Improving H5N1 Detection: How a One Health Study Helps Us Stay Ahead of the Next Influenza Virus Threat

The urgency surrounding H5N1 dates back to 1997, when an avian influenza (H5N1) outbreak in poultry in Hong Kong led to 18 human infections and six deaths [1]. Since then, the spread of various H5N1 virus strains to wildlife and domestic animals has markedly increased, especially over the past three years. Beginning in March 2024, outbreaks of H5N1 viruses occurred on many US dairy farms, an event that catalyzed this study, according to UTMB’s Dr. Yuan Chao Xue, the first author of the study [2]. In response, the CDC urged hospitals to expand influenza testing, particularly for patients hospitalized with respiratory illness [3].

While standard influenza tests can detect influenza A, they don’t distinguish between seasonal strains and highly pathogenic subtypes like H5N1. This diagnostic gap could allow serious infections to go unnoticed. As UTMB’s Professor Ping Ren, senior author of the paper, explained, “H5N1 infections may be misclassified as seasonal influenza A. This can delay appropriate clinical management and infection control.”

Ping Ren

To address this, the UTMB team evaluated three widely used multiplex respiratory assays not originally designed to differentiate avian influenza subtypes. The researchers found that all three panels successfully detected influenza A H5N1 strains at low viral loads, an important finding for early intervention. Building on this, the team developed and validated a reflex molecular assay—the H5 LDT—to subtype Flu A-positive specimens. “We offer a practical and scalable solution for subtyping Flu A-positive specimens without disrupting existing workflows,” Professor Ren said. The recently published article can be viewed here: https://journals.asm.org/doi/epub/10.1128/jcm.00681-25

A theme behind this study is the One Health approach, which emphasizes the interconnectedness of human, animal, and environmental health. “The emergence of H5N1 in Texas’s dairy industry underscores this intersection,” said Dr. Xue. According to Professor Ren, the UTMB team designed the study “to bridge the gap between veterinary and human diagnostic capabilities”, ensuring preparedness across sectors.

Beyond enhancing detection, this research could reshape how hospitals screen for influenza during outbreaks. As Professor Ren noted, reflex testing “enables hospitals to more rapidly identify potential H5N1 infections, especially in patients with relevant exposure histories”. This approach not only improves patient outcomes but also allows for faster reporting to public health authorities — critical for containing the spread.

The stakes are high if proper H5N1 testing is not implemented. Missed or delayed diagnoses “can allow the virus to silently spread within the community, increasing the risk of human-to-human transmission and the potential for viral adaptation,” warned Dr. Xue. “Without subtype data from human cases, links to animal outbreaks may go unrecognized, weakening coordinated One Health responses,” added Professor Ren.

By combining existing respiratory panels with the new H5-specific reflex assay, hospitals now have a clearer pathway for influenza surveillance. Integrating these tools into routine workflows allows clinical labs to shift from reactive to proactive detection — strengthening pandemic preparedness and reinforcing the critical links between human and animal health.

 

References

  1. Garg, S., Reinhart, K., Couture, A., Kniss, K., Davis, C. T., Kirby, M. K., Murray, E. L., Zhu, S., Kraushaar, V., Wadford, D. A., Drehoff, C., Kohnen, A., Owen, M., Morse, J., Eckel, S., Goswitz, J., Turabelidze, G., Krager, S., Unutzer, A., Gonzales, E. R., … Olsen, S. J. (2025). Highly Pathogenic Avian Influenza A(H5N1) Virus Infections in Humans. The New England journal of medicine, 392(9), 843–854. https://doi.org/10.1056/NEJMoa2414610
  2. Xue, Y. C., Bertsch, J., Monacy, K., Haynes, C., Williams-Bouyer, N., Judy, B. M., Newman, P. C., Ksiazek, T. G., Marushchak, L. V., Gray, G. C., & Ren, P. (2025). Enhancing diagnostic preparedness for H5N1: a validation study of H5 single-plex assay and detection across multiple platforms. Journal of clinical microbiology, e0068125. Advance online publication. https://doi.org/10.1128/jcm.00681-25
  3. CDC. (2025, April 15). Accelerated Subtyping of Influenza A in Hospitalized Patients. Health Alert Network (HAN). https://www.cdc.gov/han/php/notices/han00520.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fhan%2F2025%2Fhan00520.html

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