High genetic similarity between non-typhoidal Salmonella isolated from paired blood and stool samples of children in the Democratic Republic of the Congo.

Marie-France Phoba,Octavie Lunguya,Stijn Deborggraeve,Wesley Mattheus,Jan Jacobs,Barbara Barbé,Sandra Van Puyvelde,Benedikt Ley,Annelies Post

doi:10.1371/journal.pntd.0008377

Abstract

BackgroundNon-typhoidal Salmonella (NTS) serotypes Typhimurium and Enteritidis are a major cause of bloodstream infections in children in sub-Saharan Africa but their reservoir is unknown. We compared pairs of NTS blood and stool isolates (with the same NTS serotype recovered in the same patient) for genetic similarity.MethodsBetween November 2013 and April 2017, hospital-admitted children (29 days to 14 years) with culture-confirmed NTS bloodstream infections were enrolled in a cross-sectional study at Kisantu Hospital, DR Congo. Stool cultures for Salmonella were performed on a subset of enrolled children, as well as on a control group of non-febrile hospital-admitted children. Pairs of blood and stool NTS isolates were assessed for genetic similarity by multiple-locus variable-number of tandem repeats (MLVA) and genomics analysis.ResultsA total of 299 children with NTS grown from blood cultures (Typhimurium 68.6%, Enteritidis 30.4%, other NTS 1.0%) had a stool sample processed; in 105 (35.1%) of them NTS was detected (Typhimurium 70.5%, Enteritidis 25.7%, other NTS 3.8%). A total of 87/105 (82.9%) pairs of blood and stool NTS isolates were observed (representing 29.1% of the 299 children). Among 1598 controls, the proportion of NTS stool excretion was 2.1% (p < 0.0001). MLVA types among paired isolates were identical in 82/87 (94.3%) pairs (27.4% of the 299 children; 61/66 (92.4%) in Typhimurium and 21/21 (100%) in Enteritidis pairs). Genomics analysis confirmed high genetic similarity within 41/43 (95.3%) pairs, showing a median SNP difference of 1 (range 0–77) and 1 (range 0–4) for Typhimurium and Enteritidis pairs respectively. Typhimurium and Enteritidis isolates belonged to sequence types ST313 lineage II and ST11 respectively.ConclusionNearly 30% of children with NTS bloodstream infection showed stool excretion of an NTS isolate with high genetic similarity, adding to the evidence of humans as a potential reservoir for NTS.

Highlights

Non-typhoidal Salmonella (NTS) is a leading cause of bloodstream infections (BSI) with an estimated global burden of invasive NTS infections of 535,000 cases and a case fatality rate of 14.5% in 2017
We found that a high proportion of children with NTS in their blood had NTS in their stool (35.1%) when compared to a control group of children without suspicion of bloodstream infection (2.1%)
The pathogenicity of NTS differs between high-income countries and sub-Saharan Africa (sSA) with a higher risk of invasive disease and associated mortality in the latter [6]; this can be partly explained by the emergence of distinct and invasive clades of Typhimurium and Enteritidis serotypes across sSA [7,8,9,10]

Summary

Introduction

Non-typhoidal Salmonella (NTS) is a leading cause of bloodstream infections (BSI) with an estimated global burden of invasive NTS infections of 535,000 cases and a case fatality rate of 14.5% in 2017. The burden is highest in sub-Saharan Africa (sSA) and in children under five years of age [1]. Salmonella enterica subspecies enterica serotypes Typhimurium and Enteritidis are the most common causes of NTS BSI [2,3,4,5]. The role of NTS excretion in the stool has not yet been elucidated and it is unknown whether the NTS strains in the blood of BSI patients are excreted in stool [3,13]. Non-typhoidal Salmonella (NTS) serotypes Typhimurium and Enteritidis are a major cause of bloodstream infections in children in sub-Saharan Africa but their reservoir is unknown. We compared pairs of NTS blood and stool isolates (with the same NTS serotype recovered in the same patient) for genetic similarity

Objectives

Methods

Conclusion