Therapeutic Efficacy and Macrofilaricidal Activity of Doxycycline for the Treatment of River Blindness
Identifieur interne : 001678 ( Pmc/Checkpoint ); précédent : 001677; suivant : 001679Therapeutic Efficacy and Macrofilaricidal Activity of Doxycycline for the Treatment of River Blindness
Auteurs : Martin Walker [Royaume-Uni] ; Sabine Specht [Allemagne] ; Thomas S. Churcher [Royaume-Uni] ; Achim Hoerauf [Allemagne] ; Mark J. Taylor [Royaume-Uni] ; María-Gloria Basá Ez [Royaume-Uni]Source :
- Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America [ 1058-4838 ] ; 2014.
Abstract
The efficacy of 4–6 weeks of oral doxycycline in depleting
Url:
DOI: 10.1093/cid/ciu1152
PubMed: 25537873
PubMed Central: 4370165
Affiliations:
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Churcher</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Department of Infectious Disease Epidemiology</addr-line>,<institution>Imperial College London</institution>,<country>United Kingdom</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hoerauf, Achim" sort="Hoerauf, Achim" uniqKey="Hoerauf A" first="Achim" last="Hoerauf">Achim Hoerauf</name><affiliation wicri:level="1"><nlm:aff id="af2"><addr-line>Institute for Medical Microbiology, Immunology and Parasitology</addr-line>,<institution>University Hospital Bonn</institution>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</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:aff id="af3"><addr-line>Department of Parasitology</addr-line>,<institution>Liverpool School of Tropical Medicine</institution>,<country>United Kingdom</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Basa Ez, Maria Gloria" sort="Basa Ez, Maria Gloria" uniqKey="Basa Ez M" first="María-Gloria" last="Basá Ez">María-Gloria Basá Ez</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Department of Infectious Disease Epidemiology</addr-line>,<institution>Imperial College London</institution>,<country>United Kingdom</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25537873</idno><idno type="pmc">4370165</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370165</idno><idno type="RBID">PMC:4370165</idno><idno type="doi">10.1093/cid/ciu1152</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">003D49</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">003D49</idno><idno type="wicri:Area/Pmc/Curation">003D48</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">003D48</idno><idno type="wicri:Area/Pmc/Checkpoint">001678</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001678</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Therapeutic Efficacy and Macrofilaricidal Activity of Doxycycline for the Treatment of River Blindness</title><author><name sortKey="Walker, Martin" sort="Walker, Martin" uniqKey="Walker M" first="Martin" last="Walker">Martin Walker</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Department of Infectious Disease Epidemiology</addr-line>,<institution>Imperial College London</institution>,<country>United Kingdom</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Specht, Sabine" sort="Specht, Sabine" uniqKey="Specht S" first="Sabine" last="Specht">Sabine Specht</name><affiliation wicri:level="1"><nlm:aff id="af2"><addr-line>Institute for Medical Microbiology, Immunology and Parasitology</addr-line>,<institution>University Hospital Bonn</institution>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Churcher, Thomas S" sort="Churcher, Thomas S" uniqKey="Churcher T" first="Thomas S." last="Churcher">Thomas S. Churcher</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Department of Infectious Disease Epidemiology</addr-line>,<institution>Imperial College London</institution>,<country>United Kingdom</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hoerauf, Achim" sort="Hoerauf, Achim" uniqKey="Hoerauf A" first="Achim" last="Hoerauf">Achim Hoerauf</name><affiliation wicri:level="1"><nlm:aff id="af2"><addr-line>Institute for Medical Microbiology, Immunology and Parasitology</addr-line>,<institution>University Hospital Bonn</institution>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</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:aff id="af3"><addr-line>Department of Parasitology</addr-line>,<institution>Liverpool School of Tropical Medicine</institution>,<country>United Kingdom</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Basa Ez, Maria Gloria" sort="Basa Ez, Maria Gloria" uniqKey="Basa Ez M" first="María-Gloria" last="Basá Ez">María-Gloria Basá Ez</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Department of Infectious Disease Epidemiology</addr-line>,<institution>Imperial College London</institution>,<country>United Kingdom</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America</title><idno type="ISSN">1058-4838</idno><idno type="eISSN">1537-6591</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The efficacy of 4–6 weeks of oral doxycycline in depleting <italic>Wolbachia</italic> from <italic>Onchocerca volvulus</italic> is >95% in the majority of patients. <italic>Wolbachia</italic> depletion induces a 70%–80% reduction in worm life span, confirming doxycycline as a potent macrofilaricide.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Taylor, Mj" uniqKey="Taylor M">MJ Taylor</name></author><author><name sortKey="Bandi, C" uniqKey="Bandi C">C Bandi</name></author><author><name sortKey="Hoerauf, A" uniqKey="Hoerauf A">A Hoerauf</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Taylor, Mj" uniqKey="Taylor M">MJ 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uniqKey="Basa Ez M">M-G Basáñez</name></author><author><name sortKey="Pion, Sd" uniqKey="Pion S">SD Pion</name></author><author><name sortKey="Churcher, Ts" uniqKey="Churcher T">TS Churcher</name></author><author><name sortKey="Breitling, Lp" uniqKey="Breitling L">LP Breitling</name></author><author><name sortKey="Little, Mp" uniqKey="Little M">MP Little</name></author><author><name sortKey="Boussinesq, M" uniqKey="Boussinesq M">M Boussinesq</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Taylor, Mj" uniqKey="Taylor M">MJ Taylor</name></author><author><name sortKey="Awadzi, K" uniqKey="Awadzi K">K Awadzi</name></author><author><name sortKey="Basa Ez, M G" uniqKey="Basa Ez M">M-G Basáñez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Churcher, Ts" uniqKey="Churcher T">TS Churcher</name></author><author><name sortKey="Pion, Sd" uniqKey="Pion S">SD Pion</name></author><author><name sortKey="Osei Atweneboana, My" uniqKey="Osei Atweneboana M">MY Osei-Atweneboana</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Osei Atweneboana, My" uniqKey="Osei Atweneboana M">MY Osei-Atweneboana</name></author><author><name sortKey="Eng, Jk" uniqKey="Eng J">JK Eng</name></author><author><name sortKey="Boakye, Da" uniqKey="Boakye D">DA Boakye</name></author><author><name sortKey="Gyapong, Jo" uniqKey="Gyapong J">JO Gyapong</name></author><author><name sortKey="Prichard, Rk" uniqKey="Prichard R">RK Prichard</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Clin Infect Dis</journal-id><journal-id journal-id-type="iso-abbrev">Clin. Infect. Dis</journal-id><journal-id journal-id-type="publisher-id">cid</journal-id><journal-id journal-id-type="hwp">cid</journal-id><journal-title-group><journal-title>Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America</journal-title></journal-title-group><issn pub-type="ppub">1058-4838</issn><issn pub-type="epub">1537-6591</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25537873</article-id><article-id pub-id-type="pmc">4370165</article-id><article-id pub-id-type="doi">10.1093/cid/ciu1152</article-id><article-id pub-id-type="publisher-id">ciu1152</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles and Commentaries</subject></subj-group></article-categories><title-group><article-title>Therapeutic Efficacy and Macrofilaricidal Activity of Doxycycline for the Treatment of River Blindness</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Walker</surname><given-names>Martin</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Specht</surname><given-names>Sabine</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Churcher</surname><given-names>Thomas S.</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Hoerauf</surname><given-names>Achim</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Taylor</surname><given-names>Mark J.</given-names></name><xref ref-type="aff" rid="af3">3</xref></contrib><contrib contrib-type="author"><name><surname>Basáñez</surname><given-names>María-Gloria</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><aff id="af1"><label>1</label><addr-line>Department of Infectious Disease Epidemiology</addr-line>,<institution>Imperial College London</institution>,<country>United Kingdom</country></aff><aff id="af2"><label>2</label><addr-line>Institute for Medical Microbiology, Immunology and Parasitology</addr-line>,<institution>University Hospital Bonn</institution>,<country>Germany</country></aff><aff id="af3"><label>3</label><addr-line>Department of Parasitology</addr-line>,<institution>Liverpool School of Tropical Medicine</institution>,<country>United Kingdom</country></aff></contrib-group><author-notes><corresp>Correspondence: Martin Walker, PhD, Department of Infectious Disease Epidemiology, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK (<email>m.walker06@imperial.ac.uk</email>).</corresp></author-notes><pub-date pub-type="ppub"><day>15</day><month>4</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>23</day><month>12</month><year>2014</year></pub-date><pub-date pub-type="pmc-release"><day>23</day><month>12</month><year>2014</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>60</volume><issue>8</issue><fpage>1199</fpage><lpage>1207</lpage><history><date date-type="received"><day>9</day><month>1</month><year>2014</year></date><date date-type="accepted"><day>15</day><month>12</month><year>2014</year></date></history><permissions><copyright-statement>© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.</copyright-statement><copyright-year>2014</copyright-year><license license-type="creative-commons" xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><self-uri content-type="pdf" xlink:type="simple" xlink:href="ciu1152.pdf"></self-uri><abstract abstract-type="precis"><p>The efficacy of 4–6 weeks of oral doxycycline in depleting <italic>Wolbachia</italic> from <italic>Onchocerca volvulus</italic> is >95% in the majority of patients. <italic>Wolbachia</italic> depletion induces a 70%–80% reduction in worm life span, confirming doxycycline as a potent macrofilaricide.</p></abstract><abstract><p><bold><italic>Background.</italic></bold> <italic>Onchocerca volvulus</italic> and lymphatic filariae, causing river blindness and elephantiasis, depend on endosymbiotic <italic>Wolbachia</italic> bacteria for growth, development, fertility, and survival. Clinical trials have shown that doxycycline treatment eliminates <italic>Wolbachia</italic>, causing long-term sterilization of adult female filariae and effecting potent macrofilaricidal activity. The continual reinfection by drug-naive worms that occurs in these trial settings dilutes observable anti-<italic>Wolbachia</italic> and antifilarial effects, making it difficult to estimate therapeutic efficacy and compare different doxycycline regimens, evaluated at different times after treatment.</p><p><bold><italic>Methods.</italic></bold> A meta-analytical modeling framework is developed to link all usable data collected from clinical trials measuring the <italic>Wolbachia</italic> status and viability of individual female adult worms collected at various times after treatment with 4, 5, or 6 weeks of daily 100 or 200 mg oral doxycycline. The framework is used to estimate efficacy parameters that are not directly measurable as trial outcomes.</p><p><bold><italic>Results.</italic></bold> The estimated efficacy of doxycycline (the maximum proportional reduction in the percentage of adult female <italic>O. volvulus</italic> positive for <italic>Wolbachia</italic>) is 91%–94% on average, irrespective of the treatment regimen. Efficacy is >95% in the majority of trial participants. The life span of <italic>Wolbachia</italic>-depleted worms is reduced by 70%–80%, from approximately 10 years to 2–3 years.</p><p><bold><italic>Conclusions.</italic></bold> The efficacy parameters are pertinent to the prospects of using doxycycline on a “test and treat” basis for onchocerciasis control and confirm doxycycline as a potent macrofilaricidal therapy. The modeling approach is more generally relevant to the design and evaluation of clinical trials for antifilarial drugs conducted in endemic settings.</p></abstract><kwd-group><kwd>onchocerciasis</kwd><kwd>doxycycline</kwd><kwd>macrofilaricide</kwd><kwd>efficacy</kwd><kwd>clinical trials</kwd></kwd-group></article-meta></front></pmc><affiliations><list><country><li>Allemagne</li><li>Royaume-Uni</li></country></list><tree><country name="Royaume-Uni"><noRegion><name sortKey="Walker, Martin" sort="Walker, Martin" uniqKey="Walker M" first="Martin" last="Walker">Martin Walker</name></noRegion><name sortKey="Basa Ez, Maria Gloria" sort="Basa Ez, Maria Gloria" uniqKey="Basa Ez M" first="María-Gloria" last="Basá Ez">María-Gloria Basá Ez</name><name sortKey="Churcher, Thomas S" sort="Churcher, Thomas S" uniqKey="Churcher T" first="Thomas S." last="Churcher">Thomas S. Churcher</name><name sortKey="Taylor, Mark J" sort="Taylor, Mark J" uniqKey="Taylor M" first="Mark J." last="Taylor">Mark J. Taylor</name></country><country name="Allemagne"><noRegion><name sortKey="Specht, Sabine" sort="Specht, Sabine" uniqKey="Specht S" first="Sabine" last="Specht">Sabine Specht</name></noRegion><name sortKey="Hoerauf, Achim" sort="Hoerauf, Achim" uniqKey="Hoerauf A" first="Achim" last="Hoerauf">Achim Hoerauf</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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