Minocycline as a re-purposed anti-Wolbachia macrofilaricide: superiority compared with doxycycline regimens in a murine infection model of human lymphatic filariasis.
Identifieur interne : 000923 ( PubMed/Curation ); précédent : 000922; suivant : 000924Minocycline as a re-purposed anti-Wolbachia macrofilaricide: superiority compared with doxycycline regimens in a murine infection model of human lymphatic filariasis.
Auteurs : Raman Sharma [Royaume-Uni] ; Ghaith Al Jayoussi [Royaume-Uni] ; Hayley E. Tyrer [Royaume-Uni] ; Joanne Gamble [Royaume-Uni] ; Laura Hayward [Royaume-Uni] ; Ana F. Guimaraes [Royaume-Uni] ; Jill Davies [Royaume-Uni] ; David Waterhouse [Royaume-Uni] ; Darren A N. Cook [Royaume-Uni] ; Laura J. Myhill [Royaume-Uni] ; Rachel H. Clare [Royaume-Uni] ; Andrew Cassidy [Royaume-Uni] ; Andrew Steven [Royaume-Uni] ; Kelly L. Johnston [Royaume-Uni] ; Louise Ford [Royaume-Uni] ; Joseph D. Turner [Royaume-Uni] ; Stephen A. Ward [Royaume-Uni] ; Mark J. Taylor [Royaume-Uni]Source :
- Scientific reports [ 2045-2322 ] ; 2016.
Descripteurs français
- KwdFr :
- Animaux, Antibactériens (administration et posologie), Antibactériens (pharmacocinétique), Brugia malayi (), Brugia malayi (parasitologie), Doxycycline (administration et posologie), Doxycycline (pharmacocinétique), Femelle, Filariose lymphatique (), Filariose lymphatique (parasitologie), Minocycline (administration et posologie), Minocycline (pharmacocinétique), Modèles animaux de maladie humaine, Mâle, Relation dose-effet des médicaments, Souris, Souris SCID, Souris de lignée BALB C, Wolbachia (), Wolbachia (pathogénicité).
- MESH :
- administration et posologie : Antibactériens, Doxycycline, Minocycline.
- parasitologie : Brugia malayi, Filariose lymphatique.
- pathogénicité : Wolbachia.
- pharmacocinétique : Antibactériens, Doxycycline, Minocycline.
- Animaux, Brugia malayi, Femelle, Filariose lymphatique, Modèles animaux de maladie humaine, Mâle, Relation dose-effet des médicaments, Souris, Souris SCID, Souris de lignée BALB C, Wolbachia.
English descriptors
- KwdEn :
- Animals, Anti-Bacterial Agents (administration & dosage), Anti-Bacterial Agents (pharmacokinetics), Brugia malayi (drug effects), Brugia malayi (parasitology), Disease Models, Animal, Dose-Response Relationship, Drug, Doxycycline (administration & dosage), Doxycycline (pharmacokinetics), Elephantiasis, Filarial (parasitology), Elephantiasis, Filarial (prevention & control), Female, Male, Mice, Mice, Inbred BALB C, Mice, SCID, Minocycline (administration & dosage), Minocycline (pharmacokinetics), Wolbachia (drug effects), Wolbachia (pathogenicity).
- MESH :
- chemical , administration & dosage : Anti-Bacterial Agents, Doxycycline, Minocycline.
- chemical , pharmacokinetics : Anti-Bacterial Agents, Doxycycline, Minocycline.
- drug effects : Brugia malayi, Wolbachia.
- parasitology : Brugia malayi, Elephantiasis, Filarial.
- pathogenicity : Wolbachia.
- prevention & control : Elephantiasis, Filarial.
- Animals, Disease Models, Animal, Dose-Response Relationship, Drug, Female, Male, Mice, Mice, Inbred BALB C, Mice, SCID.
Abstract
Lymphatic filariasis and onchocerciasis are parasitic helminth diseases, which cause severe morbidities such as elephantiasis, skin disease and blindness, presenting a major public health burden in endemic communities. The anti-Wolbachia consortium (A·WOL: http://www.a-wol.com/) has identified a number of registered antibiotics that target the endosymbiotic bacterium, Wolbachia, delivering macrofilaricidal activity. Here we use pharmacokinetics/pharmacodynamics (PK/PD) analysis to rationally develop an anti-Wolbachia chemotherapy by linking drug exposure to pharmacological effect. We compare the pharmacokinetics and anti-Wolbachia efficacy in a murine Brugia malayi model of minocycline versus doxycycline. Doxycycline exhibits superior PK in comparison to minocycline resulting in a 3-fold greater exposure in SCID mice. Monte-Carlo simulations confirmed that a bi-daily 25-40 mg/Kg regimen is bioequivalent to a clinically effective 100-200 mg/day dose for these tetracyclines. Pharmacodynamic studies showed that minocycline depletes Wolbachia more effectively than doxycycline (99.51% vs. 90.35%) after 28 day 25 mg/Kg bid regimens with a more potent block in microfilarial production. PK/PD analysis predicts that minocycline would be expected to be 1.7 fold more effective than doxycycline in man despite lower exposure in our infection models. Our findings warrant onward clinical investigations to examine the clinical efficacy of minocycline treatment regimens against lymphatic filariasis and onchocerciasis.
DOI: 10.1038/srep23458
PubMed: 26996237
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Tyrer</name><affiliation wicri:level="1"><nlm:affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA</wicri:regionArea></affiliation></author><author><name sortKey="Gamble, Joanne" sort="Gamble, Joanne" uniqKey="Gamble J" first="Joanne" last="Gamble">Joanne Gamble</name><affiliation wicri:level="1"><nlm:affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA</wicri:regionArea></affiliation></author><author><name sortKey="Hayward, Laura" sort="Hayward, Laura" uniqKey="Hayward L" first="Laura" last="Hayward">Laura Hayward</name><affiliation wicri:level="1"><nlm:affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA</wicri:regionArea></affiliation></author><author><name sortKey="Guimaraes, Ana F" sort="Guimaraes, Ana F" uniqKey="Guimaraes A" first="Ana F" last="Guimaraes">Ana F. Guimaraes</name><affiliation wicri:level="1"><nlm:affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA</wicri:regionArea></affiliation></author><author><name sortKey="Davies, Jill" sort="Davies, Jill" uniqKey="Davies J" first="Jill" last="Davies">Jill Davies</name><affiliation wicri:level="1"><nlm:affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA</wicri:regionArea></affiliation></author><author><name sortKey="Waterhouse, David" sort="Waterhouse, David" uniqKey="Waterhouse D" first="David" last="Waterhouse">David Waterhouse</name><affiliation wicri:level="1"><nlm:affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA</wicri:regionArea></affiliation></author><author><name sortKey="Cook, Darren A N" sort="Cook, Darren A N" uniqKey="Cook D" first="Darren A N" last="Cook">Darren A N. Cook</name><affiliation wicri:level="1"><nlm:affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA</wicri:regionArea></affiliation></author><author><name sortKey="Myhill, Laura J" sort="Myhill, Laura J" uniqKey="Myhill L" first="Laura J" last="Myhill">Laura J. Myhill</name><affiliation wicri:level="1"><nlm:affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA</wicri:regionArea></affiliation></author><author><name sortKey="Clare, Rachel H" sort="Clare, Rachel H" uniqKey="Clare R" first="Rachel H" last="Clare">Rachel H. Clare</name><affiliation wicri:level="1"><nlm:affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA</wicri:regionArea></affiliation></author><author><name sortKey="Cassidy, Andrew" sort="Cassidy, Andrew" uniqKey="Cassidy A" first="Andrew" last="Cassidy">Andrew Cassidy</name><affiliation wicri:level="1"><nlm:affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA</wicri:regionArea></affiliation></author><author><name sortKey="Steven, Andrew" sort="Steven, Andrew" uniqKey="Steven A" first="Andrew" last="Steven">Andrew Steven</name><affiliation wicri:level="1"><nlm:affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA</wicri:regionArea></affiliation></author><author><name sortKey="Johnston, Kelly L" sort="Johnston, Kelly L" uniqKey="Johnston K" first="Kelly L" last="Johnston">Kelly L. Johnston</name><affiliation wicri:level="1"><nlm:affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA</wicri:regionArea></affiliation></author><author><name sortKey="Ford, Louise" sort="Ford, Louise" uniqKey="Ford L" first="Louise" last="Ford">Louise Ford</name><affiliation wicri:level="1"><nlm:affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA</wicri:regionArea></affiliation></author><author><name sortKey="Turner, Joseph D" sort="Turner, Joseph D" uniqKey="Turner J" first="Joseph D" last="Turner">Joseph D. Turner</name><affiliation wicri:level="1"><nlm:affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA</wicri:regionArea></affiliation></author><author><name sortKey="Ward, Stephen A" sort="Ward, Stephen A" uniqKey="Ward S" first="Stephen A" last="Ward">Stephen A. Ward</name><affiliation wicri:level="1"><nlm:affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA</wicri:regionArea></affiliation></author><author><name sortKey="Taylor, Mark J" sort="Taylor, Mark J" uniqKey="Taylor M" first="Mark J" last="Taylor">Mark J. Taylor</name><affiliation wicri:level="1"><nlm:affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Anti-Bacterial Agents (administration & dosage)</term><term>Anti-Bacterial Agents (pharmacokinetics)</term><term>Brugia malayi (drug effects)</term><term>Brugia malayi (parasitology)</term><term>Disease Models, Animal</term><term>Dose-Response Relationship, Drug</term><term>Doxycycline (administration & dosage)</term><term>Doxycycline (pharmacokinetics)</term><term>Elephantiasis, Filarial (parasitology)</term><term>Elephantiasis, Filarial (prevention & control)</term><term>Female</term><term>Male</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mice, SCID</term><term>Minocycline (administration & dosage)</term><term>Minocycline (pharmacokinetics)</term><term>Wolbachia (drug effects)</term><term>Wolbachia (pathogenicity)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antibactériens (administration et posologie)</term><term>Antibactériens (pharmacocinétique)</term><term>Brugia malayi ()</term><term>Brugia malayi (parasitologie)</term><term>Doxycycline (administration et posologie)</term><term>Doxycycline (pharmacocinétique)</term><term>Femelle</term><term>Filariose lymphatique ()</term><term>Filariose lymphatique (parasitologie)</term><term>Minocycline (administration et posologie)</term><term>Minocycline (pharmacocinétique)</term><term>Modèles animaux de maladie humaine</term><term>Mâle</term><term>Relation dose-effet des médicaments</term><term>Souris</term><term>Souris SCID</term><term>Souris de lignée BALB C</term><term>Wolbachia ()</term><term>Wolbachia (pathogénicité)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Anti-Bacterial Agents</term><term>Doxycycline</term><term>Minocycline</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Anti-Bacterial Agents</term><term>Doxycycline</term><term>Minocycline</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Antibactériens</term><term>Doxycycline</term><term>Minocycline</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Brugia malayi</term><term>Wolbachia</term></keywords><keywords scheme="MESH" qualifier="parasitologie" xml:lang="fr"><term>Brugia malayi</term><term>Filariose lymphatique</term></keywords><keywords scheme="MESH" qualifier="parasitology" xml:lang="en"><term>Brugia malayi</term><term>Elephantiasis, Filarial</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Wolbachia</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Wolbachia</term></keywords><keywords scheme="MESH" qualifier="pharmacocinétique" xml:lang="fr"><term>Antibactériens</term><term>Doxycycline</term><term>Minocycline</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Elephantiasis, Filarial</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Dose-Response Relationship, Drug</term><term>Female</term><term>Male</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mice, SCID</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Brugia malayi</term><term>Femelle</term><term>Filariose lymphatique</term><term>Modèles animaux de maladie humaine</term><term>Mâle</term><term>Relation dose-effet des médicaments</term><term>Souris</term><term>Souris SCID</term><term>Souris de lignée BALB C</term><term>Wolbachia</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Lymphatic filariasis and onchocerciasis are parasitic helminth diseases, which cause severe morbidities such as elephantiasis, skin disease and blindness, presenting a major public health burden in endemic communities. The anti-Wolbachia consortium (A·WOL: http://www.a-wol.com/) has identified a number of registered antibiotics that target the endosymbiotic bacterium, Wolbachia, delivering macrofilaricidal activity. Here we use pharmacokinetics/pharmacodynamics (PK/PD) analysis to rationally develop an anti-Wolbachia chemotherapy by linking drug exposure to pharmacological effect. We compare the pharmacokinetics and anti-Wolbachia efficacy in a murine Brugia malayi model of minocycline versus doxycycline. Doxycycline exhibits superior PK in comparison to minocycline resulting in a 3-fold greater exposure in SCID mice. Monte-Carlo simulations confirmed that a bi-daily 25-40 mg/Kg regimen is bioequivalent to a clinically effective 100-200 mg/day dose for these tetracyclines. Pharmacodynamic studies showed that minocycline depletes Wolbachia more effectively than doxycycline (99.51% vs. 90.35%) after 28 day 25 mg/Kg bid regimens with a more potent block in microfilarial production. PK/PD analysis predicts that minocycline would be expected to be 1.7 fold more effective than doxycycline in man despite lower exposure in our infection models. Our findings warrant onward clinical investigations to examine the clinical efficacy of minocycline treatment regimens against lymphatic filariasis and onchocerciasis.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26996237</PMID><DateCreated><Year>2016</Year><Month>03</Month><Day>21</Day></DateCreated><DateCompleted><Year>2017</Year><Month>01</Month><Day>10</Day></DateCompleted><DateRevised><Year>2017</Year><Month>09</Month><Day>02</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2045-2322</ISSN><JournalIssue CitedMedium="Internet"><Volume>6</Volume><PubDate><Year>2016</Year><Month>Mar</Month><Day>21</Day></PubDate></JournalIssue><Title>Scientific reports</Title><ISOAbbreviation>Sci Rep</ISOAbbreviation></Journal><ArticleTitle>Minocycline as a re-purposed anti-Wolbachia macrofilaricide: superiority compared with doxycycline regimens in a murine infection model of human lymphatic filariasis.</ArticleTitle><Pagination><MedlinePgn>23458</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/srep23458</ELocationID><Abstract><AbstractText>Lymphatic filariasis and onchocerciasis are parasitic helminth diseases, which cause severe morbidities such as elephantiasis, skin disease and blindness, presenting a major public health burden in endemic communities. The anti-Wolbachia consortium (A·WOL: http://www.a-wol.com/) has identified a number of registered antibiotics that target the endosymbiotic bacterium, Wolbachia, delivering macrofilaricidal activity. Here we use pharmacokinetics/pharmacodynamics (PK/PD) analysis to rationally develop an anti-Wolbachia chemotherapy by linking drug exposure to pharmacological effect. We compare the pharmacokinetics and anti-Wolbachia efficacy in a murine Brugia malayi model of minocycline versus doxycycline. Doxycycline exhibits superior PK in comparison to minocycline resulting in a 3-fold greater exposure in SCID mice. Monte-Carlo simulations confirmed that a bi-daily 25-40 mg/Kg regimen is bioequivalent to a clinically effective 100-200 mg/day dose for these tetracyclines. Pharmacodynamic studies showed that minocycline depletes Wolbachia more effectively than doxycycline (99.51% vs. 90.35%) after 28 day 25 mg/Kg bid regimens with a more potent block in microfilarial production. PK/PD analysis predicts that minocycline would be expected to be 1.7 fold more effective than doxycycline in man despite lower exposure in our infection models. Our findings warrant onward clinical investigations to examine the clinical efficacy of minocycline treatment regimens against lymphatic filariasis and onchocerciasis.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Sharma</LastName><ForeName>Raman</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Al Jayoussi</LastName><ForeName>Ghaith</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tyrer</LastName><ForeName>Hayley E</ForeName><Initials>HE</Initials><AffiliationInfo><Affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gamble</LastName><ForeName>Joanne</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hayward</LastName><ForeName>Laura</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guimaraes</LastName><ForeName>Ana F</ForeName><Initials>AF</Initials><AffiliationInfo><Affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Davies</LastName><ForeName>Jill</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Waterhouse</LastName><ForeName>David</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cook</LastName><ForeName>Darren A N</ForeName><Initials>DA</Initials><AffiliationInfo><Affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Myhill</LastName><ForeName>Laura J</ForeName><Initials>LJ</Initials><AffiliationInfo><Affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Clare</LastName><ForeName>Rachel H</ForeName><Initials>RH</Initials><AffiliationInfo><Affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cassidy</LastName><ForeName>Andrew</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Steven</LastName><ForeName>Andrew</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Johnston</LastName><ForeName>Kelly L</ForeName><Initials>KL</Initials><AffiliationInfo><Affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ford</LastName><ForeName>Louise</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Turner</LastName><ForeName>Joseph D</ForeName><Initials>JD</Initials><AffiliationInfo><Affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ward</LastName><ForeName>Stephen A</ForeName><Initials>SA</Initials><AffiliationInfo><Affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Taylor</LastName><ForeName>Mark J</ForeName><Initials>MJ</Initials><AffiliationInfo><Affiliation>Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>MRC_MR/L018756/1</GrantID><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>03</Month><Day>21</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Sci Rep</MedlineTA><NlmUniqueID>101563288</NlmUniqueID><ISSNLinking>2045-2322</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000900">Anti-Bacterial 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MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000900" MajorTopicYN="N">Anti-Bacterial Agents</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName><QualifierName UI="Q000493" MajorTopicYN="N">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017178" MajorTopicYN="N">Brugia malayi</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000469" MajorTopicYN="N">parasitology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004305" MajorTopicYN="N">Dose-Response Relationship, Drug</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004318" MajorTopicYN="N">Doxycycline</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000493" MajorTopicYN="N">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004605" MajorTopicYN="N">Elephantiasis, Filarial</DescriptorName><QualifierName UI="Q000469" MajorTopicYN="N">parasitology</QualifierName><QualifierName UI="Q000517" MajorTopicYN="Y">prevention & control</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008807" MajorTopicYN="N">Mice, Inbred BALB C</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016513" MajorTopicYN="N">Mice, SCID</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008911" MajorTopicYN="N">Minocycline</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName><QualifierName UI="Q000493" MajorTopicYN="N">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020577" MajorTopicYN="N">Wolbachia</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000472" MajorTopicYN="N">pathogenicity</QualifierName></MeshHeading></MeshHeadingList><OtherID Source="NLM">PMC4800446</OtherID></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>01</Month><Day>05</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>03</Month><Day>07</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>3</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2016</Year><Month>3</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>1</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">26996237</ArticleId><ArticleId IdType="pii">srep23458</ArticleId><ArticleId IdType="doi">10.1038/srep23458</ArticleId><ArticleId IdType="pmc">PMC4800446</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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