Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Dec;58(12):7032-40.
doi: 10.1128/AAC.03494-14. Epub 2014 Sep 8.

Role of Pfmdr1 in in vitro Plasmodium falciparum susceptibility to chloroquine, quinine, monodesethylamodiaquine, mefloquine, lumefantrine, and dihydroartemisinin

Nathalie Wurtz  1 , Bécaye Fall  2 , Aurélie Pascual  3 , Mansour Fall  4 , Eric Baret  5 , Cheikhou Camara  6 , Aminata Nakoulima  7 , Bakary Diatta  4 , Khadidiatou Ba Fall  8 , Pape Saliou Mbaye  9 , Yaya Diémé  2 , Raymond Bercion  10 , Boubacar Wade  11 , Bruno Pradines  12
Affiliations

Role of Pfmdr1 in in vitro Plasmodium falciparum susceptibility to chloroquine, quinine, monodesethylamodiaquine, mefloquine, lumefantrine, and dihydroartemisinin

Nathalie Wurtz et al. Antimicrob Agents Chemother. 2014 Dec.

Abstract

The involvement of Pfmdr1 (Plasmodium falciparum multidrug resistance 1) polymorphisms in antimalarial drug resistance is still debated. Here, we evaluate the association between polymorphisms in Pfmdr1 (N86Y, Y184F, S1034C, N1042D, and D1246Y) and Pfcrt (K76T) and in vitro responses to chloroquine (CQ), mefloquine (MQ), lumefantrine (LMF), quinine (QN), monodesethylamodiaquine (MDAQ), and dihydroartemisinin (DHA) in 174 Plasmodium falciparum isolates from Dakar, Senegal. The Pfmdr1 86Y mutation was identified in 14.9% of the samples, and the 184F mutation was identified in 71.8% of the isolates. No 1034C, 1042N, or 1246Y mutations were detected. The Pfmdr1 86Y mutation was significantly associated with increased susceptibility to MDAQ (P = 0.0023), LMF (P = 0.0001), DHA (P = 0.0387), and MQ (P = 0.00002). The N86Y mutation was not associated with CQ (P = 0.214) or QN (P = 0.287) responses. The Pfmdr1 184F mutation was not associated with various susceptibility responses to the 6 antimalarial drugs (P = 0.168 for CQ, 0.778 for MDAQ, 0.324 for LMF, 0.961 for DHA, 0.084 for QN, and 0.298 for MQ). The Pfmdr1 86Y-Y184 haplotype was significantly associated with increased susceptibility to MDAQ (P = 0.0136), LMF (P = 0.0019), and MQ (P = 0.0001). The additional Pfmdr1 86Y mutation increased significantly the in vitro susceptibility to MDAQ (P < 0.0001), LMF (P < 0.0001), MQ (P < 0.0001), and QN (P = 0.0026) in wild-type Pfcrt K76 parasites. The additional Pfmdr1 86Y mutation significantly increased the in vitro susceptibility to CQ (P = 0.0179) in Pfcrt 76T CQ-resistant parasites.

PubMed Disclaimer

Figures

FIG 1
FIG 1
Relationship between chloroquine (CQ), quinine (QN), monodesethylamodiaquine (MDAQ), lumefantrine (LMF), mefloquine (MQ), and dihydroartemisinin (DHA) and the Pfmdr1 86 and 184 haplotypes.
See this image and copyright information in PMC

References

    1. Ndiaye JLA, Faye B, Gueye A, Tine R, Ndiaye D, Tchania C, Ndiaye I, Barry A, Cisse B, Lameyre V, Gaye O. 2011. Repeated treatment of recurrent uncomplicated Plasmodium falciparum malaria in Senegal with fixed-dose artesunate plus amodiaquine versus fixed-dose artemether plus lumefantrine: a randomized, open-label trial. Malar. J. 10:237. 10.1186/1475-2875-10-237. - DOI - PMC - PubMed
    1. Thiam S, Thior M, Faye B, Diouf ML, Diouf MB, Diallo I, Fall FB, Ndiaye JL, Albertini A, Lee E, Jorgensen P, Gaye O, Bell D. 2011. Major reduction in anti-malarial drug consumption in Senegal after nation-wide introduction of malaria rapid diagnostic tests. PLoS One 6:18419. 10.1371/journal.pone.0018419. - DOI - PMC - PubMed
    1. Basco LK, Ringwald P. 1998. Molecular epidemiology of malaria in Yaoundé, Cameroon. III. Analysis of chloroquine resistance and point mutations in the multidrug resistance 1 (pfmdr 1) gene of Plasmodium falciparum. Am. J. Trop. Med. Hyg. 59:577–581. - PubMed
    1. Duraisingh MT, Drakeley CJ, Muller O, Bailey R, Snounou G, Targett GA, Greenwood BM, Warhurst DC. 1997. Evidence for selection for the tyrosine-86 allele of the pfmdr 1 gene of Plasmodium falciparum by chloroquine and amodiaquine. Parasitology 114:205–211. 10.1017/S0031182096008487. - DOI - PubMed
    1. Foote SJ, Kyle DE, Martin RK, Oduola AM, Forsyth K, Kemp DJ, Cowman AF. 1990. Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance. Nature 345:255–258. 10.1038/345255a0. - DOI - PubMed

Publication types

MeSH terms

LinkOut - more resources