Abstract
BACKGROUND: Typhoid fever is a serious infection that primarily affects humans, with approximately 20 million cases reported each year, mostly in low- and middle-income countries (LMICs). Continuous monitoring of Salmonella enterica serovar Typhi (S. Typhi) in these endemic areas is crucial for tracking trends in antimicrobial resistance (AMR) and developing effective control measures. This study focused on S. Typhi isolates from children aged ≤ 16 years who showed symptoms of fever in Mukuru and Kibera informal settlements in Nairobi County, Kenya. METHODS: Blood samples for culture were collected from participants at four health facilities within Nairobi County. Antimicrobial susceptibility profiles were assessed using the Kirby–Bauer disc diffusion technique, and whole-genome sequencing (WGS) was performed on selected multidrug-resistant (MDR) isolates. The genomes were assembled and analysed using https://pathogen.watch/ to identify genotypes, resistance genes, and phylogenetic relationships. RESULTS: Out of 120 S. Typhi isolates tested, 50% were found to be MDR. Resistance to first-line antibiotics was common, with 65.6% resistant to ampicillin, 62.3% to sulfamethoxazole-trimethoprim, and 59% to chloramphenicol. Thirty-seven selected MDR isolates underwent WGS, all belonging to the genotype 4.3.1 (H58), which is the most prevalent MDR clade globally. These were further categorised into sublineage 4.3.1.1 EA (East Africa 1), accounting for 40.5% of the sequenced isolates. Genomic analysis identified several AMR genes, including bla(TEM−1D), catA1, dfrA7, sul1, and sul2. Additionally, point mutations in the quinolone resistance-determining region (QRDR) of gyrA were found in 67.6% of the isolates, with the most common mutation being S83Y. These mutations are linked to decreased susceptibility to ciprofloxacin, a key treatment for typhoid in Kenya. CONCLUSION: The high rate of MDR S. Typhi, especially in children who are most affected by the disease, raises significant public health concerns. The presence of QRDR mutations further complicates treatment options for typhoid fever, highlighting the urgent need for alternative approaches. These may include broader use of typhoid conjugate vaccines (TCVs), strengthening antimicrobial stewardship programs, and investing in improvements in water, sanitation, and hygiene (WASH) infrastructure in these endemic settings in Kenya. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-025-12317-z.