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Fulltext A systematic review of the epidemiology of Hepatitis E virus infection in South - Eastern Asia

Raji YE, Toung OP, Mohd Taib N, Sekawi ZB

Virulence, 2021 12;12(1):114-129.
PMID: 33372843 DOI: 10.1080/21505594.2020.1865716

Hepatitis E virus (HEV) infection is an emerging zoonotic viral disease, with an increasingly international public health challenge. Despite the concerns that the global disease burden may be underestimated. Therefore, evaluation of the disease epidemiology in South - eastern Asia through a systematic review will assist in unraveling the burden of the disease in the subregion. A priori protocol was prepared for the systematic review and followed by a literature search involving five electronic databases. Identified publications were screened for high quality studies and the elimination of bias and relevant data extracted. A total of 4157 citations were captured, and only 35 were included in the review. A wide range of HEV seroprevalence was recorded from 2% (urban blood donors in Malaysia) to 77.7% (lowland communities in Lao PDR). Sporadic HEV infection and epidemics were also detected in the subregion. Indicating hyperendemicity of the disease in South - eastern Asia.

Matched MeSH terms: Hepatitis E/immunology; Hepatitis E/epidemiology*; Hepatitis E/transmission; Hepatitis E/virology; Hepatitis E virus/immunology; Hepatitis E virus/pathogenicity
Meta-analysis and moderator analysis of the seroprevalence of hepatitis E in South-Eastern Asia

Raji YE, Toung OP, Taib NM, Sekawi ZB

Sci Rep, 2023 Jul 23;13(1):11880.
PMID: 37482578 DOI: 10.1038/s41598-023-37941-0

By 2030, the World Health Organization wants to decrease viral hepatitis incidence and mortality by 90% and 65%, respectively. One of the agents responsible for the increased burden of viral hepatitis is the hepatitis E virus (HEV). This emerging pathogen is prevalent worldwide causing both acute and chronic infection. The rising risk profile of HEV has become a source of increased global public health concern. Despite this challenge, South-Eastern Asia (SEA), where many at-risk people are found, lacks uniform HEV prevalence data. Therefore, a meta-analysis was conducted to assess the overall prevalence of hepatitis E in SEA. Using R statistical software, a random effect model was used to estimate the logit-transformed prevalence. Moderator analyses were used to investigate the potential sources of variation. Thirty-two studies comprising 29,944 with 6806 anti-HEV antibody-positive individuals were evaluated. The overall HEV seroprevalence in SEA was 21% (95% confidence interval [CI]: 17-27) with high heterogeneity. At the country level, Laos has the highest prevalence estimate of 39% (CI: 16-69). Also, the studied population, year of publication, duration of sampling, and diagnostic method are significant HEV prevalence predictors accounting for 22.61% of the observed heterogeneity. The high HEV prevalence found in this study necessitates coordinated national and regional efforts to combat this emerging disease.

Matched MeSH terms: Hepatitis E virus*
Fulltext Awareness, knowledge, disease prevention practices, and immunization attitude of hepatitis E virus among food handlers in Klang Valley, Malaysia

Rajendiran S, Li Ping W, Veloo Y, Syed Abu Thahir S

Hum Vaccin Immunother, 2024 Dec 31;20(1):2318133.
PMID: 38433096 DOI: 10.1080/21645515.2024.2318133

Concern about the zoonotic Hepatitis E virus (HEV) is rising. Since, food handlers are at greater risk in contracting HEV, the present study aims to determine awareness, knowledge, prevention practices against HEV, and immunization attitudes. A cross sectional study was conducted among 400 food handlers in Klang Valley, Malaysia from December 2021 to March 2022. A structured questionnaire was employed for data collection and analysis with Statistical Package for Social Science (SPSS) version 29. Approximately 4.5% of the respondents (18) reported having heard of HEV, while the median scores for the knowledge and practice domains were 0/10 and 1/5, respectively. A total of 316 (79%) respondents expressed willingness to obtain vaccination if made available. This study also found that those respondents who completed their tertiary education were significantly possessed better knowledge of the disease [odd ratio (OR) = 8.95, and 95% confidence interval (CI) 4.98-16.10]. Respondents with HEV awareness reported considerably better practices (OR = 8.24, 95% CI 1.72-39.63). Food handlers with one to five years of experience in the industry expressed notable willingness to take vaccination (OR = 7.71, 95% CI 1.79-33.18). Addressing poor HEV awareness and knowledge and poor practices against the disease is crucial in enlightening the policy makers about awareness among food handlers and general population. Nonetheless, a good immunization attitude, significant acceptance toward vaccination even with the vaccine being unavailable in Malaysia, and limited awareness of HEV highlight a promising development.

Matched MeSH terms: Hepatitis E virus*
Hepatitis C and hepatitis E vaccines: research update

Locarnini S

Med J Malaysia, 2005 Jul;60 Suppl B:116-24.
PMID: 16108191
Matched MeSH terms: Hepatitis E/immunology; Hepatitis E/prevention & control*
Electrochemical DNA detection of hepatitis E virus genotype 3 using PbS quantum dot labelling

Ngo DB, Chaibun T, Yin LS, Lertanantawong B, Surareungchai W

Anal Bioanal Chem, 2021 Feb;413(4):1027-1037.
PMID: 33236225 DOI: 10.1007/s00216-020-03061-1

The aim of this study was to develop a highly specific electrochemical DNA sensor using functionalized lead sulphide (PbS) quantum dots for hepatitis E virus genotype 3 (HEV3) DNA target detection. Functionalized-PbS quantum dots (QDs) were used as an electrochemical label for the detection of HEV3-DNA target by the technique of square wave anodic stripping voltammetry (SWASV). The functionalized-PbS quantum dots were characterized by UV-vis, FTIR, XRD, TEM and zeta potential techniques. As-prepared, functionalized-PbS quantum dots have an average size of 4.15 ± 1.35 nm. The detection platform exhibited LOD and LOQ values of 1.23 fM and 2.11 fM, respectively. HEV3-DNA target spiked serum is also reported.Graphical abstract.

Matched MeSH terms: Hepatitis E/blood; Hepatitis E/virology*; Hepatitis E virus/genetics; Hepatitis E virus/isolation & purification*
Optimization and Implementation of the Virus Extraction Method for Hepatitis E Virus Detection from Raw Pork Liver

Zhao MY, Li D

Food Environ Virol, 2021 03;13(1):74-83.
PMID: 33449335 DOI: 10.1007/s12560-020-09452-y

Hepatitis E virus (HEV) has been frequently detected from pork liver and liver products, which can usually cause self-limiting diseases in healthy adults, yet may result in fatality in immunosuppressed groups. Nevertheless, there is so far no standardized method for HEV detection available from pork liver and/or liver products. The present study aimed to optimize the virus extraction method of HEV from raw pork liver, which is often consumed in Asia undercooked to avoid a grainy texture. By comparing different sample preparation protocols and by applying the selected protocol to 60 samples collected from Singapore retail markets, we demonstrated that homogenization of 0.25 g raw pork liver with FastPrep™ Lysing Matrix Y containing yttria-stabilized zircondium oxide beads in 2 ml tubes and with harsh mechanical force at 6 ms-1, 40 s/cycle, for 5 cycles with 300 s pause time after each cycle is promising in both releasing the potentially intracellular viruses and resulting in satisfactory virus recovery rates (> 1%). A high prevalence (52%) of HEV genome was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) from the 60 samples collected from Singapore retail markets imported from Indonesia, Australia and Malaysia. However, RNase treatment decreased the HEV prevalence to 33.3%, and all of the 20 positive samples were with high RT-qPCR Ct values above 35, suggesting that the positive RT-qPCR signals maybe largely due to the inactive viruses and/or exposed HEV RNA traces in raw pork liver products. Therefore, conscious care should be taken when interpreting molecular detection results of viruses from food samples to be correlated with public health risks.

Matched MeSH terms: Hepatitis E/virology; Hepatitis E virus/classification; Hepatitis E virus/genetics; Hepatitis E virus/isolation & purification*
Fulltext Acute Non-Fulminant Viral Hepatitis E Presenting with Acute Pancreatitis-An Unusual Presentation

Thakur A, Basu PP

Malays J Med Sci, 2017 Aug;24(4):102-105.
PMID: 28951695 DOI: 10.21315/mjms2017.24.4.12

Acute pancreatitis is considered to be an extremely rare extrahepatic manifestation of acute viral hepatitis E. The incidence is reported to be around 5%-6% in the available case series. It has usually been reported in non-fulminant cases of acute viral hepatitis E in the second or third week of illness, with a favourable outcome. Here, we report the case of a young male subject with acute viral hepatitis E presenting as acute pancreatitis at its onset and exhibiting a prolonged recovery phase. To the authors' knowledge, such a presentation of acute viral hepatitis E as acute pancreatitis at its inception has been only sparsely reported in the available literature.

Matched MeSH terms: Hepatitis E
The study of seroprevalence of hepatitis E virus and an investigation into the lifestyle behaviours of the aborigines in Malaysia

Wong LP, Alias H, Choy SH, Goh XT, Lee SC, Lim YAL, et al.

Zoonoses Public Health, 2020 05;67(3):263-270.
PMID: 31927794 DOI: 10.1111/zph.12681

Malaysia is a non-endemic country for hepatitis E virus (HEV) infection. However, seroprevalence as high as 50% among samples of aboriginal people were reported over two decades ago. A total of 207 samples collected from seven aboriginal villages in rural settlements across two states in Malaysia were analysed for anti-HEV IgG and IgM by an enzyme-linked immunoassay. Following the detection of anti-HEV seroprevalence, we organized health outreach to inform and educate the community. Qualitative interviews were conducted with individuals tested positive for anti-HEV antibodies. Data derived from interviews and observations were used to investigate possible lifestyle behaviours associated with HEV infection. Anti-HEV IgG was detected in six samples (5.9%) from the village of Dusun Kubur. Qualitative inquiry and observation study revealed poor dietary and household hygiene, contaminated food and water, contact with animal faeces, unsanitary and domestic waste disposal, and wildlife reservoirs could be the contributing factors for transmission and acquisition of HEV infection. Investigation during health outreach is important to provide insights for future empirical research and implementation for improvement of lifestyle behaviours among the aborigines. Managing the risk of HEV infection in the aborigines may reduce the risk of HEV transmission to the local communities.

Matched MeSH terms: Hepatitis E/epidemiology*; Hepatitis E/virology*; Hepatitis E virus/isolation & purification*
Seroprevalence of antibodies to hepatitis E virus in the normal blood donor population and two aboriginal communities in Malaysia

Seow HF, Mahomed NM, Mak JW, Riddell MA, Li F, Anderson DA

J Med Virol, 1999 Oct;59(2):164-8.
PMID: 10459151

The prevalence of antibodies to hepatitis E virus (HEV) has been examined in many countries, but such studies have generally been limited to majority populations such as those represented in healthy blood donors or cross sections of urban populations. Due to its major route of enteric transmission, large differences in HEV prevalence might be expected between populations in the same country but with different living conditions. Using an ELISA based on GST-ORF2.1 antigen, the prevalence of IgG-class antibodies to HEV was examined in three distinct populations in Malaysia: the normal (urban) blood donor population and two aboriginal communities located at Betau, Pahang and Parit Tanjung, Perak. IgG anti-HEV was detected in 45 (44%) of 102 samples from Betau and 15 (50%) of 30 samples from Parit Tanjung, compared to only 2 (2%) of 100 normal blood donors. The distribution of sample ELISA reactivities was also consistent with ongoing sporadic infection in the aboriginal communities, while there was no significant relationship between HEV exposure and age, sex, or malaria infection. The high prevalence of antibodies to HEV in the two aboriginal communities indicates that this group of people are at high risk of exposure to HEV compared to the general blood donors, and the results suggest that studies of HEV seroprevalence within countries must take into account the possibility of widely varying infection rates between populations with marked differences in living conditions.

Matched MeSH terms: Hepatitis E/blood; Hepatitis E/ethnology; Hepatitis E/immunology*; Hepatitis E virus/immunology*
Fulltext A seroprevalence study of viral hepatitis E infection in human immunodeficiency virus type 1 infected subjects in Malaysia

Ng KP, He J, Saw TL, Lyles CM

Med J Malaysia, 2000 Mar;55(1):58-64.
PMID: 11072492 MyJurnal

Hepatitis E virus (HEV) is a RNA virus transmitted enterically. A study of anti-HEV antibodies in 145 human immunodeficiency virus type 1 (HIV-1) infected subjects found that 14.4% of them were reactive to anti-HEV antibodies. Anti-HEV IgG and anti-HEV IgM was detected in 10.3% and 4.1% of the subjects respectively. Prevalence of anti-HEV (either IgG or IgM) was similar across all adult ages (p = 0.154), between the three ethnic groups (p = 0.378), and across risk groups (p = 0.120). The results showed that HEV infection in subjects recruited in this study was most likely transmitted via faecal-route.

Matched MeSH terms: Hepatitis E/immunology*
Target Induced-DNA strand displacement reaction using gold nanoparticle labeling for hepatitis E virus detection

Ngamdee T, Yin LS, Vongpunsawad S, Poovorawan Y, Surareungchai W, Lertanantawong B

Anal Chim Acta, 2020 Oct 16;1134:10-17.
PMID: 33059855 DOI: 10.1016/j.aca.2020.08.018

DNA strand displacement is an attractive, enzyme-free target hybridization strategy for nano-biosensing. The target DNA induces a strand displacement reaction by replacing the pre-hybridized strand that is labeled with gold nanoparticles (AuNPs). Thus, the amount of displaced-AuNP-labeled strand is proportional to the amount of target DNA in the sample. The use of a magnetogenosensing technique to isolate the target DNA allows for a simple, one-pot detection approach, which minimizes possible carry-over contamination and pipetting errors. We sought a proof-of-concept for this technology in its ability to detect DNA-equivalent of hepatitis E virus (HEV), which causes acute viral hepatitis for which rapid and simple diagnostic methods remain limited. Signal detection was done via visual observation, spectrophotometry, and electrochemistry. The sensor demonstrated good sensitivity with detection limits of 10 pM (visual), 10 pM (spectrophotometry) and 1 fM (electrochemical). This sensor also exhibited high specificity for real target amplicons and could discriminate between perfect and mismatched sequences. Lyophilized biosensor reagents stored at 4 °C, 25 °C, and outdoor ambient temperature, were stable for up to 90, 50, and 40 days, respectively. The integration of magnetic separation and target DNA-induced strand displacement reaction in a dry reagent form makes the sensing platform easy-to-use and suitable for field settings.

Matched MeSH terms: Hepatitis E virus*
Fulltext A multi-step pace towards a cure for HIV: kick, kill, and contain

López M

AIDS Rev, 2013 Jul-Sep;15(3):190-1.
PMID: 24002204

The 7th IAS Conference held in July 2013 in Kuala Lumpur, Malaysia, heard about a number of cases of "functional cure" in people who had started antiretroviral therapy soon after HIV infection, including a German case that can now be added to the "Mississippi baby" report presented at CROI 2012 and 14 individuals of the French VISCONTI cohort. All these persons maintained an undetectable viral load after coming off antiretrovirals.

Matched MeSH terms: Hepatitis E/drug therapy*; Hepatitis E/immunology
Fulltext Seroprevalence of enterically transmitted Hepatitis in North West India

Rekha Bachhiwal, Rajni Sharma, Pooja Gupta, Jyotsna Shukla

Journal of Clinical and Health Sciences, 2016;1:29-32.

To ascertain the seroprevalence of enterically transmitted Hepatitis A (HAV) and Hepatitis E (HEV) in cases with acute/subacute hepatitis attending a tertiary care hospital in North West India. Methods: A total of 2936 cases were examined for the presence of current infection with HAV and HEV, determined by demonstration of HAV-IgM and HEV-IgM antibodies using ELISA. Results: Overall seroprevalence for enterically transmitted hepatitis was found to be 24.89%. HAV IgM was present in 7.35% and HEV IgM was present in 17.54% of total cases. HAV infection was predominantly found in pediatric age group while HEV infection was mostly seen among adults. Male preponderance was noted. Enteric hepatitis cases occurred throughout the year. No definitive seasonal pattern was observed. Conclusion: Our data demonstrated high seropositivity of enterically transmitted hepatitis indicating the need for improvement in personal and public hygiene, and development of HEV vaccine

Matched MeSH terms: Hepatitis E; Hepatitis E virus
Fulltext The Risk of Transfusion-Transmitted Hepatitis E Virus: Evidence from Seroprevalence Screening of Blood Donations

Wong LP, Lee HY, Khor CS, Abdul-Jamil J, Alias H, Abu-Amin N, et al.

Indian J Hematol Blood Transfus, 2021 Apr 16.
PMID: 33879981 DOI: 10.1007/s12288-021-01428-7

Throughout the world, there has been growing concern over the risk of hepatitis E virus (HEV) transmission via blood transfusion. The present study screened blood donor samples for anti-HEV immunoglobulin M (IgM) and immunoglobulin G (IgG). The prevalence of HEV infection was assessed on a total of 1,003 archived serum samples obtained from the National Blood Centre, Malaysia. The samples were collected from healthy blood donor from Klang Valley between 2017 and 2018. All samples were tested for IgM and IgG antibodies to HEV using enzyme-linked immunosorbent assays (ELISA). HEV-specific IgG antibodies were detected in 31/1003 (3.1%; 95% confidence interval [CI] 2.1%-4.4%) and IgM in 9/1003 (0.9%; 95% CI 0.4%-1.7%) samples. In bivariate analysis, there was no significant difference in the prevalence of anti-HEV IgG with respect to gender and district of origin. Although not statistically significant, males had higher odds of having anti-HEV IgG than females (odds ratio [OR] = 2.86; 95% CI 0.95-8.64). All anti-HEV IgG positive individuals were people of Chinese descent. Anti-HEV IgG increased significantly with age, from 0.6% (95% CI 0.1%-2.6%) of 18-30-year-old donors to 7.4% (95% CI 2.7%-17.0%) of donors older than 50 years and was highest among non-professional workers (5.3%; 95% CI 2.5%-10.5%). Increasing age and a non-professional occupation remained significant predictors for anti-HEV IgG in the multivariable analysis. Screening of blood donations for HEV in Malaysia is important to safeguard the health of transfusion recipients. The higher rates of HEV infection in blood from older donors and donors who are non-professional workers may provide insights into targeted groups for blood screening.

Matched MeSH terms: Hepatitis E; Hepatitis E virus
Fulltext Detection of virus-specific polymeric immunoglobulin A in acute hepatitis A, C, E virus serum samples using novel chimeric secretory component

Mohd Hanafiah K, Garcia ML, Barnes NC, Anderson DA

BMC Res Notes, 2018 Oct 01;11(1):688.
PMID: 30285838 DOI: 10.1186/s13104-018-3799-2

OBJECTIVE: To conduct a proof-of-concept study on preferential binding of polymeric IgA (pIgA) using a novel recombinant rabbit/human chimeric secretory component (cSC) and preliminary assessment of the diagnostic potential of virus-specific pIgA in discriminating acute hepatitis A, E, and C (HAV, HEV, HCV) patients and uninfected controls using an indirect enzyme-linked immunoassay.
RESULTS: cSC binds > 0.06 μg/ml of purified human and mouse pIgA with negligible cross-reactivity against IgM and IgA. Virus-specific pIgA was significantly higher in serum of acute HAV (n = 6) and HEV (n = 12) patients than uninfected samples (HEV: p

Matched MeSH terms: Hepatitis E/blood*
Fulltext Genetic diversity of hepatitis B co-infection with hepatitis C, D and E viruses among Malaysian chronic hepatitis B patients

Hudu SA, Niazlin MT, Nordin SA, Tan SS, Omar H, Shahar H, et al.

Afr Health Sci, 2018 Dec;18(4):1117-1133.
PMID: 30766578 DOI: 10.4314/ahs.v18i4.33

Background: Hepatitis B virus co-infection with other strains of viral hepatitis is associated with increased risk of liver cirrhosis and hepatic decompensation.
Objectives: This is a prevalence study that assessed the genetic diversity of chronic hepatitis B patients and coinfection.
Methods: Chronic hepatitis B patients enrolled in this study were tested for antibodies of other hepatitis viruses using ELISA kits. Patient clinical profiles were collected and partial genes of HBV, HCV, and HEV were amplified, sequenced, and analyzed using phylogenetic analysis. The associations between variables were determined using the chi-squared test.
Results: Of the 82 patients recruited for this study, 53.7% were non-cirrhotic, 22.0% cirrhotic, 20.7% acute flare and 3.7% hepatocellular carcinoma. Majority (58%) of patients had a high level of ALT (≥34 U/L). Sequence analysis showed HBV (63.9%) belonged to genotype B, HEV belonged to genotype 4 while HCV belonged to genotype 3a and the genotypes were found to be significantly associated with the clinical stage of the patients (χ2=56.632; p<0.01). Similarly, Hepatitis B e antigen was also found to be significantly associated with the clinical stage of infection (χ2=51.952; p<0.01).
Conclusion: This study revealed that genetic diversity was found to have a significant impact on the severity of infection.

Matched MeSH terms: Hepatitis E/genetics; Hepatitis E/epidemiology*
Health problems of foreign workers - Microbiological investigations

Ngeow YF, Ng KP, Puthucheary SD, Lam SK

JUMMEC, 2002;7:67-69.

Foreign workers in Malaysia are screened for certain infectious diseases prior to their entry to the country but some escape medical screening and others acquire infection during their stay in the country. The Faculty of Medicine, University of Malaya was commissioned to study the impact of foreign labour on the local health system and, as part of the investigations, 584 foreign workers attending local outpatient clinics were examined for serological evidence of syphilis, HIV infection, viral hepatitis B, C and E, as well as for enteric infections by Salmonella, Shigella and Vibrio cholerae. The results showed that apart from viral hepatitis E, the prevalence rates of the infections looked for were not notably higher than those for the general Malaysian population. The seroprevalence rates obtained were 2.6% for syphilis, 0.2% HIV infection, 3.8% viral hepatitis B, 1.0% viral hepatitis C, 14.4% viral hepatitis E. The detection of HEV IgM in 7.7% of the workers screened indicates that these infections could have been acquired during their stay in Malaysia.

Matched MeSH terms: Hepatitis E
Fulltext MDA5 against enteric viruses through induction of interferon-like response partially via the JAK-STAT cascade

Li Y, Yu P, Qu C, Li P, Li Y, Ma Z, et al.

Antiviral Res, 2020 04;176:104743.
PMID: 32057771 DOI: 10.1016/j.antiviral.2020.104743

Enteric viruses including hepatitis E virus (HEV), human norovirus (HuNV), and rotavirus are causing global health issues. The host interferon (IFN) response constitutes the first-line defense against viral infections. Melanoma Differentiation-Associated protein 5 (MDA5) is an important cytoplasmic receptor sensing viral infection to trigger IFN production, and on the other hand it is also an IFN-stimulated gene (ISG). In this study, we investigated the effects and mode-of-action of MDA5 on the infection of enteric viruses. We found that MDA5 potently inhibited HEV, HuNV and rotavirus replication in multiple cell models. Overexpression of MDA5 induced transcription of important antiviral ISGs through IFN-like response, without triggering of functional IFN production. Interestingly, MDA5 activates the expression and phosphorylation of STAT1, which is a central component of the JAK-STAT cascade and a hallmark of antiviral IFN response. However, genetic silencing of STAT1 or pharmacological inhibition of the JAK-STAT cascade only partially attenuated the induction of ISG transcription and the antiviral function of MDA5. Thus, we have demonstrated that MDA5 effectively inhibits HEV, HuNV and rotavirus replication through provoking a non-canonical IFN-like response, which is partially dependent on JAK-STAT cascade.

Matched MeSH terms: Hepatitis E virus

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