Abstract
Non-typhoidal Salmonella enterica serovars (NTS) are generally associated with gastroenteritis; however, the very young and elderly, as well as individuals with compromised immunity, are at risk of developing disseminated infection that can manifest as bacteremia or focal infections at systemic sites. Disseminated NTS infections can be fatal and are responsible for over 600 000 deaths annually. Most of these deaths are in sub-Saharan Africa, where multidrug-resistant NTS clones are currently circulating in a population with a high proportion of individuals that are susceptible to disseminated disease. This review considers how genome degradation observed in African NTS isolates has resulted in phenotypic differences in traits related to environmental persistence and host-pathogen interactions. Further, it discusses host mechanisms promoting susceptibility to invasive infection with NTS in individuals with immunocompromising conditions. We conclude that mechanistic knowledge of how risk factors compromise immunity to disseminated NTS infection will be important for the design of interventions to protect against systemic disease.