title: Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model.
abstract: 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.
  
  
  RESULTS
  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 ~9 times longer than IVM in plasma and skin, thereby covering the mite's entire life cycle and enabling long-lasting efficacy.
  
  
  CONCLUSIONS
  Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies.
authors.affiliation: Research Group Dynamyc, EA 7380, EnvA, Université Paris-Est (UPE), Maisons-Alfort & Créteil, France.|APHP, Hôpital Henri-Mondor, Department of Dermatology, UPEC, Créteil, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Bernigaud
authors.affiliation: Research Group Dynamyc, EA 7380, EnvA, Université Paris-Est (UPE), Maisons-Alfort & Créteil, France.|Department of Parasitology, College of Animal Science and Technology, University of Guangxi, Nanning, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Infections Diseases Department, Scabies Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Katja
authors.initials: K
authors.lastname: Fischer
authors.affiliation: Toxalim, INRA, INP-ENVT, INP-EI-Purpan, Université de Toulouse III Paul Sabatier, Toulouse, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Lespine
authors.affiliation: Epidemiology and Infection Control Unit, University Hospital of Dijon, Dijon, France.
authors.forename: Ludwig Serge
authors.initials: LS
authors.lastname: Aho
authors.affiliation: Cecaveto, Saint-Allouestre, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Dreau
authors.affiliation: Department of Agriculture, Fisheries and Forestry, Queensland Animal Science Precinct, University of Queensland, Gatton Campus, Queensland, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kelly
authors.affiliation: Toxalim, INRA, INP-ENVT, INP-EI-Purpan, Université de Toulouse III Paul Sabatier, Toulouse, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Sutra
authors.affiliation: Centre de Recherche BioMédicale (CRBM), EnvA, UPE, Maisons-Alfort, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Moreau
authors.affiliation: Centre de Recherche BioMédicale (CRBM), EnvA, UPE, Maisons-Alfort, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lilin
authors.affiliation: Research Group Dynamyc, EA 7380, EnvA, Université Paris-Est (UPE), Maisons-Alfort & Créteil, France.|APHP, Hôpital Henri-Mondor, Parasitology and Mycology, Department of Microbiology, DHU VIC, UPEC, Créteil, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Botterel
authors.affiliation: Research Group Dynamyc, EA 7380, EnvA, Université Paris-Est (UPE), Maisons-Alfort & Créteil, France.|Department of Parasitology and Mycology, Biopôle d'Alfort, Ecole nationale vétérinaire d'Alfort, UPE, Maisons-Alfort, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Guillot
authors.affiliation: APHP, Hôpital Henri-Mondor, Department of Dermatology, UPEC, Créteil, France.|EA EpiDermE (Epidémiologie en Dermatologie et Evaluation des Thérapeutiques) and INSERM, CIC 1430, UPE, Créteil, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Chosidow
mesh_terms: D056810:Acaricides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000284:Administration, Oral; D000818:Animals; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D007559:Ivermectin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018942:Macrolides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D023421:Models, Animal; D012520:Sarcoptes scabiei / Q000187:drug effects; D012532:Scabies / Q000188:drug therapy*; D013552:Swine
chemical_list: D056810:Acaricides; D018942:Macrolides; D007559:Ivermectin; C027837:moxidectin