#Influenza at the #human - #animal #interface - #Summary and #risk #assessment, from 13 December 2024 to 20 January 202

New human cases{2}: 

From 13 December 2024 to 20 January 2025, the detection of influenza A(H5) virus in five humans, influenza A(H9N2) virus in two humans, and influenza A(H10N3) virus in one human were reported officially. Additionally, five human cases of infection with influenza A(H5) viruses were detected.  

Circulation of influenza viruses with zoonotic potential in animals: 

High pathogenicity avian influenza (HPAI) events in poultry and non-poultry continue to be reported to the World Organisation for Animal Health (WOAH).{3} The Food and Agriculture Organization of the United Nations (FAO) also provides a global update on avian influenza viruses with pandemic potential.{4}  

Risk assessment{5}: 

Based on information available at the time of the risk assessment, the overall public health risk from currently known influenza viruses at the human-animal interface has not changed remains low. Sustained human to human transmission has not been reported from these events and the occurrence of sustained human-to-human transmission of these viruses is currently considered unlikely. Although human infections with viruses of animal origin are infrequent, they are not unexpected at the human-animal interface.  

IHR compliance: 

All human infections caused by a new influenza subtype are required to be reported under the International Health Regulations (IHR, 2005).{6} This includes any influenza A virus that has demonstrated the capacity to infect a human and its haemagglutinin gene (or protein) is not a mutated form of those, i.e. A(H1) or A(H3), circulating widely in the human population. Information from these notifications is critical to inform risk assessments for influenza at the human-animal interface.  Avian influenza viruses in humans Current situation:  Since the last risk assessment of 12 December 2024, influenza A(H5) virus has been detected in nine humans in the United States of America (USA) and one laboratory-confirmed human case of A(H5N1) infection was reported to WHO from Cambodia. 

A(H5), USA 

On 14 December 2024, the USA notified WHO of one laboratory-confirmed human case of infection with influenza A(H5) in an adult aged over 65 years from the state of Louisiana. The patient, with underlying conditions, developed symptoms and sought care at an emergency department in early December 2024. Due to worsening symptoms, the patient returned to the emergency department a few days later, was hospitalized in critical condition with pneumonia, and started on antiviral treatment. Unfortunately, the patient passed away. No household contacts of the case tested positive for influenza viruses. The individual owned backyard poultry and had noted deaths in domestic and wild birds on the property prior to symptom onset. A(H5N1) viruses were detected in poultry on the property. The viruses identified in two clinical samples from the patent were identified as influenza A(H5N1) viruses belonging to the clade 2.3.4.4b and the genotype D1.1. Deep sequencing of the genetic sequences from the two clinical specimens were compared to A(H5N1) virus sequences from dairy cows, wild birds, poultry and other human cases in the USA and Canada. The hemagglutinin (HA) gene sequences of the viruses from the clinical specimens are closely related to other D1.1 viruses recently detected in wild birds and poultry in the Louisiana and other parts of the USA and in recent human cases detected in Canada and the USA, as well as to existing influenza A(H5N1) candidate vaccine viruses.{7} Some changes in the HA gene segment of one of the clinical specimens from the patient were detected at a low frequency. These changes have rarely been identified in specimens from previous human infections with A(H5N1) viruses and were not detected in specimens from the poultry on the property of the patient. It is possible that these changes arise during viral replication in the infected human cases. No changes in the polymerase genes associated with adaptation to mammals were identified. No changes associated with known or suspected markers of reduced susceptibility to antiviral drugs were identified.{8,9,10} Between 20 and 21 December 2024, the USA notified WHO of two additional laboratory-confirmed human case of infection with influenza A(H5) in an adult from the states of Iowa and Wisconsin. The cases developed symptoms in December 2024 and reported their illness to public health officials as part of active monitoring. The cases were not hospitalized and have recovered. Both cases were exposed to influenza A(H5N1) while working at poultry facilities. On 15 January 2025, the USA notified WHO of one additional laboratory-confirmed human case of infection with influenza A(H5) from the state of California. The case occurred in a child less than 18 years old with no known contact with influenza A(H5N1) virus-infected animals or humans. The investigation into the source of infection and contact monitoring around this case was ongoing at the time of reporting, and thus far, no human-to-human transmission has been identified. Additional analysis including genetic sequencing of the virus from the specimen from this case was underway at the time of reporting.{11}  Five additional cases of influenza A(H5) were detected in California in individuals aged over 18 years who worked at commercial dairy cattle farms in areas where highly pathogenic avian influenza (HPAI)(H5N1) viruses had been detected in cows. The individuals had mild symptoms.{12,13} Low pathogenicity and high pathogenicity avian influenza (HPAI) viruses have been detected in birds in the United States.  Since 2022, the HPAI A(H5) virus has been detected in commercial and backyard flocks in 48 states, impacting over 100 million birds. To date, 67 people have tested positive for A(H5) virus in the United States since 2022, with all but one of these cases occurring in 2024. All cases have been associated with exposure to either A(H5N1)-infected poultry or dairy cattle, except for two cases where the exposure source could not be identified.{14} To date, no humanto-human transmission of influenza A(H5) virus has been identified in the USA. A(H5N1) virus infections in dairy cattle and wild and domestic birds continue to be reported in the USA.{15} 

A(H5N1), Cambodia 

On 10 January 2025, Cambodia notified WHO of one case of human infection with influenza A(H5N1) in a 28-year-old male from Kampong Cham Province. The case had onset of fever, sore throat and chest pain on 1 January 2025. He sought care at two private local clinics and after his condition did not improve, he traveled to Phnom Penh and was hospitalized due to shortness of breath on 7 January at a national hospital, which is a severe acute respiratory infection (SARI) sentinel site. The case was isolated upon admission and provided oseltamivir and symptomatic treatment before passing away on 10 January. Nasopharyngeal (NP) and oropharyngeal (OP) swab specimens tested positive on 9 January for influenza A(H5N1) by real-time reverse transcription-polymerase chain reaction (rt-PCR) at the National Institute of Public Health of Cambodia. The Institut Pasteur du Cambodge (IPC) confirmed the results on 10 January. Sequence analysis of HA gene shows the virus belongs to clade 2.3.2.1c and is closely related to those viruses circulating among birds in Cambodia in 2024. Phylogenetic and molecular analysis is ongoing.  According to the early investigation, the case was a guard of a farm in the village where he lived and raised poultry for family consumption. There were reports of sick poultry in his farm and samples from the poultry on the farm have been collected. No further cases were detected among the contacts of the case.  According to reports received by WOAH, various influenza A(H5) subtypes continue to be detected in wild and domestic birds in the Americas, Asia and Europe. Infections in non-human mammals are also reported, including in marine and land mammals.{16} A list of bird and mammalian species affected by HPAI A(H5) viruses is maintained by FAO.{17}

Risk Assessment for avian influenza A(H5) viruses:  

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

Most human cases so far have been infections in people exposed to A(H5) viruses, for example, through contact with infected poultry or contaminated environments, including live poultry markets, and occasionally infected mammals and contaminated environments. While the viruses continue to be detected in animals and related environments humans are exposed to, further human cases associated with such exposures are expected but unusual. The impact for public health if additional cases are detected is minimal. The current overall global public health risk of additional human cases is low. 

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

No sustained human-to-human transmission has been identified associated with the recent reported human infections with avian influenza A(H5). There has been no reported human-to-human transmission of A(H5N1) viruses since 2007, although there may be gaps in investigations. In 2007 and the years prior, small clusters of A(H5) virus infections in humans were reported, including some involving health care workers, where limited human-to-human transmission could not be excluded; however, sustained human-to-human transmission was not reported.  Available evidence suggests that influenza A(H5) viruses circulating have not acquired the ability to efficiently transmit between people, therefore the likelihood of sustained human-to-human transmission is thus currently considered unlikely at this time.  

3. What is the likelihood of international spread of avian influenza A(H5) viruses by travellers?  

Should infected individuals from affected areas travel internationally, their infection may be detected in another country during travel or after arrival. If this were to occur, further communitylevel spread is considered unlikely as current evidence suggests these viruses have not acquired the ability to transmit easily among humans.  

A(H9N2), China 

Since the last risk assessment of 12 December 2024, two human cases of infection with A(H9N2) influenza viruses were notified to WHO from China (Table 1). Both cases were detected through influenza-like illness (ILI) surveillance, were mild and have recovered. Both cases had a history of exposure to live poultry markets prior the onset of symptoms. No further cases were detected among contacts of the cases. Influenza A(H9) virus was detected in the poultry-related environments associated with these cases.

Risk Assessment for avian influenza A(H9N2):  

1. What is the global public health risk of additional human cases of infection with avian influenza A(H9N2) viruses?  

Most human cases follow exposure to the A(H9N2) virus through contact with infected poultry or contaminated environments. Most human infections of A(H9N2) to date have resulted in mild clinical illness in most cases. Nearly 130 human infections with A(H9N2) cases have been reported to date since 2003, and six of these have been severe or fatal and three of these were known to have underlying medical conditions. Since the virus is endemic in poultry in multiple continues in Africa and Asia{18}, further human cases associated with exposure to infected poultry are expected but remain unusual. The impact to public health if additional cases are detected is minimal. The overall global public health risk of additional human cases is low. 

2. What is the likelihood of sustained human-to-human transmission of avian influenza A(H9N2) viruses?  

At the present time, no sustained human-to-human transmission has been identified associated with the event described above. Current evidence suggests that influenza A(H9N2) viruses from these cases have not acquired the ability of sustained transmission among humans, therefore sustained human-to-human transmission is thus currently considered unlikely.  

3. What is the likelihood of international spread of avian influenza A(H9N2) virus by travellers?  

Should infected individuals from affected areas travel internationally, their infection may be detected in another country during travel or after arrival. If this were to occur, further community level spread is considered unlikely as current evidence suggests the A(H9N2) virus subtype has not acquired the ability to transmit easily among humans.  

A(H10N3), China 

Since the last risk assessment of 12 December 2024, one human case of infection with A(H10N3) influenza viruses were notified to WHO from China on 3 January 2025. A 23-year-old female from Guangxi Zhuang Autonomous Region, with an underlying condition, had symptom onset on 12 December 2024. She was admitted to hospital on 19 December with severe pneumonia and treated with oseltamivir. Initially, she was in critical condition but has improved. A clinical sample collected on 22 December tested positive for influenza A and influenza A(H10N3) was confirmed a on 26 December. Prior to symptom onset, the patient worked at a supermarket and was exposed to freshly slaughtered poultry. No family members have developed symptoms at the time of reporting. All close contacts tested negative for influenza A(H10N3). All environmental samples collected from various locations tested negative for influenza A(H10N3). This is the fourth case of human A(H10N3) virus infection detected in China and globally to date. 

Risk Assessment for avian influenza A(H10N3):  

1. What is the global public health risk of additional human cases of infection with avian influenza A(H10N3) viruses? 

Human infections with avian influenza A(H10) viruses have been detected and reported previously. The extent of circulation and epidemiology of these viruses in birds is unclear. Avian influenza A(H10N3) viruses with different genetic characteristics have been detected previously in migratory and other wild birds since the 1970s. As long as the virus continues to circulate in birds, further human cases can be expected but remain unusual. The impact to public health if additional sporadic cases are detected is minimal. The overall global public health risk of additional sporadic human cases is low. 

2. What is the likelihood of sustained human-to-human transmission of avian influenza A(H10N3) viruses? 

No sustained human-to-human transmission has been identified associated with the event described Above or past events with human cases of influenza A(H10N3) viruses. Current epidemiologic and virologic evidence suggests that contemporary influenza A(H10N3) viruses assessed by the Global Influenza Surveillance and response System (GISRS) have not acquired the ability of sustained transmission among humans, therefore sustained human-to-human transmission is thus currently considered unlikely. 

3. What is the likelihood of international spread of avian influenza A(H10N3) virus by travellers? 

Should infected individuals from affected areas travel internationally, their infection may be detected in another country during travel or after arrival. If this were to occur, further community level spread is considered unlikely based on current limited evidence. 

Overall risk management recommendations: 

-- Surveillance and investigations 

• Due to the constantly evolving nature of influenza viruses, WHO continues to stress the importance of global strategic surveillance in animals and humans to detect virologic, epidemiologic and clinical changes associated with circulating influenza viruses that may affect human (or animal) health. Continued vigilance is needed within affected and neighbouring areas to detect infections in animals and humans. Close collaboration with the animal health and environment sectors is essential to understand the extent of the risk of human exposure and to prevent and control the spread of animal influenza. 

• As the extent of influenza virus circulation in animals is not clear, epidemiologic and virologic surveillance and the follow-up of suspected human cases should continue systematically. Guidance on investigation of non-seasonal influenza and other emerging acute respiratory diseases has been published on the WHO website. 

• Countries should increase avian influenza surveillance in domestic and wild birds, enhance surveillance for early detection in cattle populations in countries where HPAI is known to be circulating, include HPAI as a differential diagnosis in non-avian species, including cattle and other livestock populations, with high risk of exposure to HPAI viruses; monitor and investigate cases in non-avian species, including livestock, report cases of HPAI in all animal species, including unusual hosts, to WOAH and other international organizations, share genetic sequences of avian influenza viruses in publicly available databases, implement preventive and early response measures to break the HPAI transmission cycle among animals through movement restrictions of infected livestock holdings and strict biosecurity measures in all holdings, employ good production and hygiene practices when handing animal products, and protect persons in contact with suspected/infected animals.{19}  

• When there has been human exposure to a known outbreak of an influenza A virus in domestic poultry, wild birds or other animals – or when there has been an identified human case of infection with such a virus – enhanced surveillance in potentially exposed human populations becomes necessary. Enhanced surveillance should consider the health care seeking behaviour of the population, and could include a range of active and passive health care and/or communitybased approaches, including: enhanced surveillance in local influenza-like illness (ILI)/SARI systems, active screening in hospitals and of groups that may be at higher occupational risk of exposure, and inclusion of other sources such as traditional healers, private practitioners and private diagnostic laboratories. 

• Vigilance for the emergence of novel influenza viruses of pandemic potential should be maintained at all times including during a non-influenza emergency. In the context of the cocirculation of SARS-CoV-2 and influenza viruses, WHO has updated and published practical guidance for integrated surveillance. 

Notifying WHO 

• All human infections caused by a new subtype of influenza virus are notifiable under the International Health Regulations (IHR, 2005).{20} State Parties to the IHR (2005) are required to immediately notify WHO of any laboratory-confirmed{21} case of a recent human infection caused by an influenza A virus with the potential to cause a pandemic22. Evidence of illness is not required for this report. 

• WHO published the case definition for human infections with avian influenza A(H5) virus requiring notification under IHR (2005): https://www.who.int/teams/global-influenzaprogramme/avian-influenza/case-definitions. Virus sharing and risk assessment 

• It is critical that these influenza viruses from animals or from people are fully characterized in appropriate animal or human health influenza reference laboratories. Under WHO’s Pandemic Influenza Preparedness (PIP) Framework, Member States are expected to share influenza viruses with pandemic potential on a timely basis{23} with a WHO Collaborating Centre for influenza of GISRS. The viruses are used by the public health laboratories to assess the risk of pandemic influenza and to develop candidate vaccine viruses.  

• 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. The results of TIPRA complement those of the risk assessment provided here, and those of prior TIPRA analyses will be published at http://www.who.int/teams/global-influenza-programme/avian-influenza/toolfor-influenza-pandemic-risk-assessment-(tipra).  

Risk reduction 

• Given the observed extent and frequency of avian influenza in poultry, wild birds and some wild and domestic mammals, the public should avoid contact with animals that are sick or dead from unknown causes, including wild animals, and should report dead birds and mammals or request their removal by contacting local wildlife or veterinary authorities.  

• Eggs, poultry meat and other poultry food products should be properly cooked and properly handled during food preparation. Due to the potential health risks to consumers, raw milk should be avoided. WHO advises consuming pasteurized milk. If pasteurized milk isn’t available, heating raw milk until it boils makes it safer for consumption. 

• WHO has published practical interim guidance to reduce the risk of infection in people exposed to avian influenza viruses. 

Trade and travellers 

• WHO advises that travellers to countries with known outbreaks of animal influenza should avoid farms, contact with animals in live animal markets, entering areas where animals may be slaughtered, or contact with any surfaces that appear to be contaminated with animal excreta. Travelers should also wash their hands often with soap and water. All individuals should follow good food safety and hygiene practices.  

• WHO does not advise special traveller screening at points of entry or restrictions with regards to the current situation of influenza viruses at the human-animal interface. For recommendations on safe trade in animals and related products from countries affected by these influenza viruses, refer to WOAH guidance.  

Links:  

-- WHO Human-Animal Interface web page https://www.who.int/teams/global-influenza-programme/avian-influenza 

-- WHO Influenza (Avian and other zoonotic) fact sheet https://www.who.int/news-room/fact-sheets/detail/influenza-(avian-and-other-zoonotic) 

-- WHO Protocol to investigate non-seasonal influenza and other emerging acute respiratory diseases https://www.who.int/publications/i/item/WHO-WHE-IHM-GIP-2018.2 

-- WHO Public health resource pack for countries experiencing outbreaks of influenza in animals:  https://www.who.int/publications/i/item/9789240076884 

-- Cumulative Number of Confirmed Human Cases of Avian Influenza A(H5N1) Reported to WHO  https://www.who.int/teams/global-influenza-programme/avian-influenza/avian-a-h5n1-virus 

-- Avian Influenza A(H7N9) Information https://www.who.int/teams/global-influenza-programme/avian-influenza/avian-influenza-a-(h7n9)virus 

-- World Organisation of Animal Health (WOAH) web page: Avian Influenza  https://www.woah.org/en/home/ 

-- Food and Agriculture Organization of the United Nations (FAO) webpage: Avian Influenza https://www.fao.org/animal-health/avian-flu-qa/en/ 

-- OFFLU http://www.offlu.org/ 

____

{1} This summary and assessment covers information confirmed during this period and may include information received outside of this period. 

{2} For epidemiological and virological features of human infections with animal influenza viruses not reported in this assessment, see the reports on human cases of influenza at the human-animal interface published in the Weekly Epidemiological Record here.  

{3} World Organisation for Animal Health (WOAH). Avian influenza. Global situation. Available at: https://www.woah.org/en/disease/avian-influenza/#ui-id-2. 

{4} Food and Agriculture Organization of the United Nations (FAO). Global Avian Influenza Viruses with Zoonotic Potential situation update. Available at: https://www.fao.org/animal-health/situation-updates/global-aiv-withzoonotic-potential. 

{5} World Health Organization (2012). Rapid risk assessment of acute public health events. World Health Organization. Available at: https://iris.who.int/handle/10665/70810. 

{6} World Health Organization. Case definitions for the 4 diseases requiring notification to WHO in all circumstances under the International Health Regulations (2005). Case definitions for the four diseases requiring notification in all circumstances under the International Health Regulations (2005).  

{7} WHO. Zoonotic influenza: candidate vaccine viruses and potency testing reagents. Available at: https://www.who.int/teams/global-influenza-programme/vaccines/who-recommendations/zoonoticinfluenza-viruses-and-candidate-vaccine-viruses. 

{8} US CDC. CDC Confirms First Severe Case of H5N1 Bird Flu in the United States, 18 Dec 2024. Available at: https://www.cdc.gov/media/releases/2024/m1218-h5n1-flu.html. 

{9} US CDC. Genetic Sequences of Highly Pathogenic Avian Influenza A(H5N1) Viruses Identified in a Person in Louisiana, 26 Dec 2024. Available at: https://www.cdc.gov/bird-flu/spotlights/h5n1-response-12232024.html. 

{10} US CDC. First H5 Bird Flu Death Reported in United States, 6 Jan 2025. Available at: https://www.cdc.gov/media/releases/2025/m0106-h5-birdflu-death.html. 

{11} US CDC. Weekly US Influenza Surveillance Report: Key Updates for Week 2, ending January 11, 2025. Available at: https://www.cdc.gov/fluview/surveillance/2025-week-02.html. 

{12} US CDC. Weekly US Influenza Surveillance Report: Key Updates for Week 50, ending December 14, 2024. Available at: https://www.cdc.gov/fluview/surveillance/2024-week-50.html. 

{13} US CDC. Weekly US Influenza Surveillance Report: Key Updates for Week 51, ending December 21, 2024. Available at: https://www.cdc.gov/fluview/surveillance/2024-week-51.html. 

{14} United States Centers for Disease Control and Prevention. H5 Bird Flu: Current Situation. Available at: https://www.cdc.gov/bird-flu/situationsummary/index.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fbird-flu%2Fphp%2Favian-flusummary%2Findex.html. 

{15}  United States Department of Agriculture. Highly Pathogenic Avian Influenza (HPAI) Detections in Livestock, 19 July 2024. Available at: https://www.aphis.usda.gov/livestock-poultry-disease/avian/avian-influenza/hpaidetections/livestock. 

{16}  World Organisation for Animal Health (WOAH). Avian influenza. Global situation. Available at: https://www.woah.org/en/disease/avian-influenza/#ui-id-2. 

{17} Food and Agriculture Organization of the United Nations. Global Avian Influenza Viruses with Zoonotic Potential situation update. Available at: https://www.fao.org/animal-health/situation-updates/global-aiv-withzoonotic-potential/bird-species-affected-by-h5nx-hpai/en. 

{18} Food and Agriculture Organization of the United Nations (FAO). Global Avian Influenza Viruses with Zoonotic Potential situation update. Available at: https://www.fao.org/animal-health/situation-updates/global-aiv-withzoonotic-potential. 

{19} World Organisation for Animal Health. Statement on High Pathogenicity Avian Influenza in Cattle, 6 December 2024. Available at: https://www.woah.org/en/high-pathogenicity-avian-influenza-hpai-in-cattle/. 

{20} World Health Organization. Case definitions for the four diseases requiring notification in all circumstances under the International Health Regulations (2005).    

{21} World Health Organization. Manual for the laboratory diagnosis and virological surveillance of influenza (2011). Available at: https://apps.who.int/iris/handle/10665/44518 22 

{22} World Health Organization. Pandemic influenza preparedness framework for the sharing of influenza viruses and access to vaccines and other benefits, 2nd edition. Available at: https://iris.who.int/handle/10665/341850 23 

{23} World Health Organization. Operational guidance on sharing influenza viruses with human pandemic potential (IVPP) under the Pandemic Influenza Preparedness (PIP) Framework (2017). Available at: https://apps.who.int/iris/handle/10665/25940 

___

Source: World Health Organization, https://www.who.int/publications/m/item/influenza-at-the-human-animal-interface-summary-and-assessment--20-january-2025

_____