A new retrospective study published in Frontiers in Public Health offers critical insights into human cases of H5N6 avian influenza in Sichuan Province, China, from 2014 to 2024. Conducted by Chinese public health authorities, the study sheds light on the virus’s epidemiological features, high fatality rates, environmental drivers, and the pressing need for improved prevention and control strategies. With 16 confirmed human infections and a 75% case fatality rate, the report underscores the biosecurity threat posed by zoonotic influenza viruses amid dynamic viral evolution and persistent agricultural exposure.
A Decade of Sporadic but Lethal Human H5N6 Infections
Between 2014 and 2024, Sichuan Province documented 16 human H5N6 cases, resulting in 12 deaths—a staggering 75% case fatality rate. Most patients were middle-aged farmers with preexisting health conditions and frequent contact with deceased poultry. Cases were geographically concentrated in eastern and southern Sichuan, particularly in regions with intensive poultry farming and live bird markets.
Notably, no discernible seasonal pattern emerged, but virus detection in poultry environments peaked in winter and summer, hinting at ecological influences on transmission.
Environmental Drivers and Viral Ecology
Sichuan’s unique combination of high avian biodiversity, diverse topography, and dense wetland habitats makes it a hotspot for avian influenza transmission. Situated along two major migratory bird routes, the province is a key intersection point for wild birds that can carry and genetically reassort influenza viruses. Environmental surveillance found a 9.5% positivity rate for H5 subtype viruses in over 14,000 samples collected between 2019 and 2024, especially in poultry slaughter areas and wastewater from bird washing.
This high-risk environment supports continual genetic evolution. Recent strains in Sichuan show triple reassortment from H5N8, H6N6, and H9N2, raising concerns about viral adaptation and zoonotic potential.
Delayed Diagnosis and Treatment Drives Mortality
While patients typically presented to hospitals around 4 days after symptom onset, the median time to antiviral treatment initiation was 3 days post-admission. Survivors generally received treatment more promptly than those who died, but none of the timing differences reached statistical significance—likely due to the small sample size.
Still, the pattern suggests that delayed recognition and lack of standardized clinical pathways in rural health settings contributed to missed early intervention windows. Many patients initially self-medicated or sought care at lower-level facilities unfamiliar with avian influenza symptoms.
Poultry Exposure: Primary Risk Factor
In 62.5% of cases, direct contact with dead poultry was confirmed, and 75% of residential poultry tested positive for H5 subtypes. The live poultry trade, including handling, slaughtering, and transportation, was a major contributor to viral spread. Environmental contamination—especially via feces and inadequately cleaned cages—remains a persistent hazard for both poultry and humans.
Despite widespread exposure, no human-to-human transmission was detected in this study. Over 200 close contacts of infected individuals were monitored, with no secondary cases or respiratory virus detections, reaffirming that H5N6 remains poorly adapted to human-to-human spread at this time.
Policy Gaps and Recommendations
The authors advocate for urgent, multi-sectoral “One Health” interventions:
- Enhanced surveillance of live bird markets, poultry farms, and wild bird migration routes.
- Rapid diagnostic pathways in rural and frontline clinics.
- Risk communication and education for poultry handlers and farmers.
- Regulation and restructuring of live poultry trading systems.
- Development of targeted vaccination programs for high-risk populations.
International precedents, such as occupational vaccination in Finland and Canada, highlight the need for China to consider preemptive immunization strategies.
The study also emphasizes the importance of genomic surveillance, environmental virology, and integrated human-animal health systems to detect emerging strains and prevent spillover events.
Looking Ahead: A Persistent Zoonotic Threat
Although H5N6 currently shows limited capacity for sustained human transmission, the virus’s high fatality rate, environmental persistence, and genetic plasticity represent a significant pandemic risk. Strengthening early detection, rapid response, and structural disease prevention mechanisms is essential not only for China but for global health security.
Frontiers in Public Health. 2025. Investigation of human infection with H5N6 avian influenza cases in Sichuan Province from 2014 to 2024: a retrospective study. https://doi.org/10.3389/fpubh.2025.1603158