Host population structure and rare dispersal events drive leptospirosis transmission patterns amongRattus norvegicusin Boston, Massachusetts, US

Abstract

AbstractLeptospirosis (caused by pathogenic bacteria in the genusLeptospira) is prevalent worldwide but more common in tropical and subtropical regions. Transmission can occur following direct exposure to infected urine from reservoir hosts, such as rats, or a urine-contaminated environment, which then can serve as an infection source for additional rats and other mammals, including humans. The brown rat,Rattus norvegicus, is an important reservoir of leptospirosis in urban settings. We investigated leptospirosis among brown rats in Boston, Massachusetts and hypothesized that rat dispersal in this urban setting influences the movement, persistence, and diversity ofLeptospira. We analyzed DNA from 328 rat kidney samples collected from 17 sites in Boston over a seven-year period (2016–2022); 59 rats representing 12 of 17 sites were positive forLeptospira. We used 21 neutral microsatellite loci to genotype 311 rats and utilized the resulting data to investigate genetic connectivity among sampling sites. We generated whole genome sequences for 28Leptospiraisolates obtained from frozen and fresh tissue from some of the 59Leptospira-positive rat kidneys. When isolates were not obtained, we attemptedLeptospiragenomic DNA capture and enrichment, which yielded 14 additionalLeptospiragenomes from rats. We also generated an enrichedLeptospiragenome from a 2018 human case in Boston. We found evidence of high genetic structure and limited dispersal among rat populations that is likely influenced by major roads and/or other unknown dispersal barriers, resulting in distinct rat population groups within the city; at certain sites these groups persisted for multiple years. We identified multiple distinct phylogenetic clades ofL. interrogansamong rats, with specific clades tightly linked to distinct rat populations. This pattern suggestsL. interroganspersists in local rat populations and movement of leptospirosis in this urban rat community is driven by rat dispersal. Finally, our genomic analyses of the 2018 human leptospirosis case in Boston suggests a link to rats as the source. These findings will be useful for guiding rat control and human leptospirosis mitigation efforts in this and other urban settings.