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) |
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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 | ||||||||||||||||||||||||