Infectious Diseases 2025

A new study published in medRxiv reviewed and analyzed estimates for key epidemiological parameters of human H5N1 infection, including the reproduction number (R₀), serial interval, incubation period, latent and infectious periods, and severity metrics such as the case fatality risk (CFR) and infection fatality risk (IFR). The study also employed modelling to estimate the R₀ for the 2024–2025 U.S. dairy herd outbreak and calculated the serial interval using historical H5N1 transmission data from Indonesia. 
Low human-to-human transmission: Estimated R₀ values for H5N1 remain consistently low (e.g., 0.04–0.05 in the U.S. outbreak), well below the threshold required for sustained human transmission. 
Longer incubation and serial intervals: H5N1 displays a median incubation period of approximately 4 days and a serial interval of approximately 6.8 days—both longer than those typically observed for human influenza (approximately 2–3 days). 
High historical case fatality risk, but lower in the current U.S. outbreak: While historical CFRs reached up to 53%, the ongoing U.S. outbreak has shown a CFR of 1.43%, with most cases presenting mild ocular symptoms (e.g., conjunctivitis). 
Occupational exposure risk: Serological evidence indicates a heightened risk of infection among poultry cullers and dairy workers exposed to infected animals, although definitions for seropositivity vary across studies. 
Comparison to H7N7 (Netherlands, 2003): The current outbreak shares key features with the 2003 H7N7 outbreak, including a low CFR, a predominance of conjunctivitis, and a low R₀, suggesting a similar clinical and epidemiological profile.

H5N1 currently exhibits limited transmissibility in humans, with reproduction numbers well below 1, indicating low epidemic potential in its current form. The virus shows a longer incubation and serial interval compared to seasonal and pandemic influenza viruses, which may support more effective contact tracing should human-to-human transmission increase. The severity profile in the ongoing U.S. outbreak appears milder than in previous outbreaks, largely characterized by ocular symptoms and a low CFR. Continuous surveillance is crucial, particularly in high-risk occupational groups and mammalian hosts, due to the potential for viral adaptation or reassortment that could enhance transmissibility. The epidemiological characteristics of the current H5N1 outbreak closely resemble those of the 2003 H7N7 outbreak, underscoring the importance of monitoring similar symptomatology and transmission patterns.