Population structure and evolution of Salmonella enterica serotype Typhi in Zimbabwe before a typhoid conjugate vaccine immunization campaign

Background The continued emergence of Salmonella enterica serovar Typhi ( S . Typhi) with ever increasing antimicrobial resistance (AMR), necessitates the use of vaccines in endemic countries. A typhoid fever outbreak in Harare, Zimbabwe in 2018 from a multidrug resistant S . Typhi with additional resistance to ciprofloxacin was the catalyst for the introduction of a typhoid conjugate vaccine program. To investigate the historic emergence and evolution of AMR of endemic S . Typhi in Zimbabwe and determined the population structure, gene flux and sequence polymorphisms of strains isolated prior to mass typhoid vaccination to provide a baseline for future evaluation of the effect of the vaccination program. Methods We determined the population structure, gene flux and sequence polymorphisms and reconstructed the evolution of AMR. The S . Typhi population structure was investigated in the context the genome sequence of 1904 strains isolated from 65 countries to reconstruct spread of endemic strains into Zimbabwe. Findings The population structure of S . Typhi in Zimbabwe is dominated by multidrug resistant genotype 4.3.1.1 (H58) that spread to Zimbabwe from neighboring countries around 2009. Evolution of AMR within Zimbabwe included acquisition of an IncN plasmid carrying a qnrS gene and a mutation in the quinolone resistance determining region of gyrA gene, both implicated in resistance to quinolone antibiotics. A minority population of antimicrobial susceptible S . Typhi genotype 3.3.1 strains was detected in typhoid cases. Interpretation The currently dominant S . Typhi population is genotype 4.3.1.1 that spread to Zimbabwe and acquired additional AMR though acquisition of a plasmid and mutation of the gyrA gene. This study provides a baseline for future evaluation of the impact of the Typhoid Conjugate Vaccine program in Harare. Funding RAK and GT were supported by Bill and Melinda Gates Foundation project OPP1217121 and the BBSRC Institute Strategic Programme BB/R012504/1 and its constituent project BBS/E/F/000PR10348. ### Competing Interest Statement The authors have declared no competing interest.