Population structure and antimicrobial resistance patterns of Salmonella Typhi and Paratyphi A amid a phased municipal vaccination campaign in Navi Mumbai, India. undefined

Enteric fever is an acute febrile illness that causes an estimate 100,000 deaths annually, nearly all occurring in low and middle-income countries. Little is known about the population structure and spatial scale of transmission within endemic cities. We performed whole genome sequencing of Salmonella Typhi and Salmonella Paratyphi A isolates collected through prospective surveillance in the context of a phased typhoid conjugate vaccine introduction in Navi Mumbai, India between 2018 and 2020. The resulting pathogen genomic data was combined with a collection of published genomes from India to investigate the temporal and geographical patters of emergence and spread of antimicrobial resistance. We identified genomic resistance determinants and generated time phylogenies to evaluate the timing and frequency of introductions into Navi Mumbai. We evaluated the relationship between the spatial distance between households and genetic clustering of isolates using Bayesian hierarchical models. Our findings indicate that S. Typhi was repeatedly introduced into Navi Mumbai and then spread locally, with strong evidence of spatial-genetic clustering. In addition to vaccination, local interventions to improve water and sanitation will be critical to interrupt transmission.