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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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Muturi, Wachira, Wagacha, Mbae, Kavai, Mugo, Mohamed, González, Kariuki and Gunn.)

Background: The emergence and persistence of multidrug-resistant (MDR) Salmonella Typhi (S. Typhi) infections is a significant global health problem. The carrier state of typhoid makes it prudent to conduct routine surveillance for both acute cases and carriers especially those caused by MDR S. Typhi. We report on the prevalence of MDR S. Typhi, resistance phenotypes and antimicrobial resistance genes detected in symptomatic and asymptomatic children living in informal settlements in Nairobi, Kenya., Methods: 215 archived presumed S. Typhi isolates from stool samples provided by children ≤ 16 years collected from 2013 to 2018 were revived in May, 2022 and confirmed using culture and antisera serotyping. The Kirby Bauer disc diffusion technique was used to test the S. Typhi against 14 antibiotics. The MDR S. Typhi (resistant to ampicillin, chloramphenicol and sulfamethoxazole trimethoprim) which in addition were also resistant to either a cephalosporin or a fluoroquinolone were analyzed for Beta lactams and quinolone resistance genes using polymerase chain reaction., Results: A total of 215 isolates were confirmed to be positively S. Typhi; of these, 105 (49%) and 110 (51%) were from symptomatic and asymptomatic children respectively. On average, S. Typhi resistance from asymptomatic and symptomatic children against 1st line drugs was observed at; 77% &70%, ampicillin; 60% & 64%, sulfamethoxazole-trimethoprim, and 45% & 54%, chloramphenicol respectively. Multi drug resistance was observed in 90 (42%) of the isolates, of these, 44 (49%) were isolated from symptomatic and 46 (51%) from asymptomatic children. Fifteen resistance phenotypes (p) were observed with, ampicillin/chloramphenicol/sulfamethoxazole-trimethoprim/nalidixic acid (amp/chl/sxt/na) as the most common among the symptomatic 43/90 (48%) and asymptomatic 55/90 (61%) children. The bla TEM-D , AMR genes were detected in 37/44 (84%) S. Typhi isolates, out of this 18 (49%) were from symptomatic while 19 (51%) were from asymptomatic children respectively., Conclusion: The carriage of MDR S. Typhi among the asymptomatic children is concerning as they can act as potential transmitters of the typhoid disease to unsuspecting children. These study findings highlight the need for continued surveillance of antimicrobial resistance and mass immunization of children living in these urban informal areas., (© 2024. The Author(s).)

Background: Understanding the dynamics of infection and carriage of typhoid in endemic settings is critical to finding solutions to prevention and control., Methods: In a 3-year case-control study, we investigated typhoid among children aged <16 years (4670 febrile cases and 8549 age matched controls) living in an informal settlement, Nairobi, Kenya., Results: 148 S . Typhi isolates from cases and 95 from controls (stool culture) were identified; a carriage frequency of 1 %. Whole-genome sequencing showed 97% of cases and 88% of controls were genotype 4.3.1 (Haplotype 58), with the majority of each (76% and 88%) being multidrug-resistant strains in three sublineages of the H58 genotype (East Africa 1 (EA1), EA2, and EA3), with sequences from cases and carriers intermingled., Conclusions: The high rate of multidrug-resistant H58 S . Typhi, and the close phylogenetic relationships between cases and controls, provides evidence for the role of carriers as a reservoir for the community spread of typhoid in this setting., Funding: National Institutes of Health (R01AI099525); Wellcome Trust (106158/Z/14/Z); European Commission (TyphiNET No 845681); National Institute for Health Research (NIHR); Bill and Melinda Gates Foundation (OPP1175797)., Competing Interests: SK, ZD, CM, RN, SK, CW, SA, NG, RO, BO, SD, MA, JC, KH, GD No competing interests declared, (© 2021, Kariuki et al.)

Background: In Kenya, typhoid fever and invasive non-typhoidal salmonellosis present a huge burden of disease, especially in poor-resource settings where clean water supply and sanitation conditions are inadequate. The epidemiology of both diseases is poorly understood in terms of severity and risk factors. The aim of the study was to determine the disease burden and spatial distribution of salmonellosis, as well as socioeconomic and environmental risk factors for these infections, in a large informal settlement near the city of Nairobi, from 2013 to 2017., Methods: Initially, a house-to-house baseline census of 150,000 population in Mukuru informal settlement was carried out and relevant socioeconomic, demographic, and healthcare utilization information was collected using structured questionnaires. Salmonella bacteria were cultured from the blood and faeces of children < 16 years of age who reported at three outpatient facilities with fever alone or fever and diarrhea. Tests of association between specific Salmonella serotypes and risk factors were conducted using Pearson Chi-Square (χ 2 ) test., Results: A total of 16,236 children were recruited into the study. The prevalence of bloodstream infections by Non-Typhoidal Salmonella (NTS), consisting of Salmonella Typhimurium/ Enteriditis, was 1.3%; Salmonella Typhi was 1.4%, and this was highest among children < 16 years of age. Occurrence of Salmonella Typhimurium/ Enteriditis was not significantly associated with rearing any domestic animals. Rearing chicken was significantly associated with high prevalence of S. Typhi (2.1%; p = 0.011). The proportion of children infected with Salmonella Typhimurium/ Enteriditis was significantly higher in households that used water pots as water storage containers compared to using water directly from the tap (0.6%). Use of pit latrines and open defecation were significant risk factors for S. Typhi infection (1.6%; p = 0.048). The proportion of Salmonella Typhimurium/ Enteriditis among children eating street food 4 or more times per week was higher compared to 1 to 2 times/week on average (1.1%; p = 0.032)., Conclusion: Typhoidal and NTS are important causes of illness in children in Mukuru informal settlement, especially among children less than 16 years of age. Improving Water, Sanitation and Hygiene (WASH) including boiling water, breastfeeding, hand washing practices, and avoiding animal contact in domestic settings could contribute to reducing the risk of transmission of Salmonella disease from contaminated environments.