Molecular Surveillance Identifies Multiple Transmissions of Typhoid in West Africa.

BACKGROUND: The burden of typhoid in sub-Saharan African (SSA) countries has been difficult to estimate, in part, due to suboptimal laboratory diagnostics. However, surveillance blood cultures at two sites in Nigeria have identified typhoid associated with Salmonella enterica serovar Typhi (S. Typhi) as an important cause of bacteremia in children. METHODS: A total of 128 S. Typhi isolates from these studies in Nigeria were whole-genome sequenced, and the resulting data was used to place these Nigerian isolates into a worldwide context based on their phylogeny and carriage of molecular determinants of antibiotic resistance. RESULTS: Several distinct S. Typhi genotypes were identified in Nigeria that were related to other clusters of S. Typhi isolates from north, west and central regions of Africa. The rapidly expanding S. Typhi clade 4.3.1 (H58) previously associated with multiple antimicrobial resistances in Asia and in east, central and southern Africa, was not detected in this study. However, antimicrobial resistance was common amongst the Nigerian isolates and was associated with several plasmids, including the IncHI1 plasmid commonly associated with S. Typhi. CONCLUSIONS: These data indicate that typhoid in Nigeria was established through multiple independent introductions into the country, with evidence of regional spread. MDR typhoid appears to be evolving independently of the haplotype H58 found in other typhoid endemic countries. This study highlights an urgent need for routine surveillance to monitor the epidemiology of typhoid and evolution of antimicrobial resistance within the bacterial population as a means to facilitate public health interventions to reduce the substantial morbidity and mortality of typhoid.

Distinct Salmonella Enteritidis lineages associated with enterocolitis in high-income settings and invasive disease in low-income settings.

An epidemiological paradox surrounds Salmonella enterica serovar Enteritidis. In high-income settings, it has been responsible for an epidemic of poultry-associated, self-limiting enterocolitis, whereas in sub-Saharan Africa it is a major cause of invasive nontyphoidal Salmonella disease, associated with high case fatality. By whole-genome sequence analysis of 675 isolates of S. Enteritidis from 45 countries, we show the existence of a global epidemic clade and two new clades of S. Enteritidis that are geographically restricted to distinct regions of Africa. The African isolates display genomic degradation, a novel prophage repertoire, and an expanded multidrug resistance plasmid. S. Enteritidis is a further example of a Salmonella serotype that displays niche plasticity, with distinct clades that enable it to become a prominent cause of gastroenteritis in association with the industrial production of eggs and of multidrug-resistant, bloodstream-invasive infection in Africa.

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.

Relationship between antibody susceptibility and lipopolysaccharide O-antigen characteristics of invasive and gastrointestinal nontyphoidal Salmonellae isolates from Kenya.

BACKGROUND: Nontyphoidal Salmonellae (NTS) cause a large burden of invasive and gastrointestinal disease among young children in sub-Saharan Africa. No vaccine is currently available. Previous reports indicate the importance of the O-antigen of Salmonella lipopolysaccharide for virulence and resistance to antibody-mediated killing. We hypothesised that isolates with more O-antigen have increased resistance to antibody-mediated killing and are more likely to be invasive than gastrointestinal. METHODOLOGY/PRINCIPAL FINDINGS: We studied 192 NTS isolates (114 Typhimurium, 78 Enteritidis) from blood and stools, mostly from paediatric admissions in Kenya 2000-2011. Isolates were tested for susceptibility to antibody-mediated killing, using whole adult serum. O-antigen structural characteristics, including O-acetylation and glucosylation, were investigated. Overall, isolates were susceptible to antibody-mediated killing, but S. Enteritidis were less susceptible and expressed more O-antigen than Typhimurium (p<0.0001 for both comparisons). For S. Typhimurium, but not Enteritidis, O-antigen expression correlated with reduced sensitivity to killing (r = 0.29, 95% CI = 0.10-0.45, p = 0.002). Both serovars expressed O-antigen populations ranging 21-33 kDa average molecular weight. O-antigen from most Typhimurium were O-acetylated on rhamnose and abequose residues, while Enteritidis O-antigen had low or no O-acetylation. Both Typhimurium and Enteritidis O-antigen were approximately 20%-50% glucosylated. Amount of S. Typhimurium O-antigen and O-antigen glucosylation level were inversely related. There was no clear association between clinical presentation and antibody susceptibility, O-antigen level or other O-antigen features. CONCLUSION/SIGNIFICANCE: Kenyan S. Typhimurium and Enteritidis clinical isolates are susceptible to antibody-mediated killing, with degree of susceptibility varying with level of O-antigen for S. Typhimurium. This supports the development of an antibody-inducing vaccine against NTS for Africa. No clear differences were found in the phenotype of isolates from blood and stool, suggesting that the same isolates can cause invasive disease and gastroenteritis. Genome studies are required to understand whether invasive and gastrointestinal isolates differ at the genotypic level.