Fluralaner as a novel treatment for sarcoptic mange in the bare-nosed wombat (Vombatus ursinus): safety, pharmacokinetics, efficacy and practicable use.

BACKGROUND: Sarcoptic mange causes significant animal welfare and occasional conservation concerns for bare-nosed wombats (Vombatus ursinus) throughout their range. To date, in situ chemotherapeutic interventions have involved macrocytic lactones, but their short duration of action and need for frequent re-administration has limited treatment success. Fluralaner (Bravecto®; MSD Animal Health), a novel isoxazoline class ectoparasiticide, has several advantageous properties that may overcome such limitations. METHODS: Fluralaner was administered topically at 25 mg/kg (n = 5) and 85 mg/kg (n = 2) to healthy captive bare-nosed wombats. Safety was assessed over 12 weeks by clinical observation and monitoring of haematological and biochemical parameters. Fluralaner plasma pharmacokinetics were quantified using ultra-performance liquid chromatography and tandem mass spectrometry. Efficacy was evaluated through clinical assessment of response to treatment, including mange and body condition scoring, for 15 weeks after topical administration of 25 mg/kg fluralaner to sarcoptic mange-affected wild bare-nosed wombats (n = 3). Duration of action was determined through analysis of pharmacokinetic parameters and visual inspection of study subjects for ticks during the monitoring period. Methods for diluting fluralaner to enable 'pour-on' application were compared, and an economic and treatment effort analysis of fluralaner relative to moxidectin was undertaken. RESULTS: No deleterious health impacts were detected following fluralaner administration. Fluralaner was absorbed and remained quantifiable in plasma throughout the monitoring period. For the 25 mg/kg and 85 mg/kg treatment groups, the respective means for maximum recorded plasma concentrations (Cmax) were 6.2 and 16.4 ng/ml; for maximum recorded times to Cmax, 3.0 and 37.5 days; and for plasma elimination half-lives, 40.1 and 166.5 days. Clinical resolution of sarcoptic mange was observed in all study animals within 3-4 weeks of treatment, and all wombats remained tick-free for 15 weeks. A suitable product for diluting fluralaner into a 'pour-on' was found. Treatment costs were competitive, and predicted treatment effort was substantially lower relative to moxidectin. CONCLUSIONS: Fluralaner appears to be a safe and efficacious treatment for sarcoptic mange in the bare-nosed wombat, with a single dose lasting over 1-3 months. It has economic and treatment-effort-related advantages over moxidectin, the most commonly used alternative. We recommend a dose of 25 mg/kg fluralaner and, based on the conservative assumption that at least 50% of a dose makes dermal contact, Bravecto Spot-On for Large Dogs as the most appropriate formulation for adult bare-nosed wombats.

Expanded Molecular Typing of Sarcoptes scabiei Provides Further Evidence of Disease Spillover Events in the Epidemiology of Sarcoptic Mange in Australian Marsupials.

The invasive ectoparasite Sarcoptes scabiei affects the welfare and conservation of Australian marsupials. Molecular data suggest that spillover from other hosts may be responsible for the emergence of this infectious disease, but the scale of such studies is limited. We performed expanded molecular typing of the S. scabiei mitochondrial cox1 gene from 81 skin scrapings from infested wombats ( Vombatus ursinus), koalas ( Phascolarctos cinereus), red foxes ( Vulpes vulpes), and dogs ( Canis lupus familiaris) across Australia. Combined with existing S. scabiei sequences, our analysis revealed 16 haplotypes among Australian animals, sharing between 93.3% and 99.7% sequence similarity. While some sequences were unique to specific hosts or to Australia, key haplotypes could be detected across several marsupial hosts as well as to wild or domestic canids in Australia. We identified 43 cox1 haplotypes with many Australian haplotypes identical to S. scabiei mites from inside and outside Europe. We concluded that multiple introduction events were plausible explanations to the origin and emergence of this parasite into Australian marsupials and that disease spillover from canids was likely. Together, our greatly expanded S. scabiei sequence dataset provided a more nuanced picture of both spillover and sustained intraspecific transmission for this important parasite.

Mitochondrial genome sequencing reveals potential origins of the scabies mite Sarcoptes scabiei infesting two iconic Australian marsupials.

BACKGROUND: Debilitating skin infestations caused by the mite, Sarcoptes scabiei, have a profound impact on human and animal health globally. In Australia, this impact is evident across different segments of Australian society, with a growing recognition that it can contribute to rapid declines of native Australian marsupials. Cross-host transmission has been suggested to play a significant role in the epidemiology and origin of mite infestations in different species but a chronic lack of genetic resources has made further inferences difficult. To investigate the origins and molecular epidemiology of S. scabiei in Australian wildlife, we sequenced the mitochondrial genomes of S. scabiei from diseased wombats (Vombatus ursinus) and koalas (Phascolarctos cinereus) spanning New South Wales, Victoria and Tasmania, and compared them with the recently sequenced mitochondrial genome sequences of S. scabiei from humans. RESULTS: We found unique S. scabiei haplotypes among individual wombat and koala hosts with high sequence similarity (99.1% - 100%). Phylogenetic analysis of near full-length mitochondrial genomes revealed three clades of S. scabiei (one human and two marsupial), with no apparent geographic or host species pattern, suggestive of multiple introductions. The availability of additional mitochondrial gene sequences also enabled a re-evaluation of a range of putative molecular markers of S. scabiei, revealing that cox1 is the most informative gene for molecular epidemiological investigations. Utilising this gene target, we provide additional evidence to support cross-host transmission between different animal hosts. CONCLUSIONS: Our results suggest a history of parasite invasion through colonisation of Australia from hosts across the globe and the potential for cross-host transmission being a common feature of the epidemiology of this neglected pathogen. If this is the case, comparable patterns may exist elsewhere in the 'New World'. This work provides a basis for expanded molecular studies into mange epidemiology in humans and animals in Australia and other geographic regions.