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Molecular markers of resistance to antimalarial drugs
Adapted from Eboumbou Moukoko EC, Bogreau H, Briolant S, Pradines B, Rogier C. [Molecular markers of Plasmodium falciparum drug resistance]. Med Trop (Mars). 2009  69(6):606-12. French. PMID: 20099681.
Drug Resistance marker PfID Use Allel associated with resistance or decreased drug sensitivity Transcript
4-aminoquinolines
Chloroquine chloroquine resistance transporter PF3D7_0709000
Treatment of non-Plasmodium falciparum malaria K76T
multidrug resistance protein 1. MDR1, IP3 receptor PF3D7_0523000
H191Y and S437A
Amodiaquine multidrug resistance protein 1. MDR1, IP3 receptor PF3D7_0523000
Treatment in combination with artesunate N86Y
multidrug resistance-associated protein 1 MRP1 PF3D7_0112200
H191Y and S437A
multidrug resistance-associated protein 2, MRP2 PF3D7_1229100
H191Y and S437A
Bis-quinoline
Piperaquine Treatment in combination with DHA amplification of plasmepsin 2-3;exo-E415G SNP
Arylamino alcohols
Mefloquine multidrug resistance protein 1. MDR1, IP3 receptor PF3D7_0523000
Treatment or prophylaxis as monotherapy or in combination with artesunate Copy number > 1
Quinine sodium/hydrogen exchanger, Na+, H+ antiporter NHE PF3D7_1303500
Treatment, including severe malaria Number of motifs : DNNND > 2 or NHNDNHNNDDD < 3
multidrug resistance-associated protein 1 MRP1 PF3D7_0112200
H191Y and S437A
multidrug resistance-associated protein 2, MRP2 PF3D7_1229100
H191Y and S437A
Lumefantrine multidrug resistance protein 1. MDR1, IP3 receptor PF3D7_0523000
Treatment in combination with artemether N86Y & Copy number > 1
Mannich base
Pyronaridine chloroquine resistance transporter PF3D7_0709000
Treatment in combination with artesunate pfcrt 76Thr mutation associated with decreased ex vivo sensitivity
Sulfonamide folate antagonist
Sulfadoxine-Pyrimethamine bifunctional dihydrofolate reductase-thymidylate synthase PF3D7_0417200
Treatment in combination with pyrimethamine S108N
bifunctional dihydrofolate reductase-thymidylate synthase PF3D7_0417200
S108N+ N51I+ C59R
hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase PF3D7_0810800
A437G
hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase PF3D7_0810800
A437G+K540E
bifunctional dihydrofolate reductase-thymidylate synthase PF3D7_0417200
S108N+N51I+C59R/      A437G+K540E
hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase PF3D7_0810800
S108N+N51I+C59R/      A437G+K540E
multidrug resistance-associated protein 1 MRP1 PF3D7_0112200
K1466R
multidrug resistance-associated protein 2, MRP2 PF3D7_1229100
K1466R
GTP cyclohydrolase I PF3D7_1224000
used as malaria chemoprophylaxis for pregnant women and children pfgch1 duplication is associated with pfdhfr L164
Sulfadoxine hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase PF3D7_0810800
Treatment in combination with pyrimethamine Step-wise resistance with acquisition of pfdhpsmutations (primarily 437Gly, 540Glu, 581Gly)
Folate antagonists
Proguanil (cycloguanil) bifunctional dihydrofolate reductase-thymidylate synthase PF3D7_0417200
Treatment and prophylaxis, both in combination with proguanil S108T+A16V
bifunctional dihydrofolate reductase-thymidylate synthase PF3D7_0417200
S108N+N51I and/or+C59R
Pyrimethamine bifunctional dihydrofolate reductase-thymidylate synthase PF3D7_0417200
Treatment in combination with sulfadoxine Step-wise resistance with acquisition of pfdhfrmutations (108Asn, 51Ile, 59Arg, and 164Leu)
Quinone
Atovaquone cytochrome b-c1 complex subunit 6, putative PF3D7_1426900
Treatment and prophylaxis, both in combination with proguanil Y268N or Y268S
cytochrome b-c1 complex subunit Rieske, putative PF3D7_1439400
Y268N or Y268S
cytochrome b-c1 complex subunit 7, putative PF3D7_1012300
Y268N or Y268S
Tetracycline antibiotic
Doxycycline tetQ family GTPase, putative PF3D7_1235400
Treatment in combination with quinine; prophylaxis Number of motif KYNNNN < 3
tetQ family GTPase, putative PF3D7_1235400
Copy number > 1
major facilitator superfamily domain-containing protein, putative, MFS1 PF3D7_0516500
Copy number > 1
8-aminoquinolines
Primaquine Unknown Resistance not documented
Piperaquine Chloroquine resistance transporter pfcrt Treatment in combination with DHA Increased plasmepsin-2 copy number; Thr93Ser  and  Ile218Phe; exonuclease gene polymorphism on chromosome
13 (exo-E415G)
Tafenoquine Unknown Elimination of dormant stages P vivax and P ovale; elimination of gametocytes; prophylaxis Resistance not documented
Artemisinins
DHA various Treatment in combination with piperaquine K13PD mutations
Artemether calcium-transporting ATPase, ATP6 PF3D7_0106300
Treatment in combination with lumefantrine S769N, K13PD mutations
Artesunate various Treatment in combination with amodiaquine, mefloquine, or pyronaridine; severe malaria (intravenous) K13PD mutations
Online articles related to Molecular markers of resistance to antimalarial drugs retrieved from PubMed

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