Can a theoretical framework for the immunoepidemiology of non-typhoidal salmonella (NTS), using age-stratified epidemiological data, estimate a population antibody correlate of protection against invasive disease?

Invasive non-typhoidal salmonella (iNTS) causes fever, septicaemia, meningitis and death in 15% of cases, mostly in sub-Saharan Africa. It affects adults with HIV and children under the age of 5; particularly with those with malaria, malnutrition, and anaemia. Currently no vaccine exists, however, several are in development. Immune markers that correlate with a reduced risk of disease can be used to determine vaccine efficacy and accelerate early vaccine licensure. Blood samples for antibody levels and function against iNTS will be taken from 2000 children aged 0 to 5 years in a rural, high malaria region of Malawi. Malaria positivity, anaemia and malnutrition status will be determined. Additional samples collected from a peri-urban area of Malawi as part of another study (STRATAA), will also be available for analysis. Using the age-distribution of existing blood culture confirmed iNTS cases; the level of antibody that correlates with protection against invasive disease in 95% of children will be estimated using modelling techniques. Comparison of the immunological response between rural and peri-urban areas within Malawi will be made. Data from 1000 children 0 to 5 years will be available from three additional sub-Saharan African sites (within iNTS vaccine consortium) allowing comparison across different geographical settings.