Multidrug resistant invasive non-typhoidal Salmonella disease in children: The role of carriage in humans and environmental contamination in an endemic setting in Kenya

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While textbook knowledge divides between invasive typhoidal and non-invasive enteric non-typhoidal Salmonellosis (NTS), in Sub-Saharan Africa so far neglected and threatening infectious disease has emerged as a prominent cause of bloodstream infection. This disease is caused by invasive strains of NTS (iNTS). The largest number of cases annually is found in children less than 5 years of age with an associated case fatality of 20–25%. Further, increasing antimicrobial resistance (AMR) in iNTS is of great global concern, with low and middle-income countries suffering mostly as alternative drugs for effective treatment of life-threatening invasive disease are eroding rapidly. Worryingly, iNTS infections are also found in Germany with increasing prevalence. Carriage of pathogens often contributes to disease transmission, but in contrast to the well-documented prolonged carriage of typhoidal Salmonella in humans, carriage of non-typhoidal Salmonellae is far less studied. Therefore, we here aim to establish in an endemic disease setting if carriage of NTS at the household level and environmental contamination play a major role in iNTS infection occurring in vulnerable children in the community and what drives this escalating problem of antimicrobial resistance. Further, a comprehensive genome analysis of African iNTS strains in comparison to German strains from invasive infections will be performed. Specific objectives of the proposed project are: 1) To determine the prevalence, host, environmental and pathogen factors associated with persistent carriage of NTS strains in apparently healthy individuals. 2) To describe the epidemiology and genomics of multi-drug resistant iNTS strains from patients, carriers and environment and their association with persistent carriage of iNTS strains. To further compare strain genomes to those isolated from infections in Germany. 3) To determine AMR genes in homestead and environment (open sewers and water sources) as potential donors of resistance determinants to iNTS. 4) To develop simple PCR tools which can be easily adapted to improve detection and engage local community to minimize risk factors for carriage and transmission of iNTS and AMR. 5) To establish a comprehensive research training program on Salmonella classification, subtyping, genome sequencing, genome and metagenome analysis with the goal to enable African scientists to perform molecular detection and characterization of project samples.