Phenotypic variation in the lipopolysaccharide O-antigen of Salmonella Paratyphi A and implications for vaccine development.

Enteric fever remains a major public health problem in South and Southeast Asia. The recent roll-out of the typhoid conjugate vaccine protecting against S. Typhi exhibits great promise for disease reduction in high burden areas.

Social cohesion among healthcare workers during COVID-19: Qualitative research in Indonesia, Nepal, and Vietnam.

Existing literature has portrayed numerous challenges that healthcare workers (HCWs) faced during the COVID-19 pandemic, such as heightened risks of transmission against the scarcity of protective equipment, burgeoning workload, and emotional distress, to name a few. However, most studies explored HCWs' experiences at the individual level rather than examining the collective responses. Exploring these experiences could reveal the social-cultural locality of the pandemic while identifying the system constraints in public health emergencies.

The facilitators of and barriers to antimicrobial use and misuse in Lalitpur, Nepal: a qualitative study.

Background: Antimicrobial resistance (AMR) is a pressing global health concern driven by inappropriate antibiotic use, which is in turn influenced by various social, systemic, and individual factors. This study, nested within FIND's AMR Diagnostic Use Accelerator clinical trial in Nepal, aimed to (i) explore the perspectives of patients, caregivers, and healthcare workers (HCWs) on antibiotic prescription adherence and (ii) assess the impact of a training and communication (T&C) intervention on adherence to antibiotic prescriptions.

Methods: Using qualitative, semi-structured interviews, pre-intervention and Day 7 follow-up components, and the Behaviour Change Wheel process, we investigated the facilitators of and barriers to the use and misuse of antibiotic prescriptions.

Use of antimicrobials during the COVID-19 pandemic: A qualitative study among stakeholders in Nepal.

The COVID-19 pandemic was a major public health threat and the pressure to find curative therapies was tremendous. Particularly in the early critical phase of the pandemic, a lot of empirical treatments, including antimicrobials, were recommended. Drawing on interviews with patients, clinicians and drug dispensers, this article explores the use of antimicrobials for the management of COVID-19 in Nepal.

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.

Direct inference and control of genetic population structure from RNA sequencing data.

RNAseq data can be used to infer genetic variants, yet its use for estimating genetic population structure remains underexplored. Here, we construct a freely available computational tool (RGStraP) to estimate RNAseq-based genetic principal components (RG-PCs) and assess whether RG-PCs can be used to control for population structure in gene expression analyses. Using whole blood samples from understudied Nepalese populations and the Geuvadis study, we show that RG-PCs had comparable results to paired array-based genotypes, with high genotype concordance and high correlations of genetic principal components, capturing subpopulations within the dataset.

The Identification of Enteric Fever-Specific Antigens for Population-Based Serosurveillance.

Background: Enteric fever, caused by Salmonella enterica serovars Typhi and Paratyphi A, is a major public health problem in low- and middle-income countries. Moderate sensitivity and scalability of current methods likely underestimate enteric fever burden. Determining the serological responses to organism-specific antigens may improve incidence measures.

Perspectives of pharmacy employees on an inappropriate use of antimicrobials in Kathmandu, Nepal.

Background: Unregulated antimicrobial use is common in both hospital and community settings of low- and middle-income countries (LMICs). However, discrete data regarding the use/misuse of antimicrobials at pharmacies in LMICs are limited. This study was conducted to understand knowledge, attitude, and practice of pharmacy employees on antimicrobial dispensing in Nepal.

Clinical and laboratory factors associated with neonatal sepsis mortality at a major Vietnamese children's hospital.

Sepsis is a major cause of neonatal mortality and children born in low- and middle-income countries (LMICs) are at greater risk of severe neonatal infections than those in higher-income countries. Despite this disparity, there are limited contemporaneous data linking the clinical features of neonatal sepsis with outcome in LMICs. Here, we aimed to identify factors associated with mortality from neonatal sepsis in Vietnam.

Good participatory practice for coronavirus disease 2019 (COVID-19) research: the case of a COVID-19 prevention study.

The COPCOV study (chloroquine/ hydroxychloroquine prevention of coronavirus disease), which started recruitment in April 2020, is a multi-country double-blind, randomised, placebo-controlled trial which is being conducted in healthcare facilities involved in COVID-19 case management. Participants are staff employed in facilities managing people with proven or suspected COVID-19. As part of the study, we conducted a series of engagement sessions.

Identifying context-specific domains for assessing antimicrobial stewardship programmes in Asia: protocol for a scoping review.

Introduction: Antimicrobial stewardship (AMS) is an important strategy to control antimicrobial resistance. Resources are available to provide guidance for design and implementation of AMS programmes, however these may have limited applicability in resource-limited settings including those in Asia. This scoping review aims to identify context-specific domains and items for the development of a healthcare facility (HCF)-level tool to guide AMS implementation in Asia.

Genomic epidemiology, antimicrobial resistance and virulence factors of complex causing potential community-onset bloodstream infections in a tertiary care hospital of Nepal.

Objectives: Community-onset bloodstream infections (BSIs) caused by carbapenemase-producing complex (ECC) species are increasing internationally. This observation suggests that ECC are emerging pathogens, requiring for detailed understanding on their genomic epidemiology including transmission dynamics and antimicrobial resistance profiles.

Patients And Methods: We performed WGS on 79 spp.

Azithromycin and cefixime combination versus azithromycin alone for the out-patient treatment of clinically suspected or confirmed uncomplicated typhoid fever in South Asia: a randomised controlled trial protocol.

Typhoid and paratyphoid fever (enteric fever) is a common cause of non-specific febrile infection in adults and children presenting to health care facilities in low resource settings such as the South Asia.  A 7-day course of a single oral antimicrobial such as ciprofloxacin, cefixime, or azithromycin is commonly used for its treatment. Increasing antimicrobial resistance threatens the effectiveness of these treatment choices.

Epidemiology, etiology, and diagnosis of health care acquired pneumonia including ventilator-associated pneumonia in Nepal.

Epidemiologic data regarding health care acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) from Nepal are negligible. We conducted a prospective observational cohort study in the intensive care unit (ICU) of a major tertiary hospital in Nepal between April 2016 and March 2018, to calculate the incidence of VAP, and to describe clinical variables, microbiological etiology, and outcomes. Four hundred and thirty-eight patients were enrolled in the study.

Efficacy of typhoid conjugate vaccine in Nepal: final results of a phase 3, randomised, controlled trial.

Background: Typhoid fever is a major public health problem in low-resource settings. Vaccination can help curb the disease and might reduce transmission. We have previously reported an interim analysis of the efficacy of typhoid conjugate vaccine (TCV) in Nepali children.

Tebipenem as an oral alternative for the treatment of typhoid caused by XDR Salmonella Typhi.

Background: Antimicrobial therapy is essential for the treatment of enteric fever, the infection caused by Salmonella serovars Typhi and Paratyphi A. However, an increase in resistance to key antimicrobials and the emergence of MDR and XDR in Salmonella Typhi poses a major threat for efficacious outpatient treatments.

Objectives: We recently identified tebipenem, an oral carbapenem licensed for use for respiratory tract infections in Japan, as a potential alternative treatment for MDR/XDR Shigella spp.

A novel air-dried multiplex high-resolution melt assay for the detection of extended-spectrum β-lactamase and carbapenemase genes.

Objectives: This study aimed to develop and evaluate a novel air-dried high-resolution melt (HRM) assay to detect eight major extended-spectrum β-lactamase (ESBL) (bla and bla groups 1 and 9) and carbapenemase (bla, bla, bla, bla and bla) genes that confer resistance to cephalosporins and carbapenems.

Methods: The assay was evaluated using 439 DNA samples extracted from bacterial isolates from Nepal, Malawi and the UK and 390 clinical isolates from Nepal with known antimicrobial susceptibility. Assay reproducibility was evaluated across five different real-time quantitative PCR (qPCR) instruments [Rotor-Gene® Q, QuantStudio 5, CFX96, LightCycler® 480 and Magnetic Induction Cycler (Mic)].

The emergence of azithromycin-resistant Typhi in Nepal.

Background: Typhoid fever remains a significant cause of morbidity and mortality in Asia and Africa. The emergence of azithromycin resistance in South Asia is concerning, as azithromycin is one of the last effective oral drugs for treating typhoid.

Objectives: To describe the molecular mechanism and phylogenetics of azithromycin-resistant (Azith) Typhi isolates from Patan Hospital, Kathmandu, Nepal.

Risk factors for the development of neonatal sepsis in a neonatal intensive care unit of a tertiary care hospital of Nepal.

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.

Very long O-antigen chains of Salmonella Paratyphi A inhibit inflammasome activation and pyroptotic cell death.

Salmonella Paratyphi A (SPtA) remains one of the leading causes of enteric (typhoid) fever. Yet, despite the recent increased rate of isolation from patients in Asia, our understanding of its pathogenesis is incomplete. Here we investigated inflammasome activation in human macrophages infected with SPtA.