Updated joint #FAO / #WHO / #WOAH public health #assessment of recent #influenza A(#H5) virus events in #animals and people - Assessment based on data as of 1 March 2025

Key points 

-- At the present time, based on available information, FAO-WHO-WOAH assess the global public health risk of influenza A(H5) viruses to be low, while the risk of infection for occupationally exposed persons is low to moderate depending on the risk mitigation measures in place and the local avian influenza epidemiological situation. 

-- Transmission between animals continues to occur and, to date, a growing yet still limited number of human infections are being reported. Although additional human infections associated with exposure to infected animals or contaminated environments are expected to occur, the overall public health impact of such infections at a global level, at the present time, is considered minor. 

-- The assessment could change if and when additional epidemiological or virological information becomes available. 

-- This risk assessment from FAO, WHO and WOAH updates the assessment of the risk of zoonotic transmission (for example, animal to human) considering additional information made available since the previous assessment from 20 December 2024. 

-- This update is limited to the inclusion of additional information being made available globally. 

-- Due to the potential risk to human health and the far-reaching implications of the disease on the health of wild birds, poultry, livestock and other animal populations, the use of a One Health approach is essential to tackle avian influenza effectively, to monitor and characterize virus circulation, to prevent transmission within species and to new species  to reduce spread among animals, and to prevent human infections from exposure to animals. 

Infections in animals  

In March 2024, a clade 2.3.4.4b influenza A(H5N1) virus of the B3.13 genotype was detected in unpasteurized milk samples and oropharyngeal swabs from dairy cattle for the first time in the USA.{1,2} 

Since then, influenza A(H5N1) virus detections have continued to be reported through the testing of dairy cattle and bulk milk samples.{3} 

Until January 2025, analyses of virus sequence data from infected dairy cattle in the USA indicated that the detections in dairy herds since January 2024 were linked to a single wild bird-to-dairy cow transmission event of a B3.13 genotype clade 2.3.4.4b A(H5N1) virus that occurred in late 2023 or early 2024.{4}  

On 31 January 2025, the USDA APHIS National Veterinary Services Laboratories (NVSL) confirmed the first detection of clade 2.3.4.4b A(H5N1) virus of the D1.1 genotype in dairy cattle in the state of Nevada, indicating a second bird-to-dairy cow transmission event.{5, 6} 

Shortly after, on 13 February 2025, clade 2.3.4.4b A(H5N1) virus, also of the D1.1 genotype, was detected in dairy cattle in the state of Arizona. Phylogenetic analysis indicated that this was another, distinct transmission event marking the third bird-to-cow transmission event reported.{7} 

The genotype D1.1 is currently the most frequently detected genotype across North America and has affected wild birds, poultry and been detected in mammals, including wild and domestic felids and a marine mammal. 

Presently, to our knowledge, viruses from clade 2.3.4.4b A(H5N1) and  genotypes B3.13 and D1.1 have not been detected outside of North America in field conditions. 

As of 1 March 2025, 979 dairy cattle herds in 15 states of the USA have tested positive for A(H5N1), with a significant surge of confirmed outbreaks in dairy  cattle in the State of California reaching 383 herds since the first detection in California in late August 2024.{8} 

The average incidence of clinical disease on affected farms ranges between 10 and 20% with the predominant clinical signs including decreased milk production with abnormal milk, decreased feed intake, fever, dehydration, altered faecal consistency, respiratory distress and abortions.{9,10,11} 

Studies have shown that commercial milk pasteurization inactivates the virus making it safe for human consumption.{12,13,14} 

The routes and modes of transmission between cattle, the duration of virus shedding as well as the infectious period remain under investigation. A preliminary modelling study indicates the duration of infectiousness could range from 2.8 to 13.1 days with a median of 6.2 days.{15} 

Transmission between farms and states in the USA has been linked to cattle movements or possibly through feed and manure handling equipment, or on clothing or footwear of people working or visiting farms.{16} 

While there have been advancements in our understanding, transmission dynamics remain poorly understood.{17}  Experimental studies of lactating dairy cattle and non-lactating heifers have been published and have provided some insight into receptor distribution, viral replication kinetics, and infection routes (see the previous assessment from 20 December 2024). 

No further detections in swine have been reported in the USA since October 2024, which marked the first detection of H5N1 virus in swine in the USA.{18} 

A preliminary experimental study in swine indicated limited replication of a bovine-derived B3.13 genotype A(H5N1) virus and no transmission via direct contact from infected pigs to naïve pigs. Experimental infections studies conducted in pigs with other genotype A(H5N1) clade 2.3.4.4b viruses showed that mammalian-derived A(H5N1) virus strains demonstrated higher potential for replication, pathogenicity, and transmissibility as compared to avian-derived A(H5N1) virus strains.{19,20} This warrants vigilance and testing for avian influenza virus in pigs due to the genetic diversity and extent of avian influenza virus circulation as pigs  act as "mixing vessels" for genetic reassortment of avian and human influenza viruses, potentially creating new strains with pandemic potential. 

Detections of A(H5) in mammals, other than dairy cattle, and wild and domestic birds continue to be reported in the USA and in other countries worldwide. Clade 2.3.4.4b A(H5) viruses are circulating in wild and domestic birds, have been involved in multiple spillover events affecting wild carnivorous and marine mammals as well as domestic cats and dogs. Clade 2.3.4.4b virus infections reported in mammals in the Americas, Asia and Europe have resulted in severe clinical presentation (e.g., pneumonia, myocardial necrosis), with neurological signs (e.g., meningoencephalitis) in some species. {21, 22} 

Amino acid changes potentially associated with increased virulence, transmission, or adaptation to mammalian hosts have been sporadically identified.{23,24} 

Since 2022, at least 88 cases of A(H5N1) infections in domestic cats have been reported in the USA. Some of these domestic cat infections have been linked to the consumption of raw, unpasteurized milk from affected dairy farms as well as contaminated raw pet food.{25,26,27} 

Ingestion of wild birds while hunting or scavenging on carcasses is another possible route of infection, as observed in wild animal species (predators and scavengers). However, humans can carry the virus on contaminated clothing, equipment, or fomites and infect other animals such as cats. Similarly, cats may become infected from wild birds and could carry contaminated materials to their household, such as those originating from an infected wild bird, and expose people indirectly to the virus. 

Influenza A(H5N1) virus was detected in two indoor domestic cats with respiratory and neurologic illness that lived in homes of dairy workers but had no known direct exposure to influenza A(H5N1)-affected farms.{28} 

Domestic and wild felids have been reported infected with influenza A(H5) virus belonging to other clades as well. In 2024, avian influenza outbreaks were reported in captive wild felines in two zoos in southern Viet Nam. These led to the death of at least 47 tigers, three lions and a leopard, and were confirmed to be caused by clade 2.3.2.1e A(H5N1) viruses, previously classified as a 2.3.2.1c clade A(H5) viruses.{29,30} 

Additional influenza A(H5N1) infections in felids were reported in January 2025 in a wildlife rescue centre in Maharashtra State, India, causing the death of one leopard and three tigers.{31} 

Influenza A(H5N1) clade 2.3.2.1a infections were reported in domestic cats in January 2025 in Madhya Pradesh, India.{32} 

Previous A(H5N1) outbreaks in captive felines, characterized by severe pneumonia and high mortality, have been associated with the feeding of infected poultry and likely tiger-to-tiger transmission.{33,34} 

Whilst limited cat-to-human transmission has previously been reported in the USA with A(H7N2) viruses{35}, studies have not yet shown that the currently circulating H5N1 viruses have gained the ability to effectively transmit between humans and cats.  

Other A(H5) virus clades such as 2.3.2.1e and 2.3.2.1a continue to circulate and evolve in poultry in geographically restricted regions. For the latest information on avian influenza situation in animals worldwide, see the FAO Global Avian Influenza Viruses with Zoonotic Potential situation update and the WOAH situation reports on HPAI, as well as WOAH’s World Animal Health Information System. 

Detections in humans 

Since the last joint assessment of December 2024 and as of 1 March 2025, an additional 17 human cases of infection with A(H5) viruses have been reported. Of these, 12 were reported from the USA: six in persons with exposure to A(H5N1)-infected dairy cattle in California (five) and Nevada (one), three in persons with exposure while working at or involved in depopulation of A(H5N1)-infected commercial poultry farms. In Iowa, Ohio and Wisconsin, two in persons with exposure to sick and dead backyard poultry in Louisiana and Wyoming,  and one in a person from California with unknown exposure at the time of reporting. 

Samples from three cases related to exposure to dairy cattle in California were confirmed to be clade 2.3.4.4b A(H5N1) viruses of the genotype B3.13. Viruses from two cases with exposure to poultry in Louisiana and Wyoming were confirmed to be clade 2.3.4.4b A(H5N1) viruses of the D1.1 genotype, while one virus from the case in Nevada with exposure to dairy cattle was also of the D1.1 genotype. All but three of the detected cases in the USA have reported mild symptoms, including conjunctivitis and mild respiratory symptoms, and recovered without hospitalization. 

The cases detected in Wyoming and Ohio were hospitalized but have recovered while the case detected in Louisiana died.  

A serological study in 115 persons in Colorado and Michigan working on dairy farms during A(H5N1) outbreaks among dairy cattle found that eight (7.0%) had serologic evidence of recent infection (seropositive, ≥40 antibody titres to H5 2.3.4.4b by both micro-neutralization and hemagglutination inhibition assays). These seropositive individuals reporting working with dairy cattle or in the milking parlour, and four reported being ill when A(H5) was detected among the dairy cattle.{36} 

Another serosurvey conducted in September 2024 among 150 bovine veterinary practitioners found three (2%; 95% CI = 0.7%–5.7%) survey participants with antibodies to HPAI A(H5). {37}  

Two human cases of clade 2.3.2.1e{38} A(H5N1) virus infection were reported from Cambodia since the last update of December 2024. Both cases were fatal and had exposure to sick or dead backyard poultry. 

One detection of A(H5) was reported by the United Kingdom of Great Britain and Northern Ireland in January 2025. The detection was in a specimen from an individual recruited to a zoonotic influenza surveillance study while working at farms where birds were infected with A(H5N1) viruses. The individual had mild symptoms, and the virus was determined via whole genome sequencing to be an A(H5N1) virus belonging to the clade 2.3.4.4b of A(H5) viruses and the DI.2 genotype which was predominant in Europe in the 2024/25 winter season. This genotype is distinct from the genotypes of A(H5) 2.3.4.b detected in North America.{39} 

One case of A(H5) infection was reported in an individual in Viet Nam in November 2024. The individual had contact with sick and dead poultry and developed severe disease but recovered. Further information on the virus from this case is not available. 

Virus characteristics  

Regular monitoring and screening of viral sequences from birds has rarely found markers of mammalian adaptation in clade 2.3.4.4b viruses. Those that have been detected are mainly in the polymerase proteins of the virus. Sporadic events of changes in polymerase proteins have been observed more frequently detected in viruses from mammals. 

As of 1 March 2025, none of the virus sequences from dairy cattle in the USA have well-recognized markers in the HA gene associated with increased human receptor binding.  

Additional studies on some B3.13 A(H5N1) viruses indicate no differences in receptor binding, pH fusion or thermostability compared to other non-B3.13 avian A(H5N1) viruses, and that these viruses retain their avian influenza virus phenotype.{40} 

Some of the D1.1 viruses detected in dairy cattle have the change D701N in the PB2 protein, which has been associated with increased activity in mammalian cells. This change was also observed in the genetic sequence of the virus isolated from a patient infected with A(H5N1) clade 2.3.4.4b D1.1 genotype virus in Nevada.{41} 

As of 1 March 2025, this change had not been observed in D1.1 viruses detected in  wild birds nor poultry. The virus from the patient in Wyoming infected with A(H5N1) clade 2.3.4.4b genotype D1.1 had the E627K mutation in the PB2 protein which is associated with efficient virus replication in people and mammals.{42} This change has not been observed in any D1.1 viruses which have been detected in dairy cattle. 

Available virus sequences from human cases have shown some genetic markers that may reduce susceptibility to neuraminidase inhibitors (antiviral medicines such as oseltamivir) or endonuclease inhibitors (such as baloxavir marboxil). While these changes may reduce antiviral susceptibility in laboratory testing the clinical impact of these genetic changes requires further studies.{43}  

Experimental studies with A(H5N1) clade 2.3.4.4b viruses, including a B3.13 virus from the human case in Texas, have shown variable transmission between ferrets by direct contact, but no or inefficient transmission via respiratory droplets in most studies. {44,45,46,47,48,49} 

Ferrets infected with a non-B3.13 A(H5N1) clade 2.3.4.4b virus via the ocular route did experience severe disease and were able to transmit the virus to other ferrets via direct contact; these contact animals also developed severe disease.{50} 

Currently circulating A(H5N1) viruses would need further genetic changes to gain the ability to spread efficiently among humans via respiratory droplets, consistent with the current level of risk to public health, which is low. 

Based on limited seroprevalence information available on A(H5) viruses, human population immunity against the HA of A(H5) viruses is expected to be minimal; human population immunity targeting the N1 neuraminidase is found to be present although the impact of this immunity is yet to be understood.{51} 

Experimental studies suggest prior A(H1N1) immunity reduced virus replication and disease severity of bovine-derived B3.13 genotype A(H5N1) virus in ferrets and that ferrets with this pre-existing immunity expressed A(H5N1) cross-reacting antibodies to the neuraminidase protein.{52} 

Candidate vaccine viruses (CVV) 

The WHO Global Influenza Surveillance and Response System (GISRS), in collaboration with animal health partners (FAO, WOAH, OFFLU (Joint WOAH-FAO network of expertise on animal influenza) and others), continue to evaluate candidate vaccine viruses for pandemic preparedness purposes both bi-annually and on an ad hoc basis. 

Regular genetic and antigenic characterization of contemporary zoonotic influenza viruses are published here with the most recent update on A(H5) CVVs published in February 2025 following the WHO Consultation on the Composition of Influenza Virus Vaccines for Use in the 2025-2026 Northern Hemisphere Influenza Season.  

The majority of circulating clade 2.3.4.4b viruses reacted well to at least one of the post-infection ferret antisera raised against the existing CVVs. The majority of the clade 2.3.2.1e viruses characterized antigenically reacted well to ferret antisera raised against the existing and CVV proposed in September 2024. Clade 2.3.2.1a viruses detected recently in poultry and felines in India were not characterized antigenically but had HA genes similar to that of the A(H5N1) virus detected in a traveller returning to Australia from India. This virus reacted poorly with ferret antisera raised again available CVVs, thus a new clade 2.3.2.1a CVV was proposed. A new clade 2.3.4.4h CVV was also proposed due to the ongoing detections of this clade of viruses in poultry in China and continued genetic evolution leading to reduced reactivity to existing CVVs. 

The updated list of available zoonotic influenza candidate vaccine viruses (CVVs) which include A(H5N1) viruses and potency testing reagents is updated on the WHO website. Data which has not yet been peer reviewed revealed that vaccination of 39 persons with two doses of an adjuvanted inactivated A/Astrakhan/3212/2020 H5N8 virus elicited functional antibodies against European and North American A(H5N1) clade 2.3.4.4b viruses.{53} 

Assessment of current public health risk posed by influenza A(H5N1) viruses{54} 

1. What is the global public health risk of additional human cases of infection with avian influenza A(H5) viruses? 

-- Despite the continued detections of A(H5) clade 2.3.4.4b in animals and  increasing human exposures to the virus at the human-animal-environment  interface, there have been relatively few human infections reported to date.  Of  the human cases of A(H5) detections reported since the beginning of 2021, the  vast majority were infections in people associated with exposure to A(H5) viruses  through direct or indirect contact with infected animals, or contaminated  environments, such as live poultry markets or other premises with infected  animals. Severity of illness has ranged from mild to fatal, with the majority of  recent cases reported by the USA had mild illness. Thus far, among these cases,  there has been no reported or identified human-to-human transmission through  follow up epidemiologic, virologic and serologic investigations. Investigations for  some of the cases continue. Current virologic and epidemiologic information  indicates that these viruses remain avian influenza viruses without established  adaptations to mammalian hosts and have not acquired the capacity for sustained  transmission between humans.  The epidemiological situation has changed with  the ongoing spread of A(H5) virus in the USA dairy cattle population and two  additional spillover events from birds to dairy cattle identified. Persons exposed to  affected dairy cattle and other infected animals may be in prolonged and close  contact with potentially contaminated surfaces and animal products. As long as  A(H5) viruses continue to be detected in wild and domestic birds and mammals,  including dairy cattle, and related environments, including in unpasteurized/raw  milk, further human cases are expected, particularly amongst exposed individuals  not wearing appropriate personal protective equipment and/or in environments  where mitigation measures are not in place.  Based on currently available  information, FAO-WHO-WOAH assesses the global public health risk of influenza  A(H5) viruses as low. Although additional human infections  associated with exposure to infected animals or contaminated environments are  expected to occur, they remain limited in the general population and the overall  current public health impact of such infections at a global level is minor,  considering the surveillance, response, mitigation and control measures in place.  However, while the risk of infection to the general public is low, among persons  with exposure to infected birds or mammals or contaminated environments, the  risk of infection can range from low to moderate, depending on nature of the  exposure, the duration of exposure, the consistent and appropriate use of  personal protective equipment, and the use of other response, mitigation and  control measures particularly in environments where animals are kept.  The  pandemic potential of these viruses requires enhanced vigilance, especially  in animal populations where animal to animal transmission is known to  occur (poultry and dairy cattle), and close monitoring in animals and humans. It  remains essential that, while farmers enhance biosecurity on their farms,  governments focus efforts on strengthening surveillance in susceptible animal  populations and in persons exposed to infected animals, to prevention and  mitigation efforts to reduce and/or stop animal to animal transmission and reduce  environmental contamination, to prevention efforts to stop animals to human  transmission and to improve communication with at risk persons and provide  occupationally exposed persons with and train in the use of personal protective  equipment. 

2. What is the likelihood of human-to-human transmission of avian  influenza A(H5) viruses?  

There has been no reported human-to-human transmission of A(H5) viruses since  2007, although there may be knowledge gaps in investigations around identified  human infections. In 2007 and the years prior, small clusters of A(H5) virus  infections in humans were reported, including limited human to human  transmission from patients to health care workers. At the present time sustained  human-to-human transmission has not been reported of A(H5) viruses.55  The  A(H5) viruses currently detected in mammals, including in human cases, largely  retain genomic and biological characteristics of avian influenza viruses and remain  well-adapted to spread among birds. Except for within-host obtained  amino acid mutations in polymerase proteins, there is still limited evidence for  adaptation to mammals and humans even when transmission in mammals has  been suspected.{56} No changes in receptor binding tropism have been  consistently observed that would increase binding to receptors in the human  upper respiratory tract which would increase the probability of transmission to and  among people. In addition, available preliminary sero-studies and sero- investigations have not identified humanto-human transmission of A(H5N1) in the  USA. Therefore, sustained human-to-human transmission of the currently  circulating A(H5N1) viruses is considered unlikely without further genetic changes  in the virus. This is actively being assessed by agencies in affected Member  States, FAO, WHO, WOAH and partners. WHO, together with FAO and WOAH,  continues to evaluate A(H5) viruses closely and will reassess the risk associated  with the currently circulating A(H5) viruses as more information becomes  available.  Further antigenic characterization of A(H5) viruses, including in relation  to the existing CVVs, and development of specific reagents are being  prioritized at the WHO Collaborating Centres and essential Regulatory Laboratories  of GISRS in collaboration with public health, animal health, and  veterinary sector colleagues.  

Recommended actions  

It is recommended that Member States and national authorities: 

• increase surveillance and vigilance, in human populations, especially amongst  occupationally exposed persons, for the possibility of zoonotic infections,  particularly through National Influenza Centres (NICs) and other influenza  laboratories associated with GISRS; 

• assess and reduce the risk among  occupationally exposed persons using  methods such as active case finding and molecular and serologic methods, reducing environmental exposures, providing adequate and appropriate personal protective equipment; 

• conduct active case finding around suspected and confirmed human cases to determine if there are additional cases or indications of human-to-human transmission; and   

• work with national agencies and partners to better understand the exposure to and risk from raw/unpasteurized milk and milk products.  

Under the International Health Regulations (IHR) (2005),{57} States Parties are required to notify WHO within 24 hours of any laboratory-confirmed case of human influenza caused by a new subtype according to the WHO case definition.{58} WHO has published the case definition for human infections with avian influenza A(H5) virus requiring notification under IHR (2005).{59}  

Member States and national authorities are also recommended to: 

• increase surveillance and timely reporting efforts for the early detection of A(H5) influenza viruses in domestic birds, wild birds and mammals{60}; 

• include infection with an A(H5) influenza virus as a differential diagnosis, in non-avian species, including cattle, swine and other livestock and farmed domestic and wild animal populations, with high likelihood of exposure to A(H5) viruses; 

• implement preventive and early response measures to break the chain of infection among domestic animals (for example, poultry and dairy cattle), including considering the use of vaccination to reduce circulation in poultry as per national policies and according to guidance provided by animal health organizations{61,62}; 

• promptly report high pathogenicity avian influenza (HPAI) events in all animal species, including cattle (according to the WOAH case definition{63}) and other domestic and wild mammals, to WOAH and other international organizations such as FAO;  

• conduct genetic sequencing and share genetic sequences of influenza viruses and associated metadata in publicly available databases; 

• protect animals by mitigating the risk of introduction and spread of the disease through implementation and/or strengthening biosecurity in livestock holdings/premises and along the value chain; 

• protect persons by employing good production and hygiene practices when handling animals and animal products;  

• protect persons in contact with suspected/infected animals by providing appropriate personal protective equipment and communicating and educating on the importance and proper use of personal protective equipment and providing information and access to testing. 

Additional sets of recommendations related to avian influenza viruses with zoonotic potential can be found here: 

• Global strategy for the prevention and control of high pathogenicity avian influenza (2024) 

• WOAH Statement on High Pathogenicity Avian Influenza in Cattle, updated 6 December 2024 

• FAO Recommendations for the surveillance of influenza A(H5N1) in cattle with broader application to other farmed mammals, published 27 November 2024 

• FAO alert on avian influenza: Risk of upsurge and regional spread through wild birds in Latin America and the Caribbean in English and Spanish 

• FAO recommendations for Global Avian Influenza Viruses with Zoonotic Potential 

• FAO EMPRES Watch entitled ‘A(H5N1) influenza in dairy cattle in the United States of America’ 

• WHO Practical interim guidance to reduce the risk of infection in people exposed to avian influenza viruses 

• CDC Information for Workers Exposed to H5N1 Bird Flu 

Additional studies/surveillance, applying One Health principles are warranted, which could provide information to enhance confidence in the risk assessment. These may include serological studies in high-risk animal populations, in high-risk human populations, and epidemiological investigations.  Anyone who may have been exposed to infected or potentially infected animals or contaminated environments should be advised to promptly seek health care if they feel unwell, and to inform their health care provider of their possible exposure. 

Following prompt testing, early and appropriate clinical management should be initiated, and precautionary measures put in place to assess and prevent potential further spread among humans and animals.  

Clinicians should also be alerted to potential zoonotic infection in patients with an exposure history to birds or animals especially in areas where A(H5N1) viruses are known or suspected to be circulating in animals but also in areas where surveillance in animals may be limited.  

Routine epidemiologic and virologic surveillance for influenza should be conducted ideally yearround using a standard case definition in healthcare facilities according to WHO guidance.{64}  

Timely sharing of information and sequence data from both the human and animal health sectors from all regions should continue to be strongly recommended and is critical for rapid and robust joint risk assessment. The rapid sharing of virus materials with WHO Collaborating Centres of GISRS continues to be essential to conduct a thorough risk assessment and develop or adjust targeted response measures. 

The Tool for Influenza Pandemic Risk Assessment (TIPRA) provides an in-depth  assessment of risk associated with some zoonotic influenza viruses – notably the likelihood of the virus gaining human-to-human transmissibility, and the impact should the virus gain such transmissibility. TIPRA maps relative risk amongst viruses assessed using multiple elements.{65} 

Data pertaining to the risk elements within TIPRA should be generated and shared with WHO.  

Efforts to reduce human exposure to birds, livestock, and other mammals infected with or potentially infected with avian and other animal influenza viruses should be implemented and enhanced to minimize the risk of zoonotic infections. Individuals with activities that involve exposure to infected animals and/or contaminated environments are at higher risk and should take necessary precautions to prevent infection.{66} 

Those who are exposed to potentially infected animals should have access to, be trained in their use under different environmental conditions, and wear personal protective equipment including eye protection.{67} If they develop respiratory symptoms or conjunctivitis, they should be rapidly tested, and precautionary infection control measures should be put in place to prevent potential further spread among humans and to animals. 

For detailed guidance on treatment, refer to relevant global and national guidance.{68} 

Some manufacturers have initiated production of an A(H5) human vaccine that matches current circulating strains. Although a few countries are procuring vaccine to vaccinate occupationally exposed persons, this is not currently being recommended as a global strategy considering the limited number of human infections with A(H5N1) 2.3.4.4b viruses.  

Investigations are ongoing to understand the risk to humans from consuming raw/unpasteurized milk contaminated with A(H5N1) virus. FAO, WHO and WOAH advise consuming pasteurized milk. Due to the potential health risks from many dangerous zoonotic pathogens, raw/unpasteurized milk consumption should be avoided.{69} 

If pasteurized milk is not available, heating raw milk until it boils makes it safer for consumption.{70}  

More information will be available as investigations are actively ongoing in the USA and elsewhere. WHO and GISRS, jointly with FAO, WOAH and OFFLU are working closely together to continuously assess the avian influenza situation. This includes increased surveillance and testing to monitor the evolution and geographic spread of avian influenza viruses, including A(H5N1) viruses, to provide timely and updated joint risk assessments.  

References 

1} Lee D, Bahl J, Torchetti M, Killian M, Ip HS, DeLiberto TJ, et al. Highly Pathogenic Avian Influenza Viruses and Generation of Novel Reassortants, United States, 2014–2015. Emerg Infect Dis. 2016;22(7):1283-1285. doi.org/10.3201/eid2207.160048.  

2} United States Department of Agriculture (USDA). Federal and State Veterinary, Public Health Agencies Share Update on HPAI Detection in Kansas, Texas Dairy Herds. 25 March 2024. www.aphis.usda.gov/news/agencyannouncements/federal-state-veterinary-public-health-agencies-share-update-hpai. 

3} USDA. Highly Pathogenic Avian Influenza (HPAI) Detections in Livestock. www.aphis.usda.gov/livestockpoultry-disease/avian/avian-influenza/hpai-detections/livestock. 

4} Nguyen T-Q, Hutter C, Markin A, Thomas M, Lantz K, Killian ML et al. Emergence and interstate spread of highly pathogenic avian influenza A(H5N1) in dairy cattle. bioRxiv 2024.05.01.591751; doi.org/10.1101/2024.05.01.591751. 

5} USDA. APHIS Confirms D1.1 Genotype in Dairy Cattle in Nevada. www.aphis.usda.gov/news/programupdate/aphis-confirms-d11-genotype-dairy-cattle-nevada-0   

6} USDA. The Occurrence of Another Highly Pathogenic Avian Influenza (HPAI) Spillover from Wild Birds into Dairy Cattle. www.aphis.usda.gov/sites/default/files/dairy-cattle-hpai-tech-brief.pdf   

7} USDA. APHIS Identifies Third HPAI Spillover in Dairy Cattle. www.aphis.usda.gov/news/programupdate/aphis-identifies-third-hpai-spillover-dairy-cattle. 

8} USDA. Highly Pathogenic Avian Influenza (HPAI) Detections in Livestock. www.aphis.usda.gov/livestockpoultry-disease/avian/avian-influenza/hpai-detections/livestock. 

9} Burrough ER, Magstadt DR, Petersen B, Timmermans SJ, Gauger PC, Zhang J, Siepker C, Mainenti M, Li G, Thompson AC, Gorden PJ, Plummer PJ, Main R. Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus Infection in Domestic Dairy Cattle and Cats, United States, 2024. Emerg Infect Dis. 2024 Jul;30(7):1335-1343. doi: 10.3201/eid3007.240508. 

10} Caserta, L.C., Frye, E.A., Butt, S.L. et al. Spillover of highly pathogenic avian influenza H5N1 virus to dairy cattle. Nature 634, 669–676 (2024). doi.org/10.1038/s41586-024-07849-4. 

11}  Animal and Plant Health Inspection Service, USDA, 24 Sept 2024. Highly Pathogenic Avian Influenza H5N1 Genotype B3.13 in Dairy Cattle: National Epidemiologic Brief. www.aphis.usda.gov/sites/default/files/highlypathogenic-avian-influenza-national-epidemiological-brief-09-24-2024.pdf. 

12} United States Food and Drug Administration. Updates on Highly Pathogenic Avian Influenza (HPAI). Ongoing Work to Ensure Continued Effectiveness of the Federal-State Milk Safety System. 28 June 2024. www.fda.gov/food/alerts-advisories-safety-information/updates-highly-pathogenic-avian-influenzahpai?utm_medium=email&utm_source=govdelivery. 

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14} Spackman E, Anderson N, Walker S, Suarez DL, Jones DR, McCoig A et al. Inactivation of Highly Pathogenic Avian Influenza Virus with High-temperature Short Time Continuous Flow Pasteurization and Virus Detection in Bulk Milk Tanks, Journal of Food Protection, Volume 87, Issue 10, 2024, 100349, ISSN 0362-028X, doi.org/10.1016/j.jfp.2024.100349. 

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Source: World Health Organization, https://www.who.int/publications/m/item/updated-joint-fao-who-woah-public-health-assessment-of-recent-influenza-a(h5)-virus-events-in-animals-and-people_apr2025

____

Avian #Influenza A(#H5N1) - #Mexico {#WHO D.O.N., April 17 '25}

 

Situation at a glance

On 2 April 2025, the International Health Regulations (IHR) National Focal Point (NFP) for Mexico notified the World Health Organization (WHO) of the country’s first laboratory-confirmed human infection with an avian influenza A(H5N1) virus in the state of Durango. 

In response, local and national health authorities have implemented a range of measures to monitor, prevent, and control the situation. 

There have been reports of A(H5N1) outbreaks in birds in Durango, although the exact source of infection in this case remains under investigation. 

To date, no further cases of human infection with influenza A(H5N1) linked to this case have been identified. 

In accordance with the IHR (2005), any human infection caused by a new influenza A virus subtype is considered a potentially significant public health event and is subject to mandatory notification to WHO. 

Based on the information currently available on this and previous cases, WHO assesses the risk to the general population posed by A(H5N1) viruses as low. 

For individuals with occupational exposure to these viruses, the risk of infection is considered low to moderate. 

The situation may change as more information is gathered and so WHO continues to closely monitor these viruses and the global epidemiological situation.

Description of the situation

On 2 April 2025, the Mexico IHR National Focal Point (NFP) notified the World Health Organization of a laboratory-confirmed human infection with an avian influenza A(H5N1) virus in the state of Durango.

This case represents the second reported human infection with avian influenza A(H5) in Mexico, and the first confirmed case of infection with an influenza A(H5N1) virus in the country.

The case is a child under the age of 10 years from the state of Durango who tested positive for influenza A(H5N1) at the Instituto de Diagnóstico y Referencia Epidemiológicos (InDRE, by its Spanish acronym). The case did not have any underlying medical conditions, had not received seasonal influenza vaccination, and had no history of travel.

Symptoms began on 7 March 2025 with fever, malaise, and vomiting. On 13 March, the case was admitted to hospital due to respiratory failure and antiviral treatment was initiated the next day. The case was transferred to a tertiary care hospital on 16 March and died on 8 April due to respiratory complications.

On 18 March, a nasopharyngeal swab was collected, and the sample was processed by real-time polymerase chain reaction (RT-PCR). The result was influenza A, non-subtypable. The sample was sent to the Centro de Investigación Biomédica del Noroeste (CIBIN, by its Spanish acronym), IMSS Monterrey, where the result was confirmed as influenza A, non-subtypeable, along with simultaneous detection of parainfluenza 3 virus. On 31 March, the sample was forwarded to the Laboratorio Central de Epidemiología (LCE, by its Spanish acronym) “La Raza,” where it was molecularly identified as influenza A(H5). On 1 April, the sample was received by InDRE, where the positive result for influenza A(H5N1) was confirmed by RT-PCR. The sample was further characterized as avian influenza A(H5N1) clade 2.3.4.4b genotype D1.1.

The source of infection remains under investigation. During contact tracing, 91 individuals were identified, including 21 household contacts, 60 healthcare workers, and 10 individuals from a childcare center. Pharyngeal and nasopharyngeal swab samples collected from 49 contacts tested negative for influenza A(H5N1). To date, no further cases of human infection with influenza A(H5N1) linked to this case have been identified.

According to information from the National Service for Agrifood Health, Safety and Quality (SENASICA per its acronym in Spanish), between January 2022 and August 2024, 75 outbreaks of A(H5N1) in poultry were reported across various regions of Mexico including: Aguascalientes (5), Baja California (4), Chiapas (1), Chihuahua (3), Guanajuato (2), Jalisco (17), México City (7), Michoacán (1), Nuevo León (1), Oaxaca (2), Puebla (2),  Sonora (8), Tamaulipas (1), Veracruz (1), Yucatán (20). 

At the end of January 2025, SENASICA confirmed a new case of high pathogenicity avian influenza (HPAI) A(H5N1) in a sick vulture at the Sahuatoba Zoo in Durango, the state where the case lived. 

Following this, the death of a Canada goose with neurological and hemorrhagic symptoms was reported at the Peña del Aguila dam in Durango. A total of 25 sick birds were reported, and the presence of HPAI A(H5) was confirmed at a laboratory in Gómez Palacio, in Durango. A positive case of avian influenza A(H5) was also recorded in a bird at Las Auras Park.

Epidemiology

Animal influenza viruses typically circulate within animal populations but some have the potential to infect humans. Human infections are predominantly acquired through direct contact with infected animals or exposure to contaminated environments. Based on the original host species, influenza A viruses can be categorized into subtypes such as avian influenza, swine influenza, and other animal-origin influenza subtypes.

Human infection with avian influenza viruses may result in a spectrum of illness, ranging from mild upper respiratory tract symptoms to severe, life-threatening conditions. Clinical manifestations include conjunctivitis, respiratory, gastrointestinal symptoms, encephalitis, and encephalopathy. In some cases, asymptomatic infections with the A(H5N1) virus have been detected in individuals with known exposure to infected animals and environments.

A definitive diagnosis of human avian influenza infection requires laboratory confirmation. WHO regularly updates its technical guidance on the detection of zoonotic influenza, utilizing molecular diagnostic methods such as RT-PCR. Clinical evidence indicates that certain antiviral agents, particularly neuraminidase inhibitors (e.g., oseltamivir, zanamivir), have been shown to shorten the duration of viral replication and improve patient outcomes in some cases.

From 2003 to 10 April 2025, 972 cases of human infections with avian influenza A(H5N1), including 470 deaths (CFR 48.4%), have been reported to WHO from 24 countries. Almost all of these cases have been linked to close contact with infected live or dead birds, or contaminated environments.

Public health response

In response to this detection, additional investigation and surveillance activities are underway, coordinated by local and national health authorities, with involvement from both the animal and environmental sectors. These activities include:

-- Conducting a comprehensive epidemiological investigation of the case and contacts, including the collection of respiratory samples from symptomatic household contacts and healthcare workers, alongside ongoing follow-up and monitoring of close contacts.

-- Strengthening surveillance of respiratory viruses (including influenza-like illness [ILI] and severe acute respiratory infection [SARI]), with a particular focus on influenza viruses, in order to identify and analyze any atypical respiratory patterns or trends in the region.

-- Activating the One Health approach, involving SENASICA and national environmental agencies (SEMARNAT and CONANP), to ensure inter-institutional coordination, assess potential animal health risks, evaluate possible exposures within the community and animal populations, and notify the National Epidemiological Surveillance Committee (CONAVE).

-- Undertaking regular reporting of HPAI incidence in poultry and wild birds to the World Organisation for Animal Health (WOAH). The latest update on 5 March 2025 reported active surveillance and timely outbreak notifications, with a recent detection in the State of Durango. Consequently, local poultry farmers have been urged to reinforce biosecurity measures on their farms and backyard operations, and to immediately report any observed anomalies in animal health to the relevant authorities. Ongoing epidemiological surveillance is being maintained in poultry production units, backyards, federally inspected slaughterhouses, municipal slaughterhouses, and through national-level monitoring of wild bird populations.

WHO risk assessment

This case represents the second documented case of human infection with avian influenza A(H5) in Mexico and the first confirmed case of infection with an A(H5N1) influenza virus. Ongoing investigations are focused on identifying the source of infection and monitoring contacts. To date, no additional human cases of A(H5N1) virus infection have been identified in relation to this case, nor have any been detected through routine influenza surveillance.

Outbreaks of HPAI A(H5) viruses, including A(H5N1), in poultry have been reported across multiple states in Mexico since January 2022, including in the state of Durango.

When avian influenza viruses circulate in poultry populations, there is an inherent risk of human infection through exposure to infected birds or contaminated environments. As such, sporadic human cases are expected.

Although limited human-to-human transmission of A(H5) viruses was observed in isolated events between 1997 and 2007, sustained human-to-human transmission of A(H5) viruses has not been documented. Available epidemiological and virological data suggest that A(H5) viruses from previous outbreaks have not acquired the capacity for sustained human-to-human transmission.

Based on current information, the WHO assesses the overall public health risk associated with A(H5) viruses as low. However, for individuals with occupational exposure, the risk of infection is considered low to moderate.

The risk assessment will be updated as new epidemiological or virological information emerges in relation to this event.

WHO advice

This event does not change the current WHO recommendations on public health measures and surveillance of influenza.

Given the dynamic and evolving nature of influenza viruses, WHO underscores the critical importance of robust global surveillance systems to detect and monitor virological, epidemiological, and clinical changes associated with emerging or circulating influenza strains with implications for human or animal health. Timely sharing of virus isolates remains essential to inform comprehensive risk assessments.

In instances where humans are exposed to outbreaks of influenza A viruses in domestic poultry, wild birds, or other animal species—or when a human case is confirmed or suspected—enhanced surveillance of potentially exposed populations should be promptly initiated.

Surveillance strategies should account for healthcare-seeking behaviors within the affected population and may include a combination of active and passive methods, such as intensified case finding through ILI/SARI sentinel systems, active hospital-based screening, and targeted surveillance among high-risk occupational groups. Additional data sources, including traditional healers, private healthcare providers, and non-governmental diagnostic laboratories, should also be integrated where applicable to enhance the comprehensiveness of surveillance.

Considering the widespread detection of avian influenza viruses among poultry, wild birds, and select mammalian species, the general public is advised to avoid direct contact with sick or deceased animals. Any suspected dead birds or mammals, as well as any requests for their removal, should be reported to the appropriate local veterinary or wildlife authorities to ensure safe handling and testing.

All poultry products, including eggs and meat, should be thoroughly cooked and handled with proper food safety precautions. Consumption of raw milk is discouraged due to potential health risks. WHO advises consuming pasteurized milk and if pasteurized milk is not available, heating raw milk until it boils to make it safer for consumption. 

In the event of a confirmed or suspected human infection with a novel influenza A virus of pandemic potential, including avian-origin strains, a comprehensive epidemiological investigation should be initiated. This should include detailed assessment of animal exposure history, travel history, and identification of close contacts, even prior to laboratory confirmation. The epidemiological investigation should also include early identification of unusual events that could signal person-to-person transmission of the novel virus. Clinical specimens from confirmed or suspected cases should be tested and referred to a WHO Collaborating Centre for further virological characterization. Additional samples should be collected from animals, the environment or any foods suspected to be sources of infection. 

Individuals working in poultry production and processing environments should take additional health precautions as they are at higher risk of exposure to avian influenza and other zoonotic diseases due to their close contact with birds and potentially contaminated environments.

Farm workers who have direct or close contact with animals or materials infected or contaminated with avian influenza A(H5) virus should wear appropriate personal protective equipment (PPE) to minimize their risk of exposure. 

Currently, there are several vaccines licensed for preventing influenza A(H5) virus infection in humans, although their availability is limited. Candidate vaccine viruses for pandemic preparedness have been selected to protect against A(H5) disease in humans based on circulating strains. 

Existing seasonal influenza vaccines are unlikely to provide protection against avian influenza A(H5) viruses, based on currently available data. However, it is important that individuals who may have frequent exposure to infected or potentially infected birds or other animals get a seasonal influenza vaccine, as it would contribute to decreasing the risk of co-infection and possible genomic recombination of avian and human viruses, which could result in new strains with pandemic potential. 

Close monitoring of the epidemiological, clinical and virological situation, further characterization of recent human, poultry, and other animal influenza viruses, and serological investigations remain essential for assessing risk and adjusting risk management measures as needed.

WHO advises travelers to regions experiencing animal influenza outbreaks to avoid contact with live animal markets, farms, slaughter sites, or any environments with potential contamination from animal excreta. Adherence to hand hygiene and safe food handling practices is strongly recommended. Should infected individuals travel internationally, detection may occur during travel or upon arrival through routine health screening. However, further community-level spread is considered unlikely, as this virus has not yet acquired the ability to transmit easily among humans.  

All human infections caused by a novel influenza A virus subtype are notifiable under the International Health Regulations (IHR 2005) and State Parties to the IHR are required to immediately notify WHO within 24 hours of any laboratory-confirmed case of a recent human infection caused by an influenza A virus due to the potential to cause a pandemic. Evidence of illness is not required for this report. WHO has updated the influenza A(H5) confirmed case definition on the WHO website.

WHO does not recommend special traveler screening at points of entry or other restrictions due to the current situation of influenza viruses at the human-animal interface.

Further information

1) WHO Global influenza programme, human-animal interface

2) World Health Organization. (‎2025)‎. Surveillance for human infections with avian influenza A(‎H5)‎ viruses: objectives, case definitions, testing and reporting.

3) WHO (12 September 2024). Clinical practice guidelines for influenza

4) WHO Risk assessments and summaries of influenza at the human-animal interface

5) Zoonotic influenza candidate vaccine viruses and potency testing reagents

6) WHO Practical interim guidance to reduce the risk of infection in people exposed to avian influenza viruses

7) Surveillance for respiratory viruses of epidemic and pandemic potential

8) Protocol to investigate non-seasonal influenza and other emerging acute respiratory diseases

9) WHO case definition for human infections with avian influenza A(H5) virus requiring notification under IHR (2005)

10) World Health Organization. Cumulative number of confirmed human cases of avian influenza A(H5N1) reported to WHO. Geneva: WHO; 2024

11) Centers for Disease Control and Prevention. Recommended composition of influenza virus vaccines for use in the southern hemisphere 2025 influenza season and development of candidate vaccine viruses for pandemic preparedness. Atlanta: CDC; 2025

12) Pan American Health Organization / World Health Organization. Epidemiological Alert - Human infections caused by avian influenza A(H5N1) in the Region of the Americas - 5 June 2024. Washington, D.C.: PAHO/WHO; 2024

13) Public Health Risk Assessment associated with the spread of zoonotic avian influenza A(H5N1) clade 2.3.4.4b in the Region of the Americas - 12 July 2024

14) World Health Organization. Mosaic Respiratory Surveillance Framework. Geneva: WHO; 2024

15) World Health Organization. Practical interim guidance to reduce the risk of infection in people exposed to avian influenza viruses. Geneva: WHO; 2024.

16) World Health Organization. WHO case definition for human infections with avian influenza A(H5) virus requiring notification under IHR (2005) Geneva: WHO; 2024

17) World Health Organization. Case definitions for the four diseases requiring notification in all circumstances under the International Health Regulations (2005). Geneva: WHO; 2024

18) WOAH report Mexico - Influenza A viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Follow up report 7

19) Pan American Health Organization / World Health Organization. Technical note: Laboratory Diagnosis of Human Infection with Influenza A/H5

20) Pan American Health Organization / World Health Organization. Samples from patients suspected of Influenza A/H5 LABORATORY TESTING ALGORITHM

21) Pan American Health Organization / World Health Organization. Technical note: Laboratory Diagnosis of Human Infection with Influenza A/H5

22) Current technical information including monthly risk assessments at the Human-Animal Interface

23) WHO. Zoonotic Influenza Outbreak Toolbox

24) WHO. International Health Regulations (2005)

25) Terms of Reference for National Influenza Centers of the Global Influenza Surveillance and Response System

26) Pan American Health Organization / World Health Organization. Epidemiological Update: Avian Influenza A(H5N1) in the Americas Region, 15 November 2024. Washington, D.C.: PAHO/WHO; 2024

27) Pan American Health Organization / World Health Organization. Report of the Regional Consultation for the Strengthening of Intersectoral Work in the Human-Animal Interface of Influenza. 22 March 2023. Washington, D.C.: PAHO/WHO; 2023

28) Pan American Health Organization / World Health Organization. Strengthening the intersectoral work for Influenza at the Human Animal Interface in the Region of the Americas: Technical Questions and Answers. 19 May 2023. Washington, D.C.: PAHO/WHO; 2023

29) Pan American Health Organization / World Organization. Epidemiological Update: Avian Influenza A(H5N1) in the Americas Region, 4 March 2025. Washington, D.C.: PAHO/WHO; 2025

Source: World Health Organization, https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON564

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A rapid #review of the avian #influenza #PB2 #E627K #mutation in #human infection studies

Abstract 

Background: 

The current avian influenza A(H5N1) epizootic poses a significant threat to public health, with sporadic infections in humans raising concerns about potential adaptation for efficient human transmission. Laboratory studies have provided evidence that the polymerase basic protein 2 (PB2) E627K mutation facilitates more efficient replication in mammals and humans. This mutation has been detected in Canadian poultry, wild birds and mammals. 

Objective: 

Our objective was to summarize the current state of evidence on the impact of the avian influenza PB2 E627K mutation on human adaptation, transmission, epidemiology and clinical outcomes in natural human infections. 

Methods: 

We employed a search strategy across MEDLINE, Embase, Scopus, Global Health and CAB Abstracts for articles published from each database’s inception until mid-May 2023. 

Results: 

We identified nine eligible articles for review that addressed human transmission or adaptation (n=5), epidemiological or clinical implication (n=1) or both topics (n=3). Some studies suggested that the PB2 E627K mutation may play a role in zoonotic transmission from birds to humans, with studies indicating its association with parallel evolution and positive selection in A(H5) and A(H7) viruses. Other studies presented analyses that supported the notion of an increased fatality rate among cases with the PB2 E627K mutation, highlighting its potential role as a virulence factor. 

Conclusion: 

The association of the PB2 E627K mutation with human adaptation, transmission and increased fatality rates highlights the importance of genomic surveillance under One Health umbrella. Further research is warranted to explore the role of this mutation and determine how it interacts with other mutations.

Source: Canada Communicable Disease Report (CCDR),  https://doi.org/10.14745/ccdr.v51i04a04

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#Transmission and Characterization of #CJD and #CWD in the North #American Deer #Mouse

Abstract

Prion transmission into rodents is essential for understanding prion strains. However, it is often limited by a “species barrier” that makes transmission challenging and complicates the study of animal and human prion diseases. Here, we report that North American deer mice (Peromyscus maniculatus) are susceptible to infection with both human sporadic Creutzfeldt–Jakob disease (sCJD) and chronic wasting disease (CWD). Experimental transmission of both sCJD and CWD in deer mice resulted in 100% attack rates, albeit with differing incubation times, with CWD-inoculated mice taking nearly three times longer than sCJD-inoculated mice to succumb. We observed distinct patterns of spongiform vacuolation and prion-protein deposition in the brain, as well as distinct protein-glycosylation profiles and seeding kinetics in RT-QuIC for each strain. Adaptation on the second passage led to reduced incubation periods and marked strain-specific pathology, as seen predominantly in the cortex in sCJD and the thalamus in CWD. Notably, primary transmission of CWD resulted in infrequent vacuoles and widespread punctate deposits of prion protein in the brain, while diffuse staining and remarkable vacuolation of the thalamus were seen on passage. Prion seeding kinetics for sCJD and CWD were indistinguishable in the second passage; however, the distinct glycosylation patterns seen on immunoblot of the prion protein were maintained. Adaptation also resulted in extraneural dissemination of prion seeding activity distinct to CWD infection. Overall, the ability to transmit both CWD and sCJD to this model, resulting in clear differences in incubation period, biochemical properties, clinical signs, pathology and seeding kinetics, indicates that the model has the potential for use as a tool to investigate atypical cases of sCJD that may indicate CWD spillover to humans.

Source: Viruses, https://www.mdpi.com/1999-4915/17/4/576

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Characterization and evolutionary #history of novel #SARS-CoV-2-related #viruses in #bats from #Cambodia

Abstract

Circulating bat coronaviruses present a significant pandemic threat, yet our  understanding of their genetic diversity and evolutionary dynamics remains limited.  Over 3 years, we sampled 1,462 bats in Cambodia’s Steung Treng province,  identifying extensive and diverse coronaviruses co-circulation. Using  metatranscriptomic and amplicon sequencing, we generated 33 complete  sarbecovirus genomes, revealing novel lineages that cluster into four distinct  groups, each associated with different Rhinolophus bat species. Our analysis highlights rapid migration and recombination of sarbecovirus lineages over  short distances and timescales. Of note, the receptor-binding domains of two novel  viral groups exhibit high similarity to SARS-CoV-2, and pseudovirus assays  confirmed the ability of this spike protein to mediate entry into cells expressing  human ACE2, suggesting a potential zoonotic risk. The observed genetic diversity  underscores the urgent need for continuous surveillance to identify high-risk animal- to-human interfaces and inform pandemic preparedness. 

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.04.15.648942v1.full.pdf

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#Bovine #H5N1 binds poorly to #human-type sialic acid #receptors

{Excerpt}

Highly pathogenic H5N1 avian influenza (HPAI) viruses started circulating in lactating dairy cattle in the USA at the end of 2023 (ref. 1) and these viruses are now rapidly spreading between cows2. Eisfeld et al.3 found that a clade 2.3.4.4b H5N1 virus from this cattle outbreak can bind to α2,6-linked sialyl-glycopolymers on microtitre plates. Here we show that the haemagglutinin from a clade 2.3.4.4b H5N1 virus binds poorly to glycans that terminate with α2-6 sialic acids. This is an important finding, as α2,6 sialic acid is abundant in the upper respiratory tract of humans, and acquisition of α2,6 sialic acid receptor specificity is believed to be required for efficient transmission of influenza virus in humans and is considered a risk factor for the emergence of a new pandemic virus4.

(...)

Source: Nature, https://www.nature.com/articles/s41586-025-08821-6

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Safety and Immunogenicity of #Poultry #Vaccine for Protecting Critically Endangered Avian Species against Highly Pathogenic Avian #Influenza Virus, #USA

Abstract

In 2023, an outbreak of highly pathogenic avian influenza occurred among critically endangered California condors (Gymnogyps californianus), and >21 died. We evaluated safety, immunogenicity, vaccination strategies, and correlates of antibody response of an influenza vaccine for poultry in black vultures (Coragyps atratus) and then California condors. We noted differences in antibody titers between vaccinated and unvaccinated birds (vultures p<0.004; condors p­<0.02) but no adverse effects of vaccination. All vaccinated vultures and 80% of vaccinated condors showed maximum measured antibody response within the published range associated with survival of vaccinated and virally challenged chickens. We noted weak evidence of higher antibody responses for birds given two 0.5-mL vaccines versus those given one 1-mL vaccine but no correlation between antibody titers and sex for either species or between antibody titers and bone lead concentrations in vultures. Our results prompted initiation of a vaccination program for condors that could reduce spread of this disease among highly threatened species.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/6/24-1558_article

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The Q226L #mutation can convert a highly pathogenic #H5 2.3.4.4e virus to bind #human-type #receptors

Significance

We explored how H5Nx influenza viruses, which can infect many different birds and mammals, could adapt to infect humans by altering the hemagglutinin (HA). HA must change to bind human-type receptors for transmission between people. We compared two strains from viruses isolated in 2016 and found that one (2.3.4.4e) can switch to human receptor binding with a single mutation, while another (2.3.4.4b) might require more complex changes to bind simple human-type receptors. These findings highlight the potential for specific strains to evolve and become a pandemic threat, underscoring the importance of monitoring mutations that could lead to human-type receptor adaptation.

Abstract

H5Nx viruses continue to wreak havoc in avian and mammalian species worldwide. The virus distinguishes itself by the ability to replicate to high titers and transmit efficiently in a wide variety of hosts in diverse climatic environments. Fortunately, transmission to and between humans is scarce. Yet, if such an event were to occur, it could spark a pandemic as humans are immunologically naïve to H5 viruses. A significant determinant of transmission to and between humans is the ability of the influenza A virus hemagglutinin (HA) protein to shift from an avian-type to a human-type receptor specificity. Here, we demonstrate that a 2016 2.3.4.4e virus HA can convert to human-type receptor binding via a single Q226L mutation, in contrast to a cleavage-modified 2016 2.3.4.4b virus HA. Using glycan arrays, X-ray structural analyses, tissue- and direct glycan binding, we show that L133a Δ and 227Q are vital for this phenotype. Thus, whereas the 2.3.4.4e virus HA only needs a single amino acid mutation, the modified 2016 2.3.4.4b HA was not easily converted to human-type receptor specificity.

Source: Proceedings of the National Academy of Sciences of the United States of America, https://www.pnas.org/doi/10.1073/pnas.2419800122

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#Bat #sarbecovirus WIV1-CoV bears an adaptive #mutation that alters spike dynamics and enhances #ACE2 binding

Abstract

SARS-like betacoronaviruses (sarbecoviruses) endemic in bats pose a significant zoonotic threat to humans. Genetic pathways associated with spillover of bat sarbecoviruses into humans are incompletely understood. We previously showed that the WT spike of the rhinolophid bat coronavirus SHC014-CoV has poor entry activity and uncovered two distinct genetic pathways outside the receptor-binding domain (RBD) that increased spike opening, ACE2 binding, and cell entry. Herein, we show that the widely studied bat sarbecovirus WIV1-CoV is likely a cell culture-adapted variant of Rs3367-CoV, which was sequenced from the same population of rhinolophid bats as SHC014-CoV. We demonstrate that the acquisition of a single amino-acid substitution in the ‘630-loop’ of the S1 subunit was the key spike adaptation event during the successful isolation of WIV1-CoV, and that it enhances spike opening, virus-receptor recognition, and cell entry in much the same manner as the substitutions we previously identified in SHC014-CoV using a pseudotype system. The conformational constraints on both the SHC014-CoV and Rs3367-CoV spikes could be alleviated by pre-cleaving them with trypsin, suggesting that the spike-opening substitutions arose to circumvent the lack of S1–S2 cleavage. We propose that the ‘locked-down’ nature of these spikes and their requirement for S1–S2 cleavage to engage ACE2 represent viral optimizations for a fecal-oral lifestyle and immune evasion in their natural hosts. These adaptations may be a broader property of bat sarbecoviruses than currently recognized. The acquisition of a polybasic furin cleavage site at the S1–S2 boundary is accepted as a key viral adaptation for SARS-CoV-2 emergence that overcame a host protease barrier to viral entry in the mammalian respiratory tract. Our results suggest alternative spillover scenarios in which spike-opening substitutions that promote virus-receptor binding and entry could precede, or even initially replace, substitutions that enhance spike cleavage in the zoonotic host.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.04.14.648681v1?rss=1

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#Estonia - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 The barnacle goose was found sick (laying down and not moving) on the beach and later died.

Source: WOAH, https://wahis.woah.org/#/in-review/6426

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#China reported three additional cases of #human #infection with avian #influenza virus #H9N2 (HK CHP)

{Excerpt}

Avian influenza A(H9N2): 

-- Guangxi Zhuang Autonomous Region: 

- A five-year-old boy with onset on March 3, 2025. 

-- Guizhou Province: 

- A 35-year-old woman with onset on March 10, 2025. 

-- Henan Province

- A seven-year-old girl with onset on February 11, 2025. 

(...)

Source: Centre for Health Protection, Hong Kong PRC SAR, https://www.chp.gov.hk/files/pdf/2025_avian_influenza_report_vol21_wk15.pdf

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#Prevention and #control of avian #influenza virus: Recent advances in diagnostic technologies and #surveillance strategies

{Summary}

The natural host for avian influenza virus (AIV) is waterfowl. However, certain subtypes have breached species barriers, causing epizootics in many avian and mammalian species with occasional zoonotic infections in humans. The ongoing spread of highly pathogenic avian influenza (HPAI) A(H5N1) poses a significant and growing public health threat. Here, we discuss recent advances in viral detection and characterization technologies and their integration into the diagnostics and surveillance of AIV within a “One Health” framework.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-58882-4

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Coadministration of #ribavirin and #arenaviral entry #inhibitor LHF-535 enhances antiviral benefit against authentic #Lassa virus

{Excerpt}

Highlights

• A new strain of Lassa virus (LASV) was successfully isolated and characterized.

• The combination of ribavirin and LHF-535 has been demonstrated to exhibit synergistic effects in inhibiting LASV.

• The findings provide new directions for the development of antiviral drugs and vaccines for Lassa fever.

Dear Editor,

Lassa virus (LASV) is the causative agent of the acute viral hemorrhagic Lassa fever (LF), which is classified into Mammarenavirus within the Arenaviridae family, with a single-stranded, negative-sense, bi-segmented RNA genome. Due to its high pathogenicity and lethality, LASV is considered as a priority threat to public health, with an estimated cases of 300,000 infections and 5,000 deaths annually. LASV was first isolated and described as a clinical entity in 1969 in Lassa, Nigeria (Garry, 2023). LASV isolates of different geographic and host origins are highly diverse in genomic sequences and phylogenetically classified into up to seven lineages, with each lineage predominately localized in specific countries. Although the research on LF has been carried out for decades since the pathogen first characterized, there is no approved antiviral drugs or vaccines for clinical use against LASV to date (Grant et al., 2023). One possible reason that hindered the development of countermeasures is that the preclinical studies on authentic LASV are restricted in high bio-containment biosafety level 4 (BSL-4) facilities. In this letter, we describe isolation, and characterization of the LASV from the clinical samples. And we applied a coadministration assay of antiviral drugs for LASV by using a clinically isolated Mammarenavirus lassaense strain in the BSL-4 facility, aiming to investigate new therapeutic strategies for LASV infection.

(...)

Source: Virologica Sinica, https://www.sciencedirect.com/science/article/pii/S1995820X25000380?via%3Dihub

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Co-Infections with #Orthomarburgviruses, #Paramyxoviruses, and #Orthonairoviruses in Egyptian Rousette #Bats, #Uganda and Sierra Leone

Abstract

We report 1.3% (19/1,511) of Egyptian rousette bats (ERBs) in Uganda and Sierra Leone were co-infected with different combinations of Marburg, Sosuga, Kasokero, or Yogue viruses. To prevent infection by those viruses, we recommend avoiding ERB-populated areas, avoiding ERBs and ERB-contaminated objects, and thoroughly washing harvested fruits before consumption.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/5/24-1669_article

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Highly Pathogenic Avian #Influenza A(#H5N1) #Outbreak in Endangered #Cranes, Izumi Plain, #Japan, 2022–23

Abstract

During the 2022–23 winter season, >1,500 endangered cranes, including hooded crane (Grus monacha) and white-naped crane (Grus vipio), were found debilitated or dead in the Izumi Plain, Japan. Most of the cranes, particularly those collected in November, were infected with highly pathogenic avian influenza (HPAI) H5N1 viruses; virus shedding was higher from the trachea than from the cloaca. The isolation rate from the cranes’ roost water was not markedly higher than that of previous seasons, suggesting that the viruses might be more effectively transmitted among cranes via the respiratory route than through feces. Most wild bird–derived H5N1 isolates were phylogenetically distinct from viruses isolated on nearby chicken farms, indicating limited relationship between the wild bird and chicken isolates. Serologic analyses suggested that herd immunity had little effect on outbreak subsidence. This study deepens our understanding of the circumstances surrounding the unexpected HPAI outbreaks among these endangered cranes.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/5/24-1410_article

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The #WHO #Bacterial Priority #Pathogens #List 2024: a prioritisation study to guide research, development, and public health strategies against antimicrobial resistance

Summary

Background

The 2017 WHO Bacterial Priority Pathogens List (BPPL) has been instrumental in guiding global policy, research and development, and investments to address the most urgent threats from antibiotic-resistant pathogens, and it is a key public health tool for the prevention and control of antimicrobial resistance (AMR). Since its release, at least 13 new antibiotics targeting bacterial priority pathogens have been approved. The 2024 WHO BPPL aims to refine and build on the previous list by incorporating new data and evidence, addressing previous limitations, and improving pathogen prioritisation to better guide global efforts in combating AMR.

Methods

The 2024 WHO BPPL followed a similar approach to the first prioritisation exercise, using a multicriteria decision analysis framework. 24 antibiotic-resistant bacterial pathogens were scored based on eight criteria, including mortality, non-fatal burden, incidence, 10-year resistance trends, preventability, transmissibility, treatability, and antibacterial pipeline status. Pathogens were assessed on each of the criteria on the basis of available evidence and expert judgement. A preferences survey using a pairwise comparison was administered to 100 international experts (among whom 79 responded and 78 completed the survey) to determine the relative weights of the criteria. Applying these weights, the final ranking of pathogens was determined by calculating a total score in the range of 0–100% for each pathogen. Subgroup and sensitivity analyses were conducted to assess the impact of experts’ consistency, background, and geographical origin on the stability of the rankings. An independent advisory group reviewed the final list, and pathogens were subsequently streamlined and grouped into three priority tiers based on a quartile scoring system: critical (highest quartile), high (middle quartiles), and medium (lowest quartile).

Findings

The pathogens’ total scores ranged from 84% for the top-ranked bacterium (carbapenem-resistant Klebsiella pneumoniae) to 28% for the bottom-ranked bacterium (penicillin-resistant group B streptococci). Antibiotic-resistant Gram-negative bacteria (including K pneumoniae, Acinetobacter spp, and Escherichia coli), as well as rifampicin-resistant Mycobacterium tuberculosis, were ranked in the highest quartile. Among the bacteria commonly responsible for community-acquired infections, the highest rankings were for fluoroquinolone-resistant Salmonella enterica serotype Typhi (72%), Shigella spp (70%), and Neisseria gonorrhoeae (64%). Other important pathogens on the list include Pseudomonas aeruginosa and Staphylococcus aureus. The results of the preferences survey showed a strong inter-rater agreement, with Spearman's rank correlation coefficient and Kendall's coefficient of concordance both at 0·9. The final ranking showed high stability, with clustering of the pathogens based on experts’ backgrounds and origins not resulting in any substantial changes to the ranking.

Interpretation

The 2024 WHO BPPL is a key tool for prioritising research and development investments and informing global public health policies to combat AMR. Gram-negative bacteria and rifampicin-resistant M tuberculosis remain critical priority pathogens, underscoring their persistent threat and the limitations of the current antibacterial pipeline. Focused efforts and sustained investments in novel antibacterials are needed to address AMR priority pathogens, which include high-burden antibiotic-resistant bacteria such as Salmonella and Shigella spp, N gonorrhoeae, and S aureus. Beyond research and development, efforts to address these pathogens should also include expanding equitable access to existing drugs, enhancing vaccine coverage, and strengthening infection prevention and control measures.

Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00118-5/fulltext?rss=yes

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The spatiotemporal #ecology of #Oropouche virus across Latin #America: a multidisciplinary, laboratory-based, modelling study

Summary

Background

Latin America has been experiencing an Oropouche virus (OROV) outbreak of unprecedented magnitude and spread since 2023–24 for unknown reasons. We aimed to identify risk predictors of and areas at risk for OROV transmission.

Methods

In this multidisciplinary, laboratory-based, modelling study, we retrospectively tested anonymised serum samples collected between 2001 and 2022 for studies on virus epidemiology and medical diagnostics in Bolivia, Brazil, Colombia, Costa Rica, Ecuador, and Peru with nucleoprotein-based commercial ELISAs for OROV-specific IgG and IgM antibodies. Serum samples positive for IgG from different ecological regions and sampling years were tested against Guaroa virus and two OROV glycoprotein reassortants (Iquitos virus and Madre de Dios virus) via plaque reduction neutralisation testing (PRNT) to validate IgG ELISA specificity and support antigenic cartography. Three OROV strains were included in the neutralisation testing, a Cuban OROV isolate from the 2023–24 outbreak, a contemporary Peruvian OROV isolate taken from a patient in 2020, and a historical OROV isolate from Brazil. We analysed the serological data alongside age, sex, cohort, and geographical residence data for the serum samples; reported OROV incidence data; and vector occurrence data to explore OROV transmission in ecologically different regions of Latin America. We used the MaxEnt machine learning methodology to spatially analyse and predict OROV infection risk across Latin America, fitting one model with presence–absence serological data (seropositive results were recorded as presence and seronegative results were recorded as absence) and one model with presence-only, reported incidence data from 2024. We computed marginal dependency plots, variable contribution, and permutation metrics to analyse the impact of socioecological predictors and fitted a generalised linear mixed-effects model with logit link and binary error structure to analyse the potential effects of age, sex, or cohort type bias and interactions between age or sex and cohort type in our serological data. We conducted antigenic cartography and evolutionary characterisations of all available genomic sequences for all three OROV genome segments from the National Center for Biotechnology Information, including branch-specific selection pressure analysis and the construction of OROV phylogenetic trees.

Findings

In total, 9420 serum samples were included in this study, representing 76 provinces in the six Latin American countries previously mentioned. The sex distribution across the combined cohorts was 48% female (4237 of 8910 samples with available data) and 52% male (4673 of 8910 samples) and the mean age was 29·5 years (range 0–95 years). The samples were collected from census-based cohorts, cohorts of healthy individuals, and cohorts of febrile patients receiving routine health care. The average OROV IgG antibody detection rate was 6·3% (95% CI 5·8–6·8), with substantial regional heterogeneity. The presence–absence, serology-based model predicted high-risk areas for OROV transmission in the Amazon River basin, around the coastal and southern areas of Brazil, and in parts of central America and the Caribbean islands, consistent with case data from the 2023–24 outbreak reported by the Pan American Health Organization. Areas with a high predicted risk of OROV transmission with the serology-based model showed a statistically significant positive correlation with state-level incidence rates per 100 000 people in 2024 (generalised linear model, p=0·0003). The area under the curve estimates were 0·79 (95% CI 0·78–0·80) for the serology-based model and 0·66 (95% CI 0·65–0·66) for the presence-only incidence-based model. Longitudinal diagnostic testing of serum samples from cohorts of febrile patients suggested constant circulation of OROV in endemic regions at varying intensity. Climate variables accounted for more than 60% of variable contribution in both the serology-based and incidence-based models. Antigenic cartography, evolutionary analyses, and in-vitro growth comparisons showed clear differentiation between OROV and its glycoprotein reassortants, but not between the three different OROV strains. PRNT titres of OROV-neutralising serum samples were strongly correlated between all three tested OROV isolates (r>0·83; p<0·0001) but were not correlated with the two glycoprotein reassortants.

Interpretation

Our data suggest that climatic factors are major drivers of OROV spread and were potentially exacerbated during 2024 by extreme weather events. OROV glycoprotein reassortants, but not individual OROV strains, probably have distinct antigenicity. Preparedness for OROV outbreaks requires enhanced diagnostics, surveillance, and vector control in current and future endemic areas, which could all be informed by the risk predictions presented in this Article.

Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00110-0/fulltext?rss=yes

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Highly Pathogenic Avian #Influenza in Northern #Fulmars (Fulmarus glacialis) in the #Netherlands

Abstract

We report highly pathogenic avian influenza H5 virus infection in 10 Northern Fulmars (Fulmarus glacialis) found dead throughout January and February 2024 in the Netherlands. Five birds were infected with the H5N5 subtype, notable for markers of adaptation to mammals. Continuous infectious disease surveillance remains important in wild birds.

Source: US National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/40223286/

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