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
Identifieur interne : 000690 ( Pmc/Checkpoint ); précédent : 000689; suivant : 000691Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model
Auteurs : Charlotte Bernigaud [France] ; Fang Fang [France, République populaire de Chine] ; Katja Fischer [Australie] ; Anne Lespine [France] ; Ludwig Serge Aho [France] ; Dominique Dreau [France] ; Andrew Kelly [Australie] ; Jean-François Sutra [France] ; Francis Moreau [France] ; Thomas Lilin [France] ; Françoise Botterel [France] ; Jacques Guillot [France] ; Olivier Chosidow [France]Source :
- PLoS Neglected Tropical Diseases [ 1935-2727 ] ; 2016.
Abstract
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.
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-
Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies.
Url:
DOI: 10.1371/journal.pntd.0005030
PubMed: 27732588
PubMed Central: 5061321
Affiliations:
- Australie, France, République populaire de Chine
- Bourgogne, Bourgogne-Franche-Comté, Midi-Pyrénées, Occitanie (région administrative), Île-de-France
- Créteil, Dijon, Toulouse
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PMC:5061321Le document en format XML
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first="Charlotte" last="Bernigaud">Charlotte Bernigaud</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Research Group Dynamyc, EA 7380, EnvA, Université Paris-Est (UPE), Maisons-Alfort & Créteil, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Research Group Dynamyc, EA 7380, EnvA, Université Paris-Est (UPE), Maisons-Alfort & Créteil</wicri:regionArea><wicri:noRegion>Maisons-Alfort & Créteil</wicri:noRegion><wicri:noRegion>Maisons-Alfort & Créteil</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>APHP, Hôpital Henri-Mondor, Department of Dermatology, UPEC, Créteil, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>APHP, Hôpital Henri-Mondor, Department of Dermatology, UPEC, Créteil</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Créteil</settlement></placeName></affiliation></author><author><name sortKey="Fang, Fang" sort="Fang, Fang" uniqKey="Fang F" first="Fang" last="Fang">Fang Fang</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Research Group Dynamyc, EA 7380, EnvA, Université Paris-Est (UPE), Maisons-Alfort & Créteil, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Research Group Dynamyc, EA 7380, EnvA, Université Paris-Est (UPE), Maisons-Alfort & Créteil</wicri:regionArea><wicri:noRegion>Maisons-Alfort & Créteil</wicri:noRegion><wicri:noRegion>Maisons-Alfort & Créteil</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Department of Parasitology, College of Animal Science and Technology, University of Guangxi, Nanning, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Parasitology, College of Animal Science and Technology, University of Guangxi, Nanning</wicri:regionArea><wicri:noRegion>Nanning</wicri:noRegion></affiliation></author><author><name sortKey="Fischer, Katja" sort="Fischer, Katja" uniqKey="Fischer K" first="Katja" last="Fischer">Katja Fischer</name><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Infections Diseases Department, Scabies Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Infections Diseases Department, Scabies Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Lespine, Anne" sort="Lespine, Anne" uniqKey="Lespine A" first="Anne" last="Lespine">Anne Lespine</name><affiliation wicri:level="3"><nlm:aff id="aff005"><addr-line>Toxalim, INRA, INP-ENVT, INP-EI-Purpan, Université de Toulouse III Paul Sabatier, Toulouse, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Toxalim, INRA, INP-ENVT, INP-EI-Purpan, Université de Toulouse III Paul Sabatier, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Aho, Ludwig Serge" sort="Aho, Ludwig Serge" uniqKey="Aho L" first="Ludwig Serge" last="Aho">Ludwig Serge Aho</name><affiliation wicri:level="3"><nlm:aff id="aff006"><addr-line>Epidemiology and Infection Control Unit, University Hospital of Dijon, Dijon, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Epidemiology and Infection Control Unit, University Hospital of Dijon, Dijon</wicri:regionArea><placeName><region type="region">Bourgogne-Franche-Comté</region><region type="old region">Bourgogne</region><settlement type="city">Dijon</settlement></placeName></affiliation></author><author><name sortKey="Dreau, Dominique" sort="Dreau, Dominique" uniqKey="Dreau D" first="Dominique" last="Dreau">Dominique Dreau</name><affiliation wicri:level="1"><nlm:aff id="aff007"><addr-line>Cecaveto, Saint-Allouestre, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Cecaveto, Saint-Allouestre</wicri:regionArea><wicri:noRegion>Saint-Allouestre</wicri:noRegion><wicri:noRegion>Saint-Allouestre</wicri:noRegion></affiliation></author><author><name sortKey="Kelly, Andrew" sort="Kelly, Andrew" uniqKey="Kelly A" first="Andrew" last="Kelly">Andrew Kelly</name><affiliation wicri:level="1"><nlm:aff id="aff008"><addr-line>Department of Agriculture, Fisheries and Forestry, Queensland Animal Science Precinct, University of Queensland, Gatton Campus, Queensland, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Agriculture, Fisheries and Forestry, Queensland Animal Science Precinct, University of Queensland, Gatton Campus, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Sutra, Jean Francois" sort="Sutra, Jean Francois" uniqKey="Sutra J" first="Jean-François" last="Sutra">Jean-François Sutra</name><affiliation wicri:level="3"><nlm:aff id="aff005"><addr-line>Toxalim, INRA, INP-ENVT, INP-EI-Purpan, Université de Toulouse III Paul Sabatier, Toulouse, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Toxalim, INRA, INP-ENVT, INP-EI-Purpan, Université de Toulouse III Paul Sabatier, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Moreau, Francis" sort="Moreau, Francis" uniqKey="Moreau F" first="Francis" last="Moreau">Francis Moreau</name><affiliation wicri:level="1"><nlm:aff id="aff009"><addr-line>Centre de Recherche BioMédicale (CRBM), EnvA, UPE, Maisons-Alfort, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre de Recherche BioMédicale (CRBM), EnvA, UPE, Maisons-Alfort</wicri:regionArea><wicri:noRegion>Maisons-Alfort</wicri:noRegion><wicri:noRegion>Maisons-Alfort</wicri:noRegion></affiliation></author><author><name sortKey="Lilin, Thomas" sort="Lilin, Thomas" uniqKey="Lilin T" first="Thomas" last="Lilin">Thomas Lilin</name><affiliation wicri:level="1"><nlm:aff id="aff009"><addr-line>Centre de Recherche BioMédicale (CRBM), EnvA, UPE, Maisons-Alfort, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre de Recherche BioMédicale (CRBM), EnvA, UPE, Maisons-Alfort</wicri:regionArea><wicri:noRegion>Maisons-Alfort</wicri:noRegion><wicri:noRegion>Maisons-Alfort</wicri:noRegion></affiliation></author><author><name sortKey="Botterel, Francoise" sort="Botterel, Francoise" uniqKey="Botterel F" first="Françoise" last="Botterel">Françoise Botterel</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Research Group Dynamyc, EA 7380, EnvA, Université Paris-Est (UPE), Maisons-Alfort & Créteil, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Research Group Dynamyc, EA 7380, EnvA, Université Paris-Est (UPE), Maisons-Alfort & Créteil</wicri:regionArea><wicri:noRegion>Maisons-Alfort & Créteil</wicri:noRegion><wicri:noRegion>Maisons-Alfort & Créteil</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:aff id="aff010"><addr-line>APHP, Hôpital Henri-Mondor, Parasitology and Mycology, Department of Microbiology, DHU VIC, UPEC, Créteil, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>APHP, Hôpital Henri-Mondor, Parasitology and Mycology, Department of Microbiology, DHU VIC, UPEC, Créteil</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Créteil</settlement></placeName></affiliation></author><author><name sortKey="Guillot, Jacques" sort="Guillot, Jacques" uniqKey="Guillot J" first="Jacques" last="Guillot">Jacques Guillot</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Research Group Dynamyc, EA 7380, EnvA, Université Paris-Est (UPE), Maisons-Alfort & Créteil, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Research Group Dynamyc, EA 7380, EnvA, Université Paris-Est (UPE), Maisons-Alfort & Créteil</wicri:regionArea><wicri:noRegion>Maisons-Alfort & Créteil</wicri:noRegion><wicri:noRegion>Maisons-Alfort & Créteil</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff011"><addr-line>Department of Parasitology and Mycology, Biopôle d'Alfort, Ecole nationale vétérinaire d'Alfort, UPE, Maisons-Alfort, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Department of Parasitology and Mycology, Biopôle d'Alfort, Ecole nationale vétérinaire d'Alfort, UPE, Maisons-Alfort</wicri:regionArea><wicri:noRegion>Maisons-Alfort</wicri:noRegion><wicri:noRegion>Maisons-Alfort</wicri:noRegion></affiliation></author><author><name sortKey="Chosidow, Olivier" sort="Chosidow, Olivier" uniqKey="Chosidow O" first="Olivier" last="Chosidow">Olivier Chosidow</name><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>APHP, Hôpital Henri-Mondor, Department of Dermatology, UPEC, Créteil, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>APHP, Hôpital Henri-Mondor, Department of Dermatology, UPEC, Créteil</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Créteil</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff012"><addr-line>EA EpiDermE (Epidémiologie en Dermatologie et Evaluation des Thérapeutiques) and INSERM, CIC 1430, UPE, Créteil, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>EA EpiDermE (Epidémiologie en Dermatologie et Evaluation des Thérapeutiques) and INSERM, CIC 1430, UPE, Créteil</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Créteil</settlement></placeName></affiliation></author></analytic><series><title level="j">PLoS Neglected Tropical Diseases</title><idno type="ISSN">1935-2727</idno><idno type="eISSN">1935-2735</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="sec001"><title>Background</title><p>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.</p></sec><sec id="sec002"><title>Methodology/Principal Findings</title><p>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-<italic>S</italic>. <italic>scabiei</italic> 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-<italic>S</italic>. <italic>scabiei</italic> 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.</p></sec><sec id="sec003"><title>Conclusions/Significance</title><p>Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Hay, Rj" uniqKey="Hay R">RJ Hay</name></author><author><name sortKey="Johns, Ne" uniqKey="Johns N">NE Johns</name></author><author><name sortKey="Williams, Hc" uniqKey="Williams H">HC Williams</name></author><author><name sortKey="Bolliger, Iw" uniqKey="Bolliger I">IW Bolliger</name></author><author><name sortKey="Dellavalle, Rp" uniqKey="Dellavalle R">RP Dellavalle</name></author><author><name sortKey="Margolis, Dj" uniqKey="Margolis D">DJ 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS Negl Trop Dis</journal-id><journal-id journal-id-type="iso-abbrev">PLoS Negl Trop Dis</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosntds</journal-id><journal-title-group><journal-title>PLoS Neglected Tropical Diseases</journal-title></journal-title-group><issn pub-type="ppub">1935-2727</issn><issn pub-type="epub">1935-2735</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, CA USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27732588</article-id><article-id pub-id-type="pmc">5061321</article-id><article-id pub-id-type="doi">10.1371/journal.pntd.0005030</article-id><article-id pub-id-type="publisher-id">PNTD-D-16-01172</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Organisms</subject><subj-group><subject>Animals</subject><subj-group><subject>Invertebrates</subject><subj-group><subject>Arthropoda</subject><subj-group><subject>Mites</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Agriculture</subject><subj-group><subject>Livestock</subject><subj-group><subject>Swine</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Organisms</subject><subj-group><subject>Animals</subject><subj-group><subject>Vertebrates</subject><subj-group><subject>Amniotes</subject><subj-group><subject>Mammals</subject><subj-group><subject>Swine</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Parasitic Diseases</subject><subj-group><subject>Ectoparasitic Infections</subject><subj-group><subject>Scabies</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Tropical Diseases</subject><subj-group><subject>Neglected Tropical Diseases</subject><subj-group><subject>Scabies</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Infectious Diseases</subject><subj-group><subject>Sexually Transmitted Diseases</subject><subj-group><subject>Scabies</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Research and Analysis Methods</subject><subj-group><subject>Model Organisms</subject><subj-group><subject>Animal Models</subject><subj-group><subject>Pig Models</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Neuroscience</subject><subj-group><subject>Sensory Perception</subject><subj-group><subject>Pruritus</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Psychology</subject><subj-group><subject>Sensory Perception</subject><subj-group><subject>Pruritus</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Social Sciences</subject><subj-group><subject>Psychology</subject><subj-group><subject>Sensory Perception</subject><subj-group><subject>Pruritus</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Pharmacology</subject><subj-group><subject>Pharmacokinetics</subject></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Diagnostic Medicine</subject><subj-group><subject>Signs and Symptoms</subject><subj-group><subject>Lesions</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Pathology and Laboratory Medicine</subject><subj-group><subject>Signs and Symptoms</subject><subj-group><subject>Lesions</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Anatomy</subject><subj-group><subject>Head</subject><subj-group><subject>Ears</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Anatomy</subject><subj-group><subject>Head</subject><subj-group><subject>Ears</subject></subj-group></subj-group></subj-group></subj-group></article-categories><title-group><article-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</article-title><alt-title alt-title-type="running-head">Preclinical Study of Moxidectin for Human Scabies Treatment</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Bernigaud</surname><given-names>Charlotte</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="aff" rid="aff002"><sup>2</sup></xref><xref ref-type="corresp" rid="cor001">*</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Fang</surname><given-names>Fang</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="aff" rid="aff003"><sup>3</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Fischer</surname><given-names>Katja</given-names></name><xref ref-type="aff" rid="aff004"><sup>4</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Lespine</surname><given-names>Anne</given-names></name><xref ref-type="aff" rid="aff005"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Aho</surname><given-names>Ludwig Serge</given-names></name><xref ref-type="aff" rid="aff006"><sup>6</sup></xref></contrib><contrib contrib-type="author"><name><surname>Dreau</surname><given-names>Dominique</given-names></name><xref ref-type="aff" rid="aff007"><sup>7</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kelly</surname><given-names>Andrew</given-names></name><xref ref-type="aff" rid="aff008"><sup>8</sup></xref></contrib><contrib contrib-type="author"><name><surname>Sutra</surname><given-names>Jean-François</given-names></name><xref ref-type="aff" rid="aff005"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Moreau</surname><given-names>Francis</given-names></name><xref ref-type="aff" rid="aff009"><sup>9</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lilin</surname><given-names>Thomas</given-names></name><xref ref-type="aff" rid="aff009"><sup>9</sup></xref></contrib><contrib contrib-type="author"><name><surname>Botterel</surname><given-names>Françoise</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="aff" rid="aff010"><sup>10</sup></xref><xref ref-type="author-notes" rid="econtrib001"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Guillot</surname><given-names>Jacques</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="aff" rid="aff011"><sup>11</sup></xref><xref ref-type="author-notes" rid="econtrib001"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Chosidow</surname><given-names>Olivier</given-names></name><xref ref-type="aff" rid="aff002"><sup>2</sup></xref><xref ref-type="aff" rid="aff012"><sup>12</sup></xref><xref ref-type="author-notes" rid="econtrib001"><sup>‡</sup></xref></contrib></contrib-group><aff id="aff001"><label>1</label><addr-line>Research Group Dynamyc, EA 7380, EnvA, Université Paris-Est (UPE), Maisons-Alfort & Créteil, France</addr-line></aff><aff id="aff002"><label>2</label><addr-line>APHP, Hôpital Henri-Mondor, Department of Dermatology, UPEC, Créteil, France</addr-line></aff><aff id="aff003"><label>3</label><addr-line>Department of Parasitology, College of Animal Science and Technology, University of Guangxi, Nanning, China</addr-line></aff><aff id="aff004"><label>4</label><addr-line>Infections Diseases Department, Scabies Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia</addr-line></aff><aff id="aff005"><label>5</label><addr-line>Toxalim, INRA, INP-ENVT, INP-EI-Purpan, Université de Toulouse III Paul Sabatier, Toulouse, France</addr-line></aff><aff id="aff006"><label>6</label><addr-line>Epidemiology and Infection Control Unit, University Hospital of Dijon, Dijon, France</addr-line></aff><aff id="aff007"><label>7</label><addr-line>Cecaveto, Saint-Allouestre, France</addr-line></aff><aff id="aff008"><label>8</label><addr-line>Department of Agriculture, Fisheries and Forestry, Queensland Animal Science Precinct, University of Queensland, Gatton Campus, Queensland, Australia</addr-line></aff><aff id="aff009"><label>9</label><addr-line>Centre de Recherche BioMédicale (CRBM), EnvA, UPE, Maisons-Alfort, France</addr-line></aff><aff id="aff010"><label>10</label><addr-line>APHP, Hôpital Henri-Mondor, Parasitology and Mycology, Department of Microbiology, DHU VIC, UPEC, Créteil, France</addr-line></aff><aff id="aff011"><label>11</label><addr-line>Department of Parasitology and Mycology, Biopôle d'Alfort, Ecole nationale vétérinaire d'Alfort, UPE, Maisons-Alfort, France</addr-line></aff><aff id="aff012"><label>12</label><addr-line>EA EpiDermE (Epidémiologie en Dermatologie et Evaluation des Thérapeutiques) and INSERM, CIC 1430, UPE, Créteil, France</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Vinetz</surname><given-names>Joseph M.</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>University of California San Diego School of Medicine, UNITED STATES</addr-line></aff><author-notes><fn fn-type="COI-statement" id="coi001"><p>CB reports receiving a research grant from MSD France, to help establish our first cohort of the experimental porcine scabies model. OC reports receiving, lecture fees, research and travel grants from MSD France; lecture fees from Sanofi U.S.; lecture fees and travel fees from KCL Consulting; and drugs donated free of charge for research from Codexial Dermatologie. No other potential conflict of interest exists.</p></fn><fn fn-type="con"><p><list list-type="simple"><list-item><p><bold>Conceptualization:</bold> CB FF KF AL LSA DD AK TL FB JG OC.</p></list-item><list-item><p><bold>Formal analysis:</bold> CB FF KF AL LSA JFS TL FB JG OC.</p></list-item><list-item><p><bold>Funding acquisition:</bold> CB FB JG OC.</p></list-item><list-item><p><bold>Investigation:</bold> CB FF KF AL LSA JFS FM TL FB JG OC.</p></list-item><list-item><p><bold>Methodology:</bold> CB FF KF AL LSA AK JFS FM TL FB JG OC.</p></list-item><list-item><p><bold>Supervision:</bold> KF TL FB JG OC.</p></list-item><list-item><p><bold>Writing – original draft:</bold> CB FF KF AL LSA JFS FM TL FB JG OC.</p></list-item><list-item><p><bold>Writing – review & editing:</bold> CB FF KF AL LSA DD AK JFS FM TL FB JG OC.</p></list-item></list></p></fn><fn fn-type="other" id="econtrib001"><p>‡ FB, JG, and OC also contributed equally to this work.</p></fn><corresp id="cor001">* E-mail: <email>charlotte.bernigaud@univ-paris-est.fr</email></corresp></author-notes><pub-date pub-type="epub"><day>12</day><month>10</month><year>2016</year></pub-date><pub-date pub-type="collection"><month>10</month><year>2016</year></pub-date><volume>10</volume><issue>10</issue><elocation-id>e0005030</elocation-id><history><date date-type="received"><day>29</day><month>6</month><year>2016</year></date><date date-type="accepted"><day>9</day><month>9</month><year>2016</year></date></history><permissions><copyright-statement>© 2016 Bernigaud et al</copyright-statement><copyright-year>2016</copyright-year><copyright-holder>Bernigaud et al</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="pntd.0005030.pdf"></self-uri><abstract><sec id="sec001"><title>Background</title><p>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.</p></sec><sec id="sec002"><title>Methodology/Principal Findings</title><p>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-<italic>S</italic>. <italic>scabiei</italic> 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-<italic>S</italic>. <italic>scabiei</italic> 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.</p></sec><sec id="sec003"><title>Conclusions/Significance</title><p>Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies.</p></sec></abstract><abstract abstract-type="summary"><title>Author Summary</title><p>Scabies caused by the <italic>Sarcoptes scabiei</italic> mite affects many people worldwide and has been recently recognized by the WHO as a truly neglected tropical disease. Currently available treatments are insufficient to overcome this insidious disease and its co-morbidities for example impetigo, rheumatic heart disease and post-streptococcal glomerulonephritis. Treatment management is a major issue, as problems with compliance as well as mite resistance to current drugs are reported. Data have accumulated indicating that moxidectin could be a genuine new candidate drug for sustainable scabies control. To provide proof of concept, we utilized an experimental scabies pig model that closely resembles the human route of scabies infection. We demonstrated that a single moxidectin dose, when compared with the currently recommended two-doses ivermectin treatment routine, achieved a better and faster acaricidal efficacy. Importantly, the skin half-life of moxidectin is longer, potentially covering the entire mite life cycle. Our baseline data demonstrate in principle the potential and feasibility of moxidectin treatment for scabies, thereby enabling the move into larger high-powered efficacy and dose ranging studies in human populations. Moxidectin could indeed play a game-changing role in scabies control and has the potential to accelerate the steps towards elimination of this insidious disease.</p></abstract><funding-group><award-group id="award001"><funding-source><institution-wrap><institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/501100005897</institution-id><institution>Société Française de Dermatologie et de Pathologie Sexuellement Transmissible</institution></institution-wrap></funding-source><principal-award-recipient><name><surname>Bernigaud</surname><given-names>Charlotte</given-names></name></principal-award-recipient></award-group><award-group id="award002"><funding-source><institution>Fondation René Touraine pour la Dermatologie</institution></funding-source><principal-award-recipient><name><surname>Bernigaud</surname><given-names>Charlotte</given-names></name></principal-award-recipient></award-group><award-group id="award003"><funding-source><institution-wrap><institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/501100004543</institution-id><institution>China Scholarship Council</institution></institution-wrap></funding-source><principal-award-recipient><name><surname>Fang</surname><given-names>Fang</given-names></name></principal-award-recipient></award-group><award-group id="award004"><funding-source><institution>Philantropic crowdfunding</institution></funding-source><principal-award-recipient><name><surname>Bernigaud</surname><given-names>Charlotte</given-names></name></principal-award-recipient></award-group><funding-statement>This work was supported by a research grant from the Société Française de Dermatologie. CB was able to learn the Australian model with a short-term travel grant from the Fondation René Touraine. FF is supported by the Fund of the China Scholarship Council. We are grateful to the philanthropic crowdfunding from kisskissbankers (<ext-link ext-link-type="uri" xlink:href="https://www.kisskissbankbank.com/soutenez-ma-these-de-recherche-sur-la-gale">https://www.kisskissbankbank.com/soutenez-ma-these-de-recherche-sur-la-gale</ext-link>) for their help in the feasibility study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><fig-count count="6"></fig-count><table-count count="2"></table-count><page-count count="18"></page-count></counts><custom-meta-group><custom-meta id="data-availability"><meta-name>Data Availability</meta-name><meta-value>All relevant data are within the paper and its Supporting Information files.</meta-value></custom-meta></custom-meta-group></article-meta><notes><title>Data Availability</title><p>All relevant data are within the paper and its Supporting Information files.</p></notes></front></pmc><affiliations><list><country><li>Australie</li><li>France</li><li>République populaire de Chine</li></country><region><li>Bourgogne</li><li>Bourgogne-Franche-Comté</li><li>Midi-Pyrénées</li><li>Occitanie (région administrative)</li><li>Île-de-France</li></region><settlement><li>Créteil</li><li>Dijon</li><li>Toulouse</li></settlement></list><tree><country name="France"><noRegion><name sortKey="Bernigaud, Charlotte" sort="Bernigaud, Charlotte" uniqKey="Bernigaud C" first="Charlotte" last="Bernigaud">Charlotte Bernigaud</name></noRegion><name sortKey="Aho, Ludwig Serge" sort="Aho, Ludwig Serge" uniqKey="Aho L" first="Ludwig Serge" last="Aho">Ludwig Serge Aho</name><name sortKey="Bernigaud, Charlotte" sort="Bernigaud, Charlotte" uniqKey="Bernigaud C" first="Charlotte" last="Bernigaud">Charlotte Bernigaud</name><name sortKey="Botterel, Francoise" sort="Botterel, Francoise" uniqKey="Botterel F" first="Françoise" last="Botterel">Françoise Botterel</name><name sortKey="Botterel, Francoise" sort="Botterel, Francoise" uniqKey="Botterel F" first="Françoise" last="Botterel">Françoise Botterel</name><name sortKey="Chosidow, Olivier" sort="Chosidow, Olivier" uniqKey="Chosidow O" first="Olivier" last="Chosidow">Olivier Chosidow</name><name sortKey="Chosidow, Olivier" sort="Chosidow, Olivier" uniqKey="Chosidow O" first="Olivier" last="Chosidow">Olivier Chosidow</name><name sortKey="Dreau, Dominique" sort="Dreau, Dominique" uniqKey="Dreau D" first="Dominique" last="Dreau">Dominique Dreau</name><name sortKey="Fang, Fang" sort="Fang, Fang" uniqKey="Fang F" first="Fang" last="Fang">Fang Fang</name><name sortKey="Guillot, Jacques" sort="Guillot, Jacques" uniqKey="Guillot J" first="Jacques" last="Guillot">Jacques Guillot</name><name sortKey="Guillot, Jacques" sort="Guillot, Jacques" uniqKey="Guillot J" first="Jacques" last="Guillot">Jacques Guillot</name><name sortKey="Lespine, Anne" sort="Lespine, Anne" uniqKey="Lespine A" first="Anne" last="Lespine">Anne Lespine</name><name sortKey="Lilin, Thomas" sort="Lilin, Thomas" uniqKey="Lilin T" first="Thomas" last="Lilin">Thomas Lilin</name><name sortKey="Moreau, Francis" sort="Moreau, Francis" uniqKey="Moreau F" first="Francis" last="Moreau">Francis Moreau</name><name sortKey="Sutra, Jean Francois" sort="Sutra, Jean Francois" uniqKey="Sutra J" first="Jean-François" last="Sutra">Jean-François Sutra</name></country><country name="République populaire de Chine"><noRegion><name sortKey="Fang, Fang" sort="Fang, Fang" uniqKey="Fang F" first="Fang" last="Fang">Fang Fang</name></noRegion></country><country name="Australie"><noRegion><name sortKey="Fischer, Katja" sort="Fischer, Katja" uniqKey="Fischer K" first="Katja" last="Fischer">Katja Fischer</name></noRegion><name sortKey="Kelly, Andrew" sort="Kelly, Andrew" uniqKey="Kelly A" first="Andrew" last="Kelly">Andrew Kelly</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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