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Although typhoid fever has largely been eliminated in high-income countries, it remains a major global public health concern especially among low- and middle-income countries. The causative agent, Salmonella enterica serovar Typhi (S. Typhi), is a human restricted pathogen with a limited capacity to replicate outside the human host. Human carriers, 90% of whom have gallstones in their gallbladder, continue to shed the pathogen for an ill-defined period of time after treatment. The genetic mechanisms involved in establishing the carrier state are poorly understood, but S. Typhi is thought to undergo specific genetic changes within the gallbladder as an adaptive mechanism. In the current study, we aimed to identify the genetic differences in longitudinal clinical S. Typhi isolates from asymptomatic carriers with gallstones in a typhoid endemic setting in Nairobi, Kenya. Whole-genome sequences were analyzed from 22 S. Typhi isolates, 20 from stool samples, and 2 from blood samples, all genotype 4.3.1 (H58). Out of this, 19 strains were from four patients also diagnosed with gallstones, of whom three had typhoid symptoms and continued to shed S. Typhi after treatment. All isolates had point mutations in the quinolone resistance-determining region (QRDR), and only sub-lineage 4.3.1.2.EA3 encoded multidrug resistance genes. There was no variation in antimicrobial resistance patterns among strains from the same patient/household. Non-multidrug resistant (MDR) isolates formed significantly stronger biofilms in vitro than the MDR isolates, p<0.001. A point mutation within the treB gene (treB A383T) was observed in strains isolated after clinical resolution from patients living in 75% of the households. For missense mutations in Vi capsular polysaccharide genes, tviE P263S was also observed in 18% of the isolates. This study provides insights into the role of typhoid carriage, biofilm formation, AMR genes, and genetic variations in S. Typhi during asymptomatic carriage. [ABSTRACT FROM AUTHOR]

Nontyphoidal Salmonella (NTS) is a predominant cause of invasive disease in sub-Saharan Africa especially among children under 5 years. Asymptomatic fecal shedding of NTS is hypothesized to contribute to the human-to-human transmission of NTS especially in low-resource settings. However, the role of pathogen shedding in invasive disease is unknown. This study aimed to investigate the prevalence and duration of fecal shedding of NTS among children under 5 years convalescing from invasive NTS disease and among healthy individuals in the community. Children presenting with fever of ≥38°C with or without diarrhea were recruited at four health facilities in Nairobi, between June 2021 and August 2023. Blood and stool samples collected were subjected to culture for the isolation of NTS ( S . Enteritidis and S . Typhimurium). Children with NTS culture-positive samples (index cases) were followed up post-acute disease where household contacts and controls provided stool samples for isolation of NTS. NTS prevalence among the 3,293 individuals recruited was 1.52%. Asymptomatic shedding post-treatment was observed in almost one-third (31%) of the 42 index cases followed up. Of the 13 with intestinal shedding, 7 were shedding NTS of the same sequence type (ST) as the one recovered during acute disease. The longest duration of intestinal shedding was 3 months post-treatment. Of the 241 healthy individuals recruited, 8 had asymptomatic shedding of NTS, and 2 of these were closely related to those recovered from index cases. These findings support the hypothesis of human-to-human transmission of NTS in sub-Saharan Africa highlighting the possible benefit of vaccine introduction., Importance: Asymptomatic fecal shedding of nontyphoidal Salmonella (NTS) is hypothesized to contribute to the human-to-human transmission of NTS especially in low-resource settings which could lead to invasive disease among high-risk populations, especially children. Our findings reiterate the hypothesis that human reservoirs could be important in the transmission of nontyphoidal Salmonella in sub-Saharan Africa. This underscores the importance of developing infection prevention measures which could include vaccine deployment and improving water, sanitation and hygiene infrastructure., Competing Interests: The authors declare no conflict of interest.