Epidemic Hepatitis E In Pakistan: Patterns Of Serologic Response And Evidence That Antibody To Hepatitis E Virus Protects Against Disease

Abstract

IgM and IgG anti-hepatitis E virus (HEV) patterns were determined in sera collected during a hepatitis outbreak in Pakistan. HEV infection was detected serologically in 122 patients. IgM anti-HEV was detected in specimens collected up to 2 weeks before and 5-7 weeks after hospitalization in 91% and 100%, respectively, of 122 HEV-infected patients. IgG followed a similar pattern. Peak antibody titers appeared 2-4 weeks after hospitalization. At 20 months after hospitalization, IgM anti-HEV was not detected in any of 33 patients; IgG was found in all. IgG anti-HEV appeared to be protective in contracts of patients. This study confirms HEV as the cause of the outbreak, quantifies IgM and IgG anti-HEV responses, provides evidence that IgG anti-HEV protects against hepatitis E, and demonstrates that IgG anti-HEV persists, but at diminished titer, after infection. Hepatitis E in young adults is the result of primary infection with HEV and, if reinfection occurs, it does not commonly cause serious illness.

A Comprehensive Study of Neutralizing Antigenic Sites on the Hepatitis E Virus (HEV) Capsid by Constructing, Clustering, and Characterizing a Tool Box

“…Similar to the outer membrane protrusions on other viral surfaces (26 -30), the HEV E2s domain harbors the major neutralizing epitopes for protection (31)(32)(33)(34)(35). A series of recombinant proteins containing the E2s domain, which included the bacterially expressed truncated proteins pE2 (aa 394 -606) (22,23,36) and p239 (aa 368 -606) (37) and the baculovirus expression system expressed T ϭ 1 virus-like particle (21), protected non-human primates and humans efficiently against HEV infection and liver injury (32,34). Among the truncated proteins, p239 was successfully used in the only approved HEV vaccine (32).…”

Characterization of hepatitis E-specific cell-mediated immune response using IFN-γ ELISPOT assay

“…Additionally, HEV-RNA may be detected in the blood or stool from up to 50% of anti-HEV IgM positive cases (El-Sayed Zaki et al, 2006). However, these tests have not been as reliable as similar tests for hepatitis A virus (HAV) and hepatitis B virus (HBV) (Bryan et al, 1994;Dawson et al, 1992;Favorov et al, 1992;Goldsmith et al, 1992). Until recently, commercial tests for anti-HEV IgG have demonstrated inconsistent sensitivity and specificity.…”

“…However, a recently available commercial assay for anti-HEV IgM (HEV-IgM ELISA 3.0, MP Diagnostics, formerly Genelabs Diagnostic, Singapore) appears promising for detecting acute HEV infections (Chen et al, 2005). AntiIgM peaks up to four weeks after onset of AVH and is no longer detectable in half of the cases after three months (Arankalle et al, 1994;Bryan et al, 1994;Dawson et al, 1992). Additionally, it is not known how long anti-IgG persists because of differences in sensitivity of the EIA.…”

An outbreak of hepatitis E in Northern Namibia, 1983.

“…[3][4][5][6][7][8][9][10][11] One of the largest outbreaks of hepatitis E, in Delhi, India (1955) was identified retrospectively by identification of antibodies to HEV in archived serum specimens. 12 Polymerase chain reaction (PCR) tests to detect HEV RNA 8,13,14 and improved serology for HEV [15][16][17][18] have greatly increased the ability of reference laboratories to identify hepatitis E disease.…”