Genomic Analysis of Salmonella Typhi from a Typhoid Conjugate Vaccine Trial
Background  Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, continues to pose a major public health challenge in many low- and middle-income countries (LMICs). The World Health Organization recommended typhoid conjugate vaccine (TCV) use in countries with a high burden of disease, and/or high rates of antimicrobial resistance (AMR). Recent introductions of TCVs into national immunisation programmes are expected to substantially reduce this burden. In Malawi, a Phase 3, double-blind, randomized, controlled trial enrolled 28,130 healthy children aged 9 months through 12 years of age to receive either TCV (Typbar-TCV, Bharat Biotech) or meningococcal A conjugate vaccine (MCV).  Methods  To investigate the short-term evolutionary dynamics of S. Typhi after TCV vaccination, we conducted Illumina whole genome sequencing of bacterial isolates collected during a phase 3 randomized, controlled vaccine trial in Malawian children. We compared isolates from the TCV intervention arm to the MCV control arm with regard to: (i) S. Typhi lineage distribution, (ii) AMR profile, (iii) mutations in genes associated with Vi capsule biosynthesis and expression, and (iv) phylogenetic population structure.