Pathogen Genomics of Salmonella Typhi Causing Enteric Fever in Children in Borno State, North East Nigeria: Resistance Mechanisms and Phylogenetics

Whole-genome sequencing of Salmonella Typhi offers unprecedented resolution for understanding drug resistance mechanisms, phylogenetic relationships, and transmission dynamics in enteric fever, with direct implications for treatment guidelines and vaccine policy. This study characterised S. Typhi isolates causing enteric fever in children at the University of Maiduguri Teaching Hospital, Borno State, North East Nigeria, using pathogen genomics approaches. Confirmed S. Typhi blood culture isolates from 45 paediatric enteric fever cases were subjected to whole-genome sequencing on the Illumina NextSeq platform. Bioinformatic pipelines including SRST2, Kleborate-adapted workflows, and Pathogenwatch were applied for resistance gene identification, multilocus sequence typing, and phylogenetic placement within the global S. Typhi framework. Extensively drug-resistant S. Typhi of genotype 4.3.1 (H58) was identified in 40.0% of isolates, carrying blaCTX-M-15, catA1, and dfrA7 resistance genes, alongside chromosomal fluoroquinolone resistance mutations in gyrA. Remaining isolates belonged to genotypes 3.2 and 2.3.3. Phylogenetic placement showed relatedness to South Asian XDR clades, suggesting recent importation events. All XDR isolates retained azithromycin and meropenem susceptibility. The emergence of XDR S. Typhi in North East Nigeria represents a severe therapeutic challenge and demands immediate clinical notification, contact tracing, revision of empirical treatment to azithromycin or carbapenems, and accelerated Typhoid Conjugate Vaccine deployment for children in Borno State. Keywords: Salmonella Typhi, whole-genome sequencing, XDR typhoid, pathogen genomics, Borno State