Case-control investigation of invasive Salmonella disease in Malawi reveals no evidence of environmental or animal transmission of invasive strains, and supports human to human transmission

Abstract

Background Invasive Salmonella infections cause significant morbidity and mortality in Sub-Saharan Africa. However, the routes of transmission are uncertain. We conducted a case-control study of index-case and geographically-matched control households in Blantyre, Malawi, sampling Salmonella isolates from index cases, healthy people, animals, and the household environment. Methodology Sixty index cases of human invasive Salmonella infection were recruited (March 2015-Oct 2016). Twenty-eight invasive Non-Typhoidal Salmonella (iNTS) disease and 32 typhoid patients consented to household sampling. Each index-case household was geographically matched to a control household. Extensive microbiological sampling included stool sampling from healthy household members, stool or rectal swabs from household-associated animals and boot-sock sampling of the household environment. Findings 1203 samples from 120 households, yielded 43 non-Typhoidal Salmonella (NTS) isolates from 25 households (overall sample positivity 3.6%). In the 28 iNTS patients, disease was caused by 3 STs of Salmonella Typhimurium, mainly ST313. In contrast, the isolates from households spanned 15 sequence types (STs). Two S. Typhimurium isolates from index cases closely matched isolates from their respective asymptomatic household members (2 and 3 SNP differences respectively). Despite the recovery of a diverse range of NTS, there was no overlap between the STs causing iNTS disease with any environmental or animal isolates. Conclusions The finding of NTS strains from index cases that matched household members, coupled with lack of related animal or environmental isolates, supports a hypothesis of human to human transmission of iNTS infections in the household. The breadth of NTS strains found in animals and the household environment demonstrated the robustness of NTS sampling and culture methodology, and suggests a diverse ecology of Salmonella in this setting. Healthy typhoid (S. Typhi) carrier state was not detected. The lack of S. Typhi isolates from the household environment suggests that further methodological development is needed to culture S. Typhi from the environment.

Intestinal carriage of invasive non-typhoidal Salmonella among household members of children with Salmonella bloodstream infection, Kisangani, DR Congo

“…Previous index patient-household studies from Burkina Faso (rural areas) and Malawi (urban slums) also found matching index patient-household member pairs of S . Typhimurium ST313 and ST3257 (an ST type closely related to ST313), whereas animal and environmental sources did not reveal ST313 (Post et al, 2019 ; Koolman et al, 2022 ). For S .…”

“…However, this hypothesis should be further explored in longitudinal studies assessing carriage duration (Phoba et al, 2020 ). Furthermore, the incremental evidence of a human reservoir of the iNTS (Kariuki et al, 2019 , 2020 ; Post et al, 2019 ; Kasumba et al, 2021 ; Koolman et al, 2022 ) and the absence of evidence for a major environmental reservoir (Crump et al, 2015 , 2021 ) do not preclude co-existent environmental reservoirs and transmission routes of the iNTS (Kariuki et al, 2019 ; Mbae et al, 2020 ; Tack et al, 2021 ; Falay et al, 2022 ).…”

Genomic investigation and nationwide tracking of pediatric invasive nontyphoidal Salmonella in China

“…Three pairs of index patients and their households were identified by Multilocus variable‐number tandem‐repeat analysis (MLVA) (identical or similar MLVA type) and WGS analyses (household isolates have 0–2 SNPs from the index isolates), but we did not find matched pairs from livestock and water samples. Similarly, in Malawi, Koolman et al 20 observed two pairs of index cases and their asymptomatic household members from 60 index cases, but they did not detect overlaps between iNTS isolates and animal or environmental isolates. In this study, four invasive S .…”

Salmonella enterica serovar Typhimurium ST313 sublineage 2.2 has emerged in Malawi with a characteristic gene expression signature and a fitness advantage

“…It is not certain how these pathogens are transmitted, but there is increasing evidence from case-control studies that ST313 strains are human-associated but not animal-associated within households (Post et al 2019 , Koolman et al 2022 ). A recent summary concludes that the available data are consistent with iNTS disease being transmitted person-to-person (Chirwa et al 2023 ).…”