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      Outbreak of Hepatitis E in Urban Bangladesh Resulting in Maternal and Perinatal Mortality

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          Abstract

          A large outbreak of hepatitis E occurred in urban Bangladesh during 2008–2009, resulting in increased maternal and neonatal mortality in the affected community. Case-patients who took paracetamol during their illness were more likely to die than other case-patients.

          Abstract

          Background.  Hepatitis E virus (HEV) causes outbreaks of jaundice associated with maternal mortality. Four deaths among pregnant women with jaundice occurred in an urban community near Dhaka, Bangladesh, in late 2008 and were reported to authorities in January 2009. We investigated the etiology and risk factors for jaundice and death.

          Methods.  Field workers identified suspected cases, defined as acute onset of yellow eyes or skin, through house-to-house visits. A subset of persons with suspected HEV was tested for immunoglobulin M (IgM) antibodies to HEV to confirm infection. We used logistic regression analysis to identify risk factors for HEV disease and for death. We estimated the increased risk of perinatal mortality associated with jaundice during pregnancy.

          Results.  We identified 4751 suspected HEV cases during August 2008–January 2009, including 17 deaths. IgM antibodies to HEV were identified in 56 of 73 (77%) case-patients tested who were neighbors of the case-patients who died. HEV disease was significantly associated with drinking municipally supplied water. Death among persons with HEV disease was significantly associated with being female and taking paracetamol (acetaminophen). Among women who were pregnant, miscarriage and perinatal mortality was 2.7 times higher (95% confidence interval, 1.2–6.1) in pregnancies complicated by jaundice.

          Conclusions.  This outbreak of HEV was likely caused by sewage contamination of the municipal water system. Longer-term efforts to improve access to safe water and license HEV vaccines are needed. However, securing resources and support for intervention will rely on convincing data about the endemic burden of HEV disease, particularly its role in maternal and perinatal mortality.

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          Maternal and fetal outcomes in pregnant women with acute hepatitis E virus infection.

          Manju Puri, S. Patra, Ashish Kumar … (2007)
          Hepatitis E virus (HEV) infection is known to cause severe liver disease in pregnant women. It is unclear whether obstetric and fetal outcomes are worse in pregnant women with HEV infection than in women with other forms of viral hepatitis. To compare maternal, obstetric, and fetal outcomes in pregnant women with acute viral hepatitis caused by HEV and other hepatitis viruses. Observational cohort. Tertiary care hospital, New Delhi, India. 220 consecutive pregnant women presenting with jaundice caused by acute viral hepatitis. Maternal mortality and medical complications, obstetric complications, deliveries, and fetal outcomes. Infection with HEV caused acute viral hepatitis in 60% of included women. Fulminant hepatic failure was more common (relative risk, 2.7 [95% CI, 1.7 to 4.2]; P = 0.001) and maternal mortality was greater (relative risk, 6.0 [CI, 2.7 to 13.3]; P < 0.001) in HEV-infected women than in non-HEV-infected women. Women with HEV infection were more likely than those with other forms of viral hepatitis to have obstetric complications (relative risk, 4.1 [CI, 1.7 to 10.2] for antepartum hemorrhage and 1.9 [CI, 1.3 to 2.7] for intrauterine fetal death; P < 0.001 for both) and poor fetal outcomes (relative risk, 1.2 [CI, 1.0 to 1.4] for preterm delivery [P = 0.005] and 1.8 [CI, 1.2 to 2.5] for stillbirth [P = 0.026]). The findings may not apply to community settings, to women who are asymptomatic or have only minor symptoms, or in the setting of an HEV epidemic. Pregnant women with jaundice and acute viral hepatitis caused by HEV infection had a higher maternal mortality rate and worse obstetric and fetal outcomes than did pregnant women with jaundice and acute viral hepatitis caused by other types of viral hepatitis.
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            Safety and efficacy of a recombinant hepatitis E vaccine.

            Marc Fourneau, Khin Saw Aye Myint, Sanjaya Shrestha … (2007)
            Hepatitis E virus (HEV) is an important cause of viral hepatitis. We evaluated the safety and efficacy of an HEV recombinant protein (rHEV) vaccine in a phase 2, randomized, double-blind, placebo-controlled trial. In Nepal, we studied 2000 healthy adults susceptible to HEV infection who were randomly assigned to receive three doses of either the rHEV vaccine or placebo at months 0, 1, and 6. Active (including hospital) surveillance was used to identify acute hepatitis and adverse events. The primary end point was the development of hepatitis E after three vaccine doses. A total of 1794 subjects (898 in the vaccine group and 896 in the placebo group) received three vaccine doses; the total vaccinated cohort was followed for a median of 804 days. After three vaccine doses, hepatitis E developed in 69 subjects, of whom 66 were in the placebo group. The vaccine efficacy was 95.5% (95% confidence interval [CI], 85.6 to 98.6). In an intention-to-treat analysis that included all 87 subjects in whom hepatitis E developed after the first vaccine dose, 9 subjects were in the vaccine group, with a vaccine efficacy of 88.5% (95% CI, 77.1 to 94.2). Among subjects in a subgroup randomly selected for analysis of injection-site findings and general symptoms (reactogenicity subgroup) during the 8-day period after the administration of any dose, the proportion of subjects with adverse events was similar in the two study groups, except that injection-site pain was increased in the vaccine group (P=0.03). In a high-risk population, the rHEV vaccine was effective in the prevention of hepatitis E. (ClinicalTrials.gov number, NCT00287469 [ClinicalTrials.gov].). Copyright 2007 Massachusetts Medical Society.
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              A large outbreak of hepatitis E among a displaced population in Darfur, Sudan, 2004: the role of water treatment methods.

              Iza Ciglenecki, Mercedes Tatay, Francisco Diaz Cadórniga … (2006)
              The conflict in Darfur, Sudan, was responsible for the displacement of 1.8 million civilians. We investigated a large outbreak of hepatitis E virus (HEV) infection in Mornay camp (78,800 inhabitants) in western Darfur. To describe the outbreak, we used clinical and demographic information from cases recorded at the camp between 26 July and 31 December 2004. We conducted a case-cohort study and a retrospective cohort study to identify risk factors for clinical and asymptomatic hepatitis E, respectively. We collected stool and serum samples from animals and performed a bacteriological analysis of water samples. Human samples were tested for immunoglobulin G and immunoglobulin M antibody to HEV (for serum samples) and for amplification of the HEV genome (for serum and stool samples). In 6 months, 2621 hepatitis E cases were recorded (attack rate, 3.3%), with a case-fatality rate of 1.7% (45 deaths, 19 of which involved were pregnant women). Risk factors for clinical HEV infection included age of 15-45 years (odds ratio, 2.13; 95% confidence interval, 1.02-4.46) and drinking chlorinated surface water (odds ratio, 2.49; 95% confidence interval, 1.22-5.08). Both factors were also suggestive of increased risk for asymptomatic HEV infection, although this was not found to be statistically significant. HEV RNA was positively identified in serum samples obtained from 2 donkeys. No bacteria were identified from any sample of chlorinated water tested. Current recommendations to ensure a safe water supply may have been insufficient to inactivate HEV and control this epidemic. This research highlights the need to evaluate current water treatment methods and to identify alternative solutions adapted to complex emergencies.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Clin Infect Dis
                Journal ID (iso-abbrev): Clin. Infect. Dis
                Journal ID (publisher-id): cid
                Journal ID (hwp): cid
                Title: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
                Publisher: Oxford University Press
                ISSN (Print): 1058-4838
                ISSN (Electronic): 1537-6591
                Publication date (Print): 01 September 2014
                Publication date (Electronic): 22 May 2014
                Publication date PMC-release: 22 May 2014
                Volume: 59
                Issue: 5
                Pages: 658-665
                Affiliations
                [1 ]icddr,b (International Center for Diarrhoeal Disease Research, Bangladesh)
                [2 ]Ministry of Health and Family Welfare, Institute of Epidemiology, Disease Control and Research , Dhaka, Bangladesh
                [3 ]Global Disease Detection Branch, Division of Global Health Protection, Center for Global Health, Centers for Disease Control and Prevention , Atlanta, Georgia
                Author notes
                Correspondence: Emily S. Gurley, MPH, PhD, 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka 1212, Bangladesh ( egurley@ 123456icddrb.org ).
                Article
                Publisher ID: ciu383
                DOI: 10.1093/cid/ciu383
                PMC ID: 4130310
                PubMed ID: 24855146
                SO-VID: dc0b2403-15fa-4d6a-8c99-5d71ae366093
                Copyright © © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com .

                History
                Date received : 27 December 2013
                Date accepted : 14 May 2014
                Categories
                Subject: Articles and Commentaries

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: bangladesh,hepatitis e,outbreak,pregnancy,safe water
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: bangladesh, hepatitis e, outbreak, pregnancy, safe water

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