Situation at a glance
On 23 May 2024, the Mexico International Health Regulations (IHR) National Focal Point (NFP) reported to PAHO/WHO a confirmed fatal case of human infection with avian influenza A(H5N2) virus detected in a resident of the State of Mexico who was hospitalized in Mexico City. This is the first laboratory-confirmed human case of infection with an influenza A(H5N2) virus reported globally and the first avian H5 virus infection in a person reported in Mexico. Although the source of exposure to the virus in this case is currently unknown, A(H5N2) viruses have been reported in poultry in Mexico. According to the IHR (2005), a human infection caused by a novel influenza A virus subtype is an event that has the potential for high public health impact and must be notified to the WHO. Based on available information, WHO assesses the current risk to the general population posed by this virus as low.
Description of the situation
On 23 May 2024, the Mexico IHR NFP reported to PAHO/WHO a confirmed case of human infection with avian influenza A(H5N2) virus detected in a 59-year-old resident of the State of Mexico who was hospitalized in Mexico City and had no history of exposure to poultry or other animals. The case had multiple underlying medical conditions. The case’s relatives reported that the case had already been bedridden for three weeks, for other reasons, prior to the onset of acute symptoms.

On 17 April, the case developed fever, shortness of breath, diarrhoea, nausea and general malaise. On 24 April, the case sought medical attention, was hospitalized at the National Institute of Respiratory Diseases “Ismael Cosio Villegas” (INER per its acronym in Spanish) and died the same day due to complications of his condition.

Results from Real-Time Polymerase Chain Reaction (RT-PCR) of a respiratory sample collected and tested at INER on 24 April indicated a non-subtypeable influenza A virus. On 8 May, the sample was sent for sequencing to the Laboratory of Molecular Biology of Emerging Diseases Center for Research in Infectious Diseases (CIENI per its acronym in Spanish) of INER, which indicated that the sample was positive for influenza A(H5N2). On 20 May, the sample was received at the Institute of Epidemiological Diagnosis and Reference (InDRE per its acronym in Spanish) of the Mexico National Influenza Centre, for analysis by RT-PCR, obtaining a positive result for influenza A. On 22 May, sequencing of the sample confirmed the influenza subtype was A(H5N2).

No further cases were reported during the epidemiological investigation. Of the 17 contacts identified and monitored at the hospital where the case died, one reported a runny nose between 28 and 29 April. Samples taken from these hospital contacts between 27 and 29 May tested negative for influenza and SARS-CoV 2. Twelve additional contacts (seven symptomatic and five asymptomatic) were identified near the case´s residence. Samples of pharyngeal exudate, nasopharyngeal swabs and serum were obtained from these individuals. On 28 May, the InDRE reported that all twelve samples from contacts near the patient´s residence tested negative for SARS-CoV-2, influenza A and influenza B, as determined by RT-PCR. The results of the serological samples are pending.

In March 2024, a high pathogenicity avian influenza A(H5N2) outbreak was detected in a backyard poultry farm in the state of Michoacán, which borders the State of Mexico where the case was residing

Additionally, in March 2024, an outbreak of low pathogenicity avian influenza (LPAI) A(H5N2) was identified in poultry in Texcoco, State of Mexico, and a second outbreak of LPAI A(H5N2) in April in the municipality of Temascalapa in the same state. Thus far, it has not been possible to establish if this human case is related to the recent poultry outbreaks (1).

A study describing the continuous circulation of low pathogenicity avian influenza H5N2 viruses in Mexico and spread to several other countries was published in 2022 (2).

Epidemiology
Animal influenza viruses normally circulate in animals but can also infect humans. Infections in humans have primarily been acquired through direct contact with infected animals or contaminated environments. Depending on the original host, influenza A viruses can be classified as avian influenza, swine influenza, or other types of animal influenza viruses.

Avian influenza virus infections in humans may cause mild to severe upper respiratory tract infections and can be fatal. Conjunctivitis, gastrointestinal symptoms, encephalitis and encephalopathy have also been reported.

Laboratory tests are required to diagnose human infection with influenza. WHO periodically updates technical guidance protocols for the detection of zoonotic influenza using molecular methods, e.g. RT-PCR. Evidence suggests that some antiviral drugs, notably neuraminidase inhibitors (oseltamivir, zanamivir), can reduce the duration of viral replication and improve survival prospects for some cases.

Public health response
Local and national health authorities implemented the following public health measures:

Epidemiological investigation of case and contacts.
Monitoring of health care workers with a history of contact with the patient.
Monitoring and surveillance of influenza-like respiratory illness (ILI) and severe acute respiratory illness (SARI) in neighbouring municipalities (within the same health region), in order to analyze the behaviour and trends of respiratory syndromes and viruses in the region.
Analysis of the trends of pneumonia and bronchopneumonia, acute respiratory infections, and conjunctivitis by the health services of Mexico City and the State of Mexico.
Identification of transmission chains and risk factors in the municipality where the case resided, the State of Mexico and surrounding areas.
Training on the National Guide for preparedness, prevention and response to an outbreak or zoonotic influenza event at the animal-human interface.
Communicated with animal and environmental health authorities to strengthen surveillance activities in poultry and wild birds near the case´s residence and areas with a history of low pathogenic avian influenza A(H5N2) outbreaks.
PAHO/WHO implemented the following measures:

Strengthening routine and event surveillance on the human-animal interface with WHO Collaborating Centers and strategic partners.
Improvement of molecular diagnostic capacity for detection of zoonotic diseases through knowledge transfer, training and technical support with recent emphasis in avian influenza A(H5N1)
Strengthening national capacity for the prompt shipment of human and animal samples to WHO collaborating centers for additional characterization and/or vaccine composition analysis.
Regular risk assessment for transmissibility and severity for zoonotic viruses.
Update of guidelines on influenza surveillance and response at the human-animal interface.
Revision of experiences in response and lessons learned from countries that experienced zoonotic influenza outbreaks.
Technical strengthening of risk communication capacities for events at the human-animal interface.
Clinical management training on zoonotic influenza treatment, infection prevention and control (IPC), and reorganization of health services.
Animal carcass handling training, including IPC technical aspects.
PAHO published recommendations to strengthen intersectoral work in surveillance, early detection, and research at the human animal interface.
WHO risk assessment
This is the first laboratory-confirmed human case of infection with an influenza A(H5N2) virus reported globally, and the first A(H5) virus infection in a person reported in Mexico. The case had multiple underlying conditions, and the investigation by the health authorities in Mexico is ongoing to determine the likely source of exposure to the virus. Influenza A(H5N2) viruses have been detected in poultry in Mexico recently.

Whenever avian influenza viruses are circulating in poultry, there is a risk for infection and small clusters of human cases due to exposure to infected poultry or contaminated environments. Therefore, sporadic human cases are not unexpected. Human cases of infection with other H5 subtypes including A(H5N1), A(H5N6) and A(H5N8) viruses have been reported previously. Available epidemiological and virological evidence suggests that A(H5) viruses from previous events have not acquired the ability to sustain transmission between humans, thus the current likelihood of sustained human-to-human spread is low. According to the information available thus far, no further human cases of infection with A(H5N2) associated with this case have been detected.

There are no specific vaccines for preventing influenza A(H5) virus infection in humans. Candidate vaccines to prevent A(H5) infection in humans have been developed for pandemic preparedness purposes. Close analysis of the epidemiological situation, further characterization of the most recent viruses (in human and birds) and serological investigations are critical to assess associated risks and to adjust risk management measures in a timely manner.

Based on the available information, WHO assesses the current risk to the general population posed by this virus to be low. If needed, the risk assessment will be reviewed should further epidemiological or virological information, including information on A(H5N2) viruses detected in local animal populations, become available.

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

Due to the constantly evolving nature of influenza viruses, WHO continues to stress the importance of global surveillance to detect and monitor virological, epidemiological and clinical changes associated with emerging or circulating influenza viruses that may affect human and animal health and timely virus-sharing for risk assessment.

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 healthcare-seeking behaviour of the population. It could include a range of active and passive healthcare and/or community-based approaches, including enhanced surveillance in local ARI/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.

In the case of a confirmed or suspected human infection caused by a novel influenza A virus with pandemic potential, including avian influenza virus, a thorough epidemiologic investigation (even while awaiting the confirmatory laboratory results) of a history of exposure to animals and/or travel should be undertaken along with contact tracing. The epidemiologic investigation should include early identification of unusual events that could signal person-to-person transmission of the novel virus. Clinical samples collected from suspected human cases should be tested and sent to a WHO Collaboration Centre for further characterization.

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 may have been contaminated with animal faeces. Travellers should also wash their hands often with soap and water. Travelers should follow good food safety and good food hygiene practices. Should infected individuals from affected areas travel internationally, their infection may be detected in another country during travel or after arrival. If this occurs, further community-level spread is considered unlikely as this virus has not acquired the ability to transmit easily among humans.

All human infections caused by a novel influenza A virus subtype are notifiable under the IHR, and State Parties to the regulations are required to immediately notify WHO of any laboratory-confirmed case of a recent human infection caused by an influenza A virus with the potential to cause a pandemic. Evidence of illness is not required for this report.

WHO does not advise special traveller screening at points of entry or restrictions regarding the current situation of influenza viruses at the human-animal interface.