Dale Helen, Chirwa Esmeda, Patel Priyanka, Makuta Georgina, Mwakiseghile Felistas, Misiri Theresa, Kadwala Innocent, Mbewe Maurice, Banda Happy, Silungwe Niza, Chizani Kenneth, Kambiya Paul, Henrion Marc, French Neil, Nyirenda Tonny, Gordon Melita
Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, Merseyside, L69 3GF, UK.
Clinical Research, Malawi-Liverpool-Wellcome Clinical Research-Program, Blantyre, Southern Region, PO Box 30096, Malawi.
Wellcome Open Res. 2024 Aug 21;8:27. doi: 10.12688/wellcomeopenres.18054.2. eCollection 2023.
Non-typhoidal Salmonella (NTS) are a major cause of bloodstream infections amongst children in sub-Saharan Africa. A clear understanding of the seroepidemiology and correlates of protection for invasive NTS (iNTS) in relation to key risk factors (malaria, anaemia, malnutrition) in children in Africa is needed to inform strategies for disease control including vaccine implementation.
The SAiNTS study is a prospective community cohort study with paired serology samples from 2500 Malawian children 0-5 years at baseline and three months to measure age-stratified acquisition of lipopolysaccharide (LPS) O-antigen antibody (IgG) and serum bactericidal activity to the main serovars causing iNTS ( Typhimurium and . Enteritidis). Children are selected from mapped and censused randomly selected households in Chikwawa, Malawi; an area with substantial malaria burden. The sampling framework is set within a malaria vaccination (RTS,S/ AS01) phase 4 cluster randomized trial, known as the Epidemiology Study of Malaria Transmission Intensity (EPI-MAL), allowing exploration of the impact of malaria vaccination on acquisition of immunity to NTS. Risk factor data for invasive disease will be collected using rapid diagnostic tests for malaria and anaemia, anthropometry for malnutrition, and a validated questionnaire for indicators of socioeconomic status, water and sanitation. All data will be recorded through electronic case report forms using the REDCap and the Open Data Kit (ODK) platforms. Stool sample analysis includes NTS culture and pan-Salmonella polymerase chain reaction to assess enteric exposure and biomarkers of environmental enteric dysfunction. Cases with iNTS disease will be followed up for comparison with community controls.
The final cohort of 2500 children will allow investigation into the impact of risk factors for iNTS on the acquisition of immunity in children 0-5 years in an endemic setting, including comparisons to partner seroepidemiology studies in three other sub-Saharan African sites (1000 children per site). The data generated will be key to informing iNTS disease control measures including targeted risk factor interventions and vaccine implementation through investigation of correlates of protection and identifying windows of immune susceptibility in at-risk populations.
非伤寒沙门氏菌（NTS）是撒哈拉以南非洲儿童血流感染的主要原因。需要清楚了解非洲儿童侵袭性NTS（iNTS）的血清流行病学以及与关键风险因素（疟疾、贫血、营养不良）相关的保护性关联，以为包括疫苗实施在内的疾病控制策略提供信息。
SAiNTS研究是一项前瞻性社区队列研究，对2500名0至5岁马拉维儿童在基线和三个月时采集配对血清学样本，以测量脂多糖（LPS）O抗原抗体（IgG）的年龄分层获得情况以及对导致iNTS的主要血清型（鼠伤寒沙门氏菌和肠炎沙门氏菌）的血清杀菌活性。儿童从马拉维奇夸瓦随机选择的已绘制地图并进行人口普查的家庭中选取；该地区疟疾负担较重。抽样框架设定在疟疾疫苗接种（RTS,S/AS01）4期整群随机试验（称为疟疾传播强度流行病学研究（EPI-MAL））范围内，从而能够探索疟疾疫苗接种对获得NTS免疫力的影响。将使用疟疾和贫血快速诊断检测、营养不良人体测量以及经过验证的社会经济状况、水和卫生设施指标问卷收集侵袭性疾病的风险因素数据。所有数据将通过电子病例报告表使用REDCap和开放数据工具包（ODK）平台进行记录。粪便样本分析包括NTS培养和全沙门氏菌聚合酶链反应，以评估肠道暴露和环境肠道功能障碍的生物标志物。iNTS疾病病例将进行随访，以便与社区对照进行比较。
最终的2500名儿童队列将有助于调查iNTS风险因素对流行地区0至5岁儿童获得免疫力的影响，包括与撒哈拉以南非洲其他三个地点（每个地点1000名儿童）的合作血清流行病学研究进行比较。通过调查保护性关联并确定高危人群的免疫易感性窗口期，所产生的数据对于为iNTS疾病控制措施提供信息至关重要，这些措施包括针对性风险因素干预和疫苗实施。
