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Direct association between rainfall and non-typhoidal Salmonella bloodstream infections in hospital-admitted children in the Democratic Republic of Congo

ABSTRACT: Non-typhoidal Salmonella (NTS) ranks first among causes of bloodstream infection in children under five years old in the Democratic Republic of Congo and has a case fatality rate of 15%. Main host-associated risk factors are Plasmodium falciparum malaria, anemia and malnutrition. NTS transmission in sub-Saharan Africa is poorly understood. NTS bloodstream infections mostly occur during the rainy season, which may reflect seasonal variation in either environmental transmission or host susceptibility. We hypothesized that environment- and host-associated factors contribute independently to the seasonal variation in NTS bloodstream infections in children under five years old admitted to Kisantu referral hospital in 2013–2019. We used remotely sensed rainfall and temperature data as proxies for environmental factors and hospital data for host-associated factors. We used principal component analysis to disentangle the interrelated environment- and host-associated factors. With timeseries regression, we demonstrated a direct association between rainfall and NTS variation, independent of host-associated factors. While the latter explained 17.5% of NTS variation, rainfall explained an additional 9%. The direct association with rainfall points to environmental NTS transmission, which should be explored by environmental sampling studies. Environmental and climate change may increase NTS transmission directly or via host susceptibility, which highlights the importance of preventive public health interventions.

SUBMITTER: Tack B

PROVIDER: S-EPMC8566593 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundNon-typhoidal Salmonella (NTS) are a major cause of bloodstream infection (BSI) in sub-Saharan Africa. This study aimed to assess its longitudinal evolution as cause of BSI, its serotype distribution and its antibiotic resistance pattern in Kisantu, DR Congo.MethodsAs part of a national surveillance network, blood cultures were sampled in patients with suspected BSI admitted to Kisantu referral hospital from 2015-2017. Blood cultures were worked-up according to international standards. Results were compared to similar data from 2007 onwards.ResultsIn 2015-2017, NTS (n = 896) represented the primary cause of BSI. NTS were isolated from 7.6% of 11,764 suspected and 65.4% of 1371 confirmed BSI. In children <5 years, NTS accounted for 9.6% of suspected BSI. These data were in line with data from previous surveillance periods, except for the proportion of confirmed BSI, which was lower in previous surveillance periods. Salmonella Typhimurium accounted for 63.1% of NTS BSI and Salmonella Enteritidis for 36.4%. Of all Salmonella Typhimurium, 36.9% did not express the O5-antigen (i.e. variant Copenhagen). O5-negative Salmonella Typhimurium were rare before 2013, but increased gradually from then onwards. Multidrug resistance was observed in 87.4% of 864 NTS isolates, decreased ciprofloxacin susceptibility in 7.3%, ceftriaxone resistance in 15.7% and azithromycin resistance in 14.9%. A total of 14.2% of NTS isolates, that were all Salmonella Typhimurium, were multidrug resistant and ceftriaxone and azithromycin co-resistant. These Salmonella isolates were called extensively drug resistant. Compared to previous surveillance periods, proportions of NTS isolates with resistance to ceftriaxone and azithromycin and decreased ciprofloxacin susceptibility increased.ConclusionAs in previous surveillance periods, NTS ranked first as the cause of BSI in children. The emergence of O5-negative Salmonella Typhimurium needs to be considered in the light of vaccine development. The high proportions of antibiotic resistance are worrisome.

Project description:BACKGROUND:Clinical observations and animal studies have suggested that Salmonella intestinal carriage is promoted by concurrent Schistosoma infection. The present study assessed association of Salmonella intestinal carriage and Schistosoma mansoni infection among individuals in a Schistosoma endemic area in sub-Saharan Africa. METHODS:From November 2015 to March 2016, a cross-sectional community-wide study was conducted in Kifua II, a rural village in Kongo Central Province, Democratic Republic of Congo. Stool samples were collected and analyzed for Salmonella intestinal carriage (culture) and Schistosoma mansoni infection (Kato Katz microscopy with determination of egg load). Salmonella Typhimurium and Enteritidis isolates were assessed for genetic similarity with blood culture isolates obtained during the same period in a neighboring hospital using multi-locus variable-numbers tandem repeat analysis (MLVA). RESULTS:A total of 1,108 participants were included (median age 15 years (IQR: 7-36), male-to-female ratio of 1:1.1). The overall prevalence of Schistosoma mansoni infection and non-typhoidal Salmonella carriage was 51.2% (95% CI: 48.2-54.1) and 3.4% (95% CI: 2.5-4.7) respectively, with 2.2% (95% CI: 1.5-3.2) of participants coinfected. The proportion of Salmonella carriage tended to be higher among Schistosoma mansoni infected participants compared to non-infected participants but this difference did not reach statistical significance (4.2% versus 2.6%, p = 0.132). However, the proportion of Salmonella carriage among participants with a heavy Schistosoma mansoni infection was significantly higher compared to those with a light and moderate infection (8.7% versus 3.2%, p = 0.012) and compared to Schistosoma mansoni negatives (8.7% versus 2.6%, p = 0.002). The 38 Salmonella isolates comprised five and four Enteritidis and Typhimurium serotypes respectively, the majority of them had MLVA types identical or similar to those observed among blood culture isolates. CONCLUSION:Salmonella intestinal carriage was associated with a heavy intensity of Schistosoma mansoni infection. Further studies are needed to address causation.

Project description:Invasive non-typhoidal Salmonella (iNTS) (serotypes Typhimurium and Enteritidis) are major causes of bloodstream infections in sub-Saharan Africa, but their reservoir is unknown. Aiming to demonstrate human carriers as a reservoir, we assessed an iNTS disease endemic rural community (Kikonka health area, Democratic Republic of the Congo) for intestinal carriage of iNTS. After a census, healthy subjects from randomly selected households provided three successive stool samples for Salmonella culture. We next compared the stool isolates for genetic relatedness with time and health area-matched blood culture isolates obtained from hospitalized patients by multiple locus variable-number tandem repeat analysis (MLVA) and performed whole genome sequencing (WGS) on a subset of stool and blood isolates. Among 2,354 eligible subjects, 2,234 (94.9%) consented and provided at least one stool sample, and 2,219 (94.3%) provided three stool samples. The cumulative proportion of Salmonella carriers after 3 days was 4.4% (n = 98). S. Typhimurium and Enteritidis were found in 26 and 3 carriers, respectively, representing 1.3% (29 out of 2,234) of participants living in 6.0% (26 out of 482) of households. MLVA types of all 26 S. Typhimurium stool isolates matched with the corresponding MLVA types of blood isolates. The MLVA type of one out of three Enteritidis stool isolates matched the single MLVA type of the five Enteritidis blood isolates. WGS analysis of S. Typhimurium (n = 20) and S. Enteritidis (n = 4) isolates revealed Typhimurium multilocus sequence type (ST)313 Lineage 2 and Enteritidis ST11 Central/Eastern African and Outlier clades and confirmed the MLVA clustering. More than three-quarters of Typhimurium isolates showed combined multidrug resistance, ceftriaxone resistance, and fluoroquinolone non-susceptibility. In conclusion, the present study demonstrated iNTS carriage among healthy community members, with stool isolates that were genetically similar to blood culture isolates obtained in patients from the same community. These findings contribute to the evidence of a human reservoir of iNTS.

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Direct association between rainfall and non-typhoidal Salmonella bloodstream infections in hospital-admitted children in the Democratic Republic of Congo

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