Background

Hepatitis E virus (HEV) infection causes significant morbidity and mortality worldwide, particularly among pregnant women. In clinical settings blood-based testing protocols are commonly used to diagnose HEV infection, but in community settings such invasive sampling can hinder study participation and limit discovery of the ecology and natural history of HEV infection. Oral fluid is a non-invasive biospecimen that can harbor pathogen-specific antibodies and has the potential to replace blood-based testing protocols.

Objectives

To develop an immunoassay to assess past and recent HEV infection that uses oral fluid instead of serum or plasma.

Methods

The assay was validated using paired oral fluid and serum samples collected from 141 patients who presented either with (n=76) or without (n=65) symptoms of acute viral hepatitis at a clinical diagnostics center in Dhaka, Bangladesh. The sensitivity and specificity of the oral fluid-based immunoassay for HEV IgG (past HEV infection) and HEV IgA (recent HEV infection) antibodies was calculated in reference to Wantai's (Beijing Wantai) serum-based HEV enzyme-linked immunosorbent assay (ELISA) kits for IgG and IgM antibodies, respectively.

Results

The sensitivity and specificity of the oral fluid-based immunoassay for HEV-IgG antibodies were 98.7% and 98.4%, respectively. The sensitivity and specificity of the oral fluid-based immunoassay for HEV IgA were 89.5% and 98.3%, respectively.

Conclusions

The high concordance of our non-invasive oral fluid-based immunoassays (HEV IgG and HEV IgA) with commercial high-performance serum HEV ELISA kits (IgG and IgM) means that population-based surveillance of past and recent HEV infection could be expanded to improve understanding of its ecology and natural history.

Unlabelled

Exposure to hepatitis E virus (HEV) is common in the United States, but there are few data on prevalence of HEV/human immunodeficiency virus (HIV) coinfection in U.S.

Populations

We tested 2,919 plasma samples collected from HIV-infected (HIV(+)) women and men enrolled in U.S. cohort studies for HEV viremia using a high-throughput nucleic acid testing (NAT) platform. NAT(+) samples were confirmed by real-time polymerase chain reaction. Samples were selected for testing primarily on the basis of biomarkers of liver disease and immune suppression. Prevalence of HEV viremia was 3 of 2,606 and 0 of 313 in tested plasma samples collected from HIV(+) women and men, respectively. All HEV isolates were genotype 3a. Based on follow-up testing of stored samples, 1 woman had chronic HEV infection for >4 years whereas 2 women had acute HEV detectable at only a single study visit.

Conclusions

To our knowledge, this is the first reported case of chronic HEV infection in an HIV(+) U.S. individual. We also confirm that chronic HEV infection can persist despite a CD4(+) count >200 cells/mm(3). Overall, though, these data suggest that HEV infection is rare in the HIV(+) U.S. population.