Lack of prediction of mefloquine and mefloquine-artesunate treatment outcome by mutations in the Plasmodium falciparum multidrug resistance 1 (pfmdr1) gene for P. falciparum malaria in Peru.
We assessed whether mutations in the Plasmodium falciparum multidrug-resistance gene 1 (pfmdr1) (C1034S, D1042N, and Y1246D) would predict treatment outcome during a 28-day in vivo treatment trial in the Peruvian Amazon. Mefloquine (MQ) was compared with mefloquine-artesunate (MQ-AS) in a randomized, multi-clinic protocol for the first time in the Americas. Of 115 patients enrolled in the in vivo arm, 97 patients were eligible for molecular analysis. All 97 patients remained parasite-free during 28 days of follow-up (MQ, n = 46; MQ-AS, n = 51), indicating 100% clinical efficacy of the MQ and MQ-AS treatment regimens. The reported MQ-sensitive alleles (C1034, D1042, and Y1246) were present in 48.5% (n = 47) of the cases, whereas 49 isolates (50.5%) contained the D1246 mutation reported to confer MQ resistance in vitro. However, neither this mutation nor a double mutation (S1034, D1246; n = 16) was predictive of MQ treatment outcome.
Pillai
Dylan R
DR
Tropical Disease Unit, Toronto General Hospital and University of Toronto, Toronto, Ontario, Canada.
Hijar
Gisely
G
Montoya
Ysabel
Y
Marouiño
Wilmer
W
Ruebush
Trenton K
TK
Wongsrichanalai
Chansuda
C
Kain
Kevin C
KC
D018528:ATP-Binding Cassette Transporters; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D037621:Artemisinins / Q000494:pharmacology / Q000627:therapeutic use*; D000077332:Artesunate; D001483:Base Sequence; D015331:Cohort Studies; D016054:DNA, Protozoan / Q000737:chemistry; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D015767:Mefloquine / Q000494:pharmacology / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D009154:Mutation; D010568:Peru; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D011237:Predictive Value of Tests; D015800:Protozoan Proteins / Q000235:genetics*; D016415:Sequence Alignment; D012717:Sesquiterpenes / Q000494:pharmacology / Q000627:therapeutic use*
D018528:ATP-Binding Cassette Transporters; D000962:Antimalarials; D037621:Artemisinins; D016054:DNA, Protozoan; D015800:Protozoan Proteins; D012717:Sesquiterpenes; C059987:mdr gene protein, Plasmodium; D000077332:Artesunate; D015767:Mefloquine