Protocol for the challenge non-typhoidal Salmonella (CHANTS) study: a first-in-human, in-patient, double-blind, randomised, safety and dose-escalation controlled human infection model in the UK

Introduction

Invasive non-typhoidal Salmonella (iNTS) serovars are a major cause of community-acquired bloodstream infections in sub-Saharan Africa (SSA). In this setting, Salmonella enterica serovar Typhimurium accounts for two-thirds of infections and is associated with an estimated case fatality rate of 15%–20%. Several iNTS vaccine candidates are in early-stage assessment which—if found effective—would provide a valuable public health tool to reduce iNTS disease burden. The CHANTS study aims to develop a first-in-human Salmonella Typhimurium controlled human infection model, which can act as a platform for future vaccine evaluation, in addition to providing novel insights into iNTS disease pathogenesis.

Methods and analysis

This double-blind, safety and dose-escalation study will randomise 40–80 healthy UK participants aged 18–50 to receive oral challenge with one of two strains of S. Typhimurium belonging to the ST19 (strain 4/74) or ST313 (strain D23580) lineages. 4/74 is a global strain often associated with diarrhoeal illness predominantly in high-income settings, while D23580 is an archetypal strain representing invasive disease-causing isolates found in SSA. The primary objective is to determine the minimum infectious dose (colony-forming unit) required for 60%–75% of participants to develop clinical or microbiological features of systemic salmonellosis. Secondary endpoints are to describe and compare the clinical, microbiological and immunological responses following challenge. Dose escalation or de-escalation will be undertaken by continual-reassessment methodology and limited within prespecified safety thresholds. Exploratory objectives are to describe mechanisms of iNTS virulence, identify putative immune correlates of protection and describe host–pathogen interactions in response to infection.

Ethics and dissemination

Ethical approval has been obtained from the NHS Health Research Authority (London—Fulham Research Ethics Committee 21/PR/0051; IRAS Project ID 301659). The study findings will be disseminated in international peer-reviewed journals and presented at national/international stakeholder meetings. Study outcome summaries will be provided to both funders and participants.

Trial registration number

NCT05870150

Validation of CHERG’S Verbal Autopsy-Social Autopsy (VASA) tool for ascertaining determinants and causes of under-five child mortality in Pakistan

by Muhammad Bilal Siddiqui, Chiu Wan Ng, Wah Yun Low, Khadijah Abid

The majority (40%) of the world’s under-five mortality burden is concentrated in nations like Nigeria (16.5%), India (16%), Pakistan (8%), and the Democratic Republic of the Congo (6%), where an undetermined number of under-five deaths go unrecorded. In low-resource settings throughout the world, the Verbal Autopsy-Social Autopsy (VASA) technique may assist assess under-five mortality estimates, assigning medical and social causes of death, and identifying relevant determinants. Uncertainty regarding missing data in high-burden nations like Pakistan necessitates a valid and reliable VASA instrument. This is the first study to validate Child Health Epidemiology Reference Group-CHERG’s VASA tool globally. In Pakistan, data from such a valid and reliable tool is vital for policy. This paper reports on the VASA tool in Karachi, Pakistan. Validity and reliability of the CHERG VASA tool were tested using face, content, discriminant validation, and reliability tests on one hundred randomly selected mothers who had recently experienced an under-five child death event. Data were computed on SPSS (version-21) and R software. Testing revealed high Item-content Validity Index (I-CVI) (>81.43%); high Cronbach’s Alpha (0.843); the accuracy of between 75–100% of the discriminants classifying births to live and stillbirths; and I-CVI (>82.07% and 88.98% respectively) with high accuracy (92% and 97% respectively) for assigning biological and social causes of child deaths, respectively. The CHERG VASA questionnaire was found relevant to the conceptual framework and valid in Pakistan. This valid tool can assign accurate medical and non-medical causes of child mortality cases occurring in Pakistan.

Genomics-informed nursing strategies and health equity: A scoping review protocol

by Dzifa Dordunoo, Jacqueline Limoges, Patrick Chiu, Rebecca Puddester, Lindsay Carlsson, April Pike

Objective

The objective of this scoping review is to map the available evidence on strategies that nurses can use to facilitate genomics-informed healthcare to address health disparities.

Introduction

Advancements in genomics over the last two decades have led to an increase in the delivery of genomics-informed health care. Although the integration of genomics into health care services continues to enhance patient outcomes, access to genomic technologies is not equitable, exacerbating existing health disparities amongst certain populations. As the largest portion of the health workforce, nurses play a critical role in the delivery of equitable genomics-informed care. However, little is known about how nurses can help address health disparities within the context of genomics-informed health care. A review of the literature will provide the necessary foundation to identify promising practices, policy, and knowledge gaps for further areas of inquiry.

Inclusion criteria

We will include papers that explore strategies that nurses can undertake to facilitate genomics-informed care to address health disparities.

Methods

This review will be conducted using JBI methodology for scoping reviews. We will search electronic databases including MEDLINE (OVID), EMBASE, Cochrane Library, PsychInfo, and CINAHL for quantitative and qualitative studies, systematic reviews and grey literature. Theses, books, and unavailable full-text papers will be excluded. The search will be limited to papers from 2013 and beyond. Two reviewers will screen titles and abstracts followed by full-text and disagreements will be resolved by a third reviewer. We will use a data extraction tool using Microsoft Excel and analyse data using descriptive statistics and conventional content analysis. Findings will be presented in the form of evidence tables and a narrative summary. We will report findings using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR).

Discussion

Genomics will continue to transform all aspects of health care across the wellness continuum from prevention, assessment, diagnosis, management, treatment, and palliative care. The identification of nursing strategies to address health disparities will build the foundation for policy and practice to ensure that the integration of genomic technologies benefits everyone.