#18,961
Roughly 6 weeks ago we saw the brief mention in an Oct 15th PAHO H5N1 Epidemiological Report of an H5 case in Mexico City, although details on the virus were limited.
The patient - a woman in her 20's - developed symptoms on September 14th, and after two weeks of increasing respiratory distress was finally hospitalized and a bronchoalveolar lavage sample was obtained, which tested positive for an unsubtypable influenza A on Sept 29th.On 2 October 2025, Mexico's International Health Regulations (IHR) National Focal Point (NFP)notified PAHO/WHO of a laboratory-confirmed human infection caused by avian influenza A(H5) virus in Mexico City, the second confirmed human case in the country in 2025 (6, 7).
As of that initial announcement, the NA type remained undetermined.
This was the third H5 case reported from Mexico since 2024, and the source of all three remain undetermined.
- The first occurred in April of 2024 (see Mexico announced the death of a 58-year-old man) when a patient - who also suffered from serious comorbidities - tested positive for LPAI H5N2, becoming the first laboratory-confirmed human case of influenza A(H5N2) infection reported globally.
- A year later (April 2025), a 3-year old girl from Durango State died following an H5N1 infection (see WHO DON Update On Mexico's Fatal H5N1 Infection).
About a week ago, the WHO published their latest Influenza at the human-animal interface summary and assessment report, which identified the full subtype as H5N2, but further characterization of the virus was reportedly still underway.
Somewhat intriguingly, that report did disclose:
Respiratory samples collected from close contacts including hospital contacts, tested negative for influenza viruses. During the epidemiologic investigation, several animals (including birds) and bird droppings were found in the building where the case resides, in an area the case passes frequently. A dog was identified as a pet at the case’s residence. Samples collected from the animals tested positive for influenza A(H5). Information on whether this virus was a high or low pathogenicity avian influenza virus (HPAI or LPAI) is pending further testing
Overnight, a fascinating new preprint has appeared on the medRxiv server, which provides additional - and somewhat concerning - details on this latest case. It turns out this H5N2 virus was a new reassortment between the local, long-endemic, LPAI H5N2 virus in Mexico and the clade 2.3.4.4b H5N1 virus circulating globally.
While numerous H5N1 reassortments have occurred in the past, producing scores of new H5N1 genotypes (e.g. A3, B3.13, D1.1, D1.2, D1.3, etc.), this introduces a novel subtype - HPAI H5N2 - to an already crowded field.
First the abstract, and a few excerpts from this preprint, but you'll want to read it in its entirety. I'll have a bit more after the break.
Joel Armando Vazquez-Perez, Eduardo Becerril-Vargas, Jose Ernesto Ramirez-Gonzalez, Mario Solis-Hernandez, Charles Todd Davis, Pamela Garciadiego-Fossas, Marco Villanueva-Reza, Hansel Hugo Chavez-Morales, Enrique Mendoza-Ramirez, Christian Diego Olivares-Flores, America Citlai Vera-Jimenez, Uriel Rumbo-Nava, Cristobal Guadarrama-Perez, Elio German Recinos-Carrera, Joaquin Zuniga, Irma Lopez-Martinez, Lucia Hernandez-Rivas, Gisela Barrera-Badillo, Nohemi Colin-Soto, Laura Flores-Cisneros, Guillermo Carbajal-Sandoval, Diana Vidal-Aguirre, Dayanira Sarith Arellano-Suarez, Rodrigo Aparicio-Antonio, Ramiro Lopez-Elizalde, Carlos Javier Alcazar-Ramiro, Armando Garcia-Lopez, Han Di, Marie Kirby, Yunho Jang, Miguel Angel Lezana-Fernandez, Carmen Margarita Hernandez-Cardenasdoi: https://doi.org/10.1101/2025.11.21.25340167
Abstract
Background Infection of backyard and poultry with low pathogenicity avian influenza LPAI A(H5N2) viruses has occurred in Mexico since 1994, and the first human infection caused by this influenza virus was detected in 2024. Since its emergence in the Americas, frequent reassortments between high pathogenicity avian influenza HPAI A(H5N1) and LPAI viruses has occurred.
In September 2025, the Instituto Nacional de Enfermedades Respiratorias of Mexico City identified an unsubtypeable influenza A virus infection in a young adult patient later determined to be a reassortant HPAI (H5N2) virus with a clade 2.3.4.4b HA.
Methods We analyzed clinical and epidemiologic data from this patient. Respiratory samples were tested for influenza RT-qPCR assays. Genomic sequence and phylogenetics analyses were performed to provisionally assign a new genotype to the novel HPAI A(H5N2) reassortant virus.
Results The patient presented with fever and tachypnea, later developed hemoptysis and thoracic pain, with oxygen saturation decreasing to 70%. CT scan showed bilateral ground-glass opacities consistent with diffuse alveolar hemorrhage and zones consistent with consolidation. Clinical improvement was observed and the patient was discharged.
Through viral complete genome analysis, we identified an HPAI A(H5N2) virus with genes from both clade 2.3.4.4b A(H5N1) viruses similar to those detected in North America during 2022-2023 and genes from the LPAI A(H5N2) viruses detected in Mexico during 2024.
Conclusions This is the first ever laboratory-confirmed human infection caused by an HPAI A(H5N2) virus infection, suggesting a new genotype provisionally classified as B3.14. The relationship of the virus with the severity of illness remains unknown.
(SNIP)
Further studies are required to determine the predicted pathogenicity and the transmissibility of the virus and its potential threat to human health. Although obesity was the sole comorbidity, the patient exhibited unusually extensive pulmonary damage, underscoring the need for further characterization of their pathogenic potential of this or related viruses. Since no cases of this reassorted A(H5N2) influenza virus in humans have been previously reported, we are unaware of the clinical outcomes that this HPAI virus subtype may have in humans.
Given the virus's propensity for rapid genetic reassortment, genomic surveillance is essential, particularly for emerging strains. Such surveillance forms a critical component of global preparedness and rapid response strategies, enabling countries to strengthen viral diagnostics, vaccine development and therapeutic strategies to prevent widespread outbreaks.
In summary, our findings support the emergence of a new clade 2.3.4.4b reassortant virus provisionally classified as genotype B3.14 and the first ever global human case of an HPAI A(H5N2) virus infection.
While the public health implications of a one-off infection such as this are hard to assess, this is the second human infection with a novel subtype reported in North America in a matter of a few weeks (see Washington State DOH: H5N5 Avian influenza confirmed in Grays Harbor County resident).
Both cases may well end up being flukes, but they remind us that influenza A's superpower is its ability to continually reinvent itself through reassortment.
Admittedly, most reassortants end up as evolutionary failures - unable to compete against the panoply of existing flu strains - but on rare occasions an overachiever is generated.
And should that overachiever also have (or develop) an affinity for infecting humans, then our world may face yet another global health threat.
