Immune function and micronutrient status of pregnant women infected by hepatitis e virus in Bangladesh between 2001 and 2010

Abstract

Hepatitis E virus (HEV) is the leading cause of acute viral hepatitis globally and results in severe morbidity and mortality in pregnant women. There is a paucity of longitudinal data examining the incidence and disease rate of HEV in cohorts of pregnancy in endemic areas. We studied serial sera collected within two prospective cohorts totaling 110,473 incident pregnancies enrolled large randomized trials in rural northwestern Bangladesh, between 2001 - 2007 (cohort A) and 2007 - 2010 (cohort B). An NIH research immunoassay was used to identify anti-HEV IgG status in early pregnancy, late pregnancy and 3 month postpartum venous blood specimens, drawn on a subsample of the larger cohorts. Of the 1,127 specimens available for testing in cohort A, 72 were anti-HEV seropositive at baseline, indicating a seroprevalence of ~6.4%. During this period, 63 women were identifed as potential seroconverters, suggesting an incidence rate of ~56 infections per 1000 person-years. In the more recent cohort B, 1100 were available for testing, revealing a ~6.1% seroprevalence in anti-HEV IgG at early pregnancy. Within this cohort, 40 women were identifed as putative seroconverters, an incidence rate of 46 infections per 1000 person-years. Between the 2001 to 2006 cohort and the 2008 to 2010 cohort, the incidence of intrapartum HEV infections seems to be declining in rural Bangladesh, possibly refective of improved sanitation. Cytokine and micronutrient analysis of the 2008 to 2010 cohort is ongoing to characterize the immunopathology of HEV infection. In the cohort A, 4 pregnant seroconverters with high antibody titers were evaluated for cytokine profles, revealing elevated levels of pro-infammatory cytokines compared to unifected controls and women who were seropositive at baseline. Treg-associated IL-10 levels also seem to be elevated in HEV-infected cases. Although no pregnancy-related mortality was observed in this nested cohort, analysis is ongoing to assess whether any sign of immune dysregulation or immune response inconsistent with late pregnancy is evident. Initial data suggests seroconverters seem to have lower baseline serum Zinc levels than their non-infected counterparts. Vitamin D and Copper (Cu) levels were also lower, although not statistically different. This data also seeks to elucidate population-based rates of HEV disease:infection ratios within a non-epidemic context, where this pathogen is ubiquitous.