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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.

OBJECTIVE: Azithromycin is an alternative to treat invasive non-typhoidal Salmonella (iNTS) infections. We determined its epidemiological cut-off (ECOFF) and compared azithromycin susceptibility testing methods for iNTS. METHODS: We used EUCAST ECOFFinder to determine the minimum inhibitory concentrations (MIC; obtained by broth microdilution) ECOFF and corresponding disk zone diameters of 515 iNTS from blood cultures in Democratic Republic of Congo, Burkina Faso, Rwanda, and Cambodia. Transferable resistance mechanisms were determined by polymerase chain reaction. We compared azithromycin susceptibility testing by semi-automated broth microdilution (customized Sensititre panel; reference), agar dilution, gradient tests (bioMérieux, Liofilchem, HiMedia; read at 80% (MIC80%) and 100% inhibition (MIC100%)), and disk diffusion (Rosco, Oxoid, BD, Liofilchem) for 161 wild- and 198 non-wild-type iNTS. RESULTS: Azithromycin MIC ECOFF was 16 mg/L corresponding to a 12 mm zone diameter; mphA was detected in 192/197 non-wild- and 0/47 wild-type iNTS. Categorical agreement was excellent (≥98%) for all methods. Essential agreement was very good for agar dilution (>90%) but moderate for gradient tests (MIC80%: 52% to 71% and MIC100%: 72% to 91%). Repeatability was good for all methods/brands. Interreader agreement was high for broth microdilution and agar dilution (all ≤1 twofold dilution difference) and disk diffusion (>96% ≤3 mm difference) but lower for gradient tests (MIC80% & MIC100%: 83% to 94% ≤1 twofold dilution difference). DISCUSSION: Azithromycin ECOFF of iNTS was 16 mg/L, i.e. equal to Salmonella Typhi. Disk diffusion is an accurate, precise, and user-friendly alternative for agar dilution and broth microdilution. Reading gradient tests at 100% instead of 80% inhibition improved accuracy and precision. ispartof: CLINICAL MICROBIOLOGY AND INFECTION vol:28 issue:12 pages:1615-1623 ispartof: location:England status: published

Background Non-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. Methods As 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. Results In 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, Author summary We reviewed bloodstream infections caused by non-typhoidal Salmonella over a 10 year period (2007–2017) in the Democratic Republic of the Congo, with Kisantu in the Kongo Central province as the major sampling site. Non-typhoidal Salmonella were the most common cause of bloodstream infections in children in a sentinel network in DR Congo. The disease mainly occurred in young children and had a high mortality. We showed that non-typhoidal Salmonella persisted to frequently cause bloodstream infections in children under 5 years old. Salmonella Enteritidis and Salmonella Typhimurium were the main serotypes causing non-typhoidal Salmonella bloodstream infections. The emergence of O5-antigen negative Salmonella Typhimurium (i.e. variant Copenhagen) was observed and this needs to be considered when developing vaccines. Multidrug resistance to ampicillin, trimethoprim-sulfamethoxazole and chloramphenicol was widespread during the whole decade. From 2013 onwards, resistance to all other available antibiotics, i.e. third generation cephalosporins, fluoroquinolones and azithromycin, emerged. Likewise, extensive drug resistance (multidrug, ceftriaxone and azithromycin co-resistance) and multidrug resistance combined with decreased ciprofloxacin susceptibility in Salmonella Typhimurium emerged. Unfortunately, there are no clinical studies on antibiotic treatment in non-typhoidal Salmonella bloodstream infection that could allow the development of evidence based treatment guidelines. Therefore, dedicated observational studies and clinical studies are urgently needed to optimize antibiotic stewardship.

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., Author summary Salmonella intestinal carriage may be facilitated by infection with Schistosoma mansoni, which is a flatworm that lives in the small blood vessels of the human intestinal tract. This situation has been described in tropical low and middle income countries, where both pathogens are endemic. The present study aimed to assess the association of Salmonella intestinal carriage with Schistosoma mansoni infection in Kifua II village, located in the Kongo Central province of the Democratic republic of Congo. We collected stool samples from 1,108 inhabitants of the village and analysed them for Salmonella (culture) and Schistosoma mansoni eggs (microscopy). Our findings showed that 3.4% of the participants had Salmonella in their stool and 51.2% were infected with Schistosoma mansoni. There was no association between overall Schistosoma infection and Salmonella carriage but Salmonella carriage was significantly higher among participants with heavy Schistosoma infection compared to those with a light and moderate infection (8.7% versus 3.2%, p = 0.012) and compared to those without Schistosoma mansoni infection (8.7% versus 2.6%, p = 0.002). Further, we showed that some Salmonella isolates recovered from stool were very similar to isolates obtained from invasive infections (blood cultures from patients in a neighbouring hospital).

Bloodstream infections by Salmonella enterica serovar Typhimurium constitute a major health burden in sub-Saharan Africa (SSA). These invasive non-typhoidal (iNTS) infections are dominated by isolates of the antibiotic resistance-associated sequence type (ST) 313. Here, we report emergence of ST313 sublineage II.1 in the Democratic Republic of the Congo. Sublineage II.1 exhibits extensive drug resistance, involving a combination of multidrug resistance, extended spectrum β-lactamase production and azithromycin resistance. ST313 lineage II.1 isolates harbour an IncHI2 plasmid we name pSTm-ST313-II.1, with one isolate also exhibiting decreased ciprofloxacin susceptibility. Whole genome sequencing reveals that ST313 II.1 isolates have accumulated genetic signatures potentially associated with altered pathogenicity and host adaptation, related to changes observed in biofilm formation and metabolic capacity. Sublineage II.1 emerged at the beginning of the 21st century and is involved in on-going outbreaks. Our data provide evidence of further evolution within the ST313 clade associated with iNTS in SSA., Invasive non-typhoidal Salmonella (iNTS) infections are dominated by antibiotic resistant isolates of the sequence type (ST) 313. Here, the authors identify the ST313 sublineage II.1 in the Democratic Republic of the Congo exhibiting extensive drug resistance and genetic signatures potentially associated with host adaptation.

Background This study gives an overview of a decade (2007–2017) of hospital-based Salmonella Typhi bloodstream infection (BSI) surveillance in the Democratic Republic of the Congo (DRC), at 4 main sampling sites. Methods Blood cultures were sampled in hospital-admitted patients with suspected BSI, according to standardized clinical indications. The results of the surveillance period 2015–2017 were compiled with those of previous surveillance periods (2007–2010 and 2011–2014). Whole genome sequencing of isolates with decreased ciprofloxacin susceptibility (DCS) was performed. Results Salmonella Typhi was isolated in 1.4% (531/37 388) and 10.3% (531/5177) of suspected and culture-confirmed BSI episodes, respectively. Salmonella Typhi ranked first among the BSI pathogens in adults (n = 220), but was mostly (n = 301 [56.7%]) isolated from children, of which 72.1% (217/301) and 31.6% (95/301) were Conclusions Salmonella Typhi was a frequent cause of BSI in adults and children in DRC, with high rates of antibiotic resistance. Sustainable surveillance and implementation of vaccination are compelling.

BACKGROUND This study reports the microbiological landscape of Salmonella Typhi and invasive nontyphoidal Salmonella (iNTS) in the Democratic Republic of the Congo (DRC). METHODS Blood cultures obtained from hospital-admitted patients suspected of bloodstream infection (BSI) in 4 of 11 provinces in DRC (Kinshasa, Bas-Congo, Equateur, and Orientale) were processed. Sampling had started in 2007; the results for the period 2011-2014 are reported. RESULTS Salmonella Typhi and iNTS were cultured from 194 (1.4%) and 840 (5.9%), respectively, of 14,110 BSI episodes and ranked first among BSI pathogens in adults (65/300 [21.7%]) and children (783/1901 [41.2%]), respectively. A total of 948 of 1034 (91.7%) isolates were available for analysis (164 Salmonella Typhi and 784 iNTS). Salmonella Typhimurium and Salmonella Enteritidis represented 386 (49.2%) and 391 (49.9%), respectively, of iNTS isolates, fluctuating over time and geography and increasing during the rainy season. Adults accounted for