NTS is among the three most common pathogens causing systemic infections in children and adults in the sub-Saharan Africa [
7,
8]. NTS consists of many serovars, with
S. typhimurium being the serovar that is the most commonly implicated pathogen. Unlike typhoidal
Salmonella that consists of the serovars Typhi and Paratyphi and causes the systemic disease of typhoid, NTS generally induces self-limited gastroenteritis in human. However, in many parts of Africa, NTS causes highly significant invasive systemic infections [
9,
10]. The clinical features of invasive NTS (iNTS) are distinct from those of gastroenteritis or typhoid disease. These patients usually present with nonspecific fever similar to malaria, and in some patients, pneumonia, meningitis or osteomyelitis. The impact of iNTS on childhood mortality exceeds malaria in some African communities [
11]. The estimated mortality rates for iNTS among hospitalized patients in Africa ranges from 4.4 to 27% for children [
12‐
14] and 22 to 47% for adults [
15,
16]. The mortality rate is highest in those with meningitis and is higher than any other common bacterial causes of meningitis. In Malawi, the mortality rate due to NTS meningitis in the neonates was 64%, compared to 26% in those with Group B Streptococcal meningitis [
17]. The burden due to iNTS is significant. For example, it has been estimated that iNTS occurred in 88 cases per 100,000 person-years in the age group of 5 years old in rural Kenya, while in Mozambique, NTS accounted for 120 cases per 100,000 person-years [
17]. These incidences are likely grossly under-estimated since many children with iNTS died before reaching the local hospitals [
8,
11].
The use of whole genome sequencing has become important for monitoring the prevalence, movement and genotype of infectious disease agents such as
Salmonella. Sequence analysis of invasive
S. typhimurium from Malawi and Kenya identified a dominant type, designated ST313, which is rarely isolated outside of Africa [
18]. Whole-genome sequencing of ST313 NTS found genetic element encoding multi-drug resistance (MDR) genes located on a virulence-associated plasmid of the organism. Unfortunately, the factors contributing to the high prevalence of iNTS remain poorly defined. Our surveillance platform of 9345 children in Kano, Nigeria, identified that the age-adjusted odds ratio for clinically significant iNTS was much higher in SCD than those without the disease (OR 4.28, 95% CI 2.3–7.9) [
19,
20]. We have also previously shown that SCD patients have alteration of their lymphocyte phenotype and functions [
21]. In addition to splenic dysfunction associated with SCD, children with malnutrition, malaria, and human immunodeficiency virus (HIV) are also more susceptible to iNTS [
10,
22]. However, these immunocompromised states only explain the obstacles in eradicating micro-organisms that successfully enter the blood stream and do not address the disproportionally higher incidence of enteric-derived systemic infections in these patients, unless there is a breach in the gut permeability in these patients.