| Συγγραφείς: |
Fernando DD; Infection and Inflammation Program, QIMR Berghofer, 300 Herston Road, Herston, QLD 4006, Australia.; School of Veterinary Science, University of Queensland, Cnr Main Drive and Outer Ring Road, Gatton, QLD 4343, Australia.; School of Biomedical Sciences, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia., Taylor S; Infection and Inflammation Program, QIMR Berghofer, 300 Herston Road, Herston, QLD 4006, Australia.; School of Biomedical Sciences, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia., Samarawickrama GR; Infection and Inflammation Program, QIMR Berghofer, 300 Herston Road, Herston, QLD 4006, Australia.; School of Veterinary Science, University of Queensland, Cnr Main Drive and Outer Ring Road, Gatton, QLD 4343, Australia., Nammunige NA; Infection and Inflammation Program, QIMR Berghofer, 300 Herston Road, Herston, QLD 4006, Australia.; School of Biomedical Sciences, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia.; School of Biomedical Sciences, University of Queensland, St Lucia, QLD 4067, Australia., Hartel G; Statistics Unit, QIMR Berghofer, 300 Herston Road, Herston, Brisbane, QLD 4006, Australia., Bowles V; Melbourne Veterinary School, University of Melbourne, 30 Flemington Rd, Parkville, VIC 3052, Australia., Fischer K; Infection and Inflammation Program, QIMR Berghofer, 300 Herston Road, Herston, QLD 4006, Australia.; School of Veterinary Science, University of Queensland, Cnr Main Drive and Outer Ring Road, Gatton, QLD 4343, Australia.; School of Biomedical Sciences, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia. |
| Περίληψη: |
Scabies affects ∼400 million people annually, yet current therapies lack ovicidal activity, require repeat dosing, and are increasingly compromised by treatment failure and resistance. The absence of a single-application therapy capable of eliminating both motile mites and eggs represents one important limitation to effective disease control. We developed a mechanism-informed topical therapy combining abametapir, a metalloprotease inhibitor with ovicidal activity, and flavesone, a β-triketone with rapid miticidal effects, designed to target multiple parasite life stages through distinct, non-neurotoxic mechanisms. Using a porcine model that closely recapitulates human scabies, we assessed efficacy, pruritus reduction, and pharmacologic exposure after topical administration. In severe scabies, a single 4-hour treatment eradicated all live mites and eggs and reduced pruritus, outperforming a standard two-dose oral ivermectin regimen. Skin pharmacokinetics demonstrated rapid attainment of concentrations with exposure profiles, supporting single-dose efficacy despite shorter systemic half-lives than ivermectin. Together, this promising therapeutic combination may offer a simplified and potentially resistance-resilient approach to scabies management. |