Modelling the Contributions of Malaria, HIV, Malnutrition and Rainfall to the Decline in Paediatric Invasive Non-typhoidal Salmonella Disease in Malawi

Introduction Nontyphoidal Salmonellae (NTS) are responsible for a huge burden of bloodstream infection in Sub-Saharan African children. Recent reports of a decline in invasive NTS (iNTS) disease from Kenya and The Gambia have emphasised an association with malaria control. Following a similar decline in iNTS disease in Malawi, we have used 9 years of continuous longitudinal data to model the interrelationships between iNTS disease, malaria, HIV and malnutrition. Methods Trends in monthly numbers of childhood iNTS disease presenting at Queen’s Hospital, Blantyre, Malawi from 2002 to 2010 were reviewed in the context of longitudinal monthly data describing malaria slide-positivity among paediatric febrile admissions, paediatric HIV prevalence, nutritional rehabilitation unit admissions and monthly rainfall over the same 9 years, using structural equation models (SEM). Results Analysis of 3,105 iNTS episodes identified from 49,093 blood cultures, showed an 11.8% annual decline in iNTS (p < 0.001). SEM analysis produced a stable model with good fit, revealing direct and statistically significant seasonal effects of malaria and malnutrition on the prevalence of iNTS disease. When these data were smoothed to eliminate seasonal cyclic changes, these associations remained strong and there were additional significant effects of HIV prevalence. Conclusions These data suggest that the overall decline in iNTS disease observed in Malawi is attributable to multiple public health interventions leading to reductions in malaria, HIV and acute malnutrition. Understanding the impacts of public health programmes on iNTS disease is essential to plan and evaluate interventions.
Author Summary Invasive nontyphoidal Salmonella (iNTS) disease is estimated to be responsible for 680,000 deaths/year and yet this is widely under-recognised by clinicians, epidemiologists and policymakers in Sub-Saharan Africa. Recently there have been reports of a decline in childhood iNTS disease from both Kenya and The Gambia that have been attributed to malaria control, and this has led to the unsubstantiated assumption that NTS disease will disappear. While this may be true in certain settings, numerous studies have also associated HIV and malnutrition with NTS disease. We therefore re-assessed this multifaceted relationship in Malawi, where we have previously reported little change in malaria cases, but where there have been highly successful antiretroviral and malnutrition programmes. Analysis of ~50,000 blood cultures and ~240,000 malaria slides demonstrates a significant decline in iNTS attributable to malaria, HIV and malnutrition, emphasising the complex inter-relationships between these factors and suggest that malaria interventions alone are unlikely to control iNTS disease. Our findings are highly relevant to the neglected field of bacteraemia in Africa and understanding the direct and indirect impacts of public health programmes on iNTS disease in Africa is essential for policy makers to plan and evaluate interventions to control this condition.