Serological evidence of human infections with highly pathogenic avian influenza A(H5N1) virus: a systematic review and m

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RESEARCH ARTICLE

Open Access

Serological evidence of human infections with highly pathogenic avian influenza A(H5N1) virus: a systematic review and meta-analysis Xinhua Chen1†, Wei Wang1†, Yan Wang1, Shengjie Lai1,2, Juan Yang1, Benjamin J. Cowling3, Peter W. Horby4, Timothy M. Uyeki5† and Hongjie Yu1*†

Abstract Background: Highly pathogenic avian influenza A(H5N1) virus poses a global public health threat given severe and fatal zoonotic infections since 1997 and ongoing A(H5N1) virus circulation among poultry in several countries. A comprehensive assessment of the seroprevalence of A(H5N1) virus antibodies remains a gap and limits understanding of the true risk of A(H5N1) virus infection. Methods: We conducted a systematic review and meta-analysis of published serosurveys to assess the risk of subclinical and clinically mild A(H5N1) virus infections. We assessed A(H5N1) virus antibody titers and changes in titers among populations with variable exposures to different A(H5N1) viruses. Results: Across studies using the World Health Organization-recommended seropositive definition, the point estimates of the seroprevalence of A(H5N1) virus-specific antibodies were higher in poultry-exposed populations (range 0–0.6%) and persons exposed to both human A(H5N1) cases and infected birds (range 0.4–1.8%) than in close contacts of A(H5N1) cases or the general population (none to very low frequencies). Seroprevalence was higher in persons exposed to A(H5N1) clade 0 virus (1.9%, range 0.7–3.2%) than in participants exposed to other clades of A(H5N1) virus (range 0–0.5%) (p < 0.05). Seroprevalence was higher in poultry-exposed populations (range 0–1.9%) if such studies utilized antigenically similar A(H5N1) virus antigens in assays to A(H5N1) viruses circulating among poultry. Conclusions: These low seroprevalences suggest that subclinical and clinically mild human A(H5N1) virus infections are uncommon. Standardized serological survey and laboratory methods are needed to fully understand the extent and risk of human A(H5N1) virus infections. Keywords: Influenza in humans, Influenza A(H5N1), Serological evidence

* Correspondence: [email protected] † Xinhua Chen and Wei Wang contributed equally to this work. † Timothy M Uyeki and Hongjie Yu are joint senior authors. 1 School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai 200032, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is n