Hepatitis E in Pregnant Women and the Potential Use of HEV Vaccine to Prevent Maternal Infection and Mortality

Purpose of Review Hepatitis E (HEV) is a continuing public health problem in developing countries, causing high mortality in pregnant women. This article reviews the latest knowledge on HEV in pregnancy, the vaccine candidates that have reached clinical trials, and their potential use during pregnancy. Recent Findings New evidence suggests that a genotype-specific tropism to uteroplacental cells contributes to the multifactorial pathology leading to the increased severity of HEV during pregnancy. Data from pregnant women inadvertently vaccinated are limited but show similar rates of adverse events as non-pregnant women, and no evident harm to newborns. Protective anti-HEV IgG antibodies are estimated to last longer after vaccination than natural infection. Accelerated vaccination appears safe and provides protective antibodies similar to a normal dosing regimen. Summary HEV239 is the most extensively studied vaccine and has been shown to be safe and effective, but more data are needed to recommend use of this vaccine on a global basis. Further studies should focus on safety and efficacy in pregnant women, and evaluate a shorter two-dose regime, which is highly warranted in outbreak situations

Hepatitis E Virus (HEV) Synopsis: General Aspects and Focus on Bangladesh

HEV is the most common cause of acute hepatitis globally. This review summarizes the latest knowledge on the epidemiology, clinical characteristics, testing, and treatment of HEV infection. We also focused on Bangladesh to highlight the distinct challenges and the possible remedies. In low-income settings, the virus is mainly transmitted between people by fecal contamination of drinking water causing large outbreaks, and sporadic cases. The disease is usually mild and self-limiting acute hepatitis. Still, pregnant women and their offspring in low-income countries are at particular risk for severe disease, with up to 20% maternal mortality. Despite the high burden of the disease, HEV remains a relatively neglected virus, with detection hampered by costly tests and a lack of suitable treatments. Molecular PCR diagnostics, together with ELISA antibody tests, remain the preferred methods for diagnosis of HEV; however, rapid bedside diagnostics are available and could offer a practical alternative, especially in low-income countries. One vaccine (HEV 239) is only available in China and Pakistan, as efficacy against the other genotypes remains uncertain. The effectiveness trial conducted in Bangladesh might lead the way in gathering more efficacy data and could, together with improved surveillance and raised awareness, dramatically reduce the global burden of HEV

Stability and Feasibility of Dried Blood Spots for Hepatitis E Virus Serology in a Rural Setting

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. In many low-income countries it causes large outbreaks and disproportionally affects pregnant women and their offspring. Surveillance studies to find effective preventive interventions are needed but are hampered by the lack of funding and infrastructure. Dried blood spots (DBS) offer an easier and more robust way to collect, transport, and store blood samples compared to plasma/serum samples, and could ease some of the barriers for such studies. In this study we optimize an HEV IgG ELISA for DBS samples and validate it on 300 paired DBS and plasma samples collected in rural areas of Bangladesh from participants in a HEV vaccine study. We demonstrate that HEV IgG in blood stored as DBS is stable for two months at up to 40 °C, and for five freeze-thaw cycles. The specificity was 97% and the overall sensitivity of the DBS assay was 81%. The sensitivity was higher in samples from vaccinated participants (100%) compared to previously infected participants (59%), reflecting a positive correlation between IgG titer and sensitivity. We found a strong correlation between DBS and plasma samples with an r2 of 0.90, but with a higher degree of difference between individual paired samples. Our study shows that DBS offers a stable alternative to plasma/serum for HEV IgG measurements and can facilitate serological studies, particularly in resource limited areas