Repurposing drugs to treat Amoebic Gill Disease in Atlantic Salmon

Abstract

Neoparameoba perurans causes Amoebic Gill Disease (AGD), a major parasitic disease of marine-phase Atlantic salmon and rainbow trout worldwide. Treatment options are limited to freshwater baths, which are costly at scale and exhibit only limited long-term efficacy. N. perurans contains an obligate eukaryotic symbiont, Perkinsela-like organism (PLO). PLO belongs to the class Kinetoplastida, which includes medically and veterinary important parasites such as Trypanosoma and Leishmania. As such, we hypothesised that trypanocidal drugs developed against other kinetoplastids might also affect N. perurans, potentially through disruption of its PLO symbiont, and used this hypothesis as a rationale for prioritising a focused panel of candidate compounds for screening. A holographic motility-based cytotoxicity assay was established to identify promising candidates in vitro, followed by controlled host tolerance testing and finally a field efficacy sea trial using naturally AGD-exposed site in the west of Ireland. Several compounds showed activity in vitro, especially miltefosine (EC50 1.84 uM, amoebicidal) and isometamidum (EC50 4.63 uM, amoebostatic). In vivo (two intramuscular injections, two weeks apart), miltefosine (Odds Ratio (OR) 0.62), isometamidum (OR 0.61) and benznidazole (OR 0.64) significantly improved gill score over four weeks, with miltefosine showing the largest effect size. Gill parasitaemia, measured via qPCR, was not reduced. Instead, two compounds increased apparent amoeba loads. This work support trypanocidal as potential AGD treatments in the field, although optimisation of dosing, delivery and mode of action requires further study.