The genomic epidemiology of multi-drug resistant invasive non-typhoidalSalmonellain selected sub-Saharan African countries

Abstract

BackgroundInvasive non-typhoidal Salmonella (iNTS) is one of the leading causes of bacteraemia in sub-Saharan Africa. We aimed to provide a better understanding of the genetic characteristics and transmission patterns associated with multi-drug resistant (MDR) iNTS serovars across the continent.MethodsA total of 166 iNTS isolates collected from a multi-centre surveillance in 10 African countries (2010–2014) and a fever study in Ghana (2007–2009) were genome sequenced to investigate the geographical distribution, antimicrobial genetic determinants and population structure of iNTS serotypes–genotypes. Phylogenetic analyses were conducted in the context of the existing genomic frameworks for various iNTS serovars. Population-based incidence of MDR-iNTS disease was estimated in each study site.ResultsSalmonella Typhimurium sequence-type (ST) 313 and Salmonella Enteritidis ST11 were predominant, and both exhibited high frequencies of MDR; Salmonella Dublin ST10 was identified in West Africa only. Mutations in the gyrA gene (fluoroquinolone resistance) were identified in S. Enteritidis and S. Typhimurium in Ghana; an ST313 isolate carrying blaCTX-M-15 was found in Kenya. International transmission of MDR ST313 (lineage II) and MDR ST11 (West African clade) was observed between Ghana and neighbouring West African countries. The incidence of MDR-iNTS disease exceeded 100/100 000 person-years-of-observation in children aged <5 years in several West African countries.ConclusionsWe identified the circulation of multiple MDR iNTS serovar STs in the sampled sub-Saharan African countries. Investment in the development and deployment of iNTS vaccines coupled with intensified antimicrobial resistance surveillance are essential to limit the impact of these pathogens in Africa.

Genomic characterization of invasive typhoidal and non-typhoidal Salmonella in southwestern Nigeria

“…Enteritidis in our study were multidrug resistant (resistant to ampicillin, SXT, nalidixic acid). This multidrug resistant clone has also been reported in bacteraemia in other parts of Africa [37,38]. We observed that S .…”

“…Typhimurium ST313 and S . Enteritidis ST11 are dominant, human-adapted clones in sub-Saharan Africa (30) that are a major cause of invasive disease, with a corresponding high case-fatality rate (14). These serovars are justifiably vaccine development priorities.…”

Antimicrobial Resistance Rates and Surveillance in Sub-Saharan Africa: Where Are We Now?

“…In addition, resistance to third generation cephalosporins has been attributed to the presence of ESBL-encoding genes such as bla CTX-M, while non-susceptibility to fluoroquinolones has been associated with mutation of the gyr A gene. 104 Multidrug-resistant S . Typhimurium ST313 has now been reported from several countries in SSA, including Kenya, 105 Malawi, 67 Central African Republic, Senegal, Burkina Faso, 106 DRC, 107 Nigeria, 108 Ghana, 102 South Africa, and Mozambique, 79 , 109 where iNTS is endemic and produces septicemia in the absence of gastroenteritis.…”

“…In another study of the genetic characteristics and transmission patterns associated with multidrug-resistant iNTS serovars across SSA, 104 multiple multidrug-resistant iNTS serovar sequence types were identified as circulating in several countries that were sampled. High carriage rates observed in endemic sites in Kenya of MDR ST313 110 are likely to provide a reservoir for community spread of infection to vulnerable populations, adding new challenges in the control and prevention of iNTS disease.…”

“…Invasive strains of multidrug-resistant NTS circulating in SSA are predominantly S. Typhimurium ST313 and S. Enteritidis ST11, although S. Dublin ST10 has only been associated with resistance in West Africa. 96,104 These strains harbor the notorious Tn21 transposon on an incF plasmid (pSLT-BT), which contains a plethora of resistance genes. In addition, resistance to third generation cephalosporins has been attributed to the presence of ESBL-encoding genes such as blaCTX-M, while non-susceptibility to fluoroquinolones has been associated with mutation of the gyrA gene.…”