Investigating the mechanisms underlying the relationship between severe anaemia and bacterial infections

Severe anaemia and bacteraemia are strongly associated in African children, although the precise mechanisms underlying this association remain unknown. I found that this association is observed with specific organisms (e.g. Escherichia.coli, non-typhoidal Salmonella) but not others (e.g. Staphylococcus aureus). Given the multiple putative aetiologies of severe anaemia and increase in antimicrobial resistance, developing a full understanding of the mechanisms that predispose to these bacterial infections will enable the development of better interventions. I propose to test the hypothesis that disruption of iron metabolism and/or immune pathways contributes to increased risk of bacterial infections among severely anaemic children. I will utilise clinical and laboratory data and samples collected over the last 21 years to examine the associations between severe anaemia, immune responses, bacterial iron acquisition and genetic signatures of bacteria during severe anaemia. I will also evaluate the effects of anaemia on bacterial vaccine responses using data and samples from vaccine trials conducted in Kilifi. Findings from this project will elucidate key iron and immune pathways that can be targeted to develop interventions for severe anaemia and prevention of bacteraemia.