Prolonged selection of pfmdr1 polymorphisms after treatment of falciparum malaria with artemether-lumefantrine in Uganda
- PMID: 21881128
- PMCID: PMC3164433
- DOI: 10.1093/infdis/jir486
Prolonged selection of pfmdr1 polymorphisms after treatment of falciparum malaria with artemether-lumefantrine in Uganda
Abstract
We compared the prevalence of key pfmdr1 alleles between pretreatment Plasmodium falciparum parasite isolates and parasites that emerged after treatment of uncomplicated malaria in a longitudinal cohort of Ugandan children. The pfmdr1 86N, 184F, and 1246D alleles were selected after treatment with artemether-lumefantrine, but not after artesunate-amodiaquine or amodiaquine-sulfadoxine-pyrimethamine. Remarkably, selection persisted in infections presenting up to about 60 days after treatment with artemether-lumefantrine. Thus, parasites selected for decreased drug sensitivity can appear long after predicted exposure to antimalarial drugs. Continued surveillance of the clinical efficacy and in vitro activity of new combination therapies is warranted.
Figures

Comment in
-
Dynamics of Plasmodium falciparum selection after artemether-lumefantrine treatment in Africa.J Infect Dis. 2012 May 1;205(9):1473-5; author reply 1475-6. doi: 10.1093/infdis/jis227. Epub 2012 Mar 27. J Infect Dis. 2012. PMID: 22454466 No abstract available.
Similar articles
-
Impact of treatment and re-treatment with artemether-lumefantrine and artesunate-amodiaquine on selection of Plasmodium falciparum multidrug resistance gene-1 polymorphisms in the Democratic Republic of Congo and Uganda.PLoS One. 2018 Feb 1;13(2):e0191922. doi: 10.1371/journal.pone.0191922. eCollection 2018. PLoS One. 2018. PMID: 29390014 Free PMC article. Clinical Trial.
-
Selection of parasites with diminished drug susceptibility by amodiaquine-containing antimalarial regimens in Uganda.J Infect Dis. 2009 Dec 1;200(11):1650-7. doi: 10.1086/647988. J Infect Dis. 2009. PMID: 19905933 Free PMC article. Clinical Trial.
-
High efficacy of artemether-lumefantrine and declining efficacy of artesunate + sulfadoxine-pyrimethamine against Plasmodium falciparum in Sudan (2010-2015): evidence from in vivo and molecular marker studies.Malar J. 2016 May 21;15(1):285. doi: 10.1186/s12936-016-1339-x. Malar J. 2016. PMID: 27209063 Free PMC article.
-
[Combined antimalarial therapy using artemisinin].Parassitologia. 2004 Jun;46(1-2):85-7. Parassitologia. 2004. PMID: 15305693 Review. Italian.
-
Pharmacokinetic profile of artemisinin derivatives and companion drugs used in artemisinin-based combination therapies for the treatment of Plasmodium falciparum malaria in children.Clin Pharmacokinet. 2013 Mar;52(3):153-67. doi: 10.1007/s40262-012-0026-5. Clin Pharmacokinet. 2013. PMID: 23288505 Review.
Cited by
-
Differential Prevalences of Pfmdr1 Polymorphisms in Symptomatic and Asymptomatic Plasmodium falciparum Infections in Lastoursville: A Rural Area in East-Central Gabon.Infect Drug Resist. 2021 Jul 24;14:2873-2882. doi: 10.2147/IDR.S304361. eCollection 2021. Infect Drug Resist. 2021. PMID: 34335033 Free PMC article.
-
Role of Pfmdr1 in in vitro Plasmodium falciparum susceptibility to chloroquine, quinine, monodesethylamodiaquine, mefloquine, lumefantrine, and dihydroartemisinin.Antimicrob Agents Chemother. 2014 Dec;58(12):7032-40. doi: 10.1128/AAC.03494-14. Epub 2014 Sep 8. Antimicrob Agents Chemother. 2014. PMID: 25199781 Free PMC article.
-
Impact of antimalarial treatment and chemoprevention on the drug sensitivity of malaria parasites isolated from ugandan children.Antimicrob Agents Chemother. 2015;59(6):3018-30. doi: 10.1128/AAC.05141-14. Epub 2015 Mar 9. Antimicrob Agents Chemother. 2015. PMID: 25753626 Free PMC article.
-
CYP2B6*6 genotype and high efavirenz plasma concentration but not nevirapine are associated with low lumefantrine plasma exposure and poor treatment response in HIV-malaria-coinfected patients.Pharmacogenomics J. 2016 Feb;16(1):88-95. doi: 10.1038/tpj.2015.37. Epub 2015 May 12. Pharmacogenomics J. 2016. PMID: 25963334
-
Fitness Consequences of Plasmodium falciparum pfmdr1 Polymorphisms Inferred from Ex Vivo Culture of Ugandan Parasites.Antimicrob Agents Chemother. 2013 Sep;57(9):4245-4251. doi: 10.1128/AAC.00161-13. Epub 2013 Jun 24. Antimicrob Agents Chemother. 2013. PMID: 23796921 Free PMC article.