Epidemiology and genomics of invasive nontyphoidal salmonella infections in Kenya

Background. In Kenya, invasive nontyphoidal Salmonella (iNTS) disease causes severe bacteremic illness among adults with human immunodeficiency virus (HIV) and especially among children <5 years of age coinfected with HIV or malaria, or who are compromised by sickle cell disease or severe malnutrition. The incidence of iNTS disease in children ranges from 166 to 568 cases per 100 000 persons per year. Methods. We review the epidemiology of iNTS disease and genomics of strains causing invasive illness in Kenya. We analyzed a total of 192 NTS isolates (114 Typhimurium, 78 Enteritidis) from blood and stools from pediatric admissions in 2005-2013. Testing for antimicrobial susceptibility to commonly used drugs and whole-genome sequencing were performed to assess prevalence and genetic relatedness of multidrug-resistant iNTS strains, respectively. Results. A majority (88/114 [77%]) of Salmonella Typhimurium and 30% (24/79) of Salmonella Enteritidis isolates tested were found to be multidrug resistant, whereas a dominant Salmonella Typhimurium pathotype, ST313, was primarily associated with invasive disease and febrile illness. Analysis of the ST313 isolates has identified genome degradation, compared with the ST19 genotype that typically causes diarrhea in humans, especially in industrialized countries, adapting a more host-restricted lifestyle typical of Salmonella Typhi infections. Conclusions. From 2012, we have observed an emergence of ceftriaxone-resistant strains also showing reduced susceptibility to fluoroquinolones. As most cases present with nonspecific febrile illness with no laboratory-confirmed etiology, empiric treatment of iNTS disease is a major challenge in Kenya. Multidrug resistance, including to ceftriaxone, will pose further difficulty in management of iNTS disease in endemic areas.