HMN 2025: What is the Symptom-free H5N1 infection in humans: Evidence remains scarce

Evidence for symptom-free H5N1 infection in humans remains scarce
Colorized transmission electron micrograph of Avian influenza A H5N1 viruses. Credit: Public Domain

Researchers at the US Centers for Disease Control and Prevention (CDC) have identified a few instances of asymptomatic human infection with avian influenza A (H5N1) virus.

Getting to know H5N1 avian flu

Widespread in worldwide, H5N1 has been causing outbreaks in poultry for several years. Recent “egg-flation” price increases for eggs in the US were largely due to a disruption of the egg supply chain caused by the virus, which forced the culling of entire farm flocks to prevent further spread.

Since the first recorded human cases in 1997, more than a thousand people have been infected with the highly pathogenic H5N1 strain across 25 countries. According to the CDC, the mortality rate from H5N1 observed globally has been around 50%. Most cases have been traced to exposure to infected poultry, with recent cases in U.S. dairy cows linked to several recent human cases.

While asymptomatic infection with seasonal influenza viruses is well documented, far less is known about silent H5N1 infections in humans. Such infections could distort risk assessments if undetected, and are difficult to confirm because serologic and vary in sensitivity and reliability.

Global review to identify asymptomatic cases

In the study, “Asymptomatic Human Infections With Avian Influenza A(H5N1) Virus Confirmed by Molecular and Serologic Testing: A Scoping Review,” published in JAMA Network Open, investigators searched seven scientific databases for reports through August 25, 2025.

The aim was to find documented human cases meeting World Health Organization definitions for either molecular and serologic confirmation or molecular confirmation alone.

Small number of confirmed cases found worldwide

Out of 1,567 reports screened, 10 studies met the inclusion criteria of reported asymptomatic infection with respiratory or serum testing evidence, excluding studies that relied on antibody detection alone.

Within the 10 studies, there were 18 reported asymptomatic H5N1 infections with two meeting both molecular and serologic confirmation and 16 confirmed by molecular testing only.

The two fully confirmed cases occurred in adults from Pakistan and Vietnam identified during household contact investigations of symptomatic relatives. One individual likely contracted the virus through human-to-human transmission, while the other had direct exposure to infected chickens.

Among the 16 molecularly confirmed cases, 11 were identified during surveillance of individuals exposed to infected poultry in Bangladesh, Spain, and the United Kingdom. The remaining five were found through household investigations in Vietnam and Cambodia.

Most lacked serologic confirmation. Some detections, particularly those with high cycle threshold values, may have reflected environmental contamination rather than infection. Only a few cases involved follow-up testing or antiviral treatment.

Gaps in data and future research needs

CDC authors conclude that asymptomatic H5N1 infections in humans are uncommon and often lack the serologic confirmation required to confirm infection. Inconsistent symptom monitoring further limited interpretation.

Future research could clarify how often H5N1 infects humans without symptoms, how long virus shedding lasts, and whether asymptomatic individuals can transmit infection. Such information would strengthen outbreak risk assessment and infection control measures. Comprehensive data collection from exposed but symptom-free individuals remains essential for guiding future public health responses.

Written for you by our author Justin Jackson, edited by Sadie Harley, —this article is the result of careful human work. We rely on readers like you to keep independent science journalism alive.
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More information:
Fatimah S. Dawood et al, Asymptomatic Human Infections With Avian Influenza A(H5N1) Virus Confirmed by Molecular and Serologic Testing: A Scoping Review, JAMA Network Open (2025). DOI: 10.1001/jamanetworkopen.2025.40249

Rick A. Bright et al, Asymptomatic Influenza A(H5N1) Infections and Sustained Surveillance—Sustaining Surveillance Beyond the Crisis, JAMA Network Open (2025). DOI: 10.1001/jamanetworkopen.2025.40255

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