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

Xinhua Chen,Peter W Horby,Juan Yang,Wei Wang,Shengjie Lai,Timothy M Uyeki,Yan Wang,Benjamin J Cowling,Hongjie Yu

doi:10.1186/s12916-020-01836-y

Abstract

BackgroundHighly 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.MethodsWe 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.ResultsAcross 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.ConclusionsThese 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.

Highlights

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
Studies were excluded if they were reviews, published study protocols without reports on the results of serological tests, or case reports; referred to study subjects previously reported in publications; only assessed the seroprevalence of A(H5N1) virus antibodies in animals; or reported laboratory-confirmed cases regardless of clinical severity
An additional five eligible studies identified by screening of reference lists in previous reports [13, 14, 22, 23] were included in this systematic review and meta-analysis

Summary

Introduction

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. Human infections with highly pathogenic avian influenza (HPAI) A(H5N1) virus were first confirmed in Hong Kong, China, in 1997 [1], in parallel with large outbreaks in domestic poultry [2]. Ongoing A(H5N1) virus circulation among poultry is associated with genetic divergence and emergence of antigenically distinct clades and subclades of A(H5N1) virus in different geographic areas [6, 7]. These evolving genetic and antigenic features of A(H5N1) virus, as well as potential human adaptative mutations [8], continue to pose a pandemic threat

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