Advancing the understanding of neural angiostrongyliasis in Australia

Abstract

Angiostrongylus cantonensis (rat lungworm) is a parasite of rats that causes a potentiallyfatal disease in humans and other animals – neural angiostrongyliasis (NA). The infective,neurotropic stage of the worm typically develops in gastropods (slugs and snails) andmatures into adults within the definitive (rat) host. Despite an apparent increase in thedisease in dogs (canine NA, CNA) and the associated growing public health significance,limited research existed on the parasite's distribution, genetic diversity, and transmissiondynamics in Australia. Genetic typing of Angiostrongylus in dogs, wild rats and a squirrel monkey revealed thatthe Ac13 haplotype of A. cantonensis predominates over SYD.1 haplotype. Cultivation of alocal Ac13 isolate and subsequent experimental infection of rats demonstrated that Ac13triggers a distinct transcriptional response in definitive hosts. Analyses substantiated thatthe Ac13 haplotype enriches inflammatory pathways, potentially explaining the presence of Ac13 in a majority of clinically-affected dogs. Modelling uncovered relationshipsbetween rainfall and CNA occurrence; and experimental studies on aquatic snailsidentified potential transmission pathways through environmental water sources (e.g.water bowls and puddles). Additionally, the innovation of the Angie-LAMP assay offers anovel, accessible and sensitive screening method for NA. Risk-mapping analysesinformed pest management strategies, while comprehensive literature reviews andsurveys refined our understanding of A. cantonensis distribution and invasion pathways inAustralia. Future research directions include expanded host surveys which considerutilising workflows developed herein, continued genetic typing, and adoption of noveldiagnostic approaches (e.g. Angie-LAMP). In all, this thesis provides a comprehensiveupdate on NA epidemiology, with implications for future surveillance, risk mapping, anddiagnostic strategies in Australia and beyond.