High Mortality Associated with an Outbreak of Hepatitis E among Displaced Persons in Darfur, Sudan

Boccia, Delia; Guthmann, Jean-Paul; Kløvstad, Hilde; Hamid, Nuha; Tatay, Mercedes; Ciglenečki, Iza; Nizou, Jacques-Yves; Nicand, Élisabeth; Guérin, Philippe J.

doi:10.1086/504322

Cited by 189 publications

(163 citation statements)

References 23 publications

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“…The reason for the lower replication rate of gt1 and gt3 in placenta‐derived JAR cells compared to JEG‐3 and BeWo cells is currently unclear; however, this could be due to a differential host factor expression required for efficient HEV replication. The first HEV outbreak with reported cases of symptomatic pregnant women was documented in 1987 in Nepal,38 and most of the recent gt1 outbreaks were detected in refugee camps in developing countries, including Somalia,39 Kenya,40 Sudan,41 and Uganda 9. There are, in addition, reports mainly from Egypt in which gt1 infections during pregnancy were not associated with morbidity 42, 43, 44.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis E virus replication and interferon responses in human placental cells

Knegendorf

Drave

Thi

et al. 2018

Hepatology Communications

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Hepatitis E virus (HEV) is a member of the genus Orthohepevirus in the family Hepeviridae and the causative agent of hepatitis E in humans. HEV is a major health problem in developing countries, causing mortality rates up to 25% in pregnant women. However, these cases are mainly reported for HEV genotype (gt)1, while gt3 infections are usually associated with subclinical courses of disease. The pathogenic mechanisms of adverse maternal and fetal outcome during pregnancy in HEV‐infected pregnant women remain elusive. In this study, we observed that HEV is capable of completing the full viral life cycle in placental‐derived cells (JEG‐3). Following transfection of JEG‐3 cells, HEV replication of both HEV gts could be observed. Furthermore, determination of extracellular and intracellular viral capsid levels, infectivity, and biophysical properties revealed production of HEV infectious particles with similar characteristics as in liver‐derived cells. Viral entry was analyzed by infection of target cells and detection of either viral RNA or staining for viral capsid protein by immunofluorescence. HEV gt1 and gt3 were efficiently inhibited by ribavirin in placental as well as in human hepatoma cells. In contrast, interferon‐α sensitivity was lower in the placental cells compared to liver cells for gt1 but not gt3 HEV. Simultaneous determination of interferon‐stimulated gene expression levels demonstrated an efficient HEV‐dependent restriction in JEG‐3. Conclusion: We showed differential tissue‐specific host responses to HEV genotypes, adding to our understanding of the mechanisms contributing to fatal outcomes of HEV infections during pregnancy. Using this cell‐culture system, new therapeutic options for HEV during pregnancy can be identified and evaluated. (Hepatology Communications 2018;2:173–187)

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Section: Discussionmentioning

confidence: 99%

Hepatitis E virus replication and interferon responses in human placental cells

Knegendorf

Drave

Thi

et al. 2018

Hepatology Communications

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“…emerging virus | zoonosis H epatitis E virus (HEV) gained notoriety as the cause of epidemics and sporadic cases of acute hepatitis in developing countries; examples include the 29,300 cases that occurred during the New Delhi outbreak in 1956 and the 2,621 cases reported over 6 mo in an Internally Displaced Persons Camp in Darfur in which pregnant women, as has been reported previously (1), had the highest mortality rate (26-31%) (2). HEV is the most or secondmost important cause of acute hepatitis in adults in developing countries.…”

mentioning

confidence: 99%

Cross-species infections of cultured cells by hepatitis E virus and discovery of an infectious virus–host recombinant

Shukla

Nguyen

Torian

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

281

335

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The RNA virus, hepatitis E virus (HEV) is the most or second-most important cause of acute clinical hepatitis in adults throughout much of Asia, the Middle East, and Africa. In these regions it is an important cause of acute liver failure, especially in pregnant women who have a mortality rate of 20–30%. Until recently, hepatitis E was rarely identified in industrialized countries, but Hepatitis E now is reported increasingly throughout Western Europe, some Eastern European countries, and Japan. Most of these cases are caused by genotype 3, which is endemic in swine, and these cases are thought to be zoonotically acquired. However, transmission routes are not well understood. HEV that infect humans are divided into nonzoonotic (types 1, 2) and zoonotic (types 3, 4) genotypes. HEV cell culture is inefficient and limited, and thus far HEV has been cultured only in human cell lines. The HEV strain Kernow-C1 (genotype 3) isolated from a chronically infected patient was used to identify human, pig, and deer cell lines permissive for infection. Cross-species infections by genotypes 1 and 3 were studied with this set of cultures. Adaptation of the Kernow-C1 strain to growth in human hepatoma cells selected for a rare virus recombinant that contained an insertion of 174 ribonucleotides (58 amino acids) of a human ribosomal protein gene.

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“…7,24,25,43,45 Tables 3 and 4 7,11,12,[42][43][44][45][46][48][49][50] highlight the sporadic and epidemic studies of HEV induced AVH/ALF reported in pregnant females.…”

Section: Pregnant Females Are More Susceptible To Contract Hepatitis mentioning

confidence: 99%

“…52 Further, certain studies have also documented that However, the above mentioned facts have emanated predominantly from the Indian subcontinent Northern India and Pakistan, Somalia, Sudan and Nepal. 7,11,12,50 The information of HEV and its relation to pregnancy in southern India needs appropriate prospective evaluation.…”

Section: Pregnant Females Are More Susceptible To Contract Hepatitis mentioning

confidence: 99%

“…Hepatitis E related ALF is reported predominantly from developing countries, especially the Indian subcontinent and African countries such as Somalia and Sudan but a few case reports of HEV infection in pregnancy are now being reported from developed countries. 11,12 The important issues in HEV related infection in pregnancy include: a) whether acute viral hepatitis (AVH) is a risk factor for mortality in pregnancy b) increased proneness of pregnant females to contract HEV c) severity of liver disease in these patient subgroups as compared to the rest of the population d) the natural course of HEV-ALF among pregnant females and outcome of pregnancy and fetus in such patients. These issues are addressed in the present review.…”

mentioning

confidence: 99%

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