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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#Surveillance for #human #infections with avian #influenza A(#H5) viruses: objectives, case #definitions, #testing and reporting (#WHO)

Key points 

• The overall objective of continual global surveillance for human infection with avian influenza A(H5) viruses is to detect and characterize any influenza A(H5) viruses infecting humans in order to: 

- (1) promptly trigger public health control and response actions, 

- (2) assess the trends of such infections and the public health risks posed (including the risk of a pandemic); and 

- (3) inform global pandemic preparedness activities. 

• Specific surveillance objectives include rapidly detecting human cases of influenza A(H5) virus infection, monitoring the incidence of new cases over time and geographical distribution, assessing and monitoring changes in transmission patterns to promptly detect any unusual events that may signal human-to-human transmission of the virus, characterizing and monitoring changes in any influenza A(H5) viruses infecting humans relative to those circulating in animals to inform control strategies, describing the clinical presentation of illness and identifying risk factors for infection and severe outcomes. 

• Close collaboration with the animal health and environment sectors is essential to understand the extent of the risk of human exposures, to target enhanced surveillance and case finding activities, and to prevent and control the spread of influenza A viruses in animals. 

• Under the International Health Regulations (IHR) (2005) (1), 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 (2). Human infection caused by a new subtype has been established as being unusual or unexpected and may have serious public health impact. For this reason, even a single case of human infection with a new influenza subtype that fulfils the WHO case definition must always be notified immediately to WHO, regardless of the context in which it occurs. For events involving suspected cases of human influenza caused by a new subtype (e.g., in the absence of laboratory confirmation), States Parties are required to carry out an assessment of such events according to the decision instrument contained in Annex 2 of the IHR (2005), and then to notify WHO of all qualifying events within 24 hours of such an assessment. Notifications and other event-related communications under the IHR are carried out, by the most efficient means of communication available, between the National IHR Focal Point on behalf of the State Party concerned and the WHO IHR Contact Point at the respective WHO Regional Office.  

Background and rationale 

The avian influenza A(H5N1) epizootic has led to unprecedented numbers of  deaths in wild birds; outbreaks and culling in domestic poultry; and A(H5N1)  infections in mammals, including humans. Such human infections remain rare and  thus far have been associated with exposure to infected animals or to  contaminated environments, without subsequent sustained human-to-human  transmission. However, A(H5N1) viruses pose a significant public health risk, with  human infections often causing severe disease and high mortality. In addition,  such viruses have the potential to adapt to humans and with pandemic potential.  

Other influenza A(H5) virus subtypes, such as A(H5N2), A(H5N6) and (H5N8),  have also been detected in birds and mammals, including in humans. The current  influenza A(H5) situation warrants intense global monitoring and a coordinated  global response (3). 

Due to the potential significant risk to human health, and the far-reaching  implications of the disease for the health of wild birds and other animal  populations, a “One Health” approach is essential in effectively tackling avian  influenza. Close collaboration with the animal health and environment sectors is  vital for understanding the extent of the risk of human exposures, and for  preventing and controlling the spread of A(H5) and other influenza A viruses in  animals. In addition to surveillance approaches at the human-animal-environment  interface, it is recommended that countries, through their National  Influenza Centres (NICs) and other influenza laboratories within the WHO Global  Influenza Surveillance and Response System (GISRS), remain alert to the  possibility of human influenza A virus infections of zoonotic origin. 

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. Epidemiological and  virological surveillance, and the follow-up of suspected and confirmed human  cases, should be conducted systematically. (4, 5) The WHO implementation  guidance on surveillance for human infection with influenza A(H5) viruses is  summarized below and will be updated as the situation evolves or as more  information becomes available. 

Surveillance objectives 

Overall objective of continual global surveillance To promptly trigger public health  control and response actions; to detect and characterize any influenza A(H5)  viruses infecting humans to assess the public health risks posed (including the risk  of a pandemic), and to inform global pandemic influenza preparedness. 

Within these overall objectives, the specific objectives of such surveillance are to:  

1. rapidly detect any human cases of A(H5) virus infection; o assess and monitor  changes in virus transmission patterns and promptly detect any unusual events  that may signal human-to-human transmission of the virus; o monitor the  incidence of new cases over time and geographical distribution;  

2. characterize and monitor changes in any A(H5) viruses infecting humans  relative to those in animals to inform control strategies; and 

3. describe the clinical presentation of illness and identify risk factors for infection  and severe outcomes. 

Surveillance and investigation of human infections with A(H5) viruses 

For all countries 

• A collaborative, One Health approach to surveillance is needed to identify when  humans could be at risk of zoonotic influenza A virus infections, detect human  cases when they occur and monitor for human-to-human virus transmission. 

• Use information gathered from animal health surveillance on the circulation of  influenza A viruses in animals to inform the risk assessment and targeted  surveillance of human populations and guide appropriate measures. If timely and  of good quality, such information can inform the investigation of respiratory  events reported from health care or community settings and unexpected or  unexplained changes in trends observed in public health surveillance systems for  acute respiratory illnesses. 

• Vigilance for the emergence of novel influenza viruses of pandemic potential  should be maintained at all times. In the context of the co-circulation of SARS- CoV-2 and influenza viruses, WHO has published practical guidance for integrated  surveillance (6). 

• To detect human cases, event-based and indicator-based surveillance are  important. Approaches to surveillance should include respiratory event-based  surveillance at health facilities, community event-based surveillance where  appropriate, establishment of nationally notifiable diseases and conditions  reporting, the use of laboratory networks. These approaches can be  complemented with the monitoring of acute respiratory disease trends and  influenza detections in indicator-based surveillance, public media campaigns,  social media monitoring and targeted surveillance among at-risk populations. 

o It is essential to have a monitoring system for possible human-to-human virus  transmission in place to enable a rapid transition to more intensive case detection  and to provide a platform for further investigations (7). 

• Raise awareness and be prepared for the possibility of human infections with  any novel influenza virus of zoonotic origin, including influenza A(H5) viruses. 

• In hospital settings, clinicians should be alerted and consider testing patients  with severe unexplained acute respiratory illness for influenza, especially if: 

(1) the patient had, in the 14 days prior to illness onset, lived in or travelled to an  area in which influenza A(H5) infections had recently been detected in humans  and/or animals; 

(2) the patient had been exposed to live or dead wild or domestic animals, or to  environments such as exhibitions, markets or farms where live animals are kept  or sold; or 

(3) the patient had been exposed to other individuals with recent acute  respiratory illness who had such histories or exposures as outlined in (1) or (2). 

o Test any health care worker who develops an acute respiratory illness or  conjunctivitis and has been caring for patients with severe unexplained acute  respiratory illness. 

o In settings where there may be limited access to health care, or areas known to  be at risk of influenza infections and outbreaks in animals, community  representatives should be trained to report clusters1 of respiratory illness, illness  in people exposed to infected or potentially infected animals or outbreaks in  animals, through a standard reporting channel. 

o Increase awareness among laboratories of the importance of molecular  detection of influenza A(H5) viruses in human clinical specimens (respiratory and  conjunctival) and of collaboration with an affiliated NIC and provide guidance on  immediate shipping of positive but un-subtypeable influenza A or A(H5)-positive  specimens to a WHO Collaborating Centre on influenza for detailed virus characterization. 

o Maintain trained rapid response teams and establish protocols in advance for  outbreak investigation, and active and passive case finding, including through  contact tracing, for all clusters of unexplained acute respiratory illness (8, 9). 

For  countries with A(H5) viruses suspected or detected in in birds or mammals, in addition to all of the above 

• Countries should have in place an approach for assessing and monitoring the  health of individuals at risk of potential exposure to influenza A(H5) viruses. This  may include individuals who work in the poultry or other livestock industry or fur  farms or zoos (including farmers and veterinarians), visit animal farms or  premises in the course of their work (such as animal and public health  responders), transport or sell live poultry or other animals or carcasses, slaughter  or are involved in culling/depopulating/disposing of poultry or other animals or in  the decontamination of contaminated premises. Additionally, individuals may have  nonoccupational potential exposure to A(H5) viruses in the course of  interacting with infected or potentially infected animals. 

• Raise awareness among clinicians and other health care workers of the  possibility of human infection with avian influenza A(H5) viruses to facilitate early  clinical suspicion and diagnosis, isolation of patients with suspected A(H5) virus  infection, correct use of recommended personal protective equipment and prompt  initiation of antiviral treatment. 

• In outpatient settings, clinicians should consider  testing for influenza in patients  with acute respiratory infection or influenza-like illness or conjunctivitis if  the patient has been exposed to influenza-infected (or presumed to be infected)  birds or other animals in the 14 days prior to illness onset, as described below. 

• Countries should define, based on their available capacity and infrastructure,  which syndromes that clinicians should test, or refer for testing, to ensure that the  health system can effectively manage the testing process without  overburdening facilities or resources. 

Case definitions 

The case definitions provided below are used for surveillance purposes and to  standardize case classification and are not intended to provide complete  descriptions of disease in patients or to guide clinical management. They are also  not intended to be used for additional, more sensitive case finding during outbreak  investigations, which may include investigating any at risk individual  with signs or symptoms of acute respiratory illness. National authorities may  develop other case definitions for other objectives and testing strategies. The case  definitions may change as new information about the disease, epidemiology,  or the viruses become available. WHO clinical practice guidelines  for influenza have been published separately (10). Clinical decisions concerning  the treatment, care or triaging of people potentially infected with an influenza  A(H5) virus should be based on clinical judgement and epidemiological reasoning. 

While most patients infected with influenza A(H5) viruses present with fever,  cough and lower respiratory tract symptoms, the clinical spectrum is broad and  can include mild symptoms (such as upper respiratory tract symptoms or  conjunctivitis only) without fever.  

Suspected influenza A(H5) case definition 

A person presenting with unexplained acute respiratory illness with fever (> 38  °C) or cough, shortness of breath or difficulty breathing or conjunctivitis. 

AND 

One or more of the following exposures in the 14 days prior to symptom onset: 

• Close contact (within 1 metre) with a person (for example, caring for, speaking  with or touching) who is a suspected or confirmed avian influenza A(H5) case. 

• Exposures in an area where avian influenza A(H5) virus infections in animals or  humans have been suspected or confirmed, such as: 

o close contact (within 1 metre) with live, sick or dead infected animals or animal  products, or consumption or handling of raw uncooked meat, unpasteurized milk  or other raw animal meat or products;  

o direct exposure to surfaces that could be contaminated with infected animal  products or with water contaminated with such products (such as wastewater from  a live bird market or slaughtering facility); or 

o visiting or working at a live animal market, farm, zoo or other setting with  infected animals. 

• Handling samples (animal or human) suspected of containing avian influenza  A(H5) virus in a laboratory or other setting. 

Confirmed case definition 

1. A person with a laboratory-confirmed infection with an avian influenza A(H5)  virus. A laboratory-confirmed infection is considered if it has been confirmed by  positive results from polymerase chain reaction (PCR), virus isolation, or  serological testing of paired acute and convalescent serum.   

Serologic testing of paired acute and convalescent serum specimens: 

• Serological confirmation of an A(H5) case requires paired sera collection (one  acute, one convalescent specimen), with a ≥ 4-fold rise in neutralizing antibody  titres (or equivalent) to an influenza A(H5) virus2 that is antigenically similar to  the virus the person was exposed to, with a convalescent neutralizing titre ≥ 1:40.  Acute serum should be collected within 7 days of symptom onset;  convalescent serum should be collected ≥ 21 days (ideally 21–28 days) after  symptom onset. 

Serologic testing of a single convalescent serum specimen, when the following are met:   

• The criteria for seropositivity of an A(H5) infection using a single convalescent  serum specimen, collected at ≥ 21 days after symptom onset or exposure includes  a neutralizing antibody titre ≥ 1:40 to an influenza A(H5) virus; and 

• A positive result using a different serological assay such as a hemagglutination  inhibition (HI) antibody titre ≥ 1:40, or an influenza A(H5)-specific positive result  from another immunological assay such as an enzyme-linked immunosorbent  assay (ELISA), a multiplex binding antibody assay, or similar binding antibody  assay; and 

• In all assays mentioned above, sera are tested against an influenza A(H5)  virus(es)4 or antigen(s) antigenically similar to the virus the person was exposed to; and  

• The person has an epidemiological link3 to a laboratory-confirmed human case.   

Testing 

All individuals meeting the suspected surveillance case definition or other locally  adapted case definitions for other objectives should be tested according to local  protocols.  

• The types of samples to be collected for the diagnosis of viral infections of the  upper and lower respiratory tract are described in the WHO Manual for the  laboratory diagnosis and virological surveillance of influenza (11). In cases  presenting with conjunctivitis, conjunctival specimens should be collected. 

o WHO information for the molecular detection of influenza viruses can be found  on the WHO website (12). 

o All influenza A positive specimens that are not able to be subtyped should be  sent immediately to a National Influenza Centre (NIC) if originally tested  elsewhere, and from the NIC to a  WHO Collaborating Centre of GISRS (13) for further analysis in line with the relevant WHO operational guidance (14) under their Terms of Reference (15). 

o Virus isolation from specimens suspected or confirmed to contain avian influenza  A(H5) virus is not recommended, unless it is performed at a WHO  influenza CC or a WHO H5 Reference Laboratory of GISRS, due to the biosafety  requirements. 

o Serologic testing is strongly recommended to be performed or directly supported  by, or performed in collaboration with, a WHO CC or H5 Reference  Laboratory of GISRS. 

o Contact WHO Global Influenza Programme (GISRS-WHOhq@WHO.int) for  support of serology testing for A(H5) and other help to confirm a human infection  with an avian influenza A(H5) virus.  

• Testing of asymptomatic exposed individuals could also be considered on a case- by-case basis, depending on available resources and based on an exposure risk  assessment and testing objectives (for example, as part of an outbreak  investigation or special study to assess asymptomatic transmission). In this  context, the testing of respiratory samples for viable and replicating viruses needs  to be paired with serological testing of acute and convalescent serum  samples. 

Investigation of confirmed cases and monitoring of exposed individuals 

• All confirmed human cases of influenza A(H5) infection should be further  investigated and closely monitored, and contacts also monitored to detect and  rapidly interrupt potential humanto-human virus transmission and to better  understand exposure risks. More detailed guidance can be found in the WHO  Protocol to investigate non-seasonal influenza and other emerging acute  respiratory diseases (9). In addition, various protocols under WHO influenza  investigations and studies (Unity Studies) are currently being updated. When  sharing influenza A(H5)-positive specimens, the relevant WHO operational  guidance should be followed (14). 

• Case definitions for additional case finding should be developed locally and may  be shaped by information obtained from the interview with the confirmed case(s).  

• The specific public health actions that should be implemented immediately  include: 

o testing for cases of human infection with animal influenza A viruses using  appropriate investigation and laboratory protocols; 

o assessing exposure to  animals and travel history of confirmed cases; 

o identification and monitoring of household and other close contacts of a  confirmed case (including health care personnel) and active searching for other  cases; and 

o early detection of any unusual respiratory disease events that could signal  person-to-person transmission of the virus. 

• Public health and animal health authorities should conduct joint investigations of  human cases of novel influenza A virus infection (zoonotic influenza). This will  involve assessing the role of local animals as sources of exposure, understanding  patterns of illnesses or death in local animals and determining whether animal  influenza viruses are circulating in local animals so that appropriate control  measures can be implemented to reduce the risk of continued human exposure.  

Reporting under IHR and information sharing 

Under the International Health Regulations (IHR) (2005), 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 criteria for IHR  notification (2). Human influenza caused by a new subtype has been established  as being unusual or unexpected and may have serious public health impact. For  this reason, even a single case of human infection with a new influenza subtype  that fulfils the WHO case definition must always be notified immediately to WHO,  regardless of the context in which it occurs. For events involving suspected cases  of human influenza caused by a new subtype (e.g., in the absence of laboratory  confirmation), States Parties are required to carry out an assessment of such  events according to the decision instrument contained in Annex 2 of the IHR  (2005), and then to notify WHO of all qualifying events within 24 hours of such an  assessment. Notifications and other event-related communications under the  IHR are carried out, by the most efficient means of communication available, between the National IHR Focal Point on behalf of the State Party  concerned and the WHO IHR Contact Point at the respective WHO Regional Office. 

A minimum data set reporting form for human infection with an influenza virus  with pandemic potential is available in the Annex of this document. As specified in  Article 6.2 of the IHR (2005), the notification must always include or be followed  by timely and ongoing communication of accurate and sufficiently detailed public  health information about the event as well as the health measures implemented in  response to the event. As the event unfolds, more information may become  available, and the State Party must continue to share the relevant public health  information to allow WHO to conduct its risk assessment with respect to the  ongoing event in collaboration with the notifying State Party. 

WHO has published the WHO case definition for human infections with avian  influenza A(H5) virus requiring notification under IHR (2005) (16). The results of  ongoing surveillance activities, and of studies or other research activities, should  also be communicated to WHO in a timely manner to inform global risk  assessment and guidance. 

Information on human infections and information not under the IHR reporting  requirements (for example, findings from seroprevalence studies) that might be of  public health importance, should be rapidly shared with GISRS for risk  assessment purposes, via WHO CCs, WHO regional officers or the Global influenza  Programme. For example, if a single serum specimen tests positive in a  serology assay but does not meet the notification requirements under IHR as  mentioned above, it is strongly recommended to communicate this information to  a WHO CC of GISRS for surveillance and risk assessment purposes. This includes  situations where a single convalescent serum specimen tests positive by  microneutralization assay and another assay, such as ELISA, but the individual  from whom the specimen was taken did not have an epidemiological link to a  confirmed A(H5) human case, even though they may have had exposure to  A(H5)-infected animals or contaminated environments.  

Wastewater surveillance 

Although Influenza A viruses can be detected in wastewater (and can be  distinguished from influenza B viruses), most of the laboratory assays used cannot  distinguish between different influenza A virus subtypes. It is also  currently not possible to determine the source of an influenza A virus in  wastewater (human waste, animal waste or other) or to know how many cases  must occur in an area before influenza viruses can be detected through  wastewater surveillance. If used, wastewater and environmental surveillance  should be integrated as part of multimodal influenza surveillance (17).  

Methods 

This guidance is based on guidance previously developed by WHO for other  zoonotic influenza subtypes and considers the information reported on human  infections with influenza A(H5) viruses to WHO and GISRS. The guidance also  incorporates information from other WHO products that have become available  since previous versions of surveillance guidance for other zoonotic influenza subtypes were published.  

Contributors 

This surveillance guidance was developed by the World Health Organization  (WHO) Global Influenza Programme through a process of review and consultation  with internal and external experts. WHO expresses its gratitude to those who  reviewed the document for their efforts, experience and insights.  This  surveillance guidance was adapted from previous guidance by Aspen Hammond of  the WHO Global Influenza Programme. 

WHO staff and consultants who contributed to the development of this guidance in  2024 include: Vanessa Cozza (WHO headquarters, Global Influenza Programme), Helge Hollmeyer (WHO headquarters, IHR Secretariat), Joshua Mott (WHO headquarters, Epidemic & Pandemic Preparedness and Prevention), Sergejs Nikisins (WHO headquarters, Global Influenza Programme), Sarika Patel (WHO Country office Cambodia), Dmitriy Pereyaslov (WHO headquarters, Global Influenza Programme), Angel Rodriguez (WHO Regional Office for the Americas), Melissa Rolfes (WHO headquarters, Global Influenza Programme), Magdi Samaan (WHO headquarters, Global Influenza Programme), Maria Van Kerkhove, Marc-Alain Widdowson (WHO Regional Office for Europe), Reina Yamaji (WHO headquarters, Global Influenza Programme) and Wenqing Zhang (WHO headquarters, Global Influenza Programme). Technical experts from the following WHO Collaborating Centres of the Global Influenza Surveillance and Response System (GISRS) (13, 18) contributed to this document through their review of the draft document in 2024: WHO Collaborating Centre for Reference and Research on Influenza Victorian Infectious Diseases Reference Laboratory, The Peter Doherty Institute for Infection & Immunity, Australia; WHO Collaborating Centre for Reference and Research on Influenza, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (CDCD), China; WHO Collaborating Centre for Reference and Research on Influenza, National Institute of Infectious Diseases (NIID), Japan; WHO Collaborating Centre for Reference and Research on Influenza, The Francis Crick Institute, United Kingdom of Great Britain and Northern Ireland; WHO Collaborating Centre for the Surveillance, Epidemiology and Control of Influenza, Centers for Disease Control and Prevention, USA; WHO Collaborating Center for Studies on the Ecology of Influenza in Animals, St. Jude Children's Research Hospital, USA; and the WHO Collaborating Centre for Studies on Influenza at the Animalhuman Interface, State Research Center of Virology and Biotechnology "VECTOR", Rospotrebnadzor, Russian Federation.  Declaration of interests Technical experts represented institutions designated as WHO Collaborating Centres of the Global Influenza Surveillance and Response System (GISRS) and no declarations of interest were required from them for their review of the draft document. 

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{1} A “cluster” is defined as two or more persons  with onset of symptoms within the same 14-day period and who are associated  with a specific setting, such as a classroom, workplace, household, extended  family, hospital, other residential institution, military barracks or recreational  camp. 

{2} Wild type virus is preferred.  

{3} This may include close contact such as providing care for the patient, including as a health care worker or family member, or other similarly close physical contact, or staying at the same place (e.g. lived with, visited) as a confirmed case while the case was symptomatic.  

References 

1. International Health Regulations (2005). Third edition. Geneva: World Health Organization; 2016 (https://iris.who.int/handle/10665/246107, accessed 27 August 2024). 

2. Case definitions for the four diseases requiring notification to WHO in all circumstances under the IHR (2005). Geneva: World Health Organization; 2009 (https://www.who.int/publications/m/item/case-definitions-for-the-four-diseases-requiringnotification-to-who-in-all-circumstances-under-the-ihr-(2005), accessed 27 August 2024). 

3. Updated joint FAO/WHO/WOAH public health assessment of recent influenza  A(H5) virus events in animals and people. 20 December 2024  (https://www.who.int/publications/m/item/updatedjoint-fao-who-woah-assessment-of-recent-influenza-a(h5n1)-virus-events-in-animals-andpeople_dec2024, accessed 23 January 2025). 

4. Public health resource pack for countries experiencing outbreaks of influenza in animals: revised guidance. Geneva: World Health Organization; 2023 (https://iris.who.int/handle/10665/372248, accessed 27 August 2024). 

5. Practical interim guidance to reduce the risk of infection in people exposed to avian influenza viruses, 5 June 2024.Geneva: World Health Organization; 2024 (https://doi.org/10.2471/B09116, accessed 27 August 2024). 

6. Implementing the integrated sentinel surveillance of influenza and other respiratory viruses of epidemic and pandemic potential by the Global Influenza Surveillance and Response System: standards and operational guidance. Geneva: World Health Organization; 2024 (https://iris.who.int/handle/10665/379678, accessed 23 January 2025). 

7. “Crafting the mosaic”: a framework for resilient surveillance for respiratory viruses of epidemic and pandemic potential. Geneva: World Health Organization; 2023 (https://iris.who.int/handle/10665/366689, accessed 27 August 2024). 

8. Influenza Investigations & Studies (Unity Studies) [website]. Geneva: World Health Organization (https://www.who.int/teams/global-influenza-programme/surveillance-andmonitoring/influenza-investigations-studies-unity, accessed 27 August 2024). 

9. Protocol to investigate non-seasonal influenza and other emerging acute respiratory diseases. Geneva: World Health Organization; 2018 (https://iris.who.int/handle/10665/275657, accessed 27 August 2024). 

10. Clinical practice guidelines for influenza. Geneva: World Health Organization; 2024 (https://iris.who.int/bitstream/handle/10665/378872/9789240097759-eng.pdf?sequence=1, accessed 1 Oct 2024). 

11. Manual for the laboratory diagnosis and virological surveillance of influenza. Geneva: World Health Organization; 2011  (https://iris.who.int/handle/10665/44518, accessed 27 August 2024). 

12. WHO information for the molecular detection of influenza viruses. Geneva: World Health Organization; 2021 (https://www.who.int/teams/global-influenza-programme/laboratorynetwork/quality-assurance/eqa-project/information-for-molecular-diagnosis-of-influenza-virus, accessed 27 August 2024). 

13. WHO Collaborating Centres within the Global Influenza Surveillance and Response System (GISRS) [website]. Geneva: World Health Organization (https://www.who.int/initiatives/globalinfluenza-surveillance-and-response-system/who-collaboration-centererl?CxitPEOtTWx0xUd5TJdODSXcnyJqzYd7FZeivpn7xcI=, accessed 27 August 2024). 

14. Operational guidance on sharing influenza viruses with human pandemic potential (IVPP) under the Pandemic Influenza Preparedness (PIP) Framework. Geneva: World Health Organization; 2017 (https://iris.who.int/handle/10665/259402, accessed 27 August 2024). 

15. Terms of Reference for National Influenza Centres of the Global Influenza Surveillance and Response System. Geneva: World Health Organization; 2017 (https://cdn.who.int/media/docs/default-source/influenza/national-influenza-centersfiles/nic_tor_en.pdf?sfvrsn=93513e78_30, accessed 27 August 2024). 

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18. WHO Collaborating Centres Global database [website]. Geneva: World Health Organization (https://apps.who.int/whocc/, accessed 7 November 2024. 

Further reading 

• Current information on animal influenza events reported to the World Organisation for Animal Health (WOAH) can be found at: WAHIS: World Animal Health Information System [website]. World Organisation for Animal Health (https://wahis.woah.org/#/home). 

• The results of human A(H5) surveillance and public health risk assessments and related resources can be found at: Human-animal interface [website]. Geneva: World Health Organization (https://www.who.int/teams/global-influenza-programme/avian-influenza). 

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Source: World Health Organization, https://www.who.int/publications/i/item/surveillance-for-human-infections-with-avian-influenza-a(-h5)--viruses

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