» Articles » PMID: 21881128

Prolonged Selection of Pfmdr1 Polymorphisms After Treatment of Falciparum Malaria with Artemether-lumefantrine in Uganda

Overview
Journal J Infect Dis
Date 2011 Sep 2
PMID 21881128
Citations 53
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

Rebound of multiple infections and prevalence of anti-malarial resistance associated markers following malaria upsurges in Dielmo village, Senegal, West Africa.

Wotodjo A, Oboh M, Doucoure S, Diagne N, Diene-Sarr F, Niang M Malar J. 2023; 22(1):257.

PMID: 37670357 PMC: 10478411. DOI: 10.1186/s12936-023-04694-0.


Drug resistance of Plasmodium falciparum and Plasmodium vivax isolates in Indonesia.

Rahmasari F, Asih P, Dewayanti F, Rotejanaprasert C, Charunwatthana P, Imwong M Malar J. 2022; 21(1):354.

PMID: 36443817 PMC: 9703442. DOI: 10.1186/s12936-022-04385-2.


susceptibility profile of clinical isolates from Ghana to antimalarial drugs and polymorphisms in resistance markers.

Zhao W, Li X, Yang Q, Zhou L, Duan M, Pan M Front Cell Infect Microbiol. 2022; 12:1015957.

PMID: 36310880 PMC: 9614232. DOI: 10.3389/fcimb.2022.1015957.


Temporal trends in molecular markers of drug resistance in Plasmodium falciparum in human blood and profiles of corresponding resistant markers in mosquito oocysts in Asembo, western Kenya.

Zhou Z, Gimnig J, Sergent S, Liu Y, Abongo B, Otieno K Malar J. 2022; 21(1):265.

PMID: 36100912 PMC: 9472345. DOI: 10.1186/s12936-022-04284-6.


Plasmodium falciparum merozoite invasion ligands, linked antimalarial resistance loci and ex vivo responses to antimalarials in The Gambia.

Mbye H, Mane K, Diop M, Demba M, Bojang F, Mohammed N J Antimicrob Chemother. 2022; 77(11):2946-2955.

PMID: 35904009 PMC: 9616547. DOI: 10.1093/jac/dkac244.


References
1.
Clark T, Njama-Meya D, Nzarubara B, Maiteki-Sebuguzi C, Greenhouse B, Staedke S . Incidence of malaria and efficacy of combination antimalarial therapies over 4 years in an urban cohort of Ugandan children. PLoS One. 2010; 5(7):e11759. PMC: 2912768. DOI: 10.1371/journal.pone.0011759. View

2.
Valderramos S, Fidock D . Transporters involved in resistance to antimalarial drugs. Trends Pharmacol Sci. 2006; 27(11):594-601. PMC: 2944664. DOI: 10.1016/j.tips.2006.09.005. View

3.
Duraisingh M, Jones P, Sambou I, von Seidlein L, Pinder M, Warhurst D . The tyrosine-86 allele of the pfmdr1 gene of Plasmodium falciparum is associated with increased sensitivity to the anti-malarials mefloquine and artemisinin. Mol Biochem Parasitol. 2000; 108(1):13-23. DOI: 10.1016/s0166-6851(00)00201-2. View

4.
Stepniewska K, White N . Pharmacokinetic determinants of the window of selection for antimalarial drug resistance. Antimicrob Agents Chemother. 2008; 52(5):1589-96. PMC: 2346628. DOI: 10.1128/AAC.00903-07. View

5.
Happi C, Gbotosho G, Folarin O, Sowunmi A, Hudson T, ONeil M . Selection of Plasmodium falciparum multidrug resistance gene 1 alleles in asexual stages and gametocytes by artemether-lumefantrine in Nigerian children with uncomplicated falciparum malaria. Antimicrob Agents Chemother. 2008; 53(3):888-95. PMC: 2650543. DOI: 10.1128/AAC.00968-08. View