Host, pathogen, and geographic drivers of major Salmonella serovars in rural and urban Kenya

Abstract

Introduction: Salmonella serotypes are among the leading causes of bacterial infections in Africa, contributing to both diarrheal and blood stream disease. This dissertation comprises two studies to address the clinical epidemiology of non-typhoidal Salmonella (NTS) in rural Kenya (Aim 1) and the spatial and environmental epidemiology of typhoid fever in a slum in urban Kenya (Aim 2). Methods: Both studies involved data from large community-based and clinic surveys. For Aim 1, we selected a sub-cohort of individuals with NTS in whom we compared characteristics of those with NTS bacteremia to those with NTS diarrhea using logistic regression models. Cofactors assessed included those related to host immunity and co-infection (HIV status, malaria, malnutrition, and age) and pathogen-related risk factors (drug resistance, serotype, and multi-locus sequence type). NTS isolates were genotyped to investigate genetic differences in strains causing diarrheal versus bacteremic infection. For Aim 2 we conducted a spatial case-control study to determine host and geographic risk factors for typhoid fever among individuals residing in an informal urban settlement (Kibera) in Nairobi, Kenya. We used both logistic regression and spatial regression models to test whether differences in topography, a proxy for the downstream flow and accumulation of fecal contamination, explain the observed geographic pattern in risk of typhoid fever. Results: For Aim 1 we found that multi-drug resistant (MDR) non-typhoidal Salmonella (NTS) was associated with NTS bacteremia compared to NTS diarrhea, controlling for host-cofactors. NTS bacteremia was also associated with younger age and HIV infection. The association of MDR with NTS bacteremia was present in stratified analyses of HIV-infected and uninfected individuals, with a stronger association among HIV negative individuals. We observed presence of STS313 in both NTS bacteremia and diarrhea. For Aim 2 we found that the risk of typhoid fever was geographically heterogeneous across a small area within the Kibera informal settlement, with greater risk in the lower elevation areas compared to high elevation areas. The association with low elevation was seen in children but not adults. Conclusion: Our findings from Aim 1 suggest that multi-drug resistance is a key driver of NTS invasiveness, beyond the effects of host-immune function. Whether certain MDR resistant NTS lineages are, in fact, more virulent will need to be confirmed in further study. Our observation of STS313 in diarrhea cases is novel and merits evaluation in a larger group of individuals with NTS diarrhea. Our findings from Aim 2 suggest environmental transmission of typhoid fever in children, but not adults, likely due to more frequent exposure to environmental pathogens. Further investigation is needed to differentiate between possible sources of environmental risk, such as contaminated drinking water versus direct contact with contaminated environmental media like open sewers.