Abstract
Background: 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. Methodology: The SAiNTS study is a prospective community cohort study with paired serology samples from 2500 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 (Salmonella typhimurium and S. 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 (EPIMAL), allowing exploration of the impact of malaria vaccination on acquisition of immunity to NTS. Data on risk factors for invasive disease: malaria, anaemia and malnutrition as well as indicators of socioeconomic status and water and sanitation, will be collected using rapid diagnostic tests, anthropometry and electronic CRF’s. 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. Conclusions: 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 sero-epidemiology studies in three other sub-Saharan African sites. 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.
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