Polymorphisms in Plasmodium falciparum Chloroquine Resistance Transporter and Multidrug Resistance 1 Genes: Parasite Risk Factors that Affect Treatment Outcomes for P. falciparum Malaria after Artemether-Lumefantrine and Artesunate-Amodiaquine

Hdl Handle:
http://hdl.handle.net/10144/326086
Title:
Polymorphisms in Plasmodium falciparum Chloroquine Resistance Transporter and Multidrug Resistance 1 Genes: Parasite Risk Factors that Affect Treatment Outcomes for P. falciparum Malaria after Artemether-Lumefantrine and Artesunate-Amodiaquine
Authors:
Venkatesan, Meera; Gadalla, Nahla B; Stepniewska, Kasia; Dahal, Prabin; Nsanzabana, Christian; Moriera, Clarissa; Price, Ric N; Mårtensson, Andreas; Rosenthal, Philip J; Dorsey, Grant; Sutherland, Colin J; Guérin, Philippe; Davis, Timothy M E; Ménard, Didier; Adam, Ishag; Ademowo, George; Arze, Cesar; Baliraine, Frederick N; Berens-Riha, Nicole; Björkman, Anders; Borrmann, Steffen; Checchi, Francesco; Dhorda, Meghna Desai Mehul; Djimdé, Abdoulaye A; El-Sayed, Badria B; Eshetu, Teferi; Eyase, Frederick; Falade, Catherine; Faucher, Jean-François; Fröberg, Gabrielle; Grivoyannis, Anastasia; Hamour, Sally; Houzé, Sandrine; Johnson, Jacob; Kamugisha, Erasmus; Kariuki, Simon; Kiechel, Jean-René; Kironde, Fred; LeBras, Poul-Erik Kofoed Jacques; Malmberg, Maja; Mwai, Leah; Ngasala, Billy; Nosten, Francois; Nsobya, Samuel L; Oguike, Alexis Nzila Mary; Otienoburu, Sabina Dahlström; Ogutu, Bernhards; Ouédraogo, Jean-Bosco; Piola, Patrice; Rombo, Lars; Schramm, Birgit; Somé, A Fabrice; Thwing, Julie; Ursing, Johan; Wong, Rina P M; Zeynudin, Ahmed; Zongo, Issaka; Plowe, Christopher V; Sibley, Carol Hopkins
Journal:
The American Journal of Tropical Medicine and Hygiene
Abstract:
Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 - 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36-17.97, P < 0.001: were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine.
Issue Date:
21-Jul-2014
URI:
http://hdl.handle.net/10144/326086
DOI:
10.4269/ajtmh.14-0031
PubMed ID:
25048375
Additional Links:
http://www.ajtmh.org
Language:
en
ISSN:
1476-1645
Appears in Collections:
Malaria

Full metadata record

DC FieldValue Language
dc.contributor.authorVenkatesan, Meeraen_GB
dc.contributor.authorGadalla, Nahla Ben_GB
dc.contributor.authorStepniewska, Kasiaen_GB
dc.contributor.authorDahal, Prabinen_GB
dc.contributor.authorNsanzabana, Christianen_GB
dc.contributor.authorMoriera, Clarissaen_GB
dc.contributor.authorPrice, Ric Nen_GB
dc.contributor.authorMårtensson, Andreasen_GB
dc.contributor.authorRosenthal, Philip Jen_GB
dc.contributor.authorDorsey, Granten_GB
dc.contributor.authorSutherland, Colin Jen_GB
dc.contributor.authorGuérin, Philippeen_GB
dc.contributor.authorDavis, Timothy M Een_GB
dc.contributor.authorMénard, Didieren_GB
dc.contributor.authorAdam, Ishagen_GB
dc.contributor.authorAdemowo, Georgeen_GB
dc.contributor.authorArze, Cesaren_GB
dc.contributor.authorBaliraine, Frederick Nen_GB
dc.contributor.authorBerens-Riha, Nicoleen_GB
dc.contributor.authorBjörkman, Andersen_GB
dc.contributor.authorBorrmann, Steffenen_GB
dc.contributor.authorChecchi, Francescoen_GB
dc.contributor.authorDhorda, Meghna Desai Mehulen_GB
dc.contributor.authorDjimdé, Abdoulaye Aen_GB
dc.contributor.authorEl-Sayed, Badria Ben_GB
dc.contributor.authorEshetu, Teferien_GB
dc.contributor.authorEyase, Fredericken_GB
dc.contributor.authorFalade, Catherineen_GB
dc.contributor.authorFaucher, Jean-Françoisen_GB
dc.contributor.authorFröberg, Gabrielleen_GB
dc.contributor.authorGrivoyannis, Anastasiaen_GB
dc.contributor.authorHamour, Sallyen_GB
dc.contributor.authorHouzé, Sandrineen_GB
dc.contributor.authorJohnson, Jacoben_GB
dc.contributor.authorKamugisha, Erasmusen_GB
dc.contributor.authorKariuki, Simonen_GB
dc.contributor.authorKiechel, Jean-Renéen_GB
dc.contributor.authorKironde, Freden_GB
dc.contributor.authorLeBras, Poul-Erik Kofoed Jacquesen_GB
dc.contributor.authorMalmberg, Majaen_GB
dc.contributor.authorMwai, Leahen_GB
dc.contributor.authorNgasala, Billyen_GB
dc.contributor.authorNosten, Francoisen_GB
dc.contributor.authorNsobya, Samuel Len_GB
dc.contributor.authorOguike, Alexis Nzila Maryen_GB
dc.contributor.authorOtienoburu, Sabina Dahlströmen_GB
dc.contributor.authorOgutu, Bernhardsen_GB
dc.contributor.authorOuédraogo, Jean-Boscoen_GB
dc.contributor.authorPiola, Patriceen_GB
dc.contributor.authorRombo, Larsen_GB
dc.contributor.authorSchramm, Birgiten_GB
dc.contributor.authorSomé, A Fabriceen_GB
dc.contributor.authorThwing, Julieen_GB
dc.contributor.authorUrsing, Johanen_GB
dc.contributor.authorWong, Rina P Men_GB
dc.contributor.authorZeynudin, Ahmeden_GB
dc.contributor.authorZongo, Issakaen_GB
dc.contributor.authorPlowe, Christopher Ven_GB
dc.contributor.authorSibley, Carol Hopkinsen_GB
dc.date.accessioned2014-09-11T21:49:44Z-
dc.date.available2014-09-11T21:49:44Z-
dc.date.issued2014-07-21-
dc.identifier.citationPolymorphisms in Plasmodium falciparum Chloroquine Resistance Transporter and Multidrug Resistance 1 Genes: Parasite Risk Factors that Affect Treatment Outcomes for P. falciparum Malaria after Artemether-Lumefantrine and Artesunate-Amodiaquine. 2014: Am. J. Trop. Med. Hyg.en_GB
dc.identifier.issn1476-1645-
dc.identifier.pmid25048375-
dc.identifier.doi10.4269/ajtmh.14-0031-
dc.identifier.urihttp://hdl.handle.net/10144/326086-
dc.description.abstractAdequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 - 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36-17.97, P < 0.001: were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine.en_GB
dc.languageENG-
dc.language.isoenen
dc.relation.urlhttp://www.ajtmh.orgen_GB
dc.rightsArchived with thanks to The American Journal of Tropical Medicine and Hygieneen_GB
dc.subjectMalariaen_GB
dc.titlePolymorphisms in Plasmodium falciparum Chloroquine Resistance Transporter and Multidrug Resistance 1 Genes: Parasite Risk Factors that Affect Treatment Outcomes for P. falciparum Malaria after Artemether-Lumefantrine and Artesunate-Amodiaquineen
dc.identifier.journalThe American Journal of Tropical Medicine and Hygieneen_GB

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