The long-term impact of vaccine clinical research on national stakeholders involved: Experience from a low-income Country.

Clinical trials are the most rigorous scientific and regulated method to investigate the safety and efficacy of vaccines or drugs in pre-licensure stage. Clinical trial design and implementation are complex, time-consuming and involves close engagement with country's regulatory authority, clinical trial sites, investigators, and the healthcare system. Over the past few decades, a significant number of clinical trials have been conducted in low- and middle-income countries (LMICs), particularly in resource-limited settings.

Geospatial distribution of Hepatitis E seroprevalence in Nepal, 2021.

Background: Hepatitis E virus (HEV) causes acute jaundice and poses an important public health problem in low- and middle-income countries. Limited surveillance capacity and suboptimal access to diagnostics leads to under-reporting of HEV infections in affected countries, including Nepal. Serum antibodies against HEV are indicative of past infection.

Hepatitis E virus in the Kathmandu Valley: Insights from a representative longitudinal serosurvey.

Background: Hepatitis-E virus (HEV), an etiologic agent of acute inflammatory liver disease, is a significant cause of morbidity and mortality in South Asia. HEV is considered endemic in Nepal; but data on population-level infection transmission is sparse.

Methods: We conducted a longitudinal serosurvey in central Nepal to assess HEV exposure.

Estimating the Seroincidence of Scrub Typhus using Antibody Dynamics after Infection.

Scrub typhus, a vector-borne bacterial infection, is an important but neglected disease globally. Accurately characterizing the burden is challenging because of nonspecific symptoms and limited diagnostics. Prior seroepidemiology studies have struggled to find consensus cutoffs that permit comparisons of estimates across contexts and time.

Effects of a dietary intervention on cardiometabolic risk and food consumption in a workplace.

Background: Worksite-based health programs have shown positive impacts on employee health and have led to significant improvements in cardiovascular risk factor profiles. We aimed to determine the effect of cafeteria intervention on cardio-metabolic risk factors diet in a worksite setting (Dhulikhel Hospital) in Nepal.

Methods: In this one-arm pre-post intervention study, we recruited 277 non-pregnant hospital employees aged 18-60 with prediabetes or pre-hypertension.

Safety and immunogenicity of the Euvichol-S oral cholera vaccine for prevention of Vibrio cholerae O1 infection in Nepal: an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial.

Background: In October, 2017, WHO launched a strategy to eliminate cholera by 2030. A primary challenge in meeting this goal is the limited global supply capacity of oral cholera vaccine and the worsening of cholera outbreaks since 2021. To help address the current shortage of oral cholera vaccine, a WHO prequalified oral cholera vaccine, Euvichol-Plus was reformulated by reducing the number of components and inactivation methods.

Detection of Salmonella Typhi bacteriophages in surface waters as a scalable approach to environmental surveillance.

Background: Environmental surveillance, using detection of Salmonella Typhi DNA, has emerged as a potentially useful tool to identify typhoid-endemic settings; however, it is relatively costly and requires molecular diagnostic capacity. We sought to determine whether S. Typhi bacteriophages are abundant in water sources in a typhoid-endemic setting, using low-cost assays.

Safety and immunogenicity of conjugate vaccine for typhoid (Vi-DT): Finding from an observer-blind, active-controlled, randomized, non-inferiority, phase III clinical trial among healthy volunteers.

Typhoid fever is a significant public health concern with most of the sufferers between 15 and 25 y of age in Nepal. We undertook this study to demonstrate Vi polysaccharide conjugated with diphtheria toxoid (Vi-DT) conjugate vaccine which is non-inferior to Typbar typhoid conjugate vaccine, a Vi polysaccharide vaccine conjugated with tetanus toxoid (Vi-TT) with a focus on the adult population from Dhulikhel Hospital which was one of the total four sites in Nepal. In this study, we assigned the eligible participants in 1:1:1:1 ratio by block randomization, and stratified into three age groups (6 months to less than 2 y, 2 y to less than 18 y, and 18 y to 45 y), allotted to Group A, B, C, and D.

Environmental sampling for typhoidal Salmonellas in household and surface waters in Nepal identifies potential transmission pathways.

Introduction: Salmonella Typhi and Salmonella Paratyphi, fecal-oral transmitted bacterium, have temporally and geographically heterogeneous pathways of transmission. Previous work in Kathmandu, Nepal implicated stone waterspouts as a dominant transmission pathway after 77% of samples tested positive for Salmonella Typhi and 70% for Salmonella Paratyphi. Due to a falling water table, these spouts no longer provide drinking water, but typhoid fever persists, and the question of the disease's dominant pathway of transmission remains unanswered.

Genomic analysis of SARS-CoV-2 Circulating during Second and Third Wave of COVID-19 in Nepal.

Background: In Nepal, since the first detection of COVID-19 case in January 2020, the total cases have rose to almost a million with more than 12,000 deaths. Till now, WHO has classified 5 variants of SARS-Cov2 as variant of concerns at different time points causing many waves in different countries and regions at different time points. Nepal had also faced three distinct waves of COVID-19 caused by different variant of COVID 19.

Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Typhi genomes.

Background: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000).

Methods: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch.

Prevalence and factors associated with depression, anxiety, and stress symptoms among home isolated COVID-19 patients in Western Nepal.

Introduction: Globally, COVID-19 pandemic has a significant impact on mental health. In Nepal, COVID-19 positive cases have to self-isolate at home in multi-generational and multi-family households. This could be strongly associated with depression, anxiety, and stress-related health outcomes.

Stakeholder engagement in a hypertension and diabetes prevention research program: Description and lessons learned.

Background: Stakeholder engagement is important from the management point of view to capture knowledge, increase ownership, reduce conflict, encourage partnership, as well as to develop an ethical perspective that facilitates inclusive decision making and promotes equity. However, there is dearth of literature in the process of stakeholder engagement. The purpose of this paper is to describe the process of increasing stakeholder engagement and highlight the lessons learnt on stakeholder engagement while designing, implementing, and monitoring a study on diabetes and hypertension prevention in workplace settings in Nepal.

Incidence of typhoid and paratyphoid fever in Bangladesh, Nepal, and Pakistan: results of the Surveillance for Enteric Fever in Asia Project.

Background: Precise enteric fever disease burden data are needed to inform prevention and control measures, including the use of newly available typhoid vaccines. We established the Surveillance for Enteric Fever in Asia Project (SEAP) to inform these strategies.

Methods: From September, 2016, to September, 2019, we conducted prospective clinical surveillance for Salmonella enterica serotype Typhi (S Typhi) and Paratyphi (S Paratyphi) A, B, and C at health facilities in predetermined catchment areas in Dhaka, Bangladesh; Kathmandu and Kavrepalanchok, Nepal; and Karachi, Pakistan.

Consumer acceptance and preference for brown rice-A mixed-method qualitative study from Nepal.

Background: Brown rice consumption reduces the risk of diabetes. The prevalence of diabetes is increasing in Nepal; however, dietary preference remains for white rice. This study aimed to understand the perception, enablers, barriers, and facilitators of acceptance brown rice at a worksite cafeteria.

Safety and immunogenicity of the Vi-DT typhoid conjugate vaccine in healthy volunteers in Nepal: an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial.

Background: Typhoid fever is an endemic disease in many low-income and middle-income countries. The 2018 WHO position paper recommends that countries should consider typhoid vaccination in high-risk groups and for outbreak control. To address the typhoid vaccine supply and demand gap, a typhoid Vi polysaccharide-diphtheria toxoid (Vi-DT) conjugate vaccine development effort was undertaken to achieve WHO prequalification and contribute to the global supply of typhoid conjugate vaccine.

Association Between Erectile Dysfunction and Type 2 Diabetes Mellitus.

Background: Erectile dysfunction is a distressing complication of diabetes among male patients. Despite being a serious concern affecting sexual health, the issue regarding sexual dysfunction is seldom discussed by patients with physicians in developing countries. This study aimed to identify the prevalence of Erectile dysfunction and its association with other risk factors among type 2 Diabetic males attending the tertiary care hospital in Nepal.

Prevalence of Malnutrition among Elderly People Living in a Rural Area of Nepal.

Introduction: Elderly population is more likely to suffer from malnutrition due to aging-associated factors that influence nutritional status like loss of appetite, swallowing difficulties, digestive problems, and chronic illness. There is insufficient information related to the nutritional status of the elderly in Nepal. Hence, this study aims to determine the prevalence of malnutrition among elderly people living in the rural area of the Kavrepalanchok district.

Antimicrobial Resistance in Typhoidal Salmonella in Nepal: Surveillance for Enteric Fever, 2016-2019.

Background: Enteric fever (caused by Salmonella enterica) has been associated with poor hygiene and is endemic in the South-Asian countries. The increase in resistance to first line antimicrobials has been observed, while the emergence of multi/extremely drug resistance cases have been identified in several countries. The objective of this study is to analyze the current trend of antimicrobial resistance in Salmonella isolates in Nepal, and to identify the status of multi- and extremely- drug resistant isolates.

Impact of Service User Video Presentations on Explicit and Implicit Stigma toward Mental Illness among Medical Students in Nepal: A Randomized Controlled Trial.

This study evaluated the impact of didactic videos and service user testimonial videos on mental illness stigma among medical students. Two randomized controlled trials were conducted in Nepal. Study 1 examined stigma reduction for depression.

Challenges and opportunities in setting up a phase III vaccine clinical trial in resource limited settings: Experience from Nepal.

Clinical trials are complicated, time-consuming and costly. From the initial screening, informed consent and recruitment of the participants' to study completion, the sponsor must undertake a wide array of complex and closely monitored operations, complying with international standards for human subject research and local requirements. Conducting these studies in an underdeveloped country, with limited resources, infrastructure, and experience with regulated clinical trials adds to this complexity.

Utilization of Blood Culture in South Asia for the Diagnosis and Treatment of Febrile Illness.

Background: Blood culture is the current standard for diagnosing bacteremic illnesses, yet it is not clear how physicians in many low- and middle-income countries utilize blood culture for diagnostic purposes and to inform treatment decisions.

Methods: We screened suspected enteric fever cases from 6 hospitals in Bangladesh, Nepal, and Pakistan, and enrolled patients if blood culture was prescribed by the treating physician. We used generalized additive regression models to analyze the probability of receiving blood culture by age, and linear regression models to analyze changes by month to the proportion of febrile cases prescribed a blood culture compared with the burden of febrile illness, stratified by hospital.