Birendra Prasad Gupta

Phylogenetic study reveals co-circulation of Asian II and Cosmopolitan genotypes of Dengue virus serotype 2 in Nepal during 2013.

The re-emergence of dengue virus in Nepal and the recent widespread disease epidemics of unprecedented magnitude have raised a great public health concern. There are very few reports on Dengue virus (DENV) strains circulating in the country, especially at the molecular phylogenetics level. In this study, clinical samples from an outbreak in Nepal in 2013, which were positive for DENV serotype 2, were characterized by targeted genome sequencing. Envelope protein (E) coding region from fifteen samples were sequenced and compared with DENV-2 sequences of strains from different geographic regions obtained from the GenBank. Compared to the prototype New Guinea C strain, the samples had a total of eleven non-synonymous substitutions in the envelope protein coding region leading to amino acid change at positions 47, 52, 71, 126, 129, 149, 164, 390, 402, 454 and 462. However, none of these sites were found to be positively selected. A major observation was the presence of two distinct genotypes (Cosmopolitan Genotype IVa and Asian II) in the outbreak as seen by the phylogenetic analysis. It gives the first evidence of the introduction of Cosmopolitan Genotype IVa in Nepal. These strains replace the Genotype IVb strains prevalent earlier since 2004. Both genotypes had closer genetic relation to strains from other countries indicating possibility of exotic introduction. The Genotype IVa strain seems to be more adapted in C6/36 mosquito cells as indicated by its marginally increased replication rate than the Asian II strain in in vitro infection kinetics assays. The genotype replacement and co-circulation of two distinct genotypes may have significant consequences in dengue epidemiology and disease dynamics in Nepal in years to come.

Hepatitis E virus outbreak in postearthquake Nepal: is a vaccine really needed?

Dear Editor, The massive earthquakes that hit Nepal on April 25 and May 12, 2015 claimed more than 8500 lives and displaced more than one million people to temporary shelters. During the recovery period, the monsoon season raised the possibility of significant water borne diseases such as bacterial diarrhoea, typhoid, hepatitis E and cholera. Some experts recommended that the HEV239 vaccine should be used to prevent an outbreak of hepatitis E virus (HEV) infections [1]. In the past, there have been several epidemics of HEV in Nepal – in Kathmandu in 1973, 1981–1982, 1987 and 2006–2007 and Biratnagar in 2014 [2–6] – and 310 HEV-infected pregnant women were documented in those epidemics [2–4]. Repeated epidemics of HEV in the Kathmandu valley may be related to the consumption of contaminated drinking water and the periodic migration of nonimmune people from the endemic areas of the country [5]. Following the earthquake, many predicted that the monsoon would be associated with another epidemic of HEV and suggested that immunization should be introduced. Local residents of the Kathmandu valley have a high prevalence of immunity against HEV (78% of people have IgG antibodies against HEV), whereas people from other cities and nearby areas have a much lower prevalence (25%). Although outbreaks of diarrhoeal and other waterborne diseases are frequent in rural hilly areas, outbreaks of HEV have not been documented in this population, and following the earthquake, there were concerns that an outbreak of HEV may develop. Basnyat et al. projected that nearly 2000 pregnant women in disaster-affected areas might acquire HEV infection with mortality of 500 [1]. However, in our opinion, vaccinating pregnant women (comprising less than 5% of the population) would have little value as the remaining 95% of the displaced population would remain at risk of acquiring HEV. The resulting morbidity and mortality could be substantial among the nonimmune population, and we do not believe that it is justified to ignore them. Furthermore, vaccinating 48 000 pregnant women with three doses on the dawn of monsoon would take six months, and this would make the present vaccination campaign ineffective, at a considerable cost. Vaccination against HEV would clearly not protect recipients from other water borne diseases and might provoke a false sense of security. In our view, safe provision of drinking water alone would be the single most important preventive measure and would be likely to prove cost-effective and generalizable to both pregnant and nonpregnant populations. Rapid and extensive campaigns to ensure safe water at household levels would have a profound impact on prevention and control of HEV outbreaks and should be preferred to vaccination, the safety of which has yet to be established in pregnancy.

Re-emergence of dengue virus serotype 2 strains in the 2013 outbreak in Nepal

Background & objectives: Epidemiological interventions and mosquito control are the available measures for dengue control. The former approach uses serotype and genetic information on the circulating virus strains. Dengue has been frequently reported from Nepal, but this information is mostly lacking. The present study was done to generate a comprehensive clinical and virological picture of a dengue outbreak in Nepal during 2013. Methods: A hospital-based study involving patients from five districts of Nepal was carried out. Demographic information, clinical details and dengue serological status were obtained. Viral RNA was characterized at the molecular level by reverse-transcription polymerase chain reaction (RT-PCR), nucleotide sequencing and phylogenetic analysis. Results: From among the 2340 laboratory-confirmed dengue cases during the study period, 198 patients consented for the study. Clinically they had fever (100%), headache (59.1%), rashes (18.2%), retro-orbital pain (30.3%), vomiting (15.1%), joint pain (28.8%) and thrombocytopenia (74.3%). Fifteen (7.5%) of them had mucosal bleeding manifestations, and the rest were uncomplicated dengue fever. The patients were mostly adults with a mean age of 45.75 ± 38.61 yr. Of the 52 acute serum samples tested, 15 were positive in RT-PCR. The causative virus was identified as DENV serotype 2 belonging to the Cosmopolitan genotype. Interpretations & conclusions: We report here the involvement of DENV serotype 2 in an outbreak in Nepal in 2013. Earlier outbreaks in the region in 2010 were attributed to serotype 1 virus. As serotype shifts are frequently associated with secondary infections and severe disease, there is a need for enhancing surveillance especially in the monsoon and post-monsoon periods to prevent large-scale, severe dengue outbreaks in the region.

Dengue virus infection in a French traveller to the hilly region of Nepal in 2015: a case report

BackgroundDengue viral infections are known to pose a significant risk during travel to tropical regions, but it is surprising to find dengue transmission in the hilly region of Nepal, which is over 1800mtr above sea level.Case presentationA 43-year-old Caucasian female traveler from France presented with fever and abdominal pain following a diarrheal illness while visiting the central hilly region of Nepal. Over the course of 9 days, she developed fever, body aches, and joint pain, with hemorrhagic manifestation. She was hospitalized in India and treated with supportive care, with daily monitoring of her platelets. An assessment by enzyme-linked immunosorbent assay showed that she was positive for dengue non-structural protein 1. Upon her return to France, dengue virus was confirmed by reverse transcriptase-polymerase chain reaction.ConclusionThe district where this dengue case was reported is in the hilly region of Nepal, neighboring the capital city Kathmandu. To the best of our knowledge, there has previously been no dengue cases reported from the district. This study is important because it aims to establish a potential region of dengue virus circulation not only in the tropics, but also in the subtropics as well, which in Nepal may exceed elevations of 1800mtr. This recent case report has raised alarm among concerned health personnel, researchers, and organizations that this infectious disease is now on the way to becoming established in a temperate climate.

Dengue periodic outbreaks and epidemiological trends in Nepal

Dengue is a global health problem and expansion of its endemics towards new territories in the hilly regions in Nepal is a serious concern. It appeared as a new disease in Nepal in 2004 from Japanese traveler with sporadic cases every year and massive outbreaks in 2010, 2013 and 2016. The serotype was responsible for outbreak in particular year was dengue virus serotype-1 (DENV-1) in 2010, 2016; and DENV-2 in 2013. Nepal lacks basic health related infrastructure in rural areas and does not have a stringent health care policy. With severances of epidemic like dengue, a new surveillance or an upgrading of existing one are direly needed to better challenge the possible outbreaks. This review paper aims to explain the dengue trend in last one decade in Nepal and warrants concerted and timely public health interventions to minimize the deleterious effects of the disease.

Current Treatment of Acute and Chronic Hepatitis E Virus Infection: Role of Antivirals

Hepatitis E virus (HEV) infection results in nearly 20 million new infections, resulting in 70,000 deaths globally each year. Previously thought as a disease limited to developing nations with poor sanitation and hygiene, it is increasingly recognized that even the most developed nations are not spared. A clear dichotomy in epidemiology of HEV is noted between developing and industrialized nations. The HEV genotypes 1 and 2 are common in Asia and Africa and are transmitted mainly by contaminated drinking water. Sporadic as well as large-scale epidemics of acute hepatitis have been noted with HEV genotype 1 infection in developing countries of Asia and Africa. On the contrary, HEV genotypes 3 and 4 are common in industrialized nations and unlike genotypes 1 and 2, they are transmitted by consumption of raw meat products, fruits, and blood transfusion. Large epidemics have not been reported with HEV genotypes 3 and 4 and manifestation is usually indolent, though severe acute hepatitis has been reported. How to cite this article: Shrestha A, Gupta BP, Lama TK. Current Treatment of Acute and Chronic Hepatitis E Virus Infection: Role of Antivirals. Euroasian J Hepato-Gastroenterol 2017;7(1):73-77.

Acute hepatitis E virus infection in human immunodeficiency virus–positive men and women in Nepal: Not quite a rare entity

inject drugs. HEPATOLOGY 2016;63:1090-1101. 2) van der Meer AJ, Veldt BJ, Feld JJ, Wedemeyer H, Dufour JF, Lammert F, et al. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA 2012;308:2584-2593. 3) Melin P, Chousterman M, Fontanges T, Ouzan D, Rotily M, Lang JP, et al. Effectiveness of chronic hepatitis C treatment in drug users in routine clinical practice: results of a prospective cohort study. Eur J Gastroenterol Hepatol 2010;22:1050-1057. 4) Jauffret-Roustide M, Pillonel J, Weill-Barillet L, L eon L, Strat Y, Brunet S. Estimation of HIV and hepatitis C prevalence among drug users in France—first results from the ANRS-COQUELICOT 2011 survey. Bulletin Epid emiologie Hebdomadaire 2013;39:40.

Epidemiological Profile and Risk Factors for Acquiring HBV and/or HCV in HIV-Infected Population Groups in Nepal

HBV and HCV infections are widespread among the HIV-infected individuals in Nepal. The goals of this study were to investigate the epidemiological profile and risk factors for acquiring HBV and/or HCV coinfection in disadvantaged HIV-positive population groups in Nepal. We conducted a retrospective study on blood samples from HIV-positive patients from the National Public Health Laboratory at Kathmandu to assay for HBsAg, HBeAg, and anti-HCV antibodies, HIV viral load, and CD4+ T cell count. Among 579 subjects, the prevalence of HIV-HBV, HIV-HCV, and HIV-HBV-HCV coinfections was 3.62%, 2.93%, and 0.34%, respectively. Multivariate regression analysis indicated that spouses of HIV-positive migrant labourers were at significant risk for coinfection with HBV infection, and an age of >40 years in HIV-infected individuals was identified as a significant risk factor for HCV coinfection. Overall our study indicates that disadvantaged population groups such as intravenous drug users, migrant workers and their spouses, female sex workers, and men who have sex with HIV-infected men are at a high and persistent risk of acquiring viral hepatitis. We conclude that Nepalese HIV patients should receive HBV and HCV diagnostic screening on a regular basis.

Prevalence and risk of hepatitis E virus infection in the HIV population of Nepal

BackgroundInfection with the hepatitis E virus (HEV) can cause acute hepatitis in endemic areas in immune-competent hosts, as well as chronic infection in immune-compromised subjects in non-endemic areas. Most studies assessing HEV infection in HIV-infected populations have been performed in developed countries that are usually affected by HEV genotype 3. The objective of this study is to measure the prevalence and risk of acquiring HEV among HIV-infected individuals in Nepal.MethodsWe prospectively evaluated 459 Human Immunodeficiency Virus (HIV)-positive individuals from Nepal, an endemic country for HEV, for seroprevalence of HEV and assessed risk factors associated with HEV infection. All individuals were on antiretroviral therapy and healthy blood donors were used as controls.ResultsWe found a high prevalence of HEV IgG (39.4%) and HEV IgM (15.3%) in HIV-positive subjects when compared to healthy HIV-negative controls: 9.5% and 4.4%, respectively (OR: 6.17, 95% CI 4.42–8.61, p < 0.001 and OR: 3.7, 95% CI 2.35–5.92, p < 0.001, respectively). Individuals residing in the Kathmandu area showed a significantly higher HEV IgG seroprevalance compared to individuals residing outside of Kathmandu (76.8% vs 11.1%, OR: 30.33, 95% CI 18.02–51.04, p = 0.001). Mean CD4 counts, HIV viral load and presence of hepatitis B surface antigen correlated with higher HEV IgM rate, while presence of hepatitis C antibody correlated with higher rate of HEV IgG in serum. Overall, individuals with HEV IgM positivity had higher levels of alanine aminotransferase (ALT) than IgM negative subjects, suggesting active acute infection. However, no specific symptoms for hepatitis were identified.ConclusionsHIV-positive subjects living in Kathmandu are at higher risk of acquiring HEV infection as compared to the general population and to HIV-positive subjects living outside Kathmandu.

Microfilaria persistent foci during post MDA and the risk assessment of resurgence in India

BackgroundPondicherry, a union territory in India, is an endemic district for bancroftian lymphatic filariasis transmitted by Culex quinquefasciatus where eight rounds of mass drug administration (MDA) were completed in 2011 (annually once from 2004 to 2011).The objectives of this study were to conduct a focal survey to assess microfilaria and antigen (Ag) prevalence among young adults and to assess vector infection and infectivity through a focal entomological survey.MethodsMosquitoes were collected using gravid traps in Sedurapet village of Pondicherry and dissected to enumerate W. bancrofti larvae stage first larval stage (L1), second larval stage (L2), and third larval stage (L3). Microfilarias (Mf) were detected using blood smears collected from inhabitants.ResultsA total of 360 individuals from 67 houses were enrolled in this study of which 290 (80.6%) were surveyed for the presence of Mf. Two Mf carriers were detected yielding an overall prevalence of 0.69% and two out of 85 (2.35%) were Mf antigen positive. Of the 2875 mosquitoes collected by gravid trap, Culex quinquefasciatus (93.9%) was the predominant species, followed by Anopheles subpictus (2.3%) and Culex vishnui (3.8%). The density of Cx. quinquefasciatus was 28.1 per trap-night. A total of 2429 Cx. quinquefasciatus were dissected and microscopically examined for abdominal conditions (gravid 85%, semi-gravid 9.4%, unfed 3.8%, and fully fed 1.9%) and filarial infection. One mosquito (infection rate equal to 0.04%) was found to harbor a second stage filarial larva, and none of the mosquitoes had infective stage larva.ConclusionOur results show no reappearance of infection of lymphatic filariasis in Sedurapet village of Pondicherry after MDA, and thus, no further intervention is required in that area for possible resurgence of lymphatic filariasis. However, monitoring should be continued as part of post MDA activities until the endpoint of complete elimination is achieved. We demonstrated that xenomonitoring can be used to monitor the post MDA situation for possible risk of transmission to initiate control measures.