Two Generations of "Gold Standards": The Impact of a Decade in Hepatitis E Virus Testing Innovation on Population Seroprevalence.

Brittany L Kmush,Alain B Labrique,Khalequ Zaman,Kenrad E Nelson,Christopher D Heaney,Zabed B Ahmed,Harry R Dalton,John R Ticehurst

doi:10.4269/ajtmh.15-0159

Abstract

Hepatitis E virus (HEV) is a global pathogen responsible for approximately 20 million infections every year in developing countries, yet remains under-recognized. In this population-based cohort study, 1,025 randomly selected participants were enrolled from Matlab, Bangladesh (2004–2005). All participants were tested for HEV antibodies and total immunoglobulin (Ig), using an in-house enzyme immunoassay developed by Walter Reed Army Institute of Research (WRAIR). In 2014, we retested the banked sera of 1,009 of those participants using the Wantai anti-HEV IgG enzyme-linked immunosorbent assay (ELISA). The WRAIR assay estimated the overall population seroprevalence as 26.6% (95% confidence interval [CI]: 24.0, 29.5), whereas the Wantai assay produced significantly higher estimated seroprevalence, 46.7% (95% CI: 43.5–49.8) (P < 0.001). However, the two tests give nearly identical findings in those 5 years and under (N = 94) with a 98% agreement between the tests. Retesting populations with modern assays is necessary to establish better population-level estimates of disease burden.

Highlights

Hepatitis E virus (HEV) is a global pathogen responsible for approximately 20 million infections every year in developing countries alone, with an increasing recognition of high rates of autochthonous infections in developed countries as well.[1]
The Walter Reed Army Institute of Research (WRAIR) assay estimated the overall population seroprevalence as 26.6%, whereas the Wantai assay produced significantly higher estimated seroprevalence 46.7% (P < 0.001)
The WRAIR assay found 29.5% and 24.4% seroprevalence in males and females, respectively (P = 0.07)

Summary

Introduction

Hepatitis E virus (HEV) is a global pathogen responsible for approximately 20 million infections every year in developing countries alone, with an increasing recognition of high rates of autochthonous infections in developed countries as well.[1]. In the early 2000s, the Walter Reed Army Institute of Research (WRAIR, Silver Spring, MD) developed an in-house enzyme immunoassay (EIA) to diagnose current and past HEV infections, using an indirect approach to quantify antiHEV total immunoglobulin (Ig) in serum.[4] This assay uses a truncated, recombinant HEV antigen, from open reading frame (ORF)-2 of the virus, the capsid protein, expressed using the baculovirus system.[4] This quantitative assay was extensively tested and validated by western blot and found to be more sensitive than most widely used commercial assays available at that time.[4] A number of studies, including those performed by our research group, relied on this assay as the gold standard against which to validate commercial or other laboratory assays.[3,5]

Methods

Results

Conclusion