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IntroductionIncreases in global childhood vaccine delivery have led to decreases in morbidity from vaccine-preventable diseases. However, these improvements in vaccination have been heterogeneous, with some countries demonstrating greater levels of change and sustainability. Understanding what these high-performing countries have done differently and how their decision-making processes will support targeted improvements in childhood vaccine delivery.Methods and analysisWe studied three countries—Nepal, Senegal, Zambia—with exemplary improvements in coverage between 2000 and 2018 as part of the Exemplars in Global Health Programme. We apply established implementation science frameworks to understand the ‘how’ and ‘why’ underlying improvements in vaccine delivery and coverage. Through mixed-methods research, we will identify drivers of catalytic change in vaccine coverage and the decision-making process supporting these interventions and activities. Methods include quantitative analysis of available datasets and in-depth interviews and focus groups with key stakeholders in the global, national and subnational government and non-governmental organisation space, as well as community members and local health delivery system personnel.Ethics and disseminationWorking as a multinational and multidisciplinary team, and under oversight from all partner and national-level (where applicable) institutional review boards, we collect data from participants who provided informed consent. Findings are disseminated through a variety of forms, including peer-reviewed manuscripts related to country-specific case studies and vaccine system domain-specific analyses, presentations to key stakeholders in the global vaccine delivery space and narrative dissemination on the Exemplars.Health website.

IntroductionIncreases in global childhood vaccine delivery have led to decreases in morbidity from vaccine-preventable diseases. However, these improvements in vaccination have been heterogeneous, with some countries demonstrating greater levels of change and sustainability. Understanding what these high-performing countries have done differently and how their decision-making processes will support targeted improvements in childhood vaccine delivery.Methods and analysisWe studied three countries - Nepal, Senegal, Zambia - with exemplary improvements in coverage between 2000-2018 as part of the Exemplars in Global Health Program. We apply established implementation science frameworks to understand the “how” and “why” underlying improvements in vaccine delivery and coverage. Through mixed methods research we will identify drivers of catalytic change in vaccine coverage and the decision-making process supporting these interventions and activities. Methods include quantitative analysis of available datasets and in-depth interviews and focus groups with key stakeholders in the global, national, and sub-national government and non-governmental organization space, as well as community members and local health delivery system personnel.Ethics and disseminationWorking as a multinational and multidisciplinary team, and under oversight from all partner and national-level (where applicable) institutional review boards, we collect data from participants who provided informed consent. Findings are disseminated through a variety of forms, including peer-reviewed manuscripts related to country-specific case studies and vaccine system domain-specific analyses, presentations to key stakeholders in the global vaccine delivery space, and narrative dissemination on the Exemplars.Health website.Strengths and limitations of this studyThis study is led by a multidisciplinary team and grounded in several theoretical frameworks across disciplines from implementation science to behavioral theory.We utilized a cross cutting, cross-disciplinary, approach, which assessed relevant domains across our selected exemplars countries as well as within the subjects that arise from the data, over a roughly 20-year time horizon.We selected three countries with historically high unvaccinated populations to represent different geographies, cultures, and governments, as well as to highlight regions with historically high unvaccinated populations.We did not study a less successful, or “non-exemplar”, counterfactual country.The research tools identified and explored catalytic events and the implementation of external policies and development of internal policies and systems, with a focus on participants’ current experiences and perceptions of prior activities.

Community-onset bloodstream infections (BSIs) caused by carbapenemase-producingWe performed WGS on 79We identified 5 species and 13 STs of ECC.Our study highlighted that MDR ECC clones are important pathogens of BSIs in community. Though of low prevalence, carbapenem resistance observed in our ECC isolates raised concern about further community dissemination, underscoring the need for community surveillance to identify MDR ECC clones with epidemic potential.

Summary box RI emerged as one the most disrupted health services in early-2020 to mid-2020,1 a global systems shock associated with the COVID-19 pandemic. In May 2020, an estimated 80 million children were thought to be affected by interrupted vaccination services and campaigns,2 and over 60% of 105 countries reported at least partial RI disruptions to WHO.1 If left unaddressed, these disruptions are poised to halt or even reverse decades of global progress achieved in vaccine delivery and child health.3 4 Yet with great challenges can come great opportunity: knowledge and …

Nepal is a country of low endemicity for chronic hepatitis B, with a prevalence of 0.9%. However, in Dolpo District, a higher prevalence of hepatitis B virus (HBV) was reported in small samples, anecdotal reports and, recently, among pregnant women. We determined data on HBV endemicity and risk factors among people from Dolpo (Dolpopa). We conducted a cross-sectional HBV prevalence study among two separate convenience samples of overall 524 Dolpopa, assessing HBV serology on a medical supply tour to Upper Dolpo (Group 1, n = 223) and assessing detailed HBV serology, markers for hepatitis D virus (HDV) and human immunodeficiency virus (HIV) coinfection, as well as a questionnaire-based survey of risk behaviour and alcohol consumption patterns in Dolpopa visiting the Dolpali “Winter Clinic” in Kathmandu (Group 2, n = 301). The overall prevalence of hepatitis B surface antigen (HBsAg) was 18.7% [95% confidence interval (CI) 15.6–22.3%]. HBsAg prevalence was independent of age group and gender, but was significantly higher in the settlements lining the trading route between Nepal and China. From the HBsAg-positive participants, 68.8% (95% CI 56.6–78.8%) also tested positive for hepatitis B e antigen (HBeAg). Viral load among HBeAg-positive samples ranged from 3.12 × 107 to 1.42 × 109 IU/mL. HDV and HIV coinfection was not found. Questionnaires confirmed that 92% had never used a condom and 27.6% showed a risky alcohol consumption pattern. HBV prevalence in Dolpo is significantly higher than in the rest of Nepal. Targeted interventions are recommended to address liver and sexual health education, including the introduction of birth dose HBV vaccinations, HBV screening and HBV vaccinations for pregnant women in Dolpo.

Background Sepsis is an overwhelming and life-threatening response to bacteria in bloodstream and a major cause of neonatal morbidity and mortality. Understanding the etiology and potential risk factors for neonatal sepsis is urgently required, particularly in low-income countries where burden of infection is high and its epidemiology is poorly understood. Methods A prospective observational cohort study was conducted between April 2016 and October 2017 in a level three NICU at a tertiary care hospital in Nepal to determine the bacterial etiology and potential risk factors for neonatal sepsis. Results Among 142 NICU admitted neonates, 15% (21/142) and 32% (46/142) developed blood culture-positive and -negative neonatal sepsis respectively. Klebsiella pneumoniae (34%, 15/44) and Enterobacter spp. (25%, 11/44) were the most common isolates. The antimicrobial resistance of isolates to ampicillin (100%, 43/43), cefotaxime (74%, 31/42) and ampicillin-sulbactam (55%, 21/38) were the highest. BlaTEM (53%, 18/34) and blaKPC (46%, 13/28) were the commonest ESBL and carbapenemase genes respectively. In univariate logistic regression, the odds of sepsis increased with each additional day of use of invasive procedures such as mechanical ventilation (OR 1.086, 95% CI 1.008–1.170), umbilical artery catheter (OR 1.375, 95% CI 1.049–1.803), intravenous cannula (OR 1.140, 95% CI 1.062–1.225); blood transfusion events (OR 3.084, 95% CI 1.407–6.760); NICU stay (OR 1.109, 95% CI 1.040–1.182) and failure to breast feed (OR 1.130, 95% CI 1.060–1.205). Sepsis odds also increased with leukopenia (OR 1.790, 95% CI 1.04–3.082), increase in C-reactive protein (OR 1.028, 95% CI 1.016–1.040) and decrease in platelets count (OR 0.992, 95% CI 0.989–0.994). In multivariate analysis, increase in IV cannula insertion days (OR 1.147, 95% CI 1.039–1.267) and CRP level (OR 1.028, 95% CI 1.008–1.049) increased the odds of sepsis. Conclusions Our study indicated various nosocomial risk factors and underscored the need to improve local infection control measures so as to reduce the existing burden of sepsis. We have highlighted certain sepsis associated laboratory parameters along with identification of antimicrobial resistance genes, which can guide for early and better therapeutic management of sepsis. These findings could be extrapolated to other low-income settings within the region.

Understanding disease burden and transmission dynamics in resource-limited, developing countries like Nepal is often challenging due to a lack of adequate surveillance systems. These issues are exacerbated by limited access to diagnostic and research facilities throughout the country. Nepal has one of the highest COVID-19 case rates (915 cases per 100,000 people) in South Asia, with densely-populated Kathmandu experiencing the highest number of cases. Swiftly identifying case clusters and introducing effective intervention programs is crucial to mounting an effective containment strategy. The rapid identification of circulating SARS-CoV-2 variants can also provide important information on viral evolution and epidemiology. Genomic-based environmental surveillance can help in the early detection of outbreaks before clinical cases are recognized, and identify viral micro-diversity that can be used for designing real-time risk-based interventions. This research aimed to develop a genomic-based environmental surveillance system by detecting and characterizing SARS-CoV-2 in sewage samples of Kathmandu using portable next-generation DNA sequencing devices. Out of 20 selected sites in the Kathmandu Valley, sewage samples from 16 (80%) sites had detectable SARS-CoV-2. A heat-map was created to visualize transmission activity in the community based on viral load intensity and corresponding geospatial data. Further, 41 mutations were observed in the SARS-CoV-2 genome. Some detected mutations (n=9, 2%) were novel and yet to be reported in the global database, with one indicating a frameshift deletion in the spike gene. We also observed more transition than transversion on detected mutations, indicating rapid viral evolution in the host. Our study has demonstrated the feasibility of rapidly obtaining vital information on community transmission and disease dynamics of SARS-CoV-2 using genomic-based environmental surveillance.

The COVID-19 pandemic has inflicted multifaceted disruptions to routine immunisation from global to local levels, affecting every aspect of vaccine supply, access, and demand. Since March 2020, country programmes have implemented a range of strategies to either continue vaccination services during COVID-19 measures like ‘lockdown’ and/or resume services when risks of SARS-CoV-2 transmission could be appropriately mitigated. Through the Exemplars in Global Health partnership in Liberia, Nepal, and Senegal, we conducted interviews with immunisation programme managers and ministry of health leadership to better understand how they have addressed the myriad vaccination challenges posed by the ongoing pandemic. From establishing alternative modes of service delivery to combatting vaccine distrust and rumours via risk communication campaigns, many routine immunisation programmes have demonstrated how to adapt, resume, and/or maintain vital vaccination efforts during the COVID-19 crisis. Yet millions of children remain un- or under-vaccinated worldwide, and the same programmes striving to implement catch-up services for missed doses and postponed mass campaigns will also soon be tasked with COVID-19 vaccine deployment. As laid bare by the current pandemic, the world’s gains against vaccine-preventable diseases are fragile: enshrined by a delicate global ecosystem of logistics, supply, and procurement, the success of routine immunisation ultimately rests upon dedicated programme staff, the resources and support available to them, and then the trust in and demand for vaccines by their recipients. Our collective lessons learned during COVID-19 offer insights in programme adaptation and resilience that, if prioritised, could strengthen equitable, sustainable vaccine delivery for all populations.Summary boxKey message 1: As the COVID-19 pandemic affected routine immunisation services worldwide, country programmes have used a range of mitigation strategies to maintain vaccine delivery and/or resume interrupted programming. Interviews with immunisation programme managers and Ministry of Health staff provided key perspectives and lessons learned on how countries have approached routine immunisation services during the COVID-19 crisis.Key message 2: Key themes for mitigating COVID-19’s effects on routine immunisation included prioritising continued services with strengthened infection prevention control; identifying alternative locations and approaches to providing vaccine services (e.g., conducting door-to-door vaccination if facility-based services were not possible); engaging in effective communications and mobilisation activities, especially to offset misinformation about COVID-19 and vaccines; setting up systems and strategies for reaching children who missed doses amid periods of disruption; and conducting catch-up campaigns as soon as SARS-CoV-2 transmission risks could be minimised.Key message 3: The ways in which COVID-19 has affected routine immunisation services have varied over time and across settings, underscoring the importance of contextually-tailored mitigation efforts and adaptation given evolving challenges amid an ongoing pandemic. As countries prepare and initiate roll-out COVID-19 vaccines, it will be vital to avoid one-size-fits-all implementation strategies and support the continuance of routine immunisation services through this next phase of COVID-19 response.

Journalists play a crucial role in the dissemination of health-related information. In developing countries, such as Nepal, the media are integral in shaping the national agenda and informing the public of important health issues. With an increasing need for a collaborative effort to attain optimal health for people, animals, and the environment, the One Health approach was used to characterize health reporting in Nepal. A comprehensive survey was administered to health journalists regarding their public, animal, and environmental health reporting habits. Seventy-one journalists completed the survey across three study sites. Many journalists indicated a history of reporting across all three sectors but did not routinely focus on health reporting in general. The majority of journalists perceived the quality and overall coverage of health-related topics increased over the last five years. However, few journalists reported receiving specialized training in any health sector. Although the overall quality of health reporting in the Nepali media showed improvements, many journalists acknowledged a lack of understanding of common health topics and a desire to learn more skills related to accurate health reporting. One Health provides a conceptual framework for understanding and promoting health communication through mass media to benefit humans, animals, and ecosystems.

Background HIV is a major public health issue around the world, especially in developing countries. Although the overall prevalence of HIV in Nepal is relatively low, there are specific sub-populations where the prevalence is far higher than the national average. One of these sub-groups is male people who inject drugs (male PWIDs). In order to understand the reasons for the differences in prevalence, a series of socio-demographic, behavioural and knowledge-based risk factors need to be assessed. Methods The study used a series of 7 cross-sectional survey datasets from Pokhara (Nepal), collected between 2003 and 2017 (N = 2235) to investigate trends in HIV prevalence among male PWIDs by socio-demographic and behavioural and knowledge-based risk factors. A series of logistic regression models were conducted to investigate the association between study factors and HIV. Results HIV prevalence decreased from the levels seen in 2003 (22.0%) and 2005 (21.7%), with the lowest prevalence recorded in 2015 (2.6%), however prevalence has increased in the most recent period (4.9%). A lower risk of HIV was associated with younger age ( 24 years, OR = 0.17, 95% CI = 0.10–0.31), being married (OR = 1.91, 95% CI = 1.25–3.02) and shorter duration of drug use ( 4 years, OR = 0.16, 95% CI = 0.09–0.29). A higher risk of HIV was associated with low (compared to secondary or higher) education level (OR = 2.76, 95% CI = 1.75–4.36), a lack of addiction treatment (OR = 2.59, 95% CI = 1.64–4.08), and recent use of unsterilized injection equipment (OR = 2.22, 95% CI = 1.20–4.11). Conclusion The prevalence of HIV in male PWIDs in Pokhara has been variable, but overall has reduced in recent years to 2.6% before increasing in 2017 to 4.9%. The main determinants which increase the risk of HIV among male PWIDs in Pokhara are low education level, a lack of treatment for drug addiction and the recent use of unsterilised equipment. Each of these indicate the need to improve addiction treatment and education programs for intra-venous drug use to aid this key population in avoiding risk-taking behaviours.

The COVID-19 pandemic has exceeded over ten million cases globallywith no vaccine available yet. Different approaches are followed to mitigate its impact and reduce its spreading in different countries, but limiting mobility and exposure have been de-facto precaution to reduce transmission. However, a full lockdown cannot be sustained for a prolonged period. Evidence-based, multidisciplinary approach on risk zoning, personal and transmission risk assessment on a near real-time, and risk communication would support the optimized decisions to minimize the impact of coronavirus on our lives. This paper presents a framework to assess the individual and regional risk of COVID-19 along with risk communication tools and mechanisms. Relative risk scores on a scale of 100 represent the integrated risk of influential factors. The personal risk model incorporates: age, exposure history, symptoms, local risk and existing health condition, whereas regional risk is computed through the actual cases of COVID-19, public health risk factors, socioeconomic condition of the region, and immigration statistics. A web application tool (www.covira.info) has been developed, where anyone can assess their risk and find the guided information links primarily for Nepal. This study provides regional risk for Nepal, but the framework is scalable across the world. However, personal risk can be assessed immediately from anywhere.

Background Despite direct-acting antivirals (DAA), aims to “eradicate” viral hepatitis by 2030 remain unlikely. In Nepal, an expert consortium was established to treat HCV through Nepal earthquakes aftermath offering a model for HCV treatment expansion in a resource-poor setting. Methodology/Principal findings In 2015, we established a network of hepatologists, laboratory experts, and community-based leaders at 6 Opioid Substitution Treatment (OST) sites from 4 cities in Nepal screening 838 patients for a treatment cohort of 600 individuals with HCV infection and past or current drug use. During phase 1, patients were treated with interferon-based regimens (n = 46). During phase 2, 135 patients with optimal predictors (HIV controlled, without cirrhosis, low baseline HCV viral load) were treated with DAA-based regimens. During phase 3, IFN-free DAA treatment was expanded, regardless of HCV disease severity, HIV viremia or drug use. Sustained virologic response (SVR) was assessed at 12 weeks. Median age was 37 years and 95.5% were males. HCV genotype was 3 (53.2%) or 1a (40.7%) and 32% had cirrhosis; 42.5% were HIV-HCV coinfected. The intention-to-treat (ITT) SVR rates in phase 2 and 3 were 97% and 81%, respectively. The overall per-protocol and ITT SVR rates were 97% and 85%, respectively. By multivariable analysis, treatment at the Kathmandu site was protective and substance use, treatment during phase 3 were associated with failure to achieve SVR. Conclusions/Significance Very high SVR rates may be achieved in a difficult-to-treat, low-income population whatever the patient’s profile and disease severity. The excellent treatment outcomes observed in this real-life community study should prompt further HCV treatment initiatives in Nepal., Author summary Despite very effective antiviral therapies, Hepatitis C virus (HCV) eradication remains a major challenge, especially in resource-limited countries. In Nepal, which ranks among the poorest countries in the world an expert consortium was established to treat HCV patients in six centers throughout the country. A cohort of 600 individuals with HCV infection and past or current drug use were treated using different treatment strategies over time. Very high treatment response rates were achieved in a difficult-to-treat, low-income population whatever the patient’s profile and disease severity and despite the severe 2015 earthquakes in Nepal. The excellent treatment outcomes observed in this real-life community study should prompt further HCV treatment initiatives in Nepal.

Background Multi-drug resistance (MDR) and extensive-drug resistance (XDR) associated with extended-spectrum beta-lactamases (ESBLs) and carbapenemases in Gram-negative bacteria are global public health concerns. Data on circulating antimicrobial resistance (AMR) genes in Gram-negative bacteria and their correlation with MDR and ESBL phenotypes from Nepal is scarce. Methods A retrospective study was performed investigating the distribution of ESBL and carbapenemase genes and their potential association with ESBL and MDR phenotypes in E. coli, Klebsiella spp., Enterobacter spp. and Acinetobacter spp. isolated in a major tertiary hospital in Kathmandu, Nepal, between 2012 and 2018. Results During this period, the hospital isolated 719 E. coli, 532 Klebsiella spp., 520 Enterobacter spp. and 382 Acinetobacter spp.; 1955/2153 (90.1%) of isolates were MDR and half (1080/2153) were ESBL producers. Upon PCR amplification, blaTEM (1281/1771; 72%), blaCTXM-1 (930/1771; 53%) and blaCTXM-8 (419/1771; 24%) were the most prevalent ESBL genes in the enteric bacilli. BlaOXA and blaOXA-51 were the most common blaOXA family genes in the enteric bacilli (918/1771; 25%) and Acinetobacter spp. (218/382; 57%) respectively. Sixteen percent (342/2153) of all isolates and 20% (357/1771) of enteric bacilli harboured blaNDM-1 and blaKPC carbapenemase genes respectively. Of enteric bacilli, Enterobacter spp. was the most frequently positive for blaKPC gene (201/337; 60%). The presence of each blaCTX-M and blaOXA were significantly associated with non-susceptibility to third generation cephalosporins (OR 14.7, p p blaTEM, blaCTXM and blaOXA family genes were significantly associated with ESBL positivity (OR 2.96, p p p p p p Conclusions This study documents an alarming level of AMR with high prevalence of MDR ESBL- and carbapenemase-positive ESKAPE microorganisms in our clinical setting. These data suggest a scenario where the clinical management of infected patients is increasingly difficult and requires the use of last-resort antimicrobials, which in turn is likely to intensify the magnitude of global AMR crisis.

Summary Telomere length dynamics and DNA damage responses were assessed before, during, and after one-year or shorter duration missions aboard the International Space Station (ISS) in a comparatively large cohort of astronauts (n = 11). Although generally healthy individuals, astronauts tended to have significantly shorter telomeres and lower telomerase activity than age- and sex-matched ground controls before and after spaceflight. Although telomeres were longer during spaceflight irrespective of mission duration, telomere length shortened rapidly upon return to Earth, and overall astronauts had shorter telomeres after spaceflight than they did before; inter-individual differences were identified. During spaceflight, all crewmembers experienced oxidative stress, which positively correlated with telomere length dynamics. Significantly increased frequencies of chromosomal inversions were observed during and after spaceflight; changes in cell populations were also detected. We propose a telomeric adaptive response to chronic oxidative damage in extreme environments, whereby the telomerase-independent Alternative Lengthening of Telomeres (ALT) pathway is transiently activated in normal somatic cells.

BackgroundUnderstanding and describing the regional and climatic patterns associated with increasing dengue epidemics in Nepal is critical to improving vector and disease surveillance and targeting control efforts.MethodsWe investigated the spatial and temporal patterns of annual dengue incidence in Nepal from 2010 to 2019, and the impacts of seasonal meteorological conditions (mean maximum, minimum temperature and precipitation) and elevation on those patterns.ResultsMore than 25 000 laboratory-confirmed dengue cases were reported from 2010 to 2019. Epidemiological trends suggest that dengue epidemics are cyclical with major outbreaks occurring at 2- to 3-y intervals. A significant negative relationship between dengue incidence and increasing elevation (metres above sea level) driven by temperature was observed (pConclusionsThe spatial analysis and interpretation of dengue incidence over the last decade in Nepal confirms that dengue is now a well-established public health threat of increasing importance, particularly in low elevation zones and urbanised areas with a tropical or subtropical climate. Seasonal variations in temperature during the monsoon months are associated with increased transmission.

Background Antimicrobial resistance (AMR) among bacterial pathogens is a fast-growing public health concern. AMR in non-typhoidal Salmonella serovars (NTS) among food animals is of special concern as this may transmit resistant pathogens to humans during handling or consumption of animal products. In Nepal, the possibility of AMR Salmonella serovars among food animals is an important area of research, particularly in light of the rapidly growing poultry industry, lack of surveillance and proper biosecurity measures; and paucity of relevant data. This study was conducted with the aim to estimate the burden of NTS and associated antimicrobial resistance in the environments of commercial poultry farms and the poultry carcasses in slaughter house. This study also intends to find some basic knowledge of the poultry farmers and their practice relating to the use of antimicrobials, vaccination and biosecurity measures. Methods Taking one health approach, a cross-sectional study was carried out in Chitwan district of Nepal between May and October 2017. Various environmental samples viz. farm litter, feed, water, poultry faeces, vehicle swabs, farm swabs from 12 broiler poultry farms and various sections of poultry carcasses from 21 slaughter houses were aseptically collected. These were microbiologically assessed for the presence of NTS serovars and their phenotypic and genotypic indicators of antimicrobial resistance. The poultry farmers were also briefly interviewed regarding their basic biosecurity related knowledge and practices before collecting the environmental samples. Results Overall, of total environmental samples collected, 50% (31/62) tested positive for NTS serovars with environmental swabs (70%, 8/12) being the most culture positive sample types. Similarly, of 159 tissue samples collected from 24 carcasses, 79% (126/159) were culture positive for NTS serovars. Nearly 97% (153/157) of isolates showed antimicrobial resistance to tetracycline, while 11% (17/157) to ciprofloxacin and 5% (8/157) of isolates were resistant against azithromycin. All 157 isolates were sensitive to meropenem. In terms of AMR genes, tetA (83%, 131/157), QrnS (40%,64/157), mefA (8%, 13/157) and VIM-1 (0.6%, 1/157) were detected in the isolates that corresponded to the AMR to tetracycline, ciprofloxacin, azithromycin and meropenem respectively. In farmers interview, only 42% (5/12) of farmers mentioned of using basic biosecurity measures such as applying lime powder around the farm; 84% (10/12) of farmers reported vaccinating their birds with some vaccine and 75% (9/12) of farmers used various antimicrobials prophylactically such as neomycin (33%, 4/12), colistin (33%, 4/12), furaltadone (33%, 4/12), doxycycline (25%, 3/12), sulfatrimethoprim (25%, 3/12) and tylosin (16%, 2/12). Conclusions This study revealed gross contamination of farm environment and subsequent poultry meat samples with NTS serovars that were resistant to several clinically important antimicrobials. Further, inadequacy of even basic biosecurity measures and frequent prophylactic use of antimicrobials in the commercial poultry farms was observed. This reinforces an urgent need to raise awareness and implement proper biosecurity approaches from farms to slaughter houses in order to reduce the burden of NTS contamination of surrounding environment and poultry products. Further, high prevalence AMR among NTS isolates also underscores the need to strengthen the policies to prevent the rampant use of clinically used human antimicrobials in poultry sector.

BackgroundAntimicrobial resistance (AMR) among bacterial pathogens is a fast-growing public health concern. AMR in non-typhoidal Salmonella species among food animals is of special concern as this may transmit resistant pathogens to humans during handling or consumption of animal products. In Nepal, the possibility of AMR Salmonella species among food animals is an important area of research, particularly in light of the rapidly growing poultry industry, lack of surveillance, and paucity of studies that have been conducted. MethodsTaking one health approach, a cross-sectional study was carried out in Chitwan district of Nepal between May and October 2017. Various environmental samples viz. farm litter, feed, water, poultry feces, vehicle swabs, farm swabs from 12 broiler poultry farms and various sections of poultry carcasses from 21 slaughter houses were aseptically collected. These were microbiologically assessed for the presence of non-typhoidal Salmonella and their phenotypic and genotypic indicators of antimicrobial resistance. ResultsOverall, Of 62 environmental samples collected, 31(50%) tested positive for Salmonella enterica serovars with environmental swabs (70%, 8/12) being the most culture positive sample types. Similarly, of 159 tissue samples collected from 24 carcasses, 79% (126/159) were culture positive for Salmonella enterica. Nearly 97% (153/157), 11% (17/157), 5% (8/157) and none of isolates showed resistance to tetracycline, ciprofloxacin, azithromycin and meropenem respectively. Some 83% (131/157), 40% (64/157), 8% (13/157) and 0.6% (1/157) of isolates tested positive for tetA, QrnS, mefA and VIM-1 AMR genes corresponding to the above antimicrobials respectively.ConclusionsThis study revealed gross contamination of farms and subsequent poultry meat samples with Salmonella enterica serovars that were resistant to several clinically applicable antimicrobials. This reinforces an urgent need to implement proper biosecurity approaches from farms to slaughter houses and strengthen policies to cease the rampant use of clinically important antimicrobials in poultry.

Background HIV is a major public health issue around the world, especially in developing countries. Although the overall prevalence of HIV in Nepal is relatively low and the country itself is considered low risk, there are specific sub-populations where the prevalence is far higher than the national average. One of these sub-groups is male injection drug users (IDUs). In order to understand the reasons for the differences in prevalence, a series of socio-demographic, behavioural and knowledge-based risk factors need to be assessed.Methods The study used a series of 7 cross-sectional survey datasets, collected between 2003 and 2017 (N=2,235) to investigate trends in HIV prevalence among male IDUs by key socio-demographic and behavioural and knowledge-based risk factors. A series of logistic regression models were conducted to investigate the association between study factors and HIV in the Pokhara valley, Nepal.Results A lower risk of HIV was associated with younger age (≤24 years compared to >24 years, OR = 0.17, 95% CI = 0.10, 0.31), not being married (OR = 0.51, 95% CI = 0.33, 0.80) and shorter duration of drug use (≤4 years compared to >4 years, OR = 0.16, 95% CI = 0.09, 0.29). A higher risk of HIV was associated with low (compared to secondary or higher) education level (OR = 2.76, 95% CI = 1.75, 4.36), a lack of addiction treatment (OR = 2.59, 95% CI = 1.64, 4.08), and recent use of unsterilized injection equipment (OR = 2.22, 95% CI = 1.20, 4.11).Conclusion Although knowledge of HIV is high among male IDUs, the prevalence of individuals who possess comprehensive knowledge and the number of individuals who have received treatment for drug addiction has decreased. This may indicate that addiction treatment and HIV education programs need to be strengthened.

Background Nepal is facing double burden of injecting drug use and HIV, yet the problem of Hepatitis C Virus (HCV) has not been so well addressed, where there is large population known to be at risk for HCV. This study assessed the prevalence of HCV infection and HIV/HCV co-infection among male injection drug users (IDUs) in Nepal and identified factors associated with infection. Methods Cross-sectional surveys in 2015 aimed to sample 1045 male IDUs in the Kathmandu valley, Pokhara Valley and Eastern Terai districts of Nepal. Information about socio demographic characteristics, injecting and sexual risk behaviours were obtained, and biological specimens tested for HCV and HIV. The logistic regression model was used to identify the determinants associated with HCV and HIV/HCV co-infection. Results HCV prevalence was 28.8% and HIV/HCV co-infection was 4%. Among the 6% of HIV positive male IDUs, 65% were found to be co-infected. The multivariate logistic analysis revealed that HCV prevalence was higher in Eastern Terai districts, longer duration of drug use and injecting drugs and presence of HIV. Similarly, HIV/HCV co-infection was associated with Eastern highway districts, older age and longer duration of injecting drugs. Conclusion The factors strongly contributing to HCV and HIV/HCV co-infection was longer duration of injecting drugs. Highest HCV and HIV/HCV co-infection was found in Eastern Terai districts. Target health interventions need to be focused in Eastern Terai districts and IDUs with longer duration of injecting drugs for the prevention of HCV and HIV/HCV transmission.

Background The potential to strengthen routine immunization (RI) services through supplementary immunization activities (SIAs) is an important benefit of global measles and rubella elimination and polio eradication strategies. However, little evidence exists on how best to use SIAs to strengthen RI. As part the 2012 Nepal measles-rubella and polio SIA, we developed an intervention package designed to improve RI processes and evaluated its effect on specific RI process measures. Methods The intervention package was incorporated into existing SIA activities and materials to improve healthcare providers' RI knowledge and practices throughout Nepal. In 1 region (Central Region) we surveyed the same 100 randomly selected health facilities before and after the SIA and evaluated the following RI process measures: vaccine safety, RI planning, RI service delivery, vaccine supply chain, and RI data recording practices. Data collection included observations of vaccination sessions, interviews with the primary healthcare provider who administered vaccines at each facility, and administrative record reviews. Pair-matched analytical methods were used to determine whether statistically significant changes in the selected RI process measures occurred over time. Results After the SIA, significant positive changes were measured in healthcare provider knowledge of adverse events following immunization (11% increase), availability of RI microplans (+17%) and maps (+12%), and awareness of how long a reconstituted measles vial can be used before it must be discarded (+14%). For the SIA, 42% of providers created an SIA high-risk villages list, and >50% incorporated this information into RI outreach session site planning. Significant negative changes occurred in correct knowledge of measles vaccination contraindications (-11%), correct definition for a measles outbreak (-21%), and how to treat a child with a severe adverse event following immunization (-10%). Twenty percent of providers reported cancelling ≥1 RI sessions during the SIA. Many RI process measures were at high proportions (>90%) before the SIA and remained high afterward, including proper vaccine administration techniques, proper vaccine waste management, and availability of vaccine carriers and vaccine registers. Conclusions Focusing on activities that are easily linked between SIAs and RI services, such as using SIA high-risk village list to strengthen RI microplanning and examining ways to minimize the impact of an SIA on RI session scheduling, should be prioritized when implementing SIAs.

Background In Nepal, an estimated 2–4% of the population has chronic hepatitis B virus (HBV) infection. To combat this problem, from 2002 to 2004, a national three dose hepatitis B vaccination program was implemented to decrease infection rates among children. The program does not currently include a birth dose to prevent perinatal HBV transmission. In 2012, to assess the impact of the program, we conducted a serosurvey among children born before and after vaccine introduction. Methods In 2012, a cross-sectional nationally representative stratified cluster survey was conducted to estimate hepatitis B surface antigen (HBsAg) prevalence among children born from 2006 to 2007 (post-vaccine cohort) and among children born from 2000 to 2002 (pre-vaccine cohort). Demographic data, as well as written and oral vaccination history were collected. All children were tested for HBsAg; mothers of HBsAg positive children were also tested. Furthermore, we evaluated the field sensitivity and specificity of the SD Bioline HBsAg rapid diagnostic test by comparing results with an enzyme immunoassay. Results Among 2181 post-vaccination cohort children with vaccination data by either card or recall, 86% (95% confidence interval [CI] 77–95%) received ≥3 hepatitis B vaccine doses. Of 1200 children born in the pre-vaccination cohort, 0.28% (95% CI 0.09–0.85%) were positive for HBsAg; of 2187 children born in the post-vaccination cohort, 0.13% (95% CI 0.04–0.39%) were positive for HBsAg (p = 0.39). Of the six children who tested positive for HBsAg, two had mothers who were positive for HBsAg. Finally, we found the SD Bioline HBsAg rapid diagnostic test to have a sensitivity of 100% and a specificity of 100%. Conclusions This is the first nationally representative hepatitis B serosurvey conducted in Nepal. Overall, a low burden of chronic HBV infection was found in children born in both the pre and post-vaccination cohorts. Current vaccination strategies should be continued.

Summary Objectives To assess the prevalence of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) co-infections among people living with HIV (PLHIV) in Nepal. Methods A sample of 677 PLHIV representing key affected populations (KAP) in Nepal, who were undergoing antiretroviral (ART) therapy in ART clinics around the country, were voluntarily enrolled in the study. Rapid kit-based testing followed by ELISA for validation was performed, focusing on HBV surface antigen (HBsAg) and antibodies against HCV (anti-HCV). A multivariate logistic regression model was used to identify factors associated with HBV and HCV co-infection. Results HCV and HBV co-infection among the 677 PLHIV was found to be 19% (95% confidence interval (CI) 16.6–22.7%) and 4.4% (95% CI 3.1–6.6%), respectively. The Eastern Region had the highest percentage of HCV infection (48%). The age group with the highest rates of co-infection was 30–39 years (58% and 70%, respectively, for HCV and HBV co-infection). After adjusting for confounding, males were more likely to have HBV co-infection than females (adjusted odds ratio (AOR) 4.61, 95% CI 1.42–14.98). Similarly, PLHIV who were male (AOR 5.7, 95% CI 2.06–15.98), had a secondary level of education (AOR 3.04, 95% CI 1.06–8.70), or who were drug users (AOR 28.7, 95% CI 14.9–55.22) were significantly more likely to have HCV co-infection. Conclusion This first ever national assessment of HIV, HBV, and HCV co-infection performed among PLHIV in Nepal demonstrates that HCV and HBV infections are a health threat to this population and that interventions are required to mitigate the effects of co-infection and to prevent further morbidity and mortality.

As part of a comprehensive health care programme for people who use drugs in Nepal, HIV and viral hepatitis B and C status--including risk factors, HCV-genotypes and co-infections--as well as two IL28B Single-nucleotide polymorphisms (SNPs) were assessed for a random sample of 401 people who inject drugs in three regions of Nepal: mid-western Terrai (Nepalgunj), the eastern region (Dharan, Biratnagar) and the central region (Kathmandu, Lalitpur and Chitwan). Individuals were included who showed at least a minimum of health care seeking behaviour. This latter criterion was defined by being registered with any organisation offering health services. The average age of the participants was 30.5 yrs, and the average length of intravenous drug use was 8.5 yrs. The prevalence rates of HBsAg, anti-HIV antibodies and HCV-RNA were 3.5%, 13.8% and 41.9%, respectively. Spontaneous HCV clearance was evident in 16% of all of those who tested positive for anti-HCV antibodies. Independent risk factors for HCV-RNA positivity were age, gender, geographical region, duration of injecting drug use, history of imprisonment and HIV co-infection. In the age group ≤24 yrs, the rate of spontaneous HCV clearance was 43.5%. Overall, 59.8% of HCV infections were caused by HCV genotype 3 and 40.2% by HCV genotype 1. No other HCV genotypes were identified in this study. The IL28B SNP rs12979860 and rs8099917 were identified in 122 patients, and 75.4% of all participants had both favourable genotypes rs12979860 C/C and rs8099917 T/T.

Diversity studies of entericEscherichia colihave relied almost entirely on faecal isolations on the assumption that they are representative of flora found throughout the gastrointestinal tract. The authors have addressed this belief by analysing isolates obtained from the duodenum, ileum, colon and faeces of pigs.E. coliisolates were obtained from eight pigs and characterized using multi-locus enzyme electrophoresis and PCR-based screening for a range of factors thought to be associated with intestinal and extra-intestinal disease. There are four main genetic groups of commensalE. coli(A, B1, B2, D). Group A strains represented 76 % of the isolates from the duodenum, ileum and colon compared to 58 % of the strains isolated from faeces. A nested molecular analysis of variance based on the allozyme and virulence factor screening results showed that differences among individual pigs accounted for 6 % of the observed genetic diversity, whilst 27 % of the genetic variation could be explained by clonal composition differences among gut regions. Finally, the absence of virulence genes in these commensals indicates that they may be suitable as a probiotic consortium, particularly if they also display increased adherence to enterocytes and antagonistic activity against pathogenic strains ofE. coli.

Background Anti Retroviral Therapy (ART) is the cornerstone for comprehensive health sector response to Human Immunodeficiency Virus (HIV) treatment, care and support. Adherence of at least 95% is needed to keep HIV under control, as per World Health Organization (WHO) guidelines. This study was aimed at identifying the overall adherence level of, and barriers and facilitators to adherence for patients taking ART in different clinics in all five development regions of Nepal. Methods A descriptive cross-sectional study was conducted among ART clients receiving free ART from Government of Nepal ART clinics. A total of 435 clients taking ART from twelve ART clinics in different regions of Nepal, aged fifteen years and above were interviewed on one-and-one basis using questionnaires developed in reference to Adult AIDS Clinical Trial Group (AACTG) toolkit among them data from 404 were analyzed after cleaning. Data was entered and analyzed using Statistical Package for Social Sciences (SPSS) software where the P value of

Background Malaria is a major public health problem in Nepal inflicted primarily by the parasite Plasmodium vivax, - the only species responsible for relapse cases in Nepal. Knowledge on its relapse rate is important for successful malaria control, but is lacking in Nepal. The information on circulating predominant genotypes of P. vivax is equally relevant for high endemic districts of Nepal to understand the transmission dynamics of the parasite and to uncover the coverage and efficacy of potential vaccine beforehand. Methods A prospective observational study with a six months follow-up period was conducted from August 2010 to May 2011 in four health centres of Kailali and Kanchanpur districts of Nepal to access the relapse/re-infection rate of P. vivax. The prevalence and heterogeneity of its genotypes were identified by PCR-RFLP assay targeting central repeat region of circumsporozoite protein (Pvcsp). Results In total, 137 cases microscopically suspected to have P. vivax infection were enrolled in the study. Of these, 23 cases (17%) were detected for the relapse/ re-infection-during a six-month period, with a high proportion being male cases of age group 11–20 years. For genotyping, 100 whole blood samples were analysed, of which 95% of the parasite isolates were found to be of VK210 genotype. The minor genotype VK247 existed either in isolation or as mixed infection with VK210 in rest of the samples. Conclusions The relapse/re-infection rate of 17% was determined for P. vivax in Kailali and Kanchanpur districts of Nepal. A heterogeneous Pvcsp genotypic distribution of P. vivax was detected with VK210 being a predominant type, suggesting a complex transmission dynamics of the parasite. Expanding such study in other endemic regions of Nepal would help provide a complete picture on relapse/re-infection rate and parasite genotypic variability that can help in effective control and management of malaria in Nepal.

b Objectives: Cervical cancer is the commonest malignancy among women in Nepal but data are limited on which subtypes of human papillomavirus (HPV) are associated with cancer in this population. Now that vaccines against HPV types 16 and 18 are available, this evidence is of vital importance in obtaining further support for a vaccination programme. Methods: Cervical swabs from 44 histologically confirmed invasive cervical cancer cases were obtained from two tertiary referral hospitals in Nepal. Evidence of HPV subtypes was identified using an HPV multiplex polymerase chain reaction (PCR), and confirmed at the Scottish HPV Virus Reference Laboratory. Results: HPV types 16 and 18 were present in 70% of samples, along with other high-risk subtypes. HPV 6 and 11 were not observed. Epidemiological data assessment appeared to indicate that patient age, age of marriage and age of first pregnancy were associated with increased HPV infection in patients. Conclusions: This study provides further evidence of the importance of HPV types 16 and 18 in cervical cancer in Nepal and adds support to a nationwide vaccination programme and the use of HPV detection in screening programmes.

In the year 2000, Oelrichs et al. reported the presence of HIV-1 subtype C in Nepal ([3][1]). These findings were based on the env gene sequences from 36 HIV-1 patients. They reported that Nepali HIV sequences showed a close clustering pattern with the Indian reference sequences, indicating the

Background: Diarrhea is a major public health problem in Nepal. Recently, there was an outbreak of diarrheal diseases in different districts of mid and far western region of Nepal and the most affected district was Jajarkot. The objective of this study was to detect the causative organism and analyze the epidemic outbreak patterns of diarrhea in selected health institutions in Jajarkot district, Midwestern Region of Nepal, in terms of their demographic characteristics and laboratory findings of stool specimens. Methods: A descriptive study was conducted using secondary data from health institutions of two Village Development committees of Jajarkot. Stool samples were collected purposively to identify the agents of diarrheal diseases. Results: Out of the total 13 stool samples tested, 5 were diagnosed as harboring Vibrio cholerae. The Attack Rate and Case Fatality Ratio were calculated to be 8.2% and 1% respectively for the District. Age groups 15-44 were highly affected; male and female were approximately equally affected. Conclusions: Cholera appears to have been the most important cause for mortality in Jajarkot diarrhea outbreak. The diarrhea outbreak in any districts of Nepal should be closely monitored for the possibility of a Cholera epidemic in the future. Key words : cholera; diarrhea; epidemic; outbreak. DOI: 10.3126/jnhrc.v7i2.3008 Journal of Nepal Health Research Council Vol.7(2) Apr 2009 66-68

Background The true prevalence of HIV and other sexually transmitted diseases among street children in Nepal is virtually unknown while information on related behavioural risk factors in this population is non-existent. The risk of HIV infection among street children and adolescents may be especially high due to their marginalized social and economic conditions. This study was conducted to determine the prevalence of HIV infection among a sample of street children and youth of Kathmandu and to identify risk factors associated with HIV infection in this group. A sample of street children and youth was recruited based on the purposive sampling of ten streets in Kathmandu, Nepal, known to have a high density of street children and youth. A total of 251 street children (aged 11–16 years) and youth (aged 17–24 years) were enrolled, with informed consent, from November, 2008 through June, 2009. Most of the participants (95%) were male. Case status was determined by serological assessment of HIV status; data on risk factors were obtained using structured survey interviews. HIV prevalence and rates of a number of behavioural risk factors suspected to play a role in HIV transmission among street children and youth were determined, including unprotected sex, intravenous drug use, and other risky sex and substance use behaviours. Results Among the 251 children and youth, we found an overall HIV prevalence of 7.6%. As the sample size of females was small (n = 13) and the behavioural risk factors are likely to be quite different for boys and girls, we conducted separate analyses by gender. As our small sample of females is unlikely to be representative and lacks power for statistical testing, our report focuses on the results for the males surveyed.The strongest behavioural risk factor to emerge from this study was intravenous drug use; 30% of the male subjects were injecting drug users and 20% of those were HIV positive. Furthermore, frequency of drug injection was a highly significant predictor with a dose–response relationship; males reporting occasional injection drug use were nearly 9 times more likely to be HIV positive than never users, while weekly drug injectors had over 46 times the risk of non-users, controlling for exposure to group sex, the only other significant risk factor in the multivariate model. Conclusions This sample of street children and youth of Kathmandu has a nearly 20-fold higher prevalence of HIV infection than the general population of Nepal (0.39%). The children and youth engage in number of high risk behaviours, including intravenous drug use, putting them at significant risk of contracting HIV and other sexually transmitted infections.