texas (further details below), minor changes were identified in the human’s viral sequence compared to viral sequences from cattle to which they were exposed (5).

Nevertheless, both cattle and human sequences maintain primarily avian genetic characteristics (47). The genome for the human isolate had one mutation (PB2 E627K) that is known to be associated with viral adaptation to mammalian hosts (6). This mutation improves ribonucleic acid polymerase activity and replication efficiency in mammalian cells and is considered to be an early marker of mammalian adaptation. Whilst this was not observed in the cattle sequences or other human sequences, 2 other mutations, one in PB2 M631L and the other in the PA gene at position K497R, were detected and may be markers of predisposition to mammalian cell infection. Otherwise, the virus is a typical avian origin virus with a small number of mutations indicative of enhanced polymerase activity in mammalian cells, but without those suggestive of efficient adaptation to mammals or human-to-human transmission, which would have been associated with changes in the HA gene.

The spread of clinical signs among the first Michigan and Ohio dairy herds, following introduction of animals from an affected herd in Texas, suggest close contact mammal-to-mammal spread or lateral spread possibly via secretions or contaminated equipment (other transmission pathways cannot be ruled out).

While some farms had reported findings of dead wild birds on their property, this was not the case for all the affected farms and therefore the source of infection for the index farm is still unknown. Sequence analysis shows high homology between strains taken from each farm, indicative of a single point of introduction on the index farm and subsequent spread via movement of live animals, although other pathways or exposure to a common source cannot entirely be ruled out. Limited diversity of the sequenced genotypes suggests this strain first emerged in cattle in March 2024, although caution over the exact date for introduction should be used, until more sequences are available for wild bird cases (7).

On some farms, neurological signs in cats triggered testing of these animals, which confirmed AI A(H5N1) virus infection. The sequences matched those of the infected dairy cattle (2), suggesting viral transmission to the cats via direct contact with infected cattle, consumption of unpasteurised milk products on those farms or from infected wild birds associated with the premises (8).

The findings of the PB2 M631L and PA K497R mutations in the sequences from blackbirds, pigeons and common grackles on the affected farms could indicate spill-back into the birds from contact with the cattle. There have also been instances of nearby poultry farms testing positive with the same virus, which may have occurred through fomite transmission via shared farm workers or contact with bridging species, such as passerines, gulls, rodents or other mammals.

On 1 April 2024, the World Health Organization (WHO) was notified of a laboratory confirmed human case of AI A(H5N1), in an individual from Texas exposed to dairy cattle presumed to be infected with AI A(H5N1) (9). The case developed conjunctivitis on 27 March 2024 (their sole symptom). Samples from the conjunctiva and a nasal swab both tested positive for AI A(H5) virus on RT-PCR, with Ct values of 18 and 33, respectively. High Ct values (greater than 25) indicate a low concentration of viral material.

Additional testing and sequencing performed by the United States Centers for Disease Control and Prevention (US CDC) confirmed AI A(H5N1) clade 2.3.4.4b infection (10). The genotype was classified as B3.13, which was the same genotype detected in dairy cattle in Texas (5, 11). The patient was isolated, treated with oseltamivir and recovered. No illness was reported in case contacts, and no additional human cases associated with this incident have been identified. The WHO states that this case appears to be the first occurrence of mammal-to-human transmission of AI A(H5N1) virus. However, exactly how the affected individual was exposed and infected with the virus is unclear.

In May 2024, 2 additional confirmed human cases were reported from Michigan (42). These unrelated cases were both dairy workers exposed to cattle infected with AI A(H5N1) clade 2.3.4.4b genotype B3.13. One case experienced conjunctivitis, whilst the other reported mild upper respiratory symptoms. Both were treated with oseltamivir and recovered, and no additional related human cases were detected (43). 

In July 2024, the US CDC reported a fourth human case: a dairy farm worker from Colorado who was being monitored due to occupational exposure to AI A(H5N1) infected dairy cattle. The case developed conjunctivitis (their sole symptom), was treated with oseltamivir, and recovered (44R). Testing by the US CDC confirmed infection with AI A(H5). Sequencing results were pending at the time of writing.

Between 14 and 31 July 2024, the Colorado State Department of Public Health reported 10 confirmed human cases of AI in poultry workers involved in depopulating 2 commercial egg layer premises experiencing outbreaks of AI A(H5N1) clade 2.3.4.4b B3.13 genotype (45). 60 of the 160 poultry catchers / depopulation teams experienced mild conjunctival and flu-like symptoms but only 10 have tested positive out of 134 tested. These are the first cases of AI A(H5) infection in poultry workers reported in the USA since 2022. The exceptionally high heat experienced at both the poultry farms (in excess of 40°C) may have contributed to the high level of dust and contamination as well as issues wearing personal protective equipment (PPE) in such conditions (46).

The US CDC has published interim recommendations for the prevention, monitoring and public health investigations of AI A(H5N1) viruses; including monitoring of individuals for 10 days following exposure to sick or dead wild, domestic and livestock animals with suspected or confirmed AI infection (12). On 6 May 2024, the US CDC asked jurisdictions to make PPE available to workers on dairy farms, poultry farms and in slaughterhouses; prioritising those farms with affected herds (13).

The US CDC also detailed initial findings from a Michigan-led seroprevalence study, in 35 people who work on Michigan farms that had outbreaks in dairy cows. The participants were from multiple counties and had different roles, though all had worked directly with sick cows. Fewer than half stated they wore masks or goggles. None of the 35 workers had antibodies to AI A(H5N1), but many had neutralizing antibodies to seasonal flu, suggesting prior infection or vaccination. 

UK context

It should be emphasised that the AI A(H5N1) clade 2.3.4.4b genotype B3.13 reassortant virus implicated in USA dairy cattle has never been detected in the UK or Europe. Similarly, no other Eurasian-North American reassortants have been recorded in the UK or Europe, despite detections of these viruses in Canada and the USA since 2014. In Great Britain (GB), outbreaks of AI on poultry premises are followed-up with sequencing. Additionally, a proportion of wild bird cases will also be sequenced annually. Of all the GB sequences submitted to GenBank, none have been indicative of reassortants with North American strains. This can be visualised in the Global Initiative on Sharing All Influenza Data (GISAID) regional genome analysis from 2019 to 2024, where only a link for European viruses entering North America has been observed in this period (14) (Figure 1). Despite the overlap of migratory flyways, the synchronisation of the migratory seasons and circulating avian influenza viruses have not been conducive to spread from west to east via these flyways.

Figure 1: regional genome analysis and introductory routes of highly pathogenic avian influenza virus subtypes from 2019 to 2024. Source: Global Initiative on Sharing All Influenza Data. Accessed: 27 April 2024.

The likelihood of the presence in the UK of AI A(H5N1) clade 2.3.4.4b genotype B3.13 and undetected disease in cattle is considered to be very low (34). The risk level associated with AI in wild birds and poultry in the UK has recently been reduced from medium to low and for poultry with high biosecurity, to very low. On 2 April 2024, the UK self-declared zonal freedom from highly pathogenic AI (15) was published by the World Organisation for Animal Health (WOAH). There have been no recent cases of HPAI H5N1 in wild birds in the UK, since 4 April 2024.

Mastitis frequently occurs in British cattle, although rarely to the high prevalence levels as reported in these cases in the USA. It is most commonly caused by bacterial infections of the mammary glands, and only in rare cases the aetiological agent is not found. Nevertheless, mastitis cases are not routinely tested for AI viruses as there has never been any evidence to suggest a testing requirement. The Animal and Plant Health Agency’s (APHA) cattle dashboard (16) reports the number of cases of mastitis tested and the causative agents identified under a voluntary scheme (as such, underreporting is likely). In 2024, and as of 31 July 2024, there have been 120 cases of mastitis; most commonly associated with infections from:

• Streptococcal (n=44)
• Escherichia coli (n=37)
• Staphylococcal (n=12)

Between 2021 and 2024, there were 52 cases of mastitis in dairy herds in which no diagnosis was confirmed. From 2017 to 2020, there were 40 cases in which no diagnosis was confirmed.

For 6 weeks, between 20 May and 1 July 2024, samples were tested from a representative number of farms across GB. All samples tested negative, which, according to the sampling plan, gave 99% confidence that across the GB infection was not present at greater than 1% prevalence at the national herd level.

Routes of incursion into the UK

Live animal imports

There is no trade in live ruminants between the USA and the UK due to other disease issues. Within the USA, some states have established restrictions to prevent the movement of cattle from affected dairy herds (for example, the Mississippi Board of Animal Health (17)), but this had not been mandated by the USDA until a recent federal announcement (18). Therefore, movements of lactating cattle and newborn calves may have continued between 25 March and 26 April 2024, and this may give rise to further cases. It is not known if there is any transmission to calves from infected lactating cattle or any in utero infection.

Products of Animal Origin

On 1 May 2024, the USDA reported that 30 samples of beef meat collected from retail outlets tested negative for AI A(H5N1); reaffirming that the meat supply is safe (19); however, there has been no further testing that we are aware of, for beef cattle. Beef imports from the USA to the UK are restricted, due to certification requirements and tariff limits, but are not considered a significant risk pathway for introducing infection into the UK cattle herd.

The USA is an approved country for the export of raw dairy products and colostrum for human consumption and of treated colostrum for animal feed to the UK. The imports of colostrum are used for both animal feed and for human consumption. The measures on the certificates for colostrum destined to animal feed include short time pasteurisation of 72°C for 15 seconds, while some certificates for colostrum destined for human consumption have no heat treatment step. Orthomyxoviruses are enveloped viruses, which generally means they are more susceptible to heat inactivation; but in the presence of high fat and protein content, this may be reduced (20). As inactivation depends on temperature, relative humidity, stabilising matrix and level of virus present, it is unknown whether 72°C for only 15 seconds in a heavily contaminated colostrum sample may be sufficient to produce a high log reduction. It is also unknown if the process of freeze-drying to produce powdered milk sufficiently inactivates virus.

The recent finding of RT-PCR positive milk samples from grocery store pasteurised milk were tested for virus isolation and none were positive. This is, according to the U.S. Food and Drug Administration, solid evidence that pasteurisation is effective (21). However, the dilution effect of a number of cattle contributing to the bulk milk tank is not known nor is the effectivity of pasteurisation on colostrum or on a product with a naturally very high virus titre. Results from experiments with spiked milk samples concludes pasteurisation temperatures of 72°C for 15 seconds is effective (internal communication). These will be the subject of research, but for now the risk level is based purely on the level of trade in these commodities, which has been very low in the last few months.

Use of colostrum as an additive in feed for calves is a known necessity and many farmers will add this supplement for young calves to boost their intake in the first few weeks. To be eligible for import into the UK, colostrum for calves must not be sourced from herds under restriction for diseases such as foot and mouth disease, anthrax, contagious bovine pleuropneumonia, or in an official control programme for bovine tuberculosis, brucella abortus or enzootic bovine leucosis. According to industry expert opinion, it is unlikely for a British farmer to use a USA imported colostrum, rather than a domestic product. There have been no imports of raw colostrum to the UK from the USA during 2024 according to APHA Centre for International Trade.

Wild birds

Migratory wild birds generally stay within their flyways, which in the case of the USA involves 4 different routes: the Pacific, the Central, the Mississippi and the Atlantic Flyway (Figure 2). Only the Atlantic Flyway overlaps with the East Atlantic Flyway (which brings birds to Europe via Greenland and Iceland). This East Atlantic Flyway has been the route for AI incursions into West Scotland, North-West England and Ireland in the past, via movements of migratory geese during the north to south migration in the Autumn. A review of the migratory patterns of birds from the North American continent to the European continent (based on data available in the Migratory Atlas; movements of the birds of Britain and Ireland and the BTO bird migration tool avian influenza) highlighted that the range of species is narrow and the frequency low. There are some sites where for example, red knots, Tundra swans, Brent geese may arrive.

Therefore, monitoring wild bird populations for these reassortant viruses in the next season (September 2024 onwards) will be important. This new strain of AI A(H5N1), clade 2.3.4.4b genotype B3.13 has been detected in wild blackbirds, pigeons and grackles in Texas, and in Canada geese in Wyoming. Both States are within the Central Flyway which is often overlapping with the Mississippi Flyway. Therefore, the likelihood of the incursion into the UK via these migratory routes is considered very low and to only discrete parts of the British Isles, namely the sites on the West coast of Britain and in Ireland where Brent geese may overwinter.

Figure 2: an overview of the routes (or flyways) taken by wild migratory birds annually. Source: International Disease Monitoring Workgroup, APHA. Date prepared: 3 May 2024.

Where this new virus strain is not already circulating in the UK, and provided the import risk pathways are managed, the possibility of a currently circulating Eurasian virus mutating and adapting in the same manner to either infect cows or replicate to high levels in mammary gland cells is not yet known. However, the levels of circulating virus in the UK at present are the lowest they have been for several years; therefore, the likelihood of a new strain emerging and infecting poultry, wild birds or causing a spill-over infection in cattle is also very low.

Possibility of human exposure in the UK

AI A(H5N1) clade 2.3.4.4b, genotype B3.13 has not been detected in the UK.  If infection was detected in UK dairy cattle, the likely pathways of human exposure are occupational and include farm and dairy workers, abattoir workers, veterinary professionals and laboratory exposures. As poultry have been infected with the same virus strain in the USA, then poultry workers and catcher gangs should be considered also at risk, where there is a strong link to an affected dairy farm. Historically, AI infections in humans have predominantly been acquired via direct contact with an infected animal or their contaminated environments. Current evidence suggests that the likelihood of human infection and onward spread is very low, and no sustained human-to-human transmission of AI viruses has ever been reported.

The ocular infection route has been observed in ferret experimental work and is the most likely explanation for the human cases in the USA, given the clinical outcome and the likely aerosolization of virus in milk in a dairy parlour or in dust in a poultry barn.

Consumption of unpasteurised, contaminated animal products is a possible but less likely source of exposure for humans (22), due to animal health and welfare and food safety guidelines in the UK around producing and consuming raw dairy products (23), particularly for vulnerable people.

There is currently no surveillance in dairy workers for AI A(H5N1) in the UK. The only clinical signs in the USA cases have been conjunctivitis and/or mild respiratory illness, and while these are known to be possible symptoms of human infection with A(H5N1), it is unlikely that cases would be tested for AI A(H5N1) based on these symptoms.

Impact on human health

AI infections in humans cause a range of disease manifestations, from mild upper respiratory tract infections, to more severe disease that can be fatal. Conjunctivitis, gastrointestinal illness, encephalitis and encephalopathy have been reported in previous human cases of AI A(H5N1). There have also been detections in asymptomatic individuals, following exposure to infected poultry.

Disease severity in humans infected with AI A(H5N1) varies depending on lineage. For example, Asian lineage AI A(H5N1) can cause severe disease in humans, with mortality rates of up to 50%. While this lineage does not easily infect people and has not acquired the ability to cause sustained transmission among humans (24), it is considered a public health concern. It is unclear whether AI A(H5N1) viruses in certain geographical regions differ in their pathogenicity. Clade 2.1 viruses (Indonesia) appear more pathogenic than clade 1 viruses (Cambodia/Thailand/Vietnam) and 2.3 viruses (China) (25). Treatment with the antiviral oseltamivir is recommended to reduce the severity of, or act as prophylaxis against, severe disease (26).

Human cases of AI A(H5N1) continue to be sporadically detected globally, including cases of clades 2.3.2.1c and 2.3.4.4b. Since 2023, and prior to the latest human cases in the USA associated with exposure to infected dairy cattle, detections in humans either confirmed to be, or associated with, clade 2.3.4.4b viruses have been reported in Ecuador (27), China (28. 29) and Chile (30). These cases were not fatal but did develop severe disease requiring hospitalisation. No known comorbidities were reported for any of these cases.

Since 2023, the UK Health Security Agency has reported 4 human detections of AI A(H5N1) clade 2.3.4.4b in exposed persons on farms in England where AI A(H5N1) was also confirmed in the poultry on site (31). All detections were identified as part of an ongoing enhanced surveillance study of asymptomatic workers exposed to premises infected with AI. It remains unclear whether the detections in these asymptomatic individuals reflected deposition of viral particles on the mucosal surface (in other words, not causing infection) or infection with active viral replication.

Given human cases are sporadic and infrequent, there is a paucity of evidence on what risk factors may increase disease severity and poorer clinical outcomes in human cases with AI A(H5N1) clade 2.3.4.4b infections.

Within the UK, well established and robust public health interventions are implemented in response to a human becoming symptomatic following contact with known AI infection (for example in poultry). This involves the isolation and treatment of a case, and extensive contact tracing designed at preventing further transmission. There are well established pathways for the prompt diagnosis and treatment of a human case (32). Cases may be given antiviral medicine such as oseltamivir or zanamivir, which may help reduce the severity of disease, prevent complications and improve the chances of survival (33). To date, there have been no documented incidents of AI A(H5N1) transmission from infected non-avian species to humans in the UK.

Interim outcomes and recommendations

Although there are evidence gaps affecting the interpretation of the risk AI A(H5N1) clade 2.3.4.4b genotype B3.13 presents to people in contact with infected animals in the UK, the HAIRS group determined that, based on the currently available information:

• it is very unlikely this new Eurasian/North American reassortant is already circulating in dairy cattle in the UK, due to the lack of incursion pathways and the low level of AI cases in the UK since November 2023, when this virus strain emerged in the USA. Our bulk milk tank testing snapshot supports this evidence base. Furthermore, there is ongoing genomic surveillance in place that aids early detection of new AI strains in wild birds and poultry in the UK. To date, this genotype has not been detected in the UK
• the current risk to people in contact with animals infected with this strain in the UK is therefore at most very low (medium uncertainty). This is based on likelihood of exposure and impact of infection
• there are some limited imports of raw dairy products including colostrum and these are being considered by not only Defra Imports team but also the Food Standards Agency. It is not certain whether current pasteurisation methods would be effective in completely eliminating the viral load of a large volume of thick, discoloured milk from infected cattle. All research to date has confirmed that H5N1 is highly temperature-sensitive and is likely to be effectively inactivated and eliminated by pasteurisation. Additionally,  milk from cattle showing such clinical manifestation would be identified as unfit for human consumption and disposed of on the farm; it would not be added to the bulk tank, which is only for milk destined for human consumption. Nevertheless, exposure to such products (prior to pasteurisation) or equipment is a potential risk pathway which needs further assessment

Based on the above, the HAIRS Group makes the following recommendations:

For animal health and veterinary professionals

The guidance is to:

• continue close monitoring of the situation in the USA, including further understanding of likely pathways of introduction into the UK
• report to the APHA any clinical signs in cattle associated with an unexplained reduction in milk yield, thickened milk (that is uncharacteristic for the stage of lactation) combined with reduced feed intake, low rumination and/or fever in dairy cattle
• report to the APHA any unexplained mortality, neurological and/or respiratory symptoms in other animals (for example birds or other mammals) on dairy premises
• continue monitoring for new evidence as to the presence of AI A(H5N1) clade 2.3.4.4b genotype B3.13 in wild birds, poultry and livestock in the UK
• raise awareness and encourage farm and dairy workers to maintain sensible biosecurity on dairy farms (for example, the use of aprons, gloves and eye protection in parlours and sterilization of milking equipment) and to communicate guidance to anyone coming into contact with cattle while undertaking overseas work
• undertake prompt investigation into possible transmissible zoonotic diseases on farms
• test milk from UK dairy farms should be included in surveillance plans for animals that meet the case definition (as published on GOV.UK  (34))
• ensure timely sharing of data between animal and human health agencies to enable a coordinated, effective One Health approach

For public health professionals

The guidance is to:

• continue close monitoring of the situation in the USA, including likely transmission pathways to humans
• raising awareness regarding consumption of raw dairy products including colostrum
• consider the rapid investigation and testing of farm or dairy workers with respiratory or compatible symptoms, particularly on affected premises
• ensure timely sharing of data between animal and human health agencies to enable a coordinated, effective One Health approach to issues on dairy farms

Previous and current evidence gaps identified

• Source of infection to the index farm- possible sources could include wild birds or wild mammals bringing virus into the milking parlour, a person working with the cattle who also worked on a poultry farm, contaminated milking equipment, bedding, feed or water, use of poultry litter for bedding
• Testing of fomites- A single paper on the testing of fomites (for example, on milking machinery) has shown the persistence of this virus for several hours on milking machinery (48)
• Duration of viral presence (or shedding) in milk samples from affected animals – a recent paper on experimental infection in cattle shows live virus can persist in the animals and be isolated from milk up to 2 weeks post infection (36)
• Severity of clinical signs in non-lactating cattle – an epidemiological report from the USA covered a limited number of farms (49), and experimental infection of heifers suggests this is still only a mild transient (2 day) infection in other cattle (36)
• Risk to other ruminants and mammalian livestock – the only other livestock case was in alpacas, which had close contact with infected poultry, not cattle

This risk statement will be reviewed as new information becomes available.

About the Human Animal Infections and Risk Surveillance group

This document was prepared by the UK Health Security Agency (UKHSA) on behalf of the joint Human Animal Infections and Risk Surveillance (HAIRS) group.

HAIRS is a multi-agency cross-government horizon scanning and risk assessment group, which acts as a forum to identify and discuss infections with potential for interspecies transfer (particularly zoonotic infections). Its work cuts across several organisations, including:

• UK Health Security Agency (UKHSA)
• Department for Environment, Food and Rural Affairs (Defra)
• Department for Health and Social Care (DHSC)
• Animal and Plant Health Agency (APHA)
• Food Standards Agency (FSA)
• Food Standards Scotland (FSS)
• Public Health Wales (PHW)
• Public Health Scotland (PHS)
• Department of Agriculture, Environment and Rural Affairs for Northern Ireland (DAERA)
• Welsh Government
• Scottish Government
• Public Health Agency of Northern Ireland
• Department of Agriculture, Food and the Marine
• Health Service Executive, Republic of Ireland
• Infrastructure, Housing and Environment, Government of Jersey
• Isle of Man Government
• States Veterinary Officer, Bailiwick of Guernsey

Information on the risk assessment processes used by the HAIRS group can be found at HAIRS risk assessment process.

Date of this assessment

31 July 2024

Version

2.0

Completed by

HAIRS members and external subject matter experts

Non-HAIRS members consulted:

• Dr. Sophia Makki, Consultant Epidemiologist, UKHSA’s Acute Respiratory Infections team
• Dr. Angie Lackenby, Clinical Scientist, UKHSA’s Acute Respiratory Infections team
• Anissa Lakhani, Senior Epidemiologist, UKHSA’s Acute Respiratory Infections team
• Dr. Ashley Banyard, Avian Virology Workgroup Lead, Animal and Plant Health Agency
• Dr. Anthony Wilson, Microbiological Risk Assessment Lead, Food Standards Agency

References

1. United States Department of Agriculture. ‘Federal and State Veterinary, Public Health Agencies Share Update on HPAI Detection in Kansas, Texas Dairy Herds’. 2024 (viewed 25 March 2024)

2. Hu X, Saxena A, Magstadt DR and others. ‘Preprint: Highly Pathogenic Avian Influenza A (H5N1) clade 2.3.4.4b Virus detected in dairy cattle’. BioRxiv 2024. DOI: 10.1101/2024.04.16.588916

3. United States Department of Agriculture. ‘Highly Pathogenic Avian Influenza (HPAI) Detections in Livestock’. 2024 (viewed 31 July 2024)

4. Kristensen C, Jensen HE, Trebbien R and others. ‘Preprint: The avian and human influenza A virus receptors sialic acid (SA)-α2,3 and SA-α2,6 are widely expressed in the bovine mammary gland’. bioRxiv 2024: DOI: 10.1101/2024.05.03.592326

5. US Centers for Disease Control and Prevention. ‘Technical Update: Summary Analysis of Genetic Sequences of Highly Pathogenic Avian Influenza A(H5N1) Viruses in Texas’. 2024 (viewed 3 May 2024)

6. Min JY, Santos C, Fitch A and others. ‘Mammalian Adaptation in the PB2 Gene of Avian H5N1 Influenza Virus’. Journal of Virology 2013: volume 87, issue 19, pages 10,884 to 10,888. DOI: 10.1128/JVI.01016-13

7. Nguyen TQ, Hutter C, Markin A and others. ‘Preprint: Emergence and interstate spread of highly pathogenic avian influenza A(H5N1) in dairy cattle’. BioRxiv 2024: DOI: 10.1101/2024.05.01.591751

8. US Centers for Disease Control and Prevention. ‘Considerations for Veterinarians: Evaluating and Handling of Cats Potentially Exposed to Highly Pathogenic Avian Influenza A(H5N1) Virus’. 2024 (viewed 27 April 2024)

9. World Health Organization. ‘Disease Outbreak News: Avian Influenza A(H5N1) - United States of America’. 2024 (viewed 27 April 2024)

10. US Centers for Disease Control and Prevention. ‘Highly Pathogenic Avian Influenza A (H5N1) Virus Infection Reported in a Person in the U.S.’ 2024 (viewed 2 May 2024)

11. Uyeki TM, Milton S, Webb CR and others. ‘Highly Pathogenic Avian Influenza A(H5N1) Virus Infection in a Dairy Farm Worker’. The New England Journal of Medicine. 2024: DOI: 10.1056/NEJMc2405371

12. US Centers for Disease Control and Prevention. ‘Highly Pathogenic Avian Influenza A(H5N1) Virus in Animals: Interim Recommendations for Prevention, Monitoring, and Public Health Investigations’. 2024 (viewed 2 May 2024)

13. US Centers for Disease Control and Prevention. ‘Readout of CDC Call with State Public Health Partners regarding avian influenza and farmworker protection’. 2024 (viewed 7 May 2024)

14. Global Initiative on Sharing All Influenza Data. Influenza genomic epidemiology. 2024 (viewed 27 April 2024)

15. Department for Environment, Food & Rural Affairs and Animal and Plant Health Agency. ‘Bird flu (avian influenza): latest situation in England - Update 26 April 2024’. 2024 (viewed 27 April 2024)

16. Animal and Plant Health Agency. ‘Cattle Dashboard; Surveillance Intelligence Unit’. 2024 (viewed 27 April 2024)

17. Mississippi Board of Animal Health. ‘Emergency Amendment to Chapter 12 Entry Requirements Restricting Cattle from HPAI Affected Herds’. 2024 (viewed 27 April 2024)

18. United States Department for Agriculture. ‘Federal Order Requiring Testing for and Reporting of Highly Pathogenic Avian Influenza (HPAI) in Livestock’. 2024 (viewed 29 April 2024)

19. US Department of Agriculture. ‘Updates on H5N1 Beef Safety Studies’. 2024 (viewed 9 May 2024).

20. Roos YH. ‘Water and Pathogenic Viruses Inactivation - Food Engineering Perspectives’. Food Engineering Reviews 2020: volume 12, issue 3, pages 251 to 267. DOI: 10.1007/s12393-020-09234-z

21. US Food and Drug Administration. ‘Updates on Highly Pathogenic Avian Influenza (HPAI)’. 2024 (viewed 29 April 2024).

22. Food Standards Agency. Rapid Risk Assessment: Risk to UK consumers from Highly Pathogenic Avian Influenza (HPAI) H5N1 B3.13 in US dairy products. 2024 (viewed 9 May 2024)

23. Food standards agency. Raw drinking milk guidance. 2018 (viewed 9 May 2024)

24. Malik Peiris JS. ‘Avian influenza viruses in humans’. Revue scientifique et technique (International Office of Epizootics). 2009: volume 28, issue 1, pages 161 to 173

25. Writing Committee of the Second World Health Organization Consultation on Clinical Aspects of Human Infection with Avian Influenza A Virus. ‘Update on avian influenza A(H5N1) virus infection in humans’. New England Journal of Medicine. 2008: volume 358, pages 261 to 273. DOI: 10.1056/nejmra0707279

26. Smith JR. ‘Oseltamivir in human avian influenza infection’. Journal of Antimicrobial Chemotherapy. 2010: volume 65, pages 25 to 33. DOI: 10.1093/jac/dkq013

27. World Health Organization. ‘Disease Outbreak News: Human infection caused by avian influenza A(H5) - Ecuador’. 2023 (viewed 28 April 2024)

28. Hong Kong’s Centre for Health Protection. ‘CHP closely monitors human case of avian influenza A(H5N1) in Mainland’. 2023 (viewed 28 April 2024)

29. University of Minnesota’s Center for Infectious Disease Research and Policy. ‘China reports new H5N1 avian flu case’. 2023 (viewed 28 April 2024)

30. World Health Organization. ‘Disease Outbreak News: Human Infection caused by Avian Influenza A(H5N1) - Chile’. 2023 (viewed 28 April 2024)

31. UK Health Security Agency. ‘Investigation into the risk to human health of avian influenza (influenza A H5N1) in England: technical briefing 5’. 2023 (viewed 28 April 2024)

32. UK Health Security Agency. ‘Managing the human health risk of avian influenza in poultry and wild birds: Guidance for health protection teams’. 2023 (viewed 3 May 2024)

33. National Health Service. ‘Avian flu’. 2022 (viewed 3 May 2024)

34. Department for Environment Food & Rural Affairs. ‘Influenza A (H5N1) infection in mammals: suspect case definition and diagnostic testing criteria’. 2023 (viewed 10 May 2024)

35. United States Department of Agriculture. ‘Highly Pathogenic Avian Influenza H5N1 Genotype B3.13 in Dairy Cattle: National Epidemiologic Brief’. 2024 (viewed 17 July 2024).

36. Baker AL, Arruda B, Palmer MV and others. ‘Experimental reproduction of viral replication and disease in dairy calves and lactating cows inoculated with highly pathogenic avian influenza H5N1 clade 2.3.4.4b’. bioRxiv 2024. DOI: 10.1101/2024.07.12.603337

37. Burrough ER, Magstadt DR, Petersen B and others. ‘Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus Infection in Domestic Dairy Cattle and Cats, United States, 2024’. Emerging Infectious Diseases, 2024. DOI: 10.3201/eid3007.240508.

38. Good MR, Wei J, Fernández-Quintero ML and others. ‘A single mutation in dairy cow-associated H5N1 viruses increases receptor binding breadth’. bioRxiv 2024. DOI:10.1101/2024.06.22.600211.

39. Friedrich Loeffler Institut. ‘Avian influenza: No evidence of H5N1 infection in dairy cows outside the USA’. 2024 (viewed 17 July 2024).

40. Pulit-Penaloza JA, Brock N, Belser JA and others. ‘Highly pathogenic avian influenza A(H5N1) virus of clade 2.3.4.4b isolated from a human case in Chile causes fatal disease and transmits between co-housed ferrets’. Emerging Microbes and Infections. 2024: 17, 2332667. DOI: 10.1080/22221751.2024.2332667.

41. Belser JA, Sun, X, Pulit-Penaloza JA, and Maines TR. ‘Fatal Infection in Ferrets after Ocular Inoculation with Highly Pathogenic Avian Influenza A(H5N1) Virus’. Emerging Infectious Diseases, 30(7), 1484-1487. DOI:10.3201/eid3007.240520.

42. Morse J, Coyle J, Mikesell L and others. ‘Influenza A(H5N1) Virus Infection in Two Dairy Farm Workers in Michigan’. The New England Journal of Medicine. 2024: 391, 963-964. DOI: 10.1056/NEJMc2407264.

43. US Centers for Disease Control and Prevention. ‘Technical Report: June 2024 Highly Pathogenic Avian Influenza A(H5N1) Viruses’. 2024 (viewed 17 July 2024)

44. US Centers for Disease Control and Prevention. ‘CDC Reports Fourth Human Case of H5 Bird Flu Tied to Dairy Cow Outbreak’. 2024 (viewed 17 July 2024)

45. Colorado Department of Public Health and Environment. ‘Health officials confirm human cases of avian flu in Colorado poultry workers’. 2024 (viewed 17 July 2024)

46. Center for Infectious Disease Research and Policy, University of Minnesota. ‘Officials probe heat-wave factors in H5N1 spread to Colorado poultry cullers’. 2024 (viewed 17 July 2024)

47. UKHSA, APHA, FSA, and Defra. ‘Technical risk assessment and evidence review as of 17 July 2024 of Influenza A(H5N1) 2.3.4.4b: US cattle outbreak update’. 2024

48. Le Sage V, Campbell AJ, Reed DS and others. ‘Influenza H5N1 and H1N1 viruses remain infectious in unpasteurized milk on milking machinery surfaces’. medRxiv 2024. DOI: 10.1101/2024.05.22.24307745.

49. USDA. ‘Epidemiological Investigations of HPAI H5N1 Genotype 3.13 in Michigan Dairy Herds and Poultry Flocks: Observations on viral spread between premises and mitigation recommendations’. 9 June 2024.