Date Published: March 4, 2015
Publisher: Public Library of Science
Author(s): Robert S. Onsare, Francesca Micoli, Luisa Lanzilao, Renzo Alfini, Chinyere K. Okoro, Anne W. Muigai, Gunturu Revathi, Allan Saul, Samuel Kariuki, Calman A. MacLennan, Simona Rondini, Stephen Baker. http://doi.org/10.1371/journal.pntd.0003573
Abstract: BackgroundNontyphoidal 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 FindingsWe 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/SignificanceKenyan 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.
Partial Text: NTS are a major but neglected cause of invasive disease (hence iNTS disease) in Africa [1–3]. Salmonella enterica serovars Typhimurium and Enteritidis account for nearly 80% of all human isolates reported globally . While in developed countries, these predominantly cause a mild self-limiting gastroenteritis [5–7], in Africa they are responsible for bacteraemia, often associated with meningitis in young children, with incidence rates comparable to invasive S. pneumoniae disease . The true burden of iNTS disease is uncertain due to the absence of a characteristic clinical presentation. Patients often present with nonspecific fever [8–10] and blood culture is necessary for diagnosis. Even where blood culture facilities are available, rapid clinical progression of NTS bacteraemia results in many patients dying before a microbiological diagnosis can be made . No vaccine is available, and clinical management is made difficult by widespread multi-drug resistance and the need for late-generation expensive antibiotics [11–13].
NTS infections are a major problem in sub-Saharan Africa and can either present as bacteraemia, with symptoms of gastroenteritis in under half of patients, or as diarrheal disease without bloodstream infection [1,11,37]. Both presentations can be life-threatening, with case fatality rates of 20–25% for iNTS bacteremia in children [1,2,8,10] and up to 50% in HIV-infected adults , and a recognized association between NTS diarrhoea with mortality . No vaccine is currently available.