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Meta-Analysis
. 2015 Aug 15;212(4):562-9.
doi: 10.1093/infdis/jiv109. Epub 2015 Feb 23.

A Systematic Review and Meta-Analysis of the Seroprevalence of Influenza A(H9N2) Infection Among Humans

Salah Uddin Khan  1 , Benjamin D Anderson  2 , Gary L Heil  1 , Song Liang  1 , Gregory C Gray  3
Affiliations
Meta-Analysis

A Systematic Review and Meta-Analysis of the Seroprevalence of Influenza A(H9N2) Infection Among Humans

Salah Uddin Khan et al. J Infect Dis. .

Abstract

Introduction: Given that influenza A(H9N2) is recognized as a pandemic threat, we evaluated the overall burden of influenza A(H9N2) infections among avian-exposed human populations.

Methods: We performed a systematic search of PubMed, AGRICOLA, and CAB Abstracts databases for literature published during 1997-2013. Studies reporting serological evidence of human influenza A(H9N2) infection among avian-exposed populations were included. We used a World Health Organization (WHO)-recommended case definition for serological evidence of infection based on results of hemagglutination inhibition (HI) and microneutralization (MN) assays. We calculated overall seroprevalence through a random effects meta-analysis model.

Results: Seroprevalence data reported by the studies ranged from 1% to 43% (median, 9%) by HI, which was not significantly different from the seroprevalence estimated through the WHO-recommended case definition (median, 1.3%; range, 0.5%-42.6%). Reported seroprevalence by MN ranged from 0.6% to 9% (median, 2.7%), which was greater than the seroprevalence estimated through the WHO-recommended case definition (median, 0.3%; range, 0.1%-1.4%).

Conclusions: A small proportion of avian-exposed humans had evidence of influenza A(H9N2) infection. As the virus has a near global distribution in poultry, it seems likely that present surveillance efforts are missing mild or asymptomatic infections among avian-exposed persons. It seems prudent to closely monitor avian-exposed populations for influenza A(H9N2) infection to provide prepandemic warnings.

Keywords: H9N2 subtype; hemagglutination inhibition test; influenza A virus; meta-analysis; microneutralization test; seroprevalence; systematic review.

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Figures

Figure 1.
Figure 1.
Reported global distribution for influenza A(H9N2) in humans and animals from 1997 to 2013. Countries that detected influenza A(H9N2) in poultry have an orange background. Species-specific symbols were assigned to each country. When a human or animal was found to be seropositive for influenza A(H9N2), the species was colored green; if a virological sample from humans or animals tested positive, the species was colored red.
Figure 2.
Figure 2.
Flow chart of the literature search, screening, assessing influenza A(H9N2) serological data for eligibility, and selecting articles for the meta-analysis.
Figure 3.
Figure 3.
Forest plots of the overall seroprevalence calculated from hemagglutination inhibition (HI) and microneutralization (MN) assay results, using reported cutoff corresponded with the standard cutoffs recommended by the World Health Organization (WHO) (ie, HI assay titers of ≥1:160, MN assay titers of ≥1:80, or seroconversion, defined as a 4-fold rise in HI or MN titers over time). A, Forest plot of seroprevalence calculated from HI assay results, using the WHO-recommended cutoff (≥1:160). B, Forest plot of seroprevalence calculated from HI assay results, using study cutoffs. C, Forest plot of seroprevalence calculated from MN assay results, using the WHO recommended cutoff (≥1:80). D, Forest plot of seroprevalence calculated from MN assay results, using the study cutoff.
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