Background: Salmonellosis causes significant morbidity and mortality in Africa. Despite being endemic in Nigeria, information on circulating lineages of invasive Salmonella is sparse. Methods: Sixty-three Salmonella enterica isolated from blood (n=60) and cerebrospinal fluid (CSF, n=3) isolated between 2016 and 2020 from five tertiary hospitals in southwest Nigeria were Illumina-sequenced and analysed using publicly available bioinformatic tools. Results: Isolates and sequence types (STs) from blood were S. Typhi [ST1 =1 and ST2 =43] and invasive non-typhoidal Salmonella (iNTS) (S. Enteritidis [ST11, n=7], S. Durham [ST10, n=2], S. Rissen [ST8756, n=2], S. Chester [ST2063, n=1], S. Dublin [ST10, n=1], S. Infantis [ST603, n=1], S. Telelkebir [ST8757, n=1] and S. Typhimurium [ST313, n=1], whereas it was S. Typhi ST2 (n=2) and S. Adabraka ST8757 (n=1) from CSF. Most S. Typhi belonged to genotype 3.1.1 (n=44, 95.7%) and had several antibiotic resistance genes (ARGs) including blaTEM-1 (86.4%, n=38), aph(6)-Id (72.7%, n=32), tet(A) (75%, n=33), sul2 (72.7%, n=32), dfrA14 (68.18%, n=30) as well as the quinolone resistance-conferring gyrA_S83Y SNPs (n=37, 84.09%). The 3.1.1 strains included a predominant sub-lineage (n=33) harbouring gyrA_S83Y and an IncY plasmid detected at all hospitals. Typhoidal toxins cdtB, pltA and pltB were detected in S. Typhi, Rissen, Chester, and Telelkebir. Conclusion: This study revealed the West African dominant lineage 3.1.1 to be majority of S. Typhi genotype harbouring ARGs. The increasing number of iNTS, including serovars harbouring typhoidal toxins, as well as the dominance of multidrug resistant isolates emphasizes the need for better diagnosis and surveillance of invasive Salmonella.
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