Effects of liver-stage clearance by Primaquine on gametocyte carriage of Plasmodium vivax and P. falciparum
Identifieur interne : 000D46 ( Main/Exploration ); précédent : 000D45; suivant : 000D47Effects of liver-stage clearance by Primaquine on gametocyte carriage of Plasmodium vivax and P. falciparum
Auteurs : Rahel Wampfler [Suisse] ; Natalie E. Hofmann [Suisse] ; Stephan Karl [Australie] ; Inoni Betuela [Papouasie-Nouvelle-Guinée] ; Benson Kinboro [Papouasie-Nouvelle-Guinée] ; Lina Lorry [Papouasie-Nouvelle-Guinée] ; Mariabeth Silkey [Suisse] ; Leanne J. Robinson [Australie, Papouasie-Nouvelle-Guinée] ; Ivo Mueller [Australie, France] ; Ingrid Felger [Suisse]Source :
- PLoS Neglected Tropical Diseases [ 1935-2727 ] ; 2017.
Descripteurs français
- KwdFr :
- Analyse de régression, Analyse multivariée, Antipaludiques (usage thérapeutique), Artémisinines (usage thérapeutique), Association médicamenteuse, Chloroquine (usage thérapeutique), Enfant, Enfant d'âge préscolaire, Facteurs de risque, Femelle, Fluorènes (usage thérapeutique), Foie (), Foie (parasitologie), Humains, Mâle, Méthode en double aveugle, Paludisme à Plasmodium falciparum (traitement médicamenteux), Paludisme à Plasmodium vivax (traitement médicamenteux), Papouasie - Nouvelle-Guinée, Plasmodium falciparum (), Plasmodium vivax (), Primaquine (usage thérapeutique), Récidive, Sang (parasitologie), Éthanolamines (usage thérapeutique).
- MESH :
- parasitologie : Foie, Sang.
- traitement médicamenteux : Paludisme à Plasmodium falciparum, Paludisme à Plasmodium vivax.
- usage thérapeutique : Antipaludiques, Artémisinines, Chloroquine, Fluorènes, Primaquine, Éthanolamines.
- Analyse de régression, Analyse multivariée, Association médicamenteuse, Enfant, Enfant d'âge préscolaire, Facteurs de risque, Femelle, Foie, Humains, Mâle, Méthode en double aveugle, Papouasie - Nouvelle-Guinée, Plasmodium falciparum, Plasmodium vivax, Récidive.
English descriptors
- KwdEn :
- Antimalarials (therapeutic use), Artemisinins (therapeutic use), Blood (parasitology), Child, Child, Preschool, Chloroquine (therapeutic use), Double-Blind Method, Drug Combinations, Ethanolamines (therapeutic use), Female, Fluorenes (therapeutic use), Humans, Liver (drug effects), Liver (parasitology), Malaria, Falciparum (drug therapy), Malaria, Vivax (drug therapy), Male, Multivariate Analysis, Papua New Guinea, Plasmodium falciparum (drug effects), Plasmodium vivax (drug effects), Primaquine (therapeutic use), Recurrence, Regression Analysis, Risk Factors.
- MESH :
- chemical , therapeutic use : Antimalarials, Artemisinins, Chloroquine, Ethanolamines, Fluorenes, Primaquine.
- drug effects : Liver, Plasmodium falciparum, Plasmodium vivax.
- drug therapy : Malaria, Falciparum, Malaria, Vivax.
- parasitology : Blood, Liver.
- Child, Child, Preschool, Double-Blind Method, Drug Combinations, Female, Humans, Male, Multivariate Analysis, Papua New Guinea, Recurrence, Regression Analysis, Risk Factors.
Abstract
Primaquine (PQ) is the only currently licensed antimalarial that prevents
Children received radical cure with Chloroquine, Artemether-Lumefantrine plus either PQ or placebo. Blood samples were subsequently collected in 2-to 4-weekly intervals over 8 months. Gametocytes were detected by quantitative reverse transcription-PCR targeting
PQ treatment reduced the incidence of
Pv relapses and new infections are associated with similar levels of gametocytaemia. Relapses thus contribute considerably to the Pv reservoir highlighting the importance of effective anti-hypnozoite treatment for efficient control of Pv.
ClinicalTrials.gov
Url:
DOI: 10.1371/journal.pntd.0005753
PubMed: 28732068
PubMed Central: 5540608
Affiliations:
- Australie, France, Papouasie-Nouvelle-Guinée, Suisse
- Victoria (État), Île-de-France
- Melbourne, Paris
- Université de Melbourne
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Le document en format XML
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sort="Wampfler, Rahel" uniqKey="Wampfler R" first="Rahel" last="Wampfler">Rahel Wampfler</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Swiss Tropical and Public Health Institute, Basel, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Swiss Tropical and Public Health Institute, Basel</wicri:regionArea><wicri:noRegion>Basel</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>University of Basel, Basel, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>University of Basel, Basel</wicri:regionArea><wicri:noRegion>Basel</wicri:noRegion></affiliation></author><author><name sortKey="Hofmann, Natalie E" sort="Hofmann, Natalie E" uniqKey="Hofmann N" first="Natalie E." last="Hofmann">Natalie E. 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Robinson</name><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Divison of Population Health and Immunity, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Divison of Population Health and Immunity, The Walter and Eliza Hall Institute of Medical Research, Parkville</wicri:regionArea><wicri:noRegion>Parkville</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff004"><addr-line>Department of Medical Biology, University of Melbourne, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Biology, University of Melbourne, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff 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Basel</wicri:regionArea><wicri:noRegion>Basel</wicri:noRegion></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="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antimalarials (therapeutic use)</term><term>Artemisinins (therapeutic use)</term><term>Blood (parasitology)</term><term>Child</term><term>Child, Preschool</term><term>Chloroquine (therapeutic use)</term><term>Double-Blind Method</term><term>Drug Combinations</term><term>Ethanolamines (therapeutic use)</term><term>Female</term><term>Fluorenes (therapeutic use)</term><term>Humans</term><term>Liver (drug effects)</term><term>Liver (parasitology)</term><term>Malaria, Falciparum (drug therapy)</term><term>Malaria, Vivax (drug therapy)</term><term>Male</term><term>Multivariate Analysis</term><term>Papua New Guinea</term><term>Plasmodium falciparum (drug effects)</term><term>Plasmodium vivax (drug effects)</term><term>Primaquine (therapeutic use)</term><term>Recurrence</term><term>Regression Analysis</term><term>Risk Factors</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Analyse de régression</term><term>Analyse multivariée</term><term>Antipaludiques (usage thérapeutique)</term><term>Artémisinines (usage thérapeutique)</term><term>Association médicamenteuse</term><term>Chloroquine (usage thérapeutique)</term><term>Enfant</term><term>Enfant d'âge préscolaire</term><term>Facteurs de risque</term><term>Femelle</term><term>Fluorènes (usage thérapeutique)</term><term>Foie ()</term><term>Foie (parasitologie)</term><term>Humains</term><term>Mâle</term><term>Méthode en double aveugle</term><term>Paludisme à Plasmodium falciparum (traitement médicamenteux)</term><term>Paludisme à Plasmodium vivax (traitement médicamenteux)</term><term>Papouasie - Nouvelle-Guinée</term><term>Plasmodium falciparum ()</term><term>Plasmodium vivax ()</term><term>Primaquine (usage thérapeutique)</term><term>Récidive</term><term>Sang (parasitologie)</term><term>Éthanolamines (usage thérapeutique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antimalarials</term><term>Artemisinins</term><term>Chloroquine</term><term>Ethanolamines</term><term>Fluorenes</term><term>Primaquine</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Liver</term><term>Plasmodium falciparum</term><term>Plasmodium vivax</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Malaria, Falciparum</term><term>Malaria, Vivax</term></keywords><keywords scheme="MESH" qualifier="parasitologie" xml:lang="fr"><term>Foie</term><term>Sang</term></keywords><keywords scheme="MESH" qualifier="parasitology" xml:lang="en"><term>Blood</term><term>Liver</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Paludisme à Plasmodium falciparum</term><term>Paludisme à Plasmodium vivax</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Antipaludiques</term><term>Artémisinines</term><term>Chloroquine</term><term>Fluorènes</term><term>Primaquine</term><term>Éthanolamines</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Child</term><term>Child, Preschool</term><term>Double-Blind Method</term><term>Drug Combinations</term><term>Female</term><term>Humans</term><term>Male</term><term>Multivariate Analysis</term><term>Papua New Guinea</term><term>Recurrence</term><term>Regression Analysis</term><term>Risk Factors</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Analyse de régression</term><term>Analyse multivariée</term><term>Association médicamenteuse</term><term>Enfant</term><term>Enfant d'âge préscolaire</term><term>Facteurs de risque</term><term>Femelle</term><term>Foie</term><term>Humains</term><term>Mâle</term><term>Méthode en double aveugle</term><term>Papouasie - Nouvelle-Guinée</term><term>Plasmodium falciparum</term><term>Plasmodium vivax</term><term>Récidive</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="sec001"><title>Background</title><p>Primaquine (PQ) is the only currently licensed antimalarial that prevents <italic>Plasmodium vivax</italic> (<italic>Pv</italic>) relapses. It also clears mature <italic>P</italic>. <italic>falciparum</italic> (<italic>Pf</italic>) gametocytes, thereby reducing post-treatment transmission. Randomized PQ treatment in a treatment-to-reinfection cohort in Papua New Guinean children permitted the study of <italic>Pv</italic> and <italic>Pf</italic> gametocyte carriage after radical cure and to investigate the contribution of <italic>Pv</italic> relapses.</p></sec><sec id="sec002"><title>Methods</title><p>Children received radical cure with Chloroquine, Artemether-Lumefantrine plus either PQ or placebo. Blood samples were subsequently collected in 2-to 4-weekly intervals over 8 months. Gametocytes were detected by quantitative reverse transcription-PCR targeting <italic>pvs25</italic> and <italic>pfs25</italic>.</p></sec><sec id="sec003"><title>Results</title><p>PQ treatment reduced the incidence of <italic>Pv</italic> gametocytes by 73%, which was comparable to the effect of PQ on incidence of blood-stage infections. 92% of <italic>Pv</italic> and 79% of <italic>Pf</italic> gametocyte-positive infections were asymptomatic. <italic>Pv</italic> and to a lesser extent <italic>Pf</italic> gametocyte positivity and density were associated with high blood-stage parasite densities. Multivariate analysis revealed that the odds of gametocytes were significantly reduced in mixed-species infections compared to single-species infections for both species (OR<sub>Pv</sub> = 0.39 [95% CI 0.25–0.62], OR<sub>Pf</sub> = 0.33 [95% CI 0.18–0.60], p<0.001). No difference between the PQ and placebo treatment arms was observed in density of <italic>Pv</italic> gametocytes or in the proportion of <italic>Pv</italic> infections that carried gametocytes. First infections after blood-stage and placebo treatment, likely caused by a relapsing hypnozoite, were equally likely to carry gametocytes than first infections after PQ treatment, likely caused by an infective mosquito bite.</p></sec><sec id="sec004"><title>Conclusion</title><p>Pv relapses and new infections are associated with similar levels of gametocytaemia. Relapses thus contribute considerably to the Pv reservoir highlighting the importance of effective anti-hypnozoite treatment for efficient control of Pv.</p></sec><sec id="sec005"><title>Trial registration</title><p>ClinicalTrials.gov <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02143934">NCT02143934</ext-link></p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="John, Gk" uniqKey="John G">GK John</name></author><author><name sortKey="Douglas, Nm" uniqKey="Douglas N">NM Douglas</name></author><author><name sortKey="Von Seidlein, L" uniqKey="Von Seidlein L">L von Seidlein</name></author><author><name sortKey="Nosten, F" uniqKey="Nosten F">F Nosten</name></author><author><name sortKey="Baird, Jk" uniqKey="Baird J">JK Baird</name></author><author><name sortKey="White, Nj" uniqKey="White N">NJ White</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eziefula, Ac" 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Michel</name></author><author><name sortKey="Maraga, S" uniqKey="Maraga S">S Maraga</name></author><author><name sortKey="Mcnamara, Dt" uniqKey="Mcnamara D">DT McNamara</name></author><author><name sortKey="Kiniboro, B" uniqKey="Kiniboro B">B Kiniboro</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bruce, Mc" uniqKey="Bruce M">MC Bruce</name></author><author><name sortKey="Donnelly, Ca" uniqKey="Donnelly C">CA Donnelly</name></author><author><name sortKey="Alpers, Mp" uniqKey="Alpers M">MP Alpers</name></author><author><name sortKey="Galinski, Mr" uniqKey="Galinski M">MR Galinski</name></author><author><name sortKey="Barnwell, Jw" uniqKey="Barnwell J">JW Barnwell</name></author><author><name sortKey="Walliker, D" uniqKey="Walliker D">D Walliker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zimmerman, Pa" uniqKey="Zimmerman P">PA Zimmerman</name></author><author><name sortKey="Mehlotra, Rk" uniqKey="Mehlotra R">RK Mehlotra</name></author><author><name sortKey="Kasehagen, Lj" uniqKey="Kasehagen L">LJ Kasehagen</name></author><author><name sortKey="Kazura, Jw" uniqKey="Kazura J">JW Kazura</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smith, T" uniqKey="Smith T">T Smith</name></author><author><name sortKey="Genton, B" uniqKey="Genton B">B Genton</name></author><author><name sortKey="Baea, K" uniqKey="Baea K">K Baea</name></author><author><name sortKey="Gibson, N" uniqKey="Gibson N">N Gibson</name></author><author><name sortKey="Narara, A" uniqKey="Narara A">A Narara</name></author><author><name sortKey="Alpers, Mp" uniqKey="Alpers M">MP Alpers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Karl, S" uniqKey="Karl S">S Karl</name></author><author><name sortKey="Laman, M" uniqKey="Laman M">M Laman</name></author><author><name sortKey="Moore, Br" uniqKey="Moore B">BR Moore</name></author><author><name sortKey="Benjamin, Jm" uniqKey="Benjamin J">JM Benjamin</name></author><author><name sortKey="Salib, M" uniqKey="Salib M">M Salib</name></author><author><name sortKey="Lorry, L" uniqKey="Lorry L">L Lorry</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Price, R" uniqKey="Price R">R Price</name></author><author><name sortKey="Nosten, F" uniqKey="Nosten F">F Nosten</name></author><author><name sortKey="Simpson, Ja" uniqKey="Simpson J">JA Simpson</name></author><author><name sortKey="Luxemburger, C" uniqKey="Luxemburger C">C Luxemburger</name></author><author><name sortKey="Phaipun, L" uniqKey="Phaipun L">L Phaipun</name></author><author><name sortKey="Ter Kuile, F" uniqKey="Ter Kuile F">F ter Kuile</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>Papouasie-Nouvelle-Guinée</li><li>Suisse</li></country><region><li>Victoria (État)</li><li>Île-de-France</li></region><settlement><li>Melbourne</li><li>Paris</li></settlement><orgName><li>Université de Melbourne</li></orgName></list><tree><country name="Suisse"><noRegion><name sortKey="Wampfler, Rahel" sort="Wampfler, Rahel" uniqKey="Wampfler R" first="Rahel" last="Wampfler">Rahel Wampfler</name></noRegion><name sortKey="Felger, Ingrid" sort="Felger, Ingrid" uniqKey="Felger I" first="Ingrid" last="Felger">Ingrid Felger</name><name sortKey="Felger, Ingrid" sort="Felger, Ingrid" uniqKey="Felger I" first="Ingrid" last="Felger">Ingrid Felger</name><name sortKey="Hofmann, Natalie E" sort="Hofmann, Natalie E" uniqKey="Hofmann N" first="Natalie E." last="Hofmann">Natalie E. Hofmann</name><name sortKey="Hofmann, Natalie E" sort="Hofmann, Natalie E" uniqKey="Hofmann N" first="Natalie E." last="Hofmann">Natalie E. Hofmann</name><name sortKey="Silkey, Mariabeth" sort="Silkey, Mariabeth" uniqKey="Silkey M" first="Mariabeth" last="Silkey">Mariabeth Silkey</name><name sortKey="Wampfler, Rahel" sort="Wampfler, Rahel" uniqKey="Wampfler R" first="Rahel" last="Wampfler">Rahel Wampfler</name></country><country name="Australie"><noRegion><name sortKey="Karl, Stephan" sort="Karl, Stephan" uniqKey="Karl S" first="Stephan" last="Karl">Stephan Karl</name></noRegion><name sortKey="Karl, Stephan" sort="Karl, Stephan" uniqKey="Karl S" first="Stephan" last="Karl">Stephan Karl</name><name sortKey="Mueller, Ivo" sort="Mueller, Ivo" uniqKey="Mueller I" first="Ivo" last="Mueller">Ivo Mueller</name><name sortKey="Mueller, Ivo" sort="Mueller, Ivo" uniqKey="Mueller I" first="Ivo" last="Mueller">Ivo Mueller</name><name sortKey="Robinson, Leanne J" sort="Robinson, Leanne J" uniqKey="Robinson L" first="Leanne J." last="Robinson">Leanne J. Robinson</name><name sortKey="Robinson, Leanne J" sort="Robinson, Leanne J" uniqKey="Robinson L" first="Leanne J." last="Robinson">Leanne J. Robinson</name><name sortKey="Robinson, Leanne J" sort="Robinson, Leanne J" uniqKey="Robinson L" first="Leanne J." last="Robinson">Leanne J. Robinson</name></country><country name="Papouasie-Nouvelle-Guinée"><noRegion><name sortKey="Betuela, Inoni" sort="Betuela, Inoni" uniqKey="Betuela I" first="Inoni" last="Betuela">Inoni Betuela</name></noRegion><name sortKey="Kinboro, Benson" sort="Kinboro, Benson" uniqKey="Kinboro B" first="Benson" last="Kinboro">Benson Kinboro</name><name sortKey="Lorry, Lina" sort="Lorry, Lina" uniqKey="Lorry L" first="Lina" last="Lorry">Lina Lorry</name><name sortKey="Robinson, Leanne J" sort="Robinson, Leanne J" uniqKey="Robinson L" first="Leanne J." last="Robinson">Leanne J. Robinson</name></country><country name="France"><region name="Île-de-France"><name sortKey="Mueller, Ivo" sort="Mueller, Ivo" uniqKey="Mueller I" first="Ivo" last="Mueller">Ivo Mueller</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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