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  • Venkatesan, Meera (author)

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.

  • Article/chapterEnglish2014

Publisher, publication year, extent ...

  • American Society of Tropical Medicine and Hygiene,2014
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-245321
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-245321URI
  • https://doi.org/10.4269/ajtmh.14-0031DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:129864897URI

Supplementary language notes

  • Language:English
  • Summary in:English

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Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

Added entries (persons, corporate bodies, meetings, titles ...)

  • Gadalla, Nahla B (author)
  • Stepniewska, Kasia (author)
  • Dahal, Prabin (author)
  • Nsanzabana, Christian (author)
  • Moriera, Clarissa (author)
  • Price, Ric N (author)
  • Mårtensson, AndreasKarolinska Institutet,Uppsala universitet,Centrum för klinisk forskning i Sörmland (CKFD)(Swepub:uu)andma331 (author)
  • Rosenthal, Philip J (author)
  • Dorsey, Grant (author)
  • Sutherland, Colin J (author)
  • Guérin, Philippe (author)
  • Davis, Timothy M E (author)
  • Ménard, Didier (author)
  • Adam, Ishag (author)
  • Ademowo, George (author)
  • Arze, Cesar (author)
  • Baliraine, Frederick N (author)
  • Berens-Riha, Nicole (author)
  • Björkman, AndersKarolinska Institutet (author)
  • Borrmann, Steffen (author)
  • Checchi, Francesco (author)
  • Desai, Meghna (author)
  • Dhorda, Mehul (author)
  • Djimdé, Abdoulaye A (author)
  • El-Sayed, Badria B (author)
  • Eshetu, Teferi (author)
  • Eyase, Frederick (author)
  • Falade, Catherine (author)
  • Faucher, Jean-François (author)
  • Fröberg, GabrielleKarolinska Institutet (author)
  • Grivoyannis, Anastasia (author)
  • Hamour, Sally (author)
  • Houzé, Sandrine (author)
  • Johnson, JacobKarolinska Institutet (author)
  • Kamugisha, Erasmus (author)
  • Kariuki, Simon (author)
  • Kiechel, Jean-René (author)
  • Kironde, Fred (author)
  • Kofoed, Poul-Erik (author)
  • LeBras, Jacques (author)
  • Malmberg, Maja (author)
  • Mwai, Leah (author)
  • Ngasala, Billy (author)
  • Nosten, Francois (author)
  • Nsobya, Samuel L (author)
  • Nzila, Alexis (author)
  • Oguike, Mary (author)
  • Otienoburu, Sabina Dahlström (author)
  • Ogutu, Bernhards (author)
  • Ouédraogo, Jean-Bosco (author)
  • Piola, Patrice (author)
  • Rombo, LarsUppsala universitet,Centrum för klinisk forskning i Sörmland (CKFD)(Swepub:uu)larra728 (author)
  • Schramm, Birgit (author)
  • Somé, A Fabrice (author)
  • Thwing, Julie (author)
  • Ursing, Johan (author)
  • Wong, Rina P M (author)
  • Zeynudin, Ahmed (author)
  • Zongo, Issaka (author)
  • Plowe, Christopher V (author)
  • Sibley, Carol Hopkins (author)
  • Uppsala universitetCentrum för klinisk forskning i Sörmland (CKFD) (creator_code:org_t)

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  • In:The American journal of tropical medicine and hygiene: American Society of Tropical Medicine and Hygiene91:4, s. 833-431476-16450002-9637

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