Typhoidal Salmonella Disease in Mukuru Informal Settlement, Nairobi Kenya; Carriage, Strain Diversity, and Antimicrobial Resistant Genes

Abstract

Typhoid fever remains a significant public health concern globally, with approximately 26 million cases and 210,000 deaths annually. In Mukuru informal settlement—characterized by high population density, poor sanitation, and inadequate access to clean water—typhoid fever is known to be endemic. This study aimed to determine the isolation rate, antimicrobial resistance patterns, and genetic diversity of Salmonella Typhi among cases and asymptomatic individuals in Mukuru between 2021 and 2022. In total, 1014 outpatients presenting with typhoid-like symptoms were recruited from selected health centers, with blood and stool samples collected. Asymptomatic individuals, identified from contacts living in the households of positive cases, provided only stool samples to assess their potential role in disease transmission. Isolation and identification of S.Typhi were performed using standard microbiological methods, including culture on selective media, biochemical tests, the API 20E system, and serotyping with specific antisera. Antimicrobial susceptibility was assessed using the Kirby-Bauer disc diffusion method, and multi-drug resistant (MDR) strains were characterized through conventional PCR and whole-genome sequencing (WGS). Bioinformatics analysis of WGS data provided detailed phylogenetic relationships and antimicrobial resistance determinants. Of the participants, 54 (5%) tested positive for S.Typhi through serotyping, with 70% of isolates from stool samples and 30% from blood samples; 0.2% were from asymptomatic individuals. Multi-drug resistance was observed in 37% (20) of isolates, with high resistance rates to ciprofloxacin (43%) and nalidixic acid (52%). The blaTEM-1B gene was detected in 95% (19/20) of MDR isolates, all carrying IncQ1 plasmids harboring multiple resistance genes. Mutations in gyrA and gyrB genes associated with quinolone resistance were also identified. Phylogenetic analysis revealed the dominance of sub-lineage 4.3.1.2 EA3 at 46% and identified three major clusters. The prevalence of MDR S.Typhi and reduced susceptibility to first-line antibiotics in Mukuru underscores the urgent need for effective antimicrobial stewardship, routine AMR surveillance, and improved sanitation measures. The genetic relatedness between isolates from cases and carriers suggests asymptomatic carriage as a potential source of infection, highlighting the importance of comprehensive public health strategies to control typhoid fever in high-risk settings.