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

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.

肠热症（Enteric fever）是一种急性发热性疾病，据估算每年造成约10万例死亡，其中几乎所有病例均发生在中低收入国家。目前学界对流行城市内的病原体种群结构及传播的空间规模尚缺乏深入认知。本研究于2018至2020年间，在印度新孟买（Navi Mumbai）分期引入伤寒结合疫苗（typhoid conjugate vaccine）的背景下，通过前瞻性监测收集了伤寒沙门氏菌（Salmonella Typhi）与甲型副伤寒沙门氏菌（Salmonella Paratyphi A）的分离株，并对其进行了全基因组测序（whole genome sequencing）。研究将所得的病原体基因组数据与已发表的印度本地基因组数据集相结合，以探究抗菌药物耐药性（antimicrobial resistance）出现与传播的时间及地理模式。本研究鉴定了基因组耐药决定因子（genetic resistance determinants），并构建了时间系统发育树（time phylogenies），以评估病原菌传入新孟买的时间与频率。同时，本研究采用贝叶斯分层模型（Bayesian hierarchical models），分析了住户间空间距离与分离株遗传聚类（genetic clustering）之间的关联。研究结果显示，伤寒沙门氏菌多次传入新孟买并在本地扩散，存在显著的空间-遗传聚类证据。除疫苗接种外，改善供水与卫生设施的本地干预措施对于阻断传播至关重要。