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The burden of disease, most commonly expressed in terms of Disability-Adjusted Life Years, has become a crucial component in decision making processes within the health sector. In Nepal, however, burden of disease estimates are scarce and lack representativeness. To improve our understanding of the burden of disease in Nepal and thereby increase the efficiency of health policies, there is an urgent need to strengthen thelocal evidencebased. All relevant stakeholders should therefore collaborate to generate new data, improve existing data generation mechanisms, make generated data available, and optimize the use of available data.

Dengue virus (DENV) poses a significant threat to global health, infecting approximately 390 million people annually. This virus comprises four serotypes capable of causing severe disease. Genetic analyses are crucial for understanding the epidemiology, evolution, and spread of DENV. Although previous studies have focused on the envelope protein-coding (E) gene, only a few primers can efficiently detect and amplify the viral genes from multiple endemic countries simultaneously. In this study, we designed degenerate primer pairs for each DENV serotype to amplify and sequence the entire E gene, using globally representative sequences for each serotype. These primers were validated using DENV isolates from various Asian countries and demonstrated broad-spectrum detection capabilities and high-quality sequences. The primers provide effective tools for genetic analysis in the regions affected by dengue, aiding strain identification and epidemiological studies during outbreaks.

In 2023, Nepal faced its second largest dengue outbreak ever, following a record-breaking number of dengue cases in 2022, characterized by the expansion of infections into areas of higher altitudes. However, the characteristics of the 2023 circulating dengue virus (DENV) and the vector density remain poorly understood. Therefore, we performed DENV serotyping, clinical and laboratory assessment, and entomological analysis of the 2023 outbreak in central Nepal. A total of 396 fever cases in Dhading hospital suspected of being DENV positive were enrolled, and blood samples were collected and tested by different techniques including PCR. Of these, 278 (70.2%) had confirmed DENV infection. Multiple serotypes (DENV-1, -2, and -3) were detected. DENV-2 (97.5%) re-emerged after six years in Dhading while DENV-3 was identified for the first time. Dengue inpatients had significantly higher frequency of anorexia, myalgia, rash, diarrhea, nausea, vomiting, abdominal pain, and thrombocytopenia ( p < 0.05). In this area, Aedes mosquitoes largely predominated (90.7%) with the majority being A. aegypti (60.7%). We also found high levels of Aedes index (20.0%) and container index (16.7%). We confirmed multiple DENV serotype circulation with serotype re-emergence and new serotype introduction, and high vector density in 2023. These findings call for the urgent initiation and scaling up of DENV molecular surveillance in human and mosquito populations for dengue control and prevention in Nepal.

In search of a mouse model for use in evaluating dengue vaccines, we assessed A129 mice that lacked IFN-α/β receptors, rendering them susceptible to dengue virus (DENV) infection. To our knowledge, no reports have evaluated dengue vaccine efficiency using A129 mice. A129 mice were given a single intraperitoneal (IP) or subcutaneous (SC) injection of the vaccine, Dengvaxia. After 14 days of immunization via the IP or SC injection of Dengvaxia, the A129 mice exhibited notably elevated levels of anti-DENV immunoglobulin G and neutralizing antibodies (NAb) targeting all four DENV serotypes, with DENV-4 displaying the highest NAb levels. After challenge with DENV-2, Dengvaxia and mock-immunized mice survived, while only the mock group exhibited signs of morbidity. Viral genome levels in the serum and tissues (excluding the brain) were considerably lower in the immunized mice compared to those in the mock group. The SC administration of Dengvaxia resulted in lower viremia levels than IP administration did. Therefore, given that A129 mice manifest dengue-related morbidity, including viremia in the serum and other tissues, these mice represent a valuable model for investigating novel dengue vaccines and antiviral drugs and for exploring dengue pathogenesis.

Background: Nepal has achieved and sustained the elimination of leprosy as a public health problem since 2009, but 17 districts and 3 provinces with 41% (10,907,128) of Nepal's population have yet to eliminate the disease. Pediatric cases and grade-2 disabilities (G2D) indicate recent transmission and late diagnosis, respectively, which necessitate active and early case detection. This operational research was performed to identify approaches best suited for early case detection, determine community-based leprosy epidemiology, and identify hidden leprosy cases early and respond with prompt treatment., Methods: Active case detection was undertaken in two Nepali provinces with the greatest burden of leprosy, Madhesh Province (40% national cases) and Lumbini Province (18%) and at-risk prison populations in Madhesh, Lumbini and Bagmati provinces. Case detection was performed by (1) house-to-house visits among vulnerable populations (n = 26,469); (2) contact examination and tracing (n = 7608); in Madhesh and Lumbini Provinces and, (3) screening prison populations (n = 4428) in Madhesh, Lumbini and Bagmati Provinces of Nepal. Per case direct medical and non-medical costs for each approach were calculated., Results: New case detection rates were highest for contact tracing (250), followed by house-to-house visits (102) and prison screening (45) per 100,000 population screened. However, the cost per case identified was cheapest for house-to-house visits [Nepalese rupee (NPR) 76,500/case], followed by contact tracing (NPR 90,286/case) and prison screening (NPR 298,300/case). House-to-house and contact tracing case paucibacillary/multibacillary (PB:MB) ratios were 59:41 and 68:32; female/male ratios 63:37 and 57:43; pediatric cases 11% in both approaches; and grade-2 disabilities (G2D) 11% and 5%, respectively. Developing leprosy was not significantly different among household and neighbor contacts [odds ratios (OR) = 1.4, 95% confidence interval (CI): 0.24-5.85] and for contacts of MB versus PB cases (OR = 0.7, 95% CI 0.26-2.0). Attack rates were not significantly different among household contacts of MB cases (0.32%, 95% CI 0.07-0.94%) and PB cases (0.13%, 95% CI 0.03-0.73) (χ 2  = 0.07, df = 1, P = 0.9) and neighbor contacts of MB cases (0.23%, 0.1-0.46) and PB cases (0.48%, 0.19-0.98) (χ 2  = 0.8, df = 1, P = 0.7). BCG vaccination with scar presence had a significant protective effect against leprosy (OR = 0.42, 0.22-0.81)., Conclusions: The most effective case identification approach here is contact tracing, followed by house-to-house visits in vulnerable populations and screening in prisons, although house-to-house visits are cheaper. The findings suggest that hidden cases, recent transmission, and late diagnosis in the community exist and highlight the importance of early case detection., (© 2023. The Author(s).)

Few seroprevalence studies have been conducted on coronavirus disease (COVID-19) in Nepal. Here, we aimed to estimate seroprevalence and assess risk factors for infection in the general population of Nepal by conducting two rounds of sampling. The first round was in October 2020, at the peak of the first generalized wave of COVID-19, and the second round in July-August 2021, following the peak of the wave caused by the delta variant of SARS-CoV-2. We used cross-sectional probability-to-size (PPS)-based multistage cluster sampling to estimate the seroprevalence in the general population of Nepal at the national and provincial levels. We tested for anti-SARS-CoV-2 total antibody using the WANTAI SARS-CoV-2 Ab ELISA kit. In Round 1, the overall national seroprevalence was 14.4%, with provincial estimates ranging from 5.3% in Sudurpaschim to 27.3% in Madhesh Province. In Round 2, the estimated national seroprevalence was 70.7%, with the highest in the Madhesh Province (84.8%) and the lowest in the Gandaki Province (62.9%). Seroprevalence was comparable between males and females (Round 1, 15.8% vs. 12.2% and Round 2, 72.3% vs. 68.7%). The seroprevalence in the ecozones-Terai, hills, and mountains-was 76.3%, 65.3%, and 60.5% in Round 2 and 17.7%, 11.7%, and 4.6% in Round 1, respectively. In Nepal, COVID-19 vaccination was introduced in January 2021. At the peak of the first generalized wave of COVID-19, most of the population of Nepal remained unexposed to SARS-CoV-2. Towards the end of the second generalized wave in April 2021, two thirds of the population was exposed., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Nipah virus (NiV) is a zoonotic, single-stranded RNA virus from the family Paramyxoviridae, genus Henipavirus. NiV is a biosafety-level-4 pathogen that is mostly spread by Pteropus species, which serve as its natural reservoir host. NiV is one of the major public health challenges in South and South East Asia. However, few molecular studies have been conducted to characterise NiV in a specific region. The main objective of this review is to understand the epidemiology, pathogenesis, molecular surveillance, transmission dynamics, genetic diversity, reservoir host, clinical characteristics, and phylogenetics of NiV. South and South East Asian nations have experienced NiV outbreaks. Phylogenetic analysis confirmed that two primary clades of NiV are in circulation. In humans, NiV causes severe respiratory illness and/or deadly encephalitis. NiV is mainly diagnosed by ELISA along with PCR. Therefore, we recommend that the governments of the region support the One Health approach to reducing the risk of zoonotic disease transmission in their respective countries., (© 2023. Japanese Society of Tropical Medicine.)

Competing Interests: We declare no competing interests.

The largest dengue outbreak in the history of Nepal occurred in 2022, with a significant number of casualties. It affected all 77 districts, with the nation's capital, Kathmandu (altitude 1300 m), being the hardest hit. However, the molecular epidemiology of this outbreak, including the dengue virus (DENV) serotype(s) responsible for this epidemic, remain unknown. Here, we report the epidemic trends, clinico-laboratory features, and virus serotypes and their viral load profiles that are associated with this outbreak in Nepal. Dengue-suspected febrile patients were investigated by routine laboratory, serological, and molecular tools, including a real-time quantitative polymerase chain reaction (qRT-PCR). Of the 538 dengue-suspected patients enrolled, 401 (74.5%) were diagnosed with dengue. Among these dengue cases, 129 (32.2%) patients who required hospital admission had significant associations with myalgia, rash, diarrhea, retro-orbital pain, bleeding, and abdominal pain. DENV-1, -2, and -3 were identified during the 2022 epidemic, with a predominance of DENV-1 (57.1%) and DENV-3 (32.1%), exhibiting a new serotype addition. We found that multiple serotypes circulated in 2022, with a higher frequency of hospitalizations, more severe dengue, and more deaths than in the past. Therefore, precise mapping of dengue and other related infections through integrated disease surveillance, evaluation of the dynamics of population-level immunity and virus evolution should be the urgent plans of action for evidence-based policy-making for dengue control and prevention in the country.

Following the report of the first COVID-19 case in Nepal on 23 January 2020, three major waves were documented between 2020 and 2021. By the end of July 2022, 986 596 cases of confirmed COVID-19 and 11 967 deaths had been reported and 70.5% of the population had received at least two doses of a COVID-19 vaccine. Prior to the pandemic, a large dengue virus (DENV) epidemic affected 68 out of 77 districts, with 17 932 cases and six deaths recorded in 2019. In contrast, the country's Epidemiology and Disease Control Division reported 530 and 540 dengue cases in the pandemic period (2020 and 2021), respectively. Furthermore, Kathmandu reported just 63 dengue cases during 2020 and 2021, significantly lower than the 1463 cases reported in 2019. Serological assay showed 3.2% positivity rates for anti-dengue immunoglobulin M antibodies during the pandemic period, contrasting with 26.9-40% prior to it. Real-time polymerase chain reaction for DENV showed a 0.5% positive rate during the COVID-19 pandemic which is far lower than the 57.0% recorded in 2019. Continuing analyses of dengue incidence and further strengthening of surveillance and collaboration at the regional and international levels are required to fully understand whether the reduction in dengue incidence/transmission were caused by movement restrictions during the COVID-19 pandemic.

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first COVID-19 case was reported in Wuhan, China, in December 2019. In March 2020, the World Health Organization (WHO) declared COVID-19 a global pandemic. The first COVID-19 case in Nepal was reported in January 2020 in a Nepalese man who had returned from Wuhan to Nepal. This study aims to evaluate the government of Nepal's (GoN) response to the COVID-19 pandemic and explore ways to prevent COVID-19 and other pandemic diseases in the future. As of May 2022, a total of 979,140 cases and 11,951 deaths associated with COVID-19 have been reported in Nepal. To prevent the spread of the virus, the GoN initiated various preventive and control measures, including lockdown strategies. The effects of COVID-19 are expected to persist for many years; the best strategies a resource-limited country such as Nepal can implement to control pandemic diseases such as COVID-19 in the pre-vaccine stage are to increase testing, tracing, and isolation capacity.

Background: In Tsarang (at 3560 m), which is located in Mustang, 62.7% of the residents answered that they had a subjective medical history of arthritis, and 41.1% of the residents answered that their families had a subjective medical history of arthritis on a survey conducted in 2017. The expression of hypoxia-inducible factor (HIF) and its effects are deeply involved in hypoxic adaptation in Tibetan highlanders. At the same time, HIF is also related to the onset of rheumatoid arthritis. Therefore, the adaptive mechanism acquired by Tibetan highlanders may promote the development of rheumatoid arthritis. The prevalence of rheumatoid arthritis is estimated to be approximately 0.5-1.0% worldwide. The objective of this study was to estimate the prevalence of rheumatoid arthritis in Tsarang residents using existing diagnostic criteria and to explore its risk factors., Methods: An epidemiological survey was conducted in Tsarang in 2019. Data obtained from anthropometry and questionnaires were statistically analyzed. Biochemical measurements using blood samples were also performed, and the results were used to assess arthritis status. Residents' joint status was scored, and arthritis was assessed based on the clinical disease activity index and ACR/EULAR 2010 criteria., Results: Twenty-seven males and 50 females participated in this survey. In Tsarang, ACR/EULAR 2010 classified 4.3% of males and 7.1% of females as having rheumatoid arthritis, indicating a very high estimated prevalence. We also performed a multivariate analysis to explore its risk factors, and two factors, older age (standardized parameter estimate = 4.84E-01, 95% CI = [9.19E-02, 8.76E-01], p = 0.0170) and a history of living in urban areas (standardized parameter estimate = - 5.49E-01, 95% CI = [- 9.21E-01, 1.77E-01], p = 0.0050), significantly contributed to the higher ACR/EULAR 2010 score in females. In addition, three factors, having no spouse (standardized parameter estimate = 3.17E-01, 95% CI = [5.74E-02, 5.77E-01], p = 0.0179), having a smoking habit (standardized parameter estimate = 2.88E-01, 95% CI = [1.71E-02, 5.59E-01], p = 0.0377), and a history of living in urban areas (standardized parameter estimate = - 3.69E-01, 95% CI = [- 6.83E-01, - 5.60E-02], p = 0.0219), resulted in significantly higher clinical disease activity index scores in females. Furthermore, smoking habits were found to significantly increase blood hyaluronic acid in both males (standardized parameter estimate = 6.03E-01, 95% CI = [3.06E-01, 9.01E-01], p = 0.0020) and females (standardized parameter estimate = 4.87E-01, 95% CI = [5.63E-02, 9.18E-01], p = 0.0291)., Conclusions: In this study, we evaluated the symptoms of arthritis and estimated the prevalence of rheumatoid arthritis using classification criteria for Tibetan highlanders who have adapted to the hypoxic environment and fostered their own culture. The high prevalence of rheumatoid arthritis among Tsarang residents suggests that the hypoxic adaptation mechanism involving HIF in Tibetan highlanders may promote the onset or exacerbation of rheumatoid arthritis. The high prevalence of rheumatoid arthritis among Tibetan highlanders may be related not only to the environmental factors analyzed in this study but also to hypoxic adaptation genes. Further investigation is needed to clarify the genetic factors involved., (© 2022. The Author(s).)

Background: Cutaneous leishmaniasis (CL) is endemic in 70 countries worldwide. Nepal is considered non-endemic for CL and hence the control program is targeted to visceral leishmaniasis (VL) only. Here, we report the emergence of CL cases in different parts of Nepal., Methods: We analyzed the CL and VL cases reported to Epidemiology and Diseases Control Division (EDCD), Ministry of Health and Population, Nepal through District Health Information System 2 (DHIS-2) and Early Warning and Reporting System (EWRS) during the past 4 years (2016-2019). Any laboratory-confirmed case was included in the study. Demographic and clinical details of each patient were transcribed into Excel sheets, verified with the case report forms and analyzed., Results: VL has been reported in Nepal since 1980, but CL was reported very recently. From 2016 to 2019, 42 CL cases were reported from 26 different hospitals to EDCD which had been diagnosed on the basis of clinical presentation, and laboratory findings (demonstration of amastigotes in Giemsa-stained smears and rK39 test results). Majority of the patients (31.0%, 13/42) visited to the hospital within 1-6 months of onset of lesions. Facial region (38.1%, 16/42) was the common place where lesions were found ompared to other exposed parts of the body. CL was successfully treated with miltefosine for 28 days. The majority of CL patients did not have history of travel outside the endemic areas and there was no report of sandfly from these areas., Conclusion: These evidences highlight that the Government of Nepal need to pay more efforts on CL and include it in differential diagnosis by clinicians, and plan for an active surveillance when the country is targeting leishmaniasis elimination by the year 2025 with the decreasing number of VL cases., (© 2021. The Author(s).)

Dengue virus (DENV) is one of the most prevalent neglected tropical diseases, with half of the world's population at risk of infection. In Nepal, DENV was first reported in 2004, and its prevalence is increasing every year. The present study aimed to obtain and characterize the full-length genome sequence of DENV from the 2017 outbreak. Hospital-based surveillance was conducted in two provinces of Nepal during the outbreak. Acute-phase serum samples were collected from 141 clinically suspected dengue patients after the rainy season. By serological and molecular techniques, 37 (26.9%) and 49 (34.8%), respectively, were confirmed as dengue patients. The cosmopolitan genotype of DENV-2 was isolated from 27 laboratory-confirmed dengue patients. Genomic analysis showed many amino acid substitutions distributed mainly among the E, NS3, and NS5 genes. Phylogenetic analyses of the whole genome sequence revealed two clades (Asian and Indian) among DENV-2 isolates from Nepal. The DENV isolates from hilly and Terai areas were similar to Asian and Indian strains, respectively. Further genomic study on different DENV serotypes is warranted to understand DENV epidemics in Nepal, where there are limited scientific resources and infrastructure.

Background: Dengue is one of the newest emerging diseases in Nepal with increasing burden and geographic spread over the years. The main objective of this study was to explore the epidemiological patterns of dengue since its first outbreak (2006) to 2019 in Nepal., Methods: This study is a retrospective analysis that covers the last 14 years (2006-2019) of reported dengue cases from Epidemiology Diseases Control Division (EDCD), Ministry of Health and Population, Government of Nepal. Reported cases were plotted over time and maps of reported case incidence were generated (from 2016 through 2019). An ecological analysis of environmental predictors of case incidence was conducted using negative binomial regression., Results: While endemic dengue has been reported in Nepal since 2006, the case load has increased over time and in 2019 a total of 17 992 dengue cases were reported from 68 districts (from all seven provinces). Compared to the case incidence in 2016, incidence was approximately five times higher in 2018 [incidence rate ratio (IRR): 4.8; 95% confidence interval (CI) 1.5-15.3] and over 140 times higher in 2019 (IRR: 141.6; 95% CI 45.8-438.4). A one standard deviation increase in elevation was associated with a 90% decrease in reported case incidence (IRR: 0.10; 95% CI 0.01-0.20). However, the association between elevation and reported cases varied across the years. In 2018 there was a cluster of cases reported from high elevation Kaski District of Gandaki Province. Our results suggest that dengue infections are increasing in magnitude and expanding out of the lowland areas to higher elevations over time., Conclusions: There is a high risk of dengue outbreak in the lowland Terai region, with increasing spread towards the mid-mountains and beyond as seen over the last 14 years. Urgent measures are required to increase the availability of diagnostics and resources to mitigate future dengue epidemics.

Background: Tibetan highlanders have adapted to hypoxic environments through the development of unique mechanisms that suppress an increase in hemoglobin (Hb) concentration even in high-altitude areas. Hb concentrations generally decrease with increasing age. However, in the highlands, chronic altitude sickness is known to occur in the elderly population. To investigate how aging in a hypoxic environment affects Hb levels in Tibetan highlanders, we focused on the Mustang people, who live above 3500 m. We tried to clarify the pure relationship between aging and Hb levels in a hypoxic environment., Results: We found that the Hb concentration increased with increasing age in females but not in males. Multivariate analysis showed that age, pulse pressure, the poverty index, and vascular diameter were strongly correlated with the Hb concentration., Conclusions: We found unique Hb dynamics among female Tibetan highlanders. As seen in these Hb dynamics, there may be sex-based differences in the adaptive mechanism in Tibetan highlanders.

Coronavirus disease 2019 (COVID-19) pandemic has caused significant impact on the health care system. As a consequence, diagnosis and treatment of vector borne diseases including dengue has been equally affected. Nepal is no exception to this, where COVID-19 cases is exponentially increased and all resources are concentrated on its prevention, control and management. Dengue, one of the major vector-borne diseases in Nepal, is apparently overlooked despite approaching the peak season of the disease. The aim of this paper is to describe the double burden of COVID-19 and dengue in Nepal, particularly highlighting the co-circulation and possible coinfections. This has posed higher risk of increased severity, more severe cases and deaths in Nepal. Moreover, potential misdiagnosis of these viral diseases may lead to delayed or, inappropriate treatment and poor allocation of resources.

Background: Innovative approaches are required for leprosy control to reduce cases and curb transmission of Mycobacterium leprae. Early case detection, contact screening, and chemoprophylaxis are the most promising tools. We aimed to generate evidence on the feasibility of integrating contact tracing and administration of single-dose rifampicin (SDR) into routine leprosy control activities., Methods: The leprosy post-exposure prophylaxis (LPEP) programme was an international, multicentre feasibility study implemented within the leprosy control programmes of Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka, and Tanzania. LPEP explored the feasibility of combining three key interventions: systematically tracing contacts of individuals newly diagnosed with leprosy; screening the traced contacts for leprosy; and administering SDR to eligible contacts. Outcomes were assessed in terms of number of contacts traced, screened, and SDR administration rates., Findings: Between Jan 1, 2015, and Aug 1, 2019, LPEP enrolled 9170 index patients and listed 179 769 contacts, of whom 174 782 (97·2%) were successfully traced and screened. Of those screened, 22 854 (13·1%) were excluded from SDR mainly because of health reasons and age. Among those excluded, 810 were confirmed as new patients (46 per 10 000 contacts screened). Among the eligible screened contacts, 1182 (0·7%) refused prophylactic treatment with SDR. Overall, SDR was administered to 151 928 (86·9%) screened contacts. No serious adverse events were reported., Interpretation: Post-exposure prophylaxis with SDR is safe; can be integrated into different leprosy control programmes with minimal additional efforts once contact tracing has been established; and is generally well accepted by index patients, their contacts, and health-care workers. The programme has also invigorated local leprosy control through the availability of a prophylactic intervention; therefore, we recommend rolling out SDR in all settings where contact tracing and screening have been established., Funding: Novartis Foundation., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Leprosy, a leading cause of disability, remains endemic in southern Nepal. Alongside physical impairment and stigmatization, many people affected by leprosy suffer from mental health problems., Objectives: This study had two objectives: (a) Establishing a baseline level of mental wellbeing and depression among people affected by leprosy in southern Nepal, and (b) Examining factors that influence mental wellbeing and depression in this target group., Methods: A cross-sectional survey was conducted using three interview-administered questionnaires measuring level of depression (PHQ-9), mental wellbeing status (WEMWBS) and level of stigma (5-QSI-AP). Random clustering sampling was used to include leprosy-affected people from Self Help Groups (SHGs) and the reference group was matched based on socio-demographic characteristics. All participants were adults with no additional major morbidities. A sample of 142 persons affected by leprosy and 54 community controls were included., Results: People affected by leprosy participating in SHGs had a significantly lower level of mental wellbeing and higher level of depression than the general population. Both mental wellbeing and depression were influenced by gender and the level of stigma. In addition, the level of depression was associated with the disability grade of leprosy-affected people., Conclusion: Leprosy-affected people need mental health-care interventions at different organizational levels, with attention to identifying individuals at increased risk for mental health problems or with additional needs. These findings highlight the demand for further research on specific interventions to improve the mental health of leprosy-affected people.

Reactive Arthritis (ReA), a rare seronegative inflammatory arthritis, lacks exquisite classification under rheumatic autoimmunity. ReA is solely established using differential clinical diagnosis of the patient cohorts, where pathogenic triggers linked to enteric and urogenital microorganisms e.g. Salmonella, Shigella, Yersinia, Campylobacter, Chlamydia have been reported. Inflammatory Bowel Disease (IBD), an idiopathic enteric disorder co-evolved and attuned to present gut microbiome dysbiosis, can be correlated to the genesis of enteropathic arthropathies like ReA. Gut microbes symbolically modulate immune system homeostasis and are elementary for varied disease patterns in autoimmune disorders. The gut-microbiota axis structured on the core host-microbe interactions execute an imperative role in discerning the etiopathogenesis of ReA and IBD. This study predicts the molecular signatures for ReA with co-evolved IBD through the enveloped host-microbe interactions and microbe-microbe 'interspecies communication', using synonymous gene expression data for selective microbes. We have utilized a combinatorial approach that have concomitant in-silico work-pipeline and experimental validation to corroborate the findings. In-silico analysis involving text mining, metabolic network reconstruction, simulation, filtering, host-microbe interaction, docking and molecular mimicry studies results in robust drug target/s and biomarker/s for co-evolved IBD and ReA. Cross validation of the target/s or biomarker/s was done by targeted gene expression analysis following a non-probabilistic convenience sampling. Studies were performed to substantiate the host-microbe disease network consisting of protein-marker-symptom/disease-pathway-drug associations resulting in possible identification of vital drug targets, biomarkers, pathways and inhibitors for IBD and ReA.Our study identified Na (+) /H (+) anti-porter (NHAA) and Kynureninase (KYNU) to be robust early and essential host-microbe interacting targets for IBD co-evolved ReA. Other vital host-microbe interacting genes, proteins, pathways and drugs include Adenosine Deaminase (ADA), Superoxide Dismutase 2 (SOD2), Catalase (CAT), Angiotensin I Converting Enzyme (ACE), carbon metabolism (folate biosynthesis) and methotrexate. These can serve as potential prognostic/theranostic biomarkers and signatures that can be extrapolated to stratify ReA and related autoimmunity patient cohorts for further pilot studies.

A complete genome sequence was obtained for a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain isolated from an oropharyngeal swab specimen of a Nepalese patient with coronavirus disease 2019 (COVID-19), who had returned to Nepal after traveling to Wuhan, China., (Copyright © 2020 Sah et al.)

Background: Visceral Leishmaniasis (VL) is caused by a protozoan parasite Leishmania donovani that is transmitted to humans by an infected female sandfly, Phlebotomus argentipes. VL is common in the Indian sub-continent including Nepal and efforts for its elimination are ongoing. However, expansion of disease towards the higher altitude areas, previously considered as VL free in Nepal, may impact the ability to achieve the elimination target by 2020., Methods: This was an exploratory study, where VL suspected patients living exclusively in the non-program districts of Nepal and presenting with fever > 2 weeks and splenomegaly was included. The patients' blood samples were collected, and DNA was extracted. DNA was subjected to PCR amplification and subsequent sequencing. Additionally, past 10 years data of VL cases from the national databases were analysed to see the trends of the disease in program and non program districts., Results: Analysis of the past 10 years data revealed that trend of VL cases significantly decreased in the program districts (p = 0.001) while it increased in the non-program districts (p = 0.002). The national trend for overall incidence of VL also significantly decreased over this time period. Limited number of patients' samples (n = 14) were subjected to molecular investigation, and four patients were found to be positive for Leishmania species by PCR. Interestingly, these cases in non-program districts were indeed also L. donovoni complex. All four patients were male with age ranges from 10 to 68 years. GenBank BLAST of the obtained DNA sequences confirmed identified specimens as L. donovani complex. We identified additional VL cases from non-program districts (including the high lands) of Nepal, indicating that the infection could be an emerging threat for the non-program areas of Nepal., Conclusion: The demonstration of VL cases in areas initially considered non-endemic has raised concern about on-going transmission in those regions and may trigger subsequent government plan and action to include those areas in the elimination program. Thus, the government should consider revising the disease control programs to accommodate non-program districts for achieving the VL elimination goal set for 2020.

Air pollution is a major environmental problem in the Kathmandu Valley. Specifically, roadside and traffic-related air pollution exposure levels were found at very high levels exceeding Nepal air quality standards for daily PM 2.5 . In an exposure study involving traffic police officers, we collected 78 blood samples in a highly polluted spring season (16 February 2014⁻4 April 2014) and 63 blood samples in the less polluted summer season (20 July 2014⁻22 August 2014). Fourteen biomarkers, i.e., C-reactive protein (CRP), serum amyloid A (SAA), intracellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), interferon gamma (IFN-γ), interleukins (IL1-β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13), and tumor necrosis factor (TNF-α) were analyzed in collected blood samples using proinflammatory panel 1 kits and vascular injury panel 2 kits. All the inflammatory biomarker levels were higher in the summer season than in the spring season, while particulate levels were higher in the spring season than in the summer season. We did not find significant association between 24-hour average PM 2.5 or black carbon (BC) exposure levels with most of analyzed biomarkers for the traffic volunteers working and residing near busy roads in Kathmandu, Nepal, during 2014. Inflammation and vascular injury marker concentrations were generally higher in females, suggesting the important role of gender in inflammation biomarkers. Because of the small sample size of female subjects, further investigation with a larger sample size is required to confirm the role of gender in inflammation biomarkers.

Background: Epidemiology of noncommunicable diseases (NCDs) such as obesity and diabetes mellitus (DM) are influenced by multiple hosts and environmental factors. This study aims to investigate the prevalence of NCDs and determine their risk factors among the adults residing in an isolated village situated at a rural highland of Nepal., Methods: A cross-sectional survey was conducted in a village located at 3570 m. Each 188 randomly selected participants of age ≥ 18 years old answered a questionnaire and took a full physical exam that included biomedical measurements of glycosylated hemoglobin (HbA1c)., Results: The prevalence of intermediate hyperglycemia and DM was 31.6% and 4.6% respectively, and the prevalence of hypoxemia (SpO 2 < 90%) was 27.1%. A multiple logistic regression analysis for factors for the prevalence of glucose intolerance (HbA1c ≥ 6%) revealed older age (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.06-1.16, for every 1 year increase) and SpO 2 (OR for hypoxemia 3.58, 95% CI 1.20-10.68, vs SpO 2 ≥ 90%)., Conclusions: Tibetan highlanders in the remote mountainous Mustang valley of Nepal have high prevalence of impaired glucose metabolism which could be related to hypoxemia imposed by the hypoxic conditions of high altitude living.

Asia and its Hindu Kush Himalayan (HKH) region is particularly vulnerable to environmental change, especially climate and land use changes further influenced by rapid population growth, high level of poverty and unsustainable development. Asia has been a hotspot of dengue fever and chikungunya mainly due to its dense human population, unplanned urbanization and poverty. In an urban cycle, dengue virus (DENV) and chikungunya virus (CHIKV) are transmitted by Aedes aegypti and Ae. albopictus mosquitoes which are also competent vectors of Zika virus (ZIKV). Over the last decade, DENV and CHIKV transmissions by Ae. aegypti have extended to the Himalayan countries of Bhutan and Nepal and ZIKV could follow in the footsteps of these viruses in the HKH region. The already established distribution of human-biting Aedes mosquito vectors and a naïve population with lack of immunity against ZIKV places the HKH region at a higher risk of ZIKV. Some of the countries in the HKH region have already reported ZIKV cases. We have documented an increasing threat of ZIKV in Asia and its HKH region because of the high abundance and wide distribution of human-biting mosquito vectors, climate change, poverty, report of indigenous cases in the region, increasing numbers of imported cases and a naïve population with lack of immunity against ZIKV. An outbreak anywhere is potentially a threat everywhere. Therefore, in order to ensure international health security, all efforts to prevent, detect, and respond to ZIKV ought to be intensified now in Asia and its HKH region. To prepare for possible ZIKV outbreaks, Asia and the HKH region can also learn from the success stories and strategies adopted by other regions and countries in preventing ZIKV and associated complications. The future control strategies for DENV, CHIKV and ZIKV should be considered in tandem with the threat to human well-being that is posed by other emerging and re-emerging vector-borne and zoonotic diseases, and by the continuing urgent need to strengthen public primary healthcare systems in the region.

Background: Lymphatic filariasis (LF) and leprosy are disabling infectious diseases endemic in Nepal. LF infection can lead to lymphoedema and hydrocoele, while secondary effects of leprosy infection include impairments to hands, eyes and feet. The disabling effects of both conditions can be managed through self-care and the supportive effects of self-help groups (SHGs). A network of SHGs exists for people affected by leprosy in four districts in Nepal's Central Development Region, however no such service exists for people affected by LF. The aim of this study was to determine the feasibility of integrating LF affected people into existing leprosy SHGs in this area., Methods: A survey was conducted using a semi-structured questionnaire to elicit information on: (i) participant characteristics, clinical manifestation and disease burden; (ii) participants' knowledge of management of their condition and access to services; and (iii) participants' knowledge and perceptions of the alternate condition (LF affected participants' knowledge of leprosy and vice versa) and attitudes towards integration., Results: A total of 52 LF affected and 53 leprosy affected participants were interviewed from 14 SHGs. On average, leprosy affected participants were shown to have 1.8 times greater knowledge of self-care techniques, and practiced 2.5 times more frequently than LF affected participants. Only a quarter of LF affected participants had accessed a health service for their condition, compared with 94.3% of leprosy affected people accessing a service (including SHGs), at least once a week. High levels of stigma were perceived by both groups towards the alternate condition, however, the majority of LF (79%) and leprosy (94.3%) affected participants stated that they would consider attending an integrated SHG., Conclusions: LF affected participants need to increase their knowledge of self-care and access to health services. Despite stigma being a potential barrier, attitudes towards integration were positive, suggesting that the SHGs may be a good platform for LF affected people to start self-care in this area., Trial Registration: This is not a registered trial.

Objectives: Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) poses a major public health problem in Nepal. Although it has been reported as one of the dominant genotypes of MTB in Nepal, little information on the Central Asian Strain (CAS) family is available, especially isolates related to multidrug resistance (MDR) cases. This study aimed to elucidate the genetic and epidemiological characteristics of MDR CAS isolates in Nepal., Methods: A total of 145 MDR CAS isolates collected in Nepal from 2008 to 2013 were characterized by spoligotyping, mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) analysis, and drug resistance-associated gene sequencing., Results: Spoligotyping analysis showed CAS1&#95;Delhi SIT26 as predominant (60/145, 41.4%). However, by combining spoligotyping and MIRU-VNTR typing, it was possible to successfully discriminate all 145 isolates into 116 different types including 18 clusters with 47 isolates (clustering rate 32.4%). About a half of these clustered isolates shared the same genetic and geographical characteristics with other isolates in each cluster, and some of them shared rare point mutations in rpoB that are thought to be associated with rifampicin resistance., Conclusions: Although the data obtained show little evidence that large outbreaks of MDR-TB caused by the CAS family have occurred in Nepal, they strongly suggest several MDR-MTB transmission cases., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Leptospirosis is a re-emerging zoonotic disease caused by pathogenic strains of bacteria belonging to genus Leptospira whose symptoms can range from mild clinical manifestations to a severe life threatening illness. This disease may be under-recognized in resource poor settings like Nepal where many clinical laboratories lack appropriate equipment, technology and personnel for proper diagnosis., Methods: We used IgM ELISA to estimate the sero-prevalence of leptospirosis in a group of febrile patients in a western region of Nepal. We also tested for possible co-infection with two other common febrile diseases endemic to Nepal including dengue and typhoid fever., Results: Among samples from 144 febrile patients, 30 (21%) were positive for leptospiral IgM. In univariate analysis, leptospirosis was significantly associated with being of working age (p = 0.019), farming (p = 0.045) and water and animal contact (p = 0.0001). Widal and dengue serological study showed that the majority of leptospirosis infections did not have an alternative diagnosis., Conclusion: As indicated by the study, regular surveillance of animal reservoirs in collaboration with veterinary department and inclusion of leptospirosis as a differential diagnosis of febrile illness is thus recommended based on the current findings.

In Asian concentrated HIV epidemics, data on coinfection of sexually transmitted infections (STIs) among HIV-positive individuals are limited. The authors measured the prevalence of Chlamydia trachomatis (CT), Neisseria gonorrhea (NG), and syphilis, and their correlates among 319 HIV-positive individuals in Kathmandu, Nepal. The authors tested blood samples for syphilis and urine samples for CT and NG. Overall, 17 (5.3%) participants had at least 1 STI (CT: 1.3%, NG: 2.8%, and syphilis: 1.2%). Of 226 participants who had sex in past 6 months, 51.3% did not always use condoms. Older (aged 35-60 years) participants were more likely (adjusted odds ratio [AOR] = 3.83; 95% confidence interval [CI] = 1.19-12.33; P = .024) and those who were currently married (AOR = 0.30; 95% CI = 0.09-0.97; P = .046) or on antiretroviral therapy (AOR = 0.21; 95% CI = 0.06-0.71; P = .012) were less likely to have at least 1 STI. Our results suggest the need to strengthen the efforts to screen and treat STIs and to promote safer sexual practices among Nepalese HIV-positive individuals.

Background: Dengue fever, an endemic arboviral disease, represents one of the major public health concerns in Nepal. It is transmitted by bites of infected Aedes aegypti and Aedes albopictus, the former being primary vector. The bacterial community plays a significant role in biology of mosquitoes; however, the bacterial communities of primary vector A. aegypti remain unstudied in Nepal. The study was designed to determine the rate of dengue seropositivity and to explore the bacterial diversity of A. aegypti from dengue endemic districts, Kanchanpur and Parsa of Nepal., Methods: A cross-sectional study was conducted between June 2013 and November 2013 at two hospitals of Kanchanpur and Parsa. A total of 221 serum samples were collected from patients (inpatients and outpatients) suspected of suffering from dengue fever and attending Mahakali Zonal Hospital, Mahendranagar, Kanchanpur, and Narayani Zonal Hospital, Birgunj, Parsa. Detection of anti-dengue IgM was performed by using human dengue IgM capture ELISA. The larvae and pupae of mosquitoes (A. aegypti) were collected, reared, and emerged. Then, the bacteria were isolated and identified from the gut of identified mosquitoes by using standard methods., Results: Out of total 221 serum samples collected from patients suspected of suffering from dengue fever, 34 (15.38%) were positive for anti-dengue IgM. Gram-negative bacteria were isolated in largest proportion (63%) followed by gram-positive cocci (23.27%) and gram-positive rods (13.73%). The most common cultivable bacteria isolated were Staphylococcus spp., Pseudomonas spp., and Acinetobacter spp. The average bacterial load in the vectors was 3.91 × 10 4  cfu/ml., Conclusions: High rate of anti-dengue IgM seropositivity was reported in our study. The environmental bacteria were predominantly isolated and identified in A. aegypti. The paratransgenic approach to control vector might be possible by spreading the genetically modified bacteria in larval habitat or shelter of adult mosquitoes.

Background: Rabies is a vaccine-preventable viral zoonosis belonging to the group of neglected tropical diseases. Exposure to a rabid animal may result in a fatal acute encephalitis if effective post-exposure prophylaxis is not provided. Rabies occurs worldwide, but its burden is disproportionately high in developing countries, including Nepal. We aimed to summarize current knowledge on the epidemiology, impact and control of rabies in Nepal., Methods: We performed a systematic review of international and national scientific literature and searched grey literature through the World Health Organization Digital Library and the library of the National Zoonoses and Food Hygiene Research Centre, Nepal, and through searching Google and Google Scholar. Further data on animal and human rabies were obtained from the relevant Nepalese government agencies. Finally, we surveyed the archives of a Nepalese daily to obtain qualitative information on rabies in Nepal., Findings: So far, only little original research has been conducted on the epidemiology and impact of rabies in Nepal. Per year, rabies is reported to kill about 100 livestock and 10-100 humans, while about 1,000 livestock and 35,000 humans are reported to receive rabies post-exposure prophylaxis. However, these estimates are very likely to be serious underestimations of the true rabies burden. Significant progress has been made in the production of cell culture-based anti-rabies vaccine and rabies immunoglobulin, but availability and supply remain a matter of concern, especially in remote areas. Different state and non-state actors have initiated rabies control activities over the years, but efforts typically remained focalized, of short duration and not harmonized. Communication and coordination between veterinary and human health authorities is limited at present, further complicating rabies control in Nepal. Important research gaps include the reporting biases for both human and animal rabies, the ecology of stray dog populations and the true contribution of the sylvatic cycle., Interpretation: Better data are needed to unravel the true burden of animal and human rabies. More collaboration, both within the country and within the region, is needed to control rabies. To achieve these goals, high level political commitment is essential. We therefore propose to make rabies the model zoonosis for successful control in Nepal.

A descriptive cross-sectional study was carried out among 264 suspected dengue patients in two districts (Dang and Chitwan) of Nepal from June 2013 to November 2013. The anti-dengue IgM positivity was found to be (51/264)19.31% by capture ELISA, of which 21 (41.2%) were male and 30 (58.8%) were female. Symptoms of seropositive cases were fever, anorexia, nausea, headache, retro-orbital pain, skin rashes, and myalgia. Hematological features like thrombocytopenia and leucopenia were found to be significantly associated with the dengue fever (DF). Discarded tires were found as the commonest breeding habitats for the dengue vectors. Higher sero-positivity was recorded from the area having higher Breteau index (BI). The pH, chloride ion concentration and the salinity of the water from breeding habitats were found to be ranging from 6.9±0.82 to 8, 103.33±17.52 mg/L to 140.65 mg/L, and 0.19±0.032 ppt to 0.25 ppt respectively. This study may be helpful for the health authorities and public health workers for early diagnosis of DF and for the improved preventive measures to be adopted in the epidemic and possible epidemic areas.

This paper describes the isolation of the native bacterial strains from the iron ore mines slime pond and its extremophilic characteristics. The two microbial isolates designated as CNIOS-1 and CNIOS-2 were grown in selective silicate broth at pH 7.0 and the organisms were tested for their selective adhesion on silicate and alumina minerals. The silicate bacteria with their exopolymers are very potent to grow over aluminosilicates. It was established that CNIOS-1 grew preferentially in the presence of silicate mineral compared to CNIOS-2 which grew in the presence of alumina. The organisms were tested for growth at various pH and trials were carried to define their efficacy for eventual applications to remove gangue minerals of silica and alumina from the raw material.

Chikungunya virus (CHIKV) is an emerging alphaviral disease and a public health problem in South Asia including Nepal in recent years. In this study, sera were collected from patients presenting with fever, headache, muscular pain, fatigue, and joint pain of both upper and lower extremities. A total of 169 serum samples were tested for CHIKV and dengue virus (DENV) by using Immunoglobulin M (IgM) and Immunoglobulin G (IgG) antibody using enzyme-linked immunosorbent assay (ELISA) method during August to November 2013. Results showed that 3.6% and 27.8% samples were positive for CHIKV and DENV IgM positive, respectively. Similarly, results of IgG showed 3.0% samples were positive for CHIKV IgG and 29.0% were for DENV IgG positive. Further, a 50% focal reduction neutralization test (FRNT50) was performed to confirm the presence of CHIKV, which demonstrated that 8.9% of CHIKV IgM and/or IgG ELISA positive possessed neutralizing anti-CHIK antibodies. To our knowledge, this is the first report in which the presence of CHIKV is confirmed in Nepalese patients by FRNT50. Basic scientists and clinicians need to consider CHIKV as a differential diagnosis in febrile Nepalese patients, and policy makers should consider appropriate surveillance and actions for control strategies., (© The American Society of Tropical Medicine and Hygiene.)

Presently, global efforts are being made to control and eradicate the deadliest tropical diseases through the improvement of adequate interventions. A critical point for programs to succeed is the prompt and accurate diagnosis in endemic regions. Rapid diagnostic tests (RDTs) are being massively deployed and used to improve diagnosis in tropical countries. In the present report, we evaluated the hypothesis of, after use for diagnosis, the reuse of the Leishmania RDT kit as a DNA source, which can be used downstream as a molecular surveillance and/or quality control tool. As a proof of principle, a polymerase chain reaction-based method was used to detect Leishmania spp. minicircle kinetoplast DNA from leishmaniasis RDT kits. Our results show that Leishmania spp. DNA can be extracted from used RDTs and may constitute an important, reliable, and affordable tool to assist in future leishmaniasis molecular surveillance methods., (© The American Society of Tropical Medicine and Hygiene.)

Background: Depression is emerging as a highly prevalent psychiatric condition among people living with HIV/AIDS (PLWHA). Perceived family support (PFS) buffers depression among chronic disease patients. However, a similar relationship among PLWHA is unexplored., Objective: To examine the relationship between PFS and depression among PLWHA in the Kathmandu Valley, Nepal., Methods: In this cross-sectional study, depression was measured by Beck Depression Inventory Ia. Perceived family support was measured by Nepali Family Support and Difficulties Scale. The status of depression was compared between 208 PLWHA and 208 HIV-negative participants. The relationship between PFS and depression was examined only among PLWHA., Results: Among each of the 208 participants, the number of depressed PLWHA (n = 61,29.3%) was higher than that of HIV-negative participants (n = 13,6.2%; P < .001). Perceived family support had a negative association with depression in PLWHA (adjusted odds ratio [AOR] = 0.20, 95% confidence interval [CI] = 0.08-0.53)., Conclusion: In Nepal, PLWHA display a higher level of depression than HIV-negative people, and a lower level of PFS is associated with depression among PLWHA. Improved family support might be helpful in reducing depression among Nepalese PLWHA.