THE EPIDEMIOLOGY OF HEPATITIS E VIRUS INFECTIONS IN RURAL BANGLADESH
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Hepatitis E virus (HEV) is an emerging enteric pathogen responsible for most acute hepatitis worldwide. This dissertation presents data from studies conducted from 2001-2006 in the Matlab Health Research Center population under the International Center for Diarrheal Disease Research, Bangladesh. These studies define the previously unknown burden of HEV in rural Bangladesh and address gaps in HEV epidemiology. This work begins with a literature review, focusing on the challenges presented by this virus: the unexplained high case fatality in pregnancy, the absence of HEV in children, the rapid deterioration of immunity, and recent evidence implicating some HEV genotypes as zoonoses. The first study is a cross-sectional assessment of antibody seroprevalence to three hepatitis viruses (B,C&E) in a representative random population sample (n=1134). This study revealed a 22.5% seroprevalence of anti-HEV, 35.2% anti- HBc and 1.5% anti-HCV. Anti-HEV seroprevalence peaked in the second/third decades of life, as seen in India/Nepal. Male gender and outdoor employment were significantly associated with seropositivity. The second study follows this baseline cohort longitudinally for 18 months to determine HEV infection and disease rates. From 837 person-years (P-Y) of exposure, an incidence rate of 60.3/1000P-Y was estimated. Agespecific seroincidence increased in subsequent 10-year categories, peaking at 41-50y. Although clinical illness seemed infrequent, a disease:infection ratio as high as 49 per 100 (95%CI:31–73) was estimated. Third, an exploratory nested case control study attempts to identify putative risk factors for sporadic hepatitis E disease. Over 22 months, 13 field workers used a morbidity-scoring algorithm to identify acute hepatitis-like illness in their catchment population of 23,500. Finally, 46 confirmed HEV infections were iii compared to 134 sero-naïve age-matched controls. Cases were less likely to be <15y, female or use unsanitary latrines in their homes. Outdoor employment, work outside the home, and travel to a town/city emerged as risk factors. Unlike in previous studies, recent contact with a “jaundice” patient and injection exposures were significant. These studies establish that: HEV is endemic in rural Bangladesh; sporadic infections are frequent in the absence of outbreaks; and, aside from classic hygiene risk factors, there may be other pathways through which HEV is transmitted.