This chapter primarily focuses on two human viruses as a means to explore the conserved similarities and unique differences of DNA viruses. Human papilloma viruses (HPV) and Kaposi's sarcoma-associated herpes virus (KSHV), also known as human herpesvirus-8, are of particular interest because both viruses are causative agents of several human cancers, and therefore represent a subset of DNA viruses that are highly relevant to human disease. The chapter highlights the common viral themes of all DNA viruses including: members of Geminiviridae, Herpesviridae, Nanoviridae, Papillomaviridae, Poxviridae, Parvoviridae, Polyomaviridae, Adenoviridae and Circoviridae, specifically T4 bacteriophage, various large nucleocytoplasmic large DNA viruses, torque teno virus, Hepatitis B virus, Epstein–Barr virus, pox viruses, Simian virus-40 and variola virus. DNA viruses are everywhere, on animals, plants, soil, and fresh and salt water. KSHV is the most recent of the eight human Herpes viridae known family members to be identified.
Herpesviruses are prevalent throughout the animal kingdom, and they have coexisted and coevolved along with their host species for millions of years. Herpesviruses carry a large (120-230 kb) double-stranded DNA genome surrounded by a protein capsid, a tegument layer consisting of viral and host proteins, and a lipid bilayer envelope with surface glycoproteins. A key characteristic of these viruses is their ability to enter a latent state following primary infection, allowing them to evade the host’s immune system and persist permanently. Herpesviruses can reactivate from their dormant state, usually during times of stress or when the host’s immune responses are impaired. While herpesviruses can cause complications with severe disease in immune-compromised people, most of the population experiences few ill effects from herpesvirus infections. Indeed, herpes simplex virus 1 (HSV-1) in particular has several features that make it an attractive tool for therapeutic gene delivery. Herpes simplex virus 1 targets and infects specific cell types, such as epithelial cells and neurons. The HSV-1 genome can also accommodate large insertions of up to 14 kb. The HSV-1-based vectors have already achieved success for the oncolytic treatment of melanoma. In addition to serving as a vehicle for therapeutic gene delivery and targeted cell lysis, comparative genomics of herpesviruses HSV-1 and 2 has revealed valuable information about the evolutionary history of both viruses and their hosts. This review focuses on the adaptability of HSV-1 as an instrument for gene delivery and an evolutionary marker. Overall, HSV-1 shows great promise as a tool for treating human disease and studying human migration patterns, disease outbreaks, and evolution.
BACKGROUND:Worldwide, approximately 257 million people have chronic hepatitis B virus (HBV) infection, with the highest infection rates recorded in Africa and Asia. Although HBV infection has been associated with dyslipidemia, which may lead to death via liver related complications, the effect of the virus on the lipid profile of patients remain unclear. This study was designed to evaluate the effect of chronic hepatitis B virus infection on lipid profile of sero-positive individuals from Ghana.METHODS:Blood samples were collected from chronic HBV infected patients who were recruited from the Korle-Bu Teaching Hospital, Accra, and HBV sero-negative healthy volunteers who were used as controls. Demographic and clinical data were obtained using a structured questionnaire. Blood pressure and body mass index were determined, and HBV profile markers and lipid profiles of the patients were determined using a commercially available kit and a chemistry analyzer, respectively.RESULTS:Triglycerides, low density lipoproteins (LDL), high density lipoproteins (HDL), very low density lipoproteins (VLDL), and total cholesterol were used as indices of lipid metabolism disorder. Body mass index and diastolic blood pressures were significantly elevated in patients compared to healthy volunteers.CONCLUSION:The observed high total cholesterol and LDL, with a significantly lower HDL levels compared to healthy controls suggest an increased cardiovascular disease risk index in the patients. There is therefore the need to regularly monitor HBV infected patients for signs of cardiovascular diseases.
Filoviruses cause outbreaks which lead to high fatality in humans and non-human primates, thus tagging them as major threats to public health and species conservation. In this review, we give account of index cases responsible for filovirus disease outbreaks that have occurred over the past 52 years in a chronological fashion, by describing the circumstances that led to the outbreaks, and how each of the outbreaks broke out. Since the discovery of Marburg virus and Ebola virus in 1967 and 1976, respectively, more than 40 filovirus disease outbreaks have been reported; majority of which have occurred in Africa. The chronological presentation of this review is to provide a concise overview of filovirus disease outbreaks since the discovery of the viruses, and highlight the patterns in the occurrence of the outbreaks. This review will help researchers to better appreciate the need for surveillance, especially in areas where there have been no filovirus disease outbreaks. We conclude by summarizing some recommendations that have been proposed by health and policy decision makers over the years.
Background: Cytomegalovirus (CMV) infection risk in the first month after transplantation is felt to be minimal; however, the epidemiology has not been specifically investigated, particularly in the modern era of potent immunosuppressive regimens and universal CMV prophylaxis. Objective: The aim of this study was to describe the incidence of and risk factors associated with CMV occurring less than 30 days after transplant and evaluate the effect of very early CMV on outcomes. Methods: Retrospective, single-center study of adult renal transplant (RTX) recipients between January 1, 1994 and December 31, 2014. Results: A total of 5225 patients who received a renal transplant in the study time period were reviewed for the presence of CMV infection occurring less than 30 days after transplant. Of these, only 14 patients demonstrated this finding for an overall incidence of 0.27%. Half of these patients were considered to be at heightened risk due to being a recipient of a non-primary transplant or on chronic immunosuppression. This left seven patients without known risk factors for very early CMV to evaluate. In this group, time from transplant to CMV infection was 13.5 ± 7 days. The majority (57.1%, n = 4) were high-risk serostatus (CMV D+/R−) and occurred in the valganciclovir era (71.4%, n = 5). Lymphocyte-depleting induction predominated (57.1%, n = 4). Average cold ischemic time (CIT) was 19.7 ± 7.7 hours. Three patients had post-operative complications, two required exploratory-laparotomy for hemorrhage. When evaluating outcomes, 43% (n = 3) had subsequent episodes of CMV infection, 28.6% (n = 2) developed rejection, and 28.6% (n = 2) died. Outcomes between patients with CMV infection less than 30 days and those with CMV infection more than 30 days after transplant were not significantly different. Conclusions: In our review of over 5000 kidney transplants, the incidence of CMV infection in the first 30 days after renal transplant is 0.2%. Notable common patient characteristics include hemorrhage requiring re-operation and prolonged CIT. Outcomes were similar to CMV occurring more than 30 days after transplant. This study should provide the clinician with some reassurance; despite potent immunosuppressive therapy, CMV infection in the first 30 days is unlikely.
BACKGROUND:Though measures are being put in place for the management of Hepatitis B virus (HBV) infection in Nigeria, children remain the most vulnerable to develop chronic hepatitis. Routine screening in children is therefore necessary for effective control. However, the performance of the commonly used immunochromatographic test (ICT) strips has been challenging. Also, identifying the risk factors of transmission in this age group is of importance for the implementation of preventive measures. Hence, the goal of this study was to assess the test performance of the routinely used ICT strip and identify the associated clinical manifestations and risk factors of HBV.METHODS:A cross sectional study involving 270 children below six years of age was conducted at ESUTH and Favor Child Pediatrics Hospital in Enugu, Nigeria. The subjects were screened for HBV by ICT and ELISA assays and a structured questionnaire was used to obtain participants data including demographic, socioeconomic, signs and symptoms, risk factors and vaccination.RESULTS:BBased on ELISA, 31 out of 270 children were positive for HBV with an infection rate of 11.5%. ICT kit showed a low sensitivity of 51.6% in diagnosing HBV but was highly specific (100%) and accurate (94.4%). HBV infection was not associated with sex (χ2: 0.209; p = 0.401). The prevalence of HBV infection was similar in all the age group and HBV infection was not associated (χ2: 2.099; p = 0.914) with age group. All the clinical manifestations were not associated (p > 0.05) with HBV infection. Blood transfusion, shared items, tattoo marks and history of surgery associated significantly (p < 0.05) with HBV infections having odd ratios of 4.247, 4.224, 3.134 and 3.195 respectively. The vaccination rate was 55.2% (159/270) and only 3 (1.1%) out of 159 vaccinated subjected contracted the infection (OR: 0.068, p < 0.0001).CONCLUSIONS:HBV was prevalent (11.5%) in children below six years old in Enugu metropolis. Moreover, the routinely used ICT test was less reliable than ELISA in diagnosis HBV infection. More so, shared items, blood transfusion, tattooing and history of surgery were potential risk factors while vaccination served as a protective factor against the infection.
Influenza A virus subtypes are determined based on envelope proteins encoded by the hemagglutinin (HA) gene and the neuraminidase (NA) gene, which are involved in attachment to the host, pathogenicity, and progeny production. Here, we evaluated such differences through co-evolution analysis between the HA and NA genes based on subtype and host. Event-based cophylogeny analysis revealed that humans had higher cospeciation values than avian. In particular, the yearly ML phylogenetic trees for the H1N1 and H3N2 subtypes in humans displayed similar topologies between the two genes in humans. Substitution analysis was verifying the strong positive correlation between the two genes in the H1N1 and H3N2 subtypes in humans compared with those in avian and swine. These results provided a proof of principle for the further development of vaccines according to hosts and subtypes against Influenza A virus.
We investigate the protective effect of combined vaccination based on live attenuated influenza vaccine (LAIV) and group B streptococcus (GBS) recombinant polypeptides against potential pandemic H7N9 influenza infection followed by GBS burden. Mice were intranasally immunized using 107 50% egg infectious dose (EID50) of H7N3 LAIV, the mix of the 4 GBS peptides (group B streptococcus vaccine [GBSV]), or combined LAIV + GBSV vaccine. The LAIV raised serum hemagglutination-inhibition antibodies against H7N9 in higher titers than against H7N3. Combined vaccination provided advantageous protection against infections with A/Shanghai/2/2013(H7N9)CDC-RG influenza and serotype II GBS. Combined vaccine significantly improved bacterial clearance from the lungs after infection compared with other vaccine groups. The smallest lung lesions due to combined LAIV + GBSV vaccination were associated with a prevalence of lung interferon-γ messenger RNA expression. Thus, combined viral and bacterial intranasal immunization using H7N3 LAIV and recombinant bacterial polypeptides induced balanced adaptive immune response, providing protection against potential pandemic influenza H7N9 and bacterial complications.
In 1964, Epstein, Barr, and Achong published a report outlining their discovery of viral particles in lymphoblasts isolated from a patient with Burkitt lymphoma. The Epstein-Barr virus (EBV) was the first human cancer virus to be described, and its discovery paved the way for further investigations into the oncogenic potential of viruses. In the decades following the discovery of EBV, multinational research efforts led to the discovery of further viral causes of various human cancers. Lymphomas are perhaps the cancer type that is most closely associated with oncogenic viruses: infection with EBV, human T-lymphotropic virus 1 (HTLV-1), human immunodeficiency virus (HIV), Kaposi sarcoma-associated herpesvirus/human herpesvirus 8, and hepatitis C virus have all been associated with lymphomagenesis. Lymphomas have also played an important role in the history of oncoviruses, as both the first human oncovirus (EBV) and the first human retrovirus (HTLV-1) were discovered through isolates taken from patients with unique lymphoma syndromes. The history of the discovery of these 2 key oncoviruses is presented here, and their impact on further medical research, using the specific example of HIV research, is briefly discussed.
Dengue disease is an emerging mosquito-borne viral infection transmitted between humans by Aedes spp. that are distributed mainly in the tropical and subtropical region along with chikungunya and zika diseases. The distribution of dengue disease is influenced by local variation, such as geography, rainfall, temperature, and rapid urbanization or migration. The epidemy of mosquito-borne infection significantly led to increased number of cases and hyperendemicity which induce a more severe form of dengue accompanied by cocirculation of chikungunya and zika. The rapid global spreading of dengue disease created public health burdens that are presently unfulfilled by the absence of specific therapy, simple diagnosis tool for the early phase, and effective and efficient vector control system. This review highlights the current situation of dengue distribution, epidemiology, and new strategies for early dengue diagnosis and risk prediction of severity that can be used to improve oversight and alleviate the heavy burden of the disease.
Zika virus (ZIKV) is a mosquito-borne arbovirus from the family Flaviviridae, which had caused some epidemics since its discovery in 1947 without any significant impacts on public health. In 2015, however, a 20-fold increase in congenital microcephaly cases in northeastern Brazil was attributed to prenatally acquired ZIKV infection. Traditionally, TORCH agents have 4 common characteristics including causing a mild illness in infected mother, vertical transmission to fetus, developing several anomalies in the affected fetus, and in some instances, maternal therapy may not ameliorate fetal prognosis. Prenatal ZIKV infection has shown the aforementioned characteristics during the recent epidemics in South America and the Caribbean region; therefore, it should be considered as an emerging TORCH agent that may seriously threaten public health. Fetal ultrasound can be used as a safe, inexpensive, and easy-to-access imaging modality for detecting suspicious cases of congenital Zika syndrome in utero and suggesting confirmatory diagnostic examinations to these patients.
Background: Threat to blood transfusion–transmitted dengue virus (DENV) and its antibodies has recently emerged worldwide. Dengue fever is an endemic disease in Saudi Arabia, particularly in its Western region. The aim of this study was to estimate the seroprevalence of asymptomatic DENV infection and its antibodies among eligible Saudi blood donors. Methods: Serum samples from 910 healthy/eligible adult male Saudi blood donors, who reside in Holy Makkah City of Saudi Arabia, were collected between March 2015 and August 2016 and screened for the detection of DENV nonstructural protein 1 (NS1) antigen and anti-DENV IgM and IgG antibodies using commercial enzyme-linked immunosorbent assay kits (Panbio, Brisbane, QLD, Australia). Results: Among the tested donors, 48 (5.3%) were seropositive for DENV-NS1 antigen, whereas 50 (5.5%) and 354 (38.9%) were seropositive for anti-DENV IgM and IgG antibodies, respectively. Seropositivity for DENV-NS1 antigen and/or anti-DENV IgM antibody among the tested donors reflects their ongoing asymptomatic viremic infectious stage with DENV during their donation time, whereas high prevalence of anti-DENV IgG seropositivity reflects the high endemicity of dengue disease in this region of Saudi Arabia. Conclusions: These results show high prevalence of asymptomatic DENV infection and its antibodies among Saudi blood donors, raising the importance of establishing blood screening for dengue disease at different blood donation services and units in Saudi Arabia to improve the guarantee of blood transfusions and to control DENV dissemination.
About 40 years ago, the large and small tumor antigens (LT-Ag and sT-Ag) of the polyomavirus (PyVs) simian vacuolating virus 40 have been identified and characterized. To date, it is well known that all the discovered human PyVs (HPyVs) encode these 2 multifunctional and tumorigenic proteins, expressed at viral replication early stage. The 2 T-Ags are able to transform cells both in vitro and in vivo and seem to play a distinct role in the pathogenesis of some tumors in humans. In addition, they are involved in viral DNA replication, transcription, and virion assembly. This short review focuses on the structural and functional features of the HPyVs' LT-Ag and sT-Ag, with special attention to their transforming properties.
Malaria and hepatitis C virus (HCV) infections are very common causes of human suffering with overlapping global geographic distributions. With the growing incidence of HCV infections in malaria-endemic zones and malaria in areas with exceptionally high HCV prevalence, coinfections and syndemism of both pathogens are likely to occur. However, studies of malaria and HCV coinfections are very rare despite the fact that liver-stage plasmodiasis and hepatitis C develop in hepatocytes which may synergistically interact. The fact that both pathogens share similar entry molecules or receptors in early invasive steps of hepatocytes further makes hepatopathologic investigations of coinfected hosts greatly important. This review sought to emphasize the public health significance of malaria/HCV coinfections and elucidate the mechanisms of pathogens’ entrance and invasion of susceptible host to improve on existing or develop antiplasmodial drugs and hepatitis C therapeutics that can intervene at appropriate stages of pathogens’ life cycles.
BACKGROUND:Although virologically confirmed dengue fever has been recognized in Jeddah, Saudi Arabia, since 1994, causing yearly outbreaks, no proper seroepidemiologic studies on dengue virus have been conducted in this region. Such studies can define the extent of infection by this virus and estimate the proportion that may result in disease. The aim of this study was to measure the seroprevalence of past dengue virus infection in healthy Saudi nationals from different areas in the city of Jeddah and to investigate demographic and environmental factors that may increase exposure to infection.METHODS:Sera were collected from 1984 Saudi subjects attending primary health care centers in six districts of Jeddah. These included general patients of various ages seeking routine vaccinations, antenatal care or treatment of different illnesses excluding fever or suspected dengue. A number of blood donors were also tested. Serum samples were tested by enzyme immunoassay (EIA) for IgG antibodies to dengue viruses 1, 2, 3, 4. A questionnaire was completed for each patient recording various anthropometric data and factors that may indicate possible risk of exposure to mosquito bites and dengue infection. Patients with missing data and those who reported a history of dengue fever were excluded from analysis, resulting in a sample of 1939 patients to be analyzed.RESULTS:The overall prevalence of dengue virus infection as measured by anti-dengue IgG antibodies from asymptomatic residents in Jeddah was 47.8% (927/1939) and 37% (68/184) in blood donors. Infection mostly did not result in recognizable disease, as only 19 of 1956 subjects with complete information (0.1%) reported having dengue fever in the past. Anti dengue seropositivity increased with age and was higher in males than females and in residents of communal housing and multistory buildings than in villas. One of the six districts showed significant increase in exposure rate as compared to the others. Availability of public sewage was associated with lower infection at a nearly significant level. No other clear risk factors were identifiable. Infection was not related to travel abroad.CONCLUSIONS:Our results indicate a relatively high exposure of Jeddah residents to infection by dengue viruses, which must be considered endemic to this region. Infection largely remained asymptomatic or was only associated with minor illness for which patients did not seek treatment. These results call for continued vigilance for clinical cases of dengue that may arise from this wide exposure. They also call for more extensive control efforts to reduce exposure to and transmission of dengue viruses.
Hepatitis B and C are serious public health problems worldwide. Thalassemia patients are dependent on blood transfusions throughout their life and are at high risk of viral infections. The aim of this study was to estimate the prevalence of hepatitis B/C infections and different clinical parameters in multitransfused thalassemia population. In this study, 262 multitransfused β-thalassemia patients were enrolled from the capital twin cities of Pakistan. The presence of hepatitis B virus (HBV)/hepatitis C virus (HCV), alanine aminotransferase (ALT) level, serum creatinine, serum ferritin, hepatomegaly, splenomegaly, and splenectomy were analyzed. The overall prevalence of HBV and HCV was 3.08% and 55.73%, respectively, with 100% of patients older than 20 years had HCV infection. The ALT levels among HBV- and HCV-positive thalassemia patients were 92.62 ± 41.57 U/L and 98 ± 63.65 U/L, respectively; creatinine values observed were 0.4 ± 0.35 mg/dL (for HBV) and 0.39 ± 0.24 mg/dL (for HCV), while serum ferritin levels were 6865.87 ± 1649.13 ng/dL (for HBV) and 5445.95 ± 3059.28 ng/dL (for HCV). A total of 74.8% and 82.20% of HBV- and HCV-positive patients had hepatomegaly with an average increase in liver size of 4.17 and 4.33 cm, respectively. Splenomegaly was observed in 64.9% and 67.12% of HBV- and HCV-positive patients with an average increase in spleen size of 4 and 4.46 cm, respectively. Splenectomy was observed among 14.50% and 15.75% of HBV- and HCV-infected thalassemia patients. There is a strong need to properly screen blood before transfusions to reduce the future load of viral hepatitis from Pakistan.
Hepatitis C virus (HCV) infection is a major health problem recognized globally. HCV is a common cause of liver fibrosis that may lead to liver cirrhosis or hepatocellular carcinoma. The aim of this study was to estimate the prevalence of HCV infection and genotyping among Egyptian and Saudi Arabian chronic patients using different molecular techniques. HCV RNA viral load was assessed by real-time polymerase chain reaction (RT-PCR) technology. For HCV genotyping, RT-PCR hybridization fluorescence-based method and reverse hybridization line probe assay (INNO-LiPA) were used. A total of 40 anti-HCV-positive patients with chronic hepatitis C were examined for HCV RNA, genotyping, and different laboratory investigations. In the present study, HCV genotypes 4, mixed 4.1b, and 1 were detected in patients of both countries, while genotype 2 was only detected in Saudi Arabian patients. Genotyping methods for HCV showed no difference in the classification at the genotype level. With regard to HCV subtypes, INNO-LiPA assay was a reliable test in HCV genotyping for the detection of major genotypes and subtypes, while RT-PCR-based assay was a good test at the genotype level only. HCV genotype 4 was found to be the predominant genotype among Egyptian and Saudi Arabian chronic patients. In conclusion, data analysis for detecting and genotyping HCV was an important factor for understanding the epidemiology and treatment strategies of HCV among Egyptian and Saudi Arabian chronic patients.
Background Individuals with human T-cell lymphotrophic virus type-1 (HTLV-1)/HIV-1 coinfection have been demonstrated to undergo CD4+ lymphocytosis even in the face of immunodeficiency and increased vulnerability to opportunistic pathogens that can lead to poor prognosis. Objective This study investigated the prevalence as well as the effects of HIV-1/HTLV-1 coinfection on CD4+ cell counts, routine hematology, and biochemical parameters of study participants. Materials and Methods This prospective cross-sectional study involved 184 blood samples collected from HIV-1-seropositive individuals attending HIV-special clinic of the University of Abuja Teaching Hospital, Gwagwalada, Nigeria. These samples were analyzed for anti-HTLV-1/2 IgM antibodies using enzyme-linked immunosorbent assay, CD4+ cell counts, and some routine hematological and biochemical parameters. All samples were also tested for HTLV-1 provirus DNA using real-time polymerase chain reaction (PCR) assay. Results Of the 184 subjects studied, 9 (4.9%) were anti-HTLV-1/2 IgM seropositive; however, upon real-time PCR testing, 12 (6.5%) had detectable HTLV-1 provirus DNA. The CD4+ cell count was significantly high in HTLV-1-positive (742 ± 40.2) subjects compared to their HTLV-1-negative (380 ± 28.5) counterpart (P-value = 0.025). However, there was no significant association between HTLV-1 positivity with other hematology and biochemical parameters studied (P > 0.05). Conclusion All subjects (100%) who were HTLV-1/HIV-1-coinfected had normal CD4+ counts. This gives contrasting finding on the true extent of immunodeficiency of subjects. So it is suggested to be very careful in using only CD4+ counts to monitor disease progression and as indicators for antiretroviral therapy (ART) in resource-limited settings. In such conditions, there may be a need to test for HTLV-1 alongside HIV viral loads in order to begin appropriate ART regimens that contain both pathogens.
Almost 7 million children under the age 5 die each year, and most of these deaths are attributable to vaccine-preventable infections. Young infants respond poorly to infections and vaccines. In particular, dendritic cells secrete less IL-12 and IL-18, CD8pos T cells and NK cells have defective cytolysis and cytokine production, and CD4pos T cell responses tend to bias towards a Th2 phenotype and promotion of regulatory T cells (Tregs). The basis for these differences is not well understood and may be in part explained by epigenetic differences, as well as immaturity of the infant's immune system. Here we present a third possibility, which involves active suppression by immune regulatory cells and place in context the immune suppressive pathways of mesenchymal stromal cells (MSC), myeloid-derived suppressor cells (MDSC), CD5pos B cells, and Tregs. The immune pathways that these immune regulatory cells inhibit are similar to those that are defective in the infant. Therefore, the immune deficiencies seen in infants could be explained, in part, by active suppressive cells, indicating potential new avenues for intervention.
A cross-sectional study in Nigeria was undertaken to determine the epidemiology, seroprevalence, and associated risk factors, of hepatitis E virus (HEV). A total of 462 subjects were used for the study, categorized into four groups: apparently healthy persons, pregnant women, HIV positive subjects, and animal handlers. Information was obtained from subjects using interviewer-administered questionnaire. Blood samples were collected and analyzed for HEV antibodies (IgG and IgM) using enzyme-linked immunosorbent assay (ELISA) technique. Results obtained were analyzed using Statistical Package for Social Sciences (SPSS) version 17.0 statistical software. The overall seroprevalence of IgG and IgM was 42.7 and 0.9%, respectively. Animal handlers had the highest seroprevalence (66.7%). The associated risk factors for IgM seroprevalence were rural dwelling (P = 0.039, odds ratio (OR) 3.3, 95% confidence interval (CI) 0.7–15.4), blood transfusion (P < 0.001, OR 9.6, 95% CI 2.6–35.6), attending to animals (P = 0.032, OR 4.9, 95% CI 0.9–26.6), and waste disposal (P < 0.001). Factors associated with IgG were age (P = 0.044), location (P < 0.001), marital status (P < 0.001), formal education (P < 0.001), farming as occupation (P < 0.001), rural dwelling (P = 0.001), waste disposal (P < 0.001), alcohol consumption (P = 0.001, OR 2.4, 95% CI 1.4–4.0), open defecation (P < 0.001, OR 2.9, 95% CI 1.4–5.7), attending to animals (P < 0.001, OR 2.3, 95% CI 1.6–3.4), consuming unwashed fruits/vegetables (P < 0.001, OR 4.2, 95% CI 0.3–54.1), and stream/river as a source of drinking water (P < 0.001, OR 3.6, 95% CI 1.6–7.8). Preventive public health measures should be reinforced among all communities, particularly domestic animal handlers and pregnant women. Potable water should be provided for all communities. Data suggest that HEV remains an under-recognized and significant public health problem, warranting further attention and research.
