Safety and effectiveness of mass drug administration to accelerate elimination of artemisinin-resistant falciparum malaria: A pilot trial in four villages of Eastern Myanmar
Identifieur interne : 002B93 ( Pmc/Curation ); précédent : 002B92; suivant : 002B94Safety and effectiveness of mass drug administration to accelerate elimination of artemisinin-resistant falciparum malaria: A pilot trial in four villages of Eastern Myanmar
Auteurs : Jordi Landier [Thaïlande] ; Ladda Kajeechiwa [Thaïlande] ; May Myo Thwin [Thaïlande] ; Daniel M. Parker [Thaïlande] ; Victor Chaumeau [Thaïlande, France] ; Jacher Wiladphaingern [Thaïlande] ; Mallika Imwong [Thaïlande] ; Olivo Miotto [Thaïlande, Royaume-Uni] ; Krittaya Patumrat [Thaïlande] ; Jureeporn Duanguppama [Thaïlande] ; Dominique Cerqueira [Thaïlande] ; Benoit Malleret [Singapour] ; Laurent Rénia [Singapour] ; Suphak Nosten [Thaïlande] ; Lorenz Von Seidlein [Thaïlande] ; Clare Ling [Thaïlande] ; Stéphane Proux [Thaïlande] ; Vincent Corbel [France] ; Julie A. Simpson [Australie] ; Arjen M. Dondorp [Thaïlande, Royaume-Uni] ; Nicholas J. White [Thaïlande, Royaume-Uni] ; François H. Nosten [Thaïlande, Royaume-Uni]Source :
- Wellcome Open Research [ 2398-502X ] ; 2017.
Abstract
This pilot trial aimed to evaluate the acceptability, safety, feasibility and effectiveness of mass-drug administration (MDA) in reducing malaria in four villages in Eastern Myanmar.
Url:
DOI: 10.12688/wellcomeopenres.12240.1
PubMed: 29062913
PubMed Central: 5635445
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<affiliation wicri:level="1"><nlm:aff id="a7">Wellcome Trust Sanger Institute, Cambridge, CB10 1SA, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Cambridge, CB10 1SA</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Patumrat, Krittaya" sort="Patumrat, Krittaya" uniqKey="Patumrat K" first="Krittaya" last="Patumrat">Krittaya Patumrat</name>
<affiliation wicri:level="1"><nlm:aff id="a5">Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Duanguppama, Jureeporn" sort="Duanguppama, Jureeporn" uniqKey="Duanguppama J" first="Jureeporn" last="Duanguppama">Jureeporn Duanguppama</name>
<affiliation wicri:level="1"><nlm:aff id="a5">Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Cerqueira, Dominique" sort="Cerqueira, Dominique" uniqKey="Cerqueira D" first="Dominique" last="Cerqueira">Dominique Cerqueira</name>
<affiliation wicri:level="1"><nlm:aff id="a4">Mahidol Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Mahidol Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Malleret, Benoit" sort="Malleret, Benoit" uniqKey="Malleret B" first="Benoit" last="Malleret">Benoit Malleret</name>
<affiliation wicri:level="1"><nlm:aff id="a8">Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119077, Singapore</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119077</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a9">Singapore Immunology Network (SIgN), Agency for Science & Technology, Singapore, 138632, Singapore</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Singapore Immunology Network (SIgN), Agency for Science & Technology, Singapore, 138632</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Renia, Laurent" sort="Renia, Laurent" uniqKey="Renia L" first="Laurent" last="Rénia">Laurent Rénia</name>
<affiliation wicri:level="1"><nlm:aff id="a9">Singapore Immunology Network (SIgN), Agency for Science & Technology, Singapore, 138632, Singapore</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Singapore Immunology Network (SIgN), Agency for Science & Technology, Singapore, 138632</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Nosten, Suphak" sort="Nosten, Suphak" uniqKey="Nosten S" first="Suphak" last="Nosten">Suphak Nosten</name>
<affiliation wicri:level="1"><nlm:aff id="a1">Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Von Seidlein, Lorenz" sort="Von Seidlein, Lorenz" uniqKey="Von Seidlein L" first="Lorenz" last="Von Seidlein">Lorenz Von Seidlein</name>
<affiliation wicri:level="1"><nlm:aff id="a4">Mahidol Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Mahidol Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ling, Clare" sort="Ling, Clare" uniqKey="Ling C" first="Clare" last="Ling">Clare Ling</name>
<affiliation wicri:level="1"><nlm:aff id="a1">Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Proux, Stephane" sort="Proux, Stephane" uniqKey="Proux S" first="Stéphane" last="Proux">Stéphane Proux</name>
<affiliation wicri:level="1"><nlm:aff id="a1">Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Corbel, Vincent" sort="Corbel, Vincent" uniqKey="Corbel V" first="Vincent" last="Corbel">Vincent Corbel</name>
<affiliation wicri:level="1"><nlm:aff id="a2">Maladies Infectieuses et Vecteurs Ecologie, Génétique, Evolution et Contrôle (IRD 224-CNRS 4280 UM1-UM2), Institut de Recherche pour le Développement, Montpellier, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Maladies Infectieuses et Vecteurs Ecologie, Génétique, Evolution et Contrôle (IRD 224-CNRS 4280 UM1-UM2), Institut de Recherche pour le Développement, Montpellier</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Simpson, Julie A" sort="Simpson, Julie A" uniqKey="Simpson J" first="Julie A." last="Simpson">Julie A. Simpson</name>
<affiliation wicri:level="1"><nlm:aff id="a10">Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, 3053, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, 3053</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Dondorp, Arjen M" sort="Dondorp, Arjen M" uniqKey="Dondorp A" first="Arjen M." last="Dondorp">Arjen M. Dondorp</name>
<affiliation wicri:level="1"><nlm:aff id="a4">Mahidol Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Mahidol Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a11">Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="White, Nicholas J" sort="White, Nicholas J" uniqKey="White N" first="Nicholas J." last="White">Nicholas J. White</name>
<affiliation wicri:level="1"><nlm:aff id="a4">Mahidol Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Mahidol Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a11">Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Nosten, Francois H" sort="Nosten, Francois H" uniqKey="Nosten F" first="François H." last="Nosten">François H. Nosten</name>
<affiliation wicri:level="1"><nlm:aff id="a1">Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a11">Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Wellcome Open Research</title>
<idno type="eISSN">2398-502X</idno>
<imprint><date when="2017">2017</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p><bold>Background: </bold>
Artemisinin and partner drug-resistant falciparum malaria is expanding over the Greater Mekong Sub-region (GMS). Eliminating falciparum malaria in the GMS while drugs still retain enough efficacy could prevent global spread of antimalarial resistance. Eliminating malaria rapidly requires targeting the reservoir of asymptomatic parasite carriers.</p>
<p> This pilot trial aimed to evaluate the acceptability, safety, feasibility and effectiveness of mass-drug administration (MDA) in reducing malaria in four villages in Eastern Myanmar.</p>
<p><bold>Methods: </bold>
Villages with ≥30% malaria prevalence were selected. Long-lasting insecticidal bednets (LLINs) and access to malaria early diagnosis and treatment (EDT) were provided. Two villages received MDA immediately and two were followed for nine months pre-MDA. MDA consisted of a 3-day supervised course of dihydroartemisinin-piperaquine and single low-dose primaquine administered monthly for three months. Adverse events (AE) were monitored by interviews and consultations. Malaria prevalence was assessed by ultrasensitive PCR quarterly for 24 months. Symptomatic malaria incidence,entomological indices, and antimalarial resistance markers were monitored.</p>
<p><bold>Results: </bold>
MDA was well tolerated. There were no serious AE and mild to moderate AE were reported in 5.6%(212/3931) interviews. In the smaller villages, participation to three MDA courses was 61% and 57%, compared to 28% and 29% in the larger villages. Baseline prevalence was higher in intervention than in control villages (18.7% (95%CI=16.1-21.6) versus 6.8%(5.2-8.7), p<0.0001) whereas three months after starting MDA, prevalence was lower in intervention villages (0.4%(0.04-1.3) versus 2.7%(1.7-4.1), p=0.0014). After nine months the difference was no longer significant (2.0%(1.0-3.5) versus 0.9%(0.04-1.8), p=0.10). M0-M9 symptomatic falciparum incidence was similar between intervention and control. Before/after MDA comparisons showed that asymptomatic
<italic>P. falciparum </italic>
carriage and anopheline vector positivity decreased significantly whereas prevalence of the artemisinin-resistance molecular marker remained stable.</p>
<p><bold>Conclusions: </bold>
This MDA was safe and feasible, and, could accelerate elimination of
<italic>P. falciparum </italic>
in addition to EDT and LLINs
<italic></italic>
when community participation was sufficient.</p>
</div>
</front>
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</TEI>
<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Wellcome Open Res</journal-id>
<journal-id journal-id-type="iso-abbrev">Wellcome Open Res</journal-id>
<journal-id journal-id-type="pmc">Wellcome Open Res</journal-id>
<journal-title-group><journal-title>Wellcome Open Research</journal-title>
</journal-title-group>
<issn pub-type="epub">2398-502X</issn>
<publisher><publisher-name>F1000Research</publisher-name>
<publisher-loc>London, UK</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">29062913</article-id>
<article-id pub-id-type="pmc">5635445</article-id>
<article-id pub-id-type="doi">10.12688/wellcomeopenres.12240.1</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
<subj-group><subject>Articles</subject>
<subj-group><subject>Epidemiology</subject>
</subj-group>
<subj-group><subject>Health Systems & Services Research</subject>
</subj-group>
<subj-group><subject>Parasitology</subject>
</subj-group>
<subj-group><subject>Preventive Medicine</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>Safety and effectiveness of mass drug administration to accelerate elimination of artemisinin-resistant falciparum malaria: A pilot trial in four villages of Eastern Myanmar</article-title>
<fn-group content-type="pub-status"><fn><p>[version 1; referees: 2 approved]</p>
</fn>
</fn-group>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Landier</surname>
<given-names>Jordi</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data Curation</role>
<role content-type="http://credit.casrai.org/">Formal Analysis</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Visualization</role>
<role content-type="http://credit.casrai.org/">Writing – Original Draft Preparation</role>
<role content-type="http://credit.casrai.org/">Writing – Review & Editing</role>
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8619-9775</contrib-id>
<xref ref-type="corresp" rid="c1">a</xref>
<xref ref-type="aff" rid="a1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kajeechiwa</surname>
<given-names>Ladda</given-names>
</name>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Project Administration</role>
<role content-type="http://credit.casrai.org/">Writing – Review & Editing</role>
<xref ref-type="aff" rid="a1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Thwin</surname>
<given-names>May Myo</given-names>
</name>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Project Administration</role>
<role content-type="http://credit.casrai.org/">Writing – Review & Editing</role>
<xref ref-type="aff" rid="a1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Parker</surname>
<given-names>Daniel M.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Visualization</role>
<role content-type="http://credit.casrai.org/">Writing – Review & Editing</role>
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5352-7338</contrib-id>
<xref ref-type="aff" rid="a1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chaumeau</surname>
<given-names>Victor</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data Curation</role>
<role content-type="http://credit.casrai.org/">Formal Analysis</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Writing – Review & Editing</role>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a2">2</xref>
<xref ref-type="aff" rid="a3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wiladphaingern</surname>
<given-names>Jacher</given-names>
</name>
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<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Writing – Review & Editing</role>
<xref ref-type="aff" rid="a1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Imwong</surname>
<given-names>Mallika</given-names>
</name>
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<role content-type="http://credit.casrai.org/">Resources</role>
<role content-type="http://credit.casrai.org/">Writing – Review & Editing</role>
<xref ref-type="aff" rid="a4">4</xref>
<xref ref-type="aff" rid="a5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Miotto</surname>
<given-names>Olivo</given-names>
</name>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Resources</role>
<role content-type="http://credit.casrai.org/">Writing – Review & Editing</role>
<xref ref-type="aff" rid="a4">4</xref>
<xref ref-type="aff" rid="a6">6</xref>
<xref ref-type="aff" rid="a7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Patumrat</surname>
<given-names>Krittaya</given-names>
</name>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Writing – Review & Editing</role>
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6585-9997</contrib-id>
<xref ref-type="aff" rid="a5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Duanguppama</surname>
<given-names>Jureeporn</given-names>
</name>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Writing – Review & Editing</role>
<xref ref-type="aff" rid="a5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cerqueira</surname>
<given-names>Dominique</given-names>
</name>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Writing – Review & Editing</role>
<xref ref-type="aff" rid="a4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Malleret</surname>
<given-names>Benoit</given-names>
</name>
<role content-type="http://credit.casrai.org/">Resources</role>
<xref ref-type="aff" rid="a8">8</xref>
<xref ref-type="aff" rid="a9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rénia</surname>
<given-names>Laurent</given-names>
</name>
<role content-type="http://credit.casrai.org/">Resources</role>
<role content-type="http://credit.casrai.org/">Writing – Review & Editing</role>
<xref ref-type="aff" rid="a9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Nosten</surname>
<given-names>Suphak</given-names>
</name>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Project Administration</role>
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<xref ref-type="aff" rid="a1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>von Seidlein</surname>
<given-names>Lorenz</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Project Administration</role>
<role content-type="http://credit.casrai.org/">Writing – Review & Editing</role>
<xref ref-type="aff" rid="a4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ling</surname>
<given-names>Clare</given-names>
</name>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Project Administration</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
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<xref ref-type="aff" rid="a1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Proux</surname>
<given-names>Stéphane</given-names>
</name>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Project Administration</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
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<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4201-5473</contrib-id>
<xref ref-type="aff" rid="a1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Corbel</surname>
<given-names>Vincent</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Project Administration</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Writing – Review & Editing</role>
<xref ref-type="aff" rid="a2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Simpson</surname>
<given-names>Julie A.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Formal Analysis</role>
<role content-type="http://credit.casrai.org/">Writing – Original Draft Preparation</role>
<role content-type="http://credit.casrai.org/">Writing – Review & Editing</role>
<xref ref-type="aff" rid="a10">10</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Dondorp</surname>
<given-names>Arjen M.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Funding Acquisition</role>
<role content-type="http://credit.casrai.org/">Project Administration</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Writing – Review & Editing</role>
<xref ref-type="aff" rid="a4">4</xref>
<xref ref-type="aff" rid="a11">11</xref>
</contrib>
<contrib contrib-type="author"><name><surname>White</surname>
<given-names>Nicholas J.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Funding Acquisition</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Project Administration</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Writing – Original Draft Preparation</role>
<role content-type="http://credit.casrai.org/">Writing – Review & Editing</role>
<xref ref-type="aff" rid="a4">4</xref>
<xref ref-type="aff" rid="a11">11</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Nosten</surname>
<given-names>François H.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Funding Acquisition</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Project Administration</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Writing – Original Draft Preparation</role>
<role content-type="http://credit.casrai.org/">Writing – Review & Editing</role>
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7951-0745</contrib-id>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a11">11</xref>
</contrib>
<aff id="a1"><label>1</label>
Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand</aff>
<aff id="a2"><label>2</label>
Maladies Infectieuses et Vecteurs Ecologie, Génétique, Evolution et Contrôle (IRD 224-CNRS 4280 UM1-UM2), Institut de Recherche pour le Développement, Montpellier, France</aff>
<aff id="a3"><label>3</label>
Centre Hospitalier Régional Universitaire de Montpellier, Montpellier, France</aff>
<aff id="a4"><label>4</label>
Mahidol Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand</aff>
<aff id="a5"><label>5</label>
Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand</aff>
<aff id="a6"><label>6</label>
Centre for Genomics and Global Health, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK</aff>
<aff id="a7"><label>7</label>
Wellcome Trust Sanger Institute, Cambridge, CB10 1SA, UK</aff>
<aff id="a8"><label>8</label>
Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119077, Singapore</aff>
<aff id="a9"><label>9</label>
Singapore Immunology Network (SIgN), Agency for Science & Technology, Singapore, 138632, Singapore</aff>
<aff id="a10"><label>10</label>
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, 3053, Australia</aff>
<aff id="a11"><label>11</label>
Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK</aff>
</contrib-group>
<author-notes><corresp id="c1"><label>a</label>
<email xlink:href="mailto:jordi.landier@gmail.com">jordi.landier@gmail.com</email>
</corresp>
<fn fn-type="COI-statement"><p><bold>Competing interests: </bold>
No competing interests were disclosed.</p>
</fn>
</author-notes>
<pub-date pub-type="epub"><day>6</day>
<month>9</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="collection"><year>2017</year>
</pub-date>
<volume>2</volume>
<elocation-id>81</elocation-id>
<history><date date-type="accepted"><day>21</day>
<month>8</month>
<year>2017</year>
</date>
</history>
<permissions><copyright-statement>Copyright: © 2017 Landier J et al.</copyright-statement>
<copyright-year>2017</copyright-year>
<license 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 Licence, which permits unrestricted use, 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="wellcomeopenres-2-13252.pdf"></self-uri>
<abstract><p><bold>Background: </bold>
Artemisinin and partner drug-resistant falciparum malaria is expanding over the Greater Mekong Sub-region (GMS). Eliminating falciparum malaria in the GMS while drugs still retain enough efficacy could prevent global spread of antimalarial resistance. Eliminating malaria rapidly requires targeting the reservoir of asymptomatic parasite carriers.</p>
<p> This pilot trial aimed to evaluate the acceptability, safety, feasibility and effectiveness of mass-drug administration (MDA) in reducing malaria in four villages in Eastern Myanmar.</p>
<p><bold>Methods: </bold>
Villages with ≥30% malaria prevalence were selected. Long-lasting insecticidal bednets (LLINs) and access to malaria early diagnosis and treatment (EDT) were provided. Two villages received MDA immediately and two were followed for nine months pre-MDA. MDA consisted of a 3-day supervised course of dihydroartemisinin-piperaquine and single low-dose primaquine administered monthly for three months. Adverse events (AE) were monitored by interviews and consultations. Malaria prevalence was assessed by ultrasensitive PCR quarterly for 24 months. Symptomatic malaria incidence,entomological indices, and antimalarial resistance markers were monitored.</p>
<p><bold>Results: </bold>
MDA was well tolerated. There were no serious AE and mild to moderate AE were reported in 5.6%(212/3931) interviews. In the smaller villages, participation to three MDA courses was 61% and 57%, compared to 28% and 29% in the larger villages. Baseline prevalence was higher in intervention than in control villages (18.7% (95%CI=16.1-21.6) versus 6.8%(5.2-8.7), p<0.0001) whereas three months after starting MDA, prevalence was lower in intervention villages (0.4%(0.04-1.3) versus 2.7%(1.7-4.1), p=0.0014). After nine months the difference was no longer significant (2.0%(1.0-3.5) versus 0.9%(0.04-1.8), p=0.10). M0-M9 symptomatic falciparum incidence was similar between intervention and control. Before/after MDA comparisons showed that asymptomatic
<italic>P. falciparum </italic>
carriage and anopheline vector positivity decreased significantly whereas prevalence of the artemisinin-resistance molecular marker remained stable.</p>
<p><bold>Conclusions: </bold>
This MDA was safe and feasible, and, could accelerate elimination of
<italic>P. falciparum </italic>
in addition to EDT and LLINs
<italic></italic>
when community participation was sufficient.</p>
</abstract>
<kwd-group kwd-group-type="author"><kwd>Plasmodium falciparum</kwd>
<kwd>Plasmodium vivax</kwd>
<kwd>Mass Drug Administration</kwd>
<kwd>Asymptomatic carriage</kwd>
<kwd>submicroscopic infection</kwd>
<kwd>artemisinin-resistance</kwd>
<kwd>transmission</kwd>
</kwd-group>
<funding-group><award-group id="fund-1" xlink:href="http://dx.doi.org/10.13039/100004440"><funding-source>Wellcome Trust</funding-source>
<award-id>101148</award-id>
</award-group>
<award-group id="fund-2" xlink:href="http://dx.doi.org/10.13039/100000865"><funding-source>Bill and Melinda Gates Foundation</funding-source>
<award-id>GHOPP1081420</award-id>
</award-group>
<funding-statement>This work was supported by the Wellcome Trust [101148]; and the Bill and Melinda Gates Foundation [GH OPP 1081420]. </funding-statement>
<funding-statement><italic>The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</italic>
</funding-statement>
</funding-group>
</article-meta>
</front>
<sub-article id="report25742" article-type="ref-report"><front-stub><article-id pub-id-type="doi">10.21956/wellcomeopenres.13252.r25742</article-id>
<title-group><article-title>Referee response for version 1</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Drakeley</surname>
<given-names>Chris J.</given-names>
</name>
<xref ref-type="aff" rid="r25742a1">1</xref>
<role>Referee</role>
</contrib>
<contrib contrib-type="author"><name><surname>Goncalves</surname>
<given-names>Bronner</given-names>
</name>
<xref ref-type="aff" rid="r25742a2">2</xref>
<role>Co-referee</role>
</contrib>
<contrib contrib-type="author"><name><surname>Stresman</surname>
<given-names>Gillian</given-names>
</name>
<xref ref-type="aff" rid="r25742a3">3</xref>
<role>Co-referee</role>
</contrib>
<aff id="r25742a1"><label>1</label>
Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK</aff>
<aff id="r25742a2"><label>2</label>
Department of Immunology and Infection, London School of Hygiene & Tropical Medicine, London, UK</aff>
<aff id="r25742a3"><label>3</label>
Faculty of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK</aff>
</contrib-group>
<author-notes><fn fn-type="COI-statement"><p><bold>Competing interests: </bold>
No competing interests were disclosed.</p>
</fn>
</author-notes>
<pub-date pub-type="epub"><day>9</day>
<month>10</month>
<year>2017</year>
</pub-date>
<related-article id="d35e4498" related-article-type="peer-reviewed-article" ext-link-type="doi" xlink:href="10.12688/wellcomeopenres.12240.1"></related-article>
<custom-meta-group><custom-meta><meta-name>recommendation</meta-name>
<meta-value>approve</meta-value>
</custom-meta>
</custom-meta-group>
</front-stub>
<body><p>This is a comprehensive presentation of findings from a pilot trial in which Landier and colleagues show that mass drug administration had an immediate effect on falciparum parasite carriage, in both human and vector populations. In 3 of the 4 study villages, prevalence of falciparum infection remained low during the 24 month follow-up period. The effects of MDA are particularly impressive given the fluid nature of the population and relatively low level of effective coverage (especially in larger villages). MDA appeared not to affect the incidence of clinical malaria episodes when compared to the control (‘pre-MDA’) villages. However, in the control villages, early diagnosis and treatment provided by MP was associated with reductions in malaria transmission, comparable to that seen in villages with MP and MDA. The relative contribution of MDA over MP is a key question for malaria control programmes as they seek to decide whether ensuring basic diagnostics and treatment is sufficient to eliminate malaria. The data are interesting but fall short of answering this comprehensively given the small sample size - presumably this will be a focus of the main study.</p>
<p><underline>Abstract:</underline>
</p>
<p> It is not clear what refers to falciparum and what refers to
<italic>vivax</italic>
infections. It seems from the methods section that the criterion was >10% falciparum prevalence. Also, it is not clear by what method this prevalence is assessed.</p>
<p> What population size is village size small or large?</p>
<p> Vector positivity presumably means sporozoite.</p>
<p><underline>Introduction:</underline>
</p>
<p> The evidence for the effect of treatment of the reduction of transmission is quite sparse and typically from areas with good health systems and low transmission. Context could be improved here.</p>
<p> It might help to cite studies that show mosquito feeding experiments in SE Asia have shown that most infections come from symptomatic infections.</p>
<p> Primaquine does not strictly sterilize infections – it has little demonstrable effect on asexual parasites.</p>
<p><underline>Methods:</underline>
</p>
<p> Were the numbers malaria posts proportional to population?</p>
<p> What was the rationale for no radical cure for
<italic>P.vivax</italic>
?</p>
<p> Why was parasite prevalence was not assessed in infants? One might expect that the overall transmission effect of MDA (and MP) on parasite prevalence would also be seen in this group.</p>
<p> Does malaria infection prevalence represent for each or for either ?</p>
<p> Why the change in time for MDA from M12 to M9? this seems irrational and inconsistent with the rigour of the general context of the study. It does not allow similar follow up periods and confounds any potential seasonal effects.</p>
<p><underline>Results:</underline>
</p>
<p> How did population movement relate to coverage? Were those individuals who spent less time in villages less likely to receive MDA? What was the prevalence of infection in this group?</p>
<p> There is a lack of spatial analysis. The authors could use the georeferenced data to estimate whether MDA coverage predicted residual parasite prevalence spatially. Similarly, it would be interesting to understand if compliance was spatially aggregated (presumably it was). Also, were AEs related to coverage? The prevalence of AEs declined after each round, but that could be related to individuals most likely to develop AEs refusing to receive additional treatment. What was the prevalence of AEs in the different rounds in those individuals who received all 3 treatments?</p>
<p> The most informative analysis is the comparison in the control villages before MDA (so effect due to MP alone) versus after MDA (combined MDA and MP effects). The GEE model estimated that the post-MDA period was associated with 5 fold reduction in falciparum carriage. However there was a clear trend of declining falciparum prevalence during the pre-MDA period. How much of this 5-fold reduction is related to the continued reduction in transmission due to MP.</p>
<p> “During the pre-MDA control period, individual with baseline
<italic>P. falciparum</italic>
infections had a significantly increased odds of subsequent
<italic>P. falciparum</italic>
carriage…” – is this related to age? To occupation? Residence?</p>
<p> It would be interesting to see a graph that shows temporal variation in the entomological parameters together with human prevalence and comments on the effect of seasonality.</p>
<p><underline>Discussion</underline>
</p>
<p> The authors argue that access to diagnosis and treatment had an important effect on transmission that was “augmented by MDA”. The design of the study and the limited number of villages does not really justify this conclusion. In the control villages, where MDA was implemented 9 months after improved access to diagnosis and treatment, there was a clear trend of decreasing transmission before MDA. It is not clear how the authors expect to quantify effectiveness of MDA, that is independent of MP, using this design. This needs to be mentioned early in the discussion as this comparison is the main question the study wants to address: the added value of MDA in area with improved access to diagnosis and treatment.</p>
<p> Authors could discuss what additional interventions should be considered to sustain vivax transmission reduction.</p>
<p> It might be worth speculating how malaria elimination can be delayed by not treating first trimester pregnant women and infants.</p>
<p>We have read this submission. We believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.</p>
</body>
</sub-article>
<sub-article id="report25746" article-type="ref-report"><front-stub><article-id pub-id-type="doi">10.21956/wellcomeopenres.13252.r25746</article-id>
<title-group><article-title>Referee response for version 1</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Fairhurst</surname>
<given-names>Rick M.</given-names>
</name>
<xref ref-type="aff" rid="r25746a1">1</xref>
<role>Referee</role>
</contrib>
<aff id="r25746a1"><label>1</label>
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Rockville, MD, USA</aff>
</contrib-group>
<author-notes><fn fn-type="COI-statement"><p><bold>Competing interests: </bold>
No competing interests were disclosed.</p>
</fn>
</author-notes>
<pub-date pub-type="epub"><day>27</day>
<month>9</month>
<year>2017</year>
</pub-date>
<related-article id="d35e4626" related-article-type="peer-reviewed-article" ext-link-type="doi" xlink:href="10.12688/wellcomeopenres.12240.1"></related-article>
<custom-meta-group><custom-meta><meta-name>recommendation</meta-name>
<meta-value>approve</meta-value>
</custom-meta>
</custom-meta-group>
</front-stub>
<body><p>Suggest line numbers be added to future manuscript versions to facilitate peer review.</p>
<p> Page 3, right column, para 1, line 2: Suggest mentioning the net-to-person ratio for bed net distribution. Were all individuals provided a net, was each household provided a single net to share, etc.?</p>
<p> Page 3, right column, para 2, line 8: Suggest mentioning the lower age at which assent was obtained.</p>
<p> Page 5, right column, para 2: Can the authors explain why uptake was higher in the smaller versus the larger villages? Did the larger villages experience more out-migration during the study period, were there logistical problems in tracking down all previous participants in the larger villages, etc.?</p>
<p> Page 5, right column, para 3, line 1: Is the acceptability of MDA simply inferred because AEs were mild or moderate? Or was a specific assessment of acceptability made?</p>
<p> Page 5, right column, para 3: Suggest mentioning whether any of the AEs were treatment-limiting.</p>
<p> Page 8, left column, para 1, line 1: Suggest mentioning why the other 31% of newcomers could not be included in the first survey.</p>
<p> Page 8, Figure 2, panels A, B and D: The reappearance of Pv parasites within 3-6 months are obviously due to relapsing Pv from the liver, but do the authors know whether this rate of reappearance is typical following DP/MDA in this area? Also, can they speculate why there was very little Pv relapse in B1-TPN? This finding is mentioned twice in the manuscript text, but no speculation is offered.</p>
<p> Page 10, right column, para 2, line 6: Is the difference in K13 mutation prevalence before and after MDA significant? Had the authors hypothesized a priori that MDA would have a selective effect on reducing the prevalence of K13-mutant infections?</p>
<p> Page 10, right column, para 4, line 3: Suggest adding a citation to support the notion that these vectors are the contemporaneous primary malaria vectors in this area.</p>
<p>I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.</p>
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