#Asymptomatic #Human #Infections With Avian #Influenza #H5N1 Virus Confirmed by Molecular and Serologic Testing

#Asymptomatic #Human #Infections With Avian #Influenza #H5N1 Virus Confirmed by Molecular and Serologic Testing - A Scoping Review

Key Points

-- Question: Have asymptomatic infections with highly pathogenic avian influenza A(H5N1) virus been reported in humans?

-- Findings: This scoping review of published reports through August 25, 2025, identified 10 reports of 18 cases of asymptomatic infection with A(H5N1) virus, including 2 cases with molecular and serologic confirmation and 16 cases with molecular confirmation alone. Symptom ascertainment methods varied among reported cases.

-- Meaning: Asymptomatic human avian influenza A(H5N1) virus infections have been infrequently reported, with most lacking serologic confirmation; prospective surveillance studies with serial respiratory and serum sampling and detailed symptom monitoring for persons with high-risk exposures could provide data to inform future public health responses.

Abstract

Importance

Since 1997, more than 1000 infections with highly pathogenic avian influenza A(H5N1) virus among humans have been reported globally. Given ongoing A(H5N1) outbreaks in animals, understanding the frequency of A(H5N1) virus infections among asymptomatic persons can inform public health risk assessments and infection prevention guidance.

Objective

To identify and characterize reported cases of asymptomatic A(H5N1) virus infection among humans with confirmation by both molecular testing of 1 or more respiratory specimens and 1 or more serum specimens meeting World Health Organization criteria (molecularly and serologically confirmed [MSC]) or molecular confirmation (MC) alone.

Evidence Review

MEDLINE, Embase, Global Health, Cochrane, Scopus, Virtual Health Library, and Europe PubMed Central were searched for publication through August 25, 2025. Articles for full-text screening were evaluated by 2 investigators. Studies published through August 25, 2025, were included if they reported a confirmed A(H5N1) virus infection that met MSC or MC criteria and had a full-text report in English. Articles were excluded if they reported results from A(H5N1) serologic testing alone, serosurveys, or other immunologic studies.

Findings

Of 1567 unique reports that underwent title or abstract screening, 42 were selected for full-text screening, of which 10 met inclusion criteria (3 reports about 2 MSC cases and 7 reports about 16 MC cases). The 2 MSC cases occurred among adults in Pakistan and Vietnam who were identified by investigations of household contacts of index A(H5N1) case patients; 1 case patient also had exposure to A(H5N1) virus–infected chickens as the possible infection source and 1 is thought to have been infected through human-to-human transmission. Neither MSC case patient used personal protective equipment. Of 16 reported MC cases (14 adults, 2 children), 11 were identified by enhanced surveillance of persons exposed to A(H5N1) virus–infected poultry (8 in Bangladesh, 2 in Spain, and 1 in the UK) and the remaining 5 MC cases (3 in Vietnam, 2 in Cambodia) were identified by investigations of household contacts of index A(H5N1) case patients.

Conclusions and Relevance

Asymptomatic human infections with A(H5N1) virus have been infrequently reported, with most cases identified through enhanced surveillance or household contact investigations of persons with known exposure. Robust data collection is needed from persons with possible asymptomatic A(H5N1) virus infection to inform future public health responses.

Source: JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2840680

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