Preclinical study of single-dose moxidectin, a new oral treatment for scabies: Efficacy, safety, and pharmacokinetics compared to two-Ddose Iiermectin in a porcine model

Charlotte Bernigaud (1, 2) , Fang Fang (3, 2) , Katja Fischer (4) , Anne Lespine (5) , Ludwig Serge Aho (6) , Dominique Dreau (7) , Andrew Kelly (8) , Jean-Francois Sutra (5) , Francis Moreau (9) , Thomas Lilin (9) , Françoise Botterel (2, 10) , Jacques Guillot (11, 2) , Olivier Chosidow (12, 13, 14)

1 Departement de Dermatolgie
2 DYNAMIC - Dynamic Microbiology - EA 7380
3 Department of Parasitology, College of Animal Science and Technology
4 nfections Diseases Department, Scabies Laboratory, QIMR Berghofer Medical Research Institute
5 ToxAlim - ToxAlim
6 Epidemiology and Infection Control Unit
7 Cecaveto
8 Department of Agriculture, Fisheries and Forestry, Queensl and Animal Science Precinct
9 CRBM - Centre de recherche biomédicale
10 Hôpital Henri Mondor
11 Department of Parasitology and Mycology, Biopole d’Alfort, Ecole Nationale Vétérinaire d’Alfort
12 EpiDermE - Epidemiology in Dermatology and Evaluation in Therapeutics
13 UPE - Université Paris-Est
14 INSERM - Institut National de la Santé et de la Recherche Médicale

Background Scabies is one of the commonest dermatological conditions globally; however it is a largely underexplored and truly neglected infectious disease. Foremost, improvement in the management of this public health burden is imperative. Current treatments with topical agents and/or oral ivermectin (IVM) are insufficient and drug resistance is emerging. Moxidectin (MOX), with more advantageous pharmacological profiles may be a promising alternative. Methodology/Principal Findings Using a porcine scabies model, 12 pigs were randomly assigned to receive orally either MOX (0.3 mg/kg once), IVM (0.2 mg/kg twice) or no treatment. We evaluated treatment efficacies by assessing mite count, clinical lesions, pruritus and ELISA-determined anti-S. scabiei IgG antibodies reductions. Plasma and skin pharmacokinetic profiles were determined. At day 14 post-treatment, all four MOX-treated but only two IVM-treated pigs were mite-free. MOX efficacy was 100% and remained unchanged until study-end (D47), compared to 62% (range 26-100%) for IVM, with one IVM-treated pig remaining infected until D47. Clinical scabies lesions, pruritus and anti-S. scabiei IgG antibodies had completely disappeared in all MOX-treated but only 75% of IVM-treated pigs. MOX persisted similar to 9 times longer than IVM in plasma and skin, thereby covering the mite's entire life cycle and enabling long-lasting efficacy. Conclusions/Significance Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies.

Mots clés: sarcoptes-scabiei; disposition kinetics; p-glycoprotein; skin-disease; itch mites; head lice; moxidectin; pigs; plasma; cattle

Domaines: Sciences du Vivant [q-bio]

Charlotte Bernigaud, Fang Fang, Katja Fischer, Anne Lespine, Ludwig Serge Aho, et al.. Preclinical study of single-dose moxidectin, a new oral treatment for scabies: Efficacy, safety, and pharmacokinetics compared to two-Ddose Iiermectin in a porcine model. PLoS Neglected Tropical Diseases, 2016, 10 (10), ⟨10.1371/journal.pntd.0005030⟩. ⟨hal-01608099⟩