Asymptomatic Human H5N1 Infections Confirmed by Laboratory Testing
Since 1997, more than 1,000 human infections with the highly pathogenic avian influenza A(H5N1) virus have been documented worldwide. Although most cases involve symptomatic illness, understanding the prevalence of asymptomatic infections is essential for assessing public health risks and developing effective infection control strategies. A review published in JAMA Network Open systematically analyzed published reports through August 2025 to identify laboratory-confirmed asymptomatic human infections with A(H5N1).
The review identified ten reports encompassing eighteen cases of asymptomatic A(H5N1) infection confirmed by laboratory methods. These cases primarily emerged from contact investigations and enhanced surveillance, with most lacking serologic confirmation. The findings challenge the traditional perception that human H5N1 infections are almost always symptomatic and severe, and that no human-to-human transmission of H5N1 has occurred.
Asymptomatic infections in humans exposed to avian influenza viruses have been documented across several subtypes, but the most thoroughly studied event occurred during the 2003 H7N7 outbreak in the Netherlands. Epidemiological investigations and serological surveys demonstrated that a substantial proportion of infections were either asymptomatic or limited to mild conjunctivitis. Eighty-nine laboratory-confirmed human H7N7 cases were identified during the outbreak, primarily among poultry workers. Retrospective analyses by Dutch public health authorities estimated that approximately one thousand individuals exposed to infected poultry were infected, with most showing no clinical signs. The 2003 Netherlands H7N7 episode illustrates that avian influenza virus infections in humans may be far more frequent than suggested by clinical case counts.
