High prevalence of pfcrt K76t mutants among Plasmodium falciparum isolates from Sabah, Malaysia.
Chloroquine (CQ) remains the first line drug for the prevention and treatment of malaria in Malaysia in spite of the fact that resistance to CQ has been observed in Malaysia since the 1960s. CQ-resistance is associated with various mutations in pfcrt, which encodes a putative transporter located in the digestive vacuolar membrane of P. falciparum. Substitution of lysine (K) to threonine (T) at amino acid 76 (K76T) in pfcrt is the primary genetic marker conferring resistance to CQ. To determine the presence of T76 mutation in pfcrt from selected areas of Kalabakan, Malaysia 619 blood samples were screened for P. falciparum, out of which 31 were positive. Blood samples were collected on 3 MM Whatman filter papers and DNA was extracted using QIAmp DNA mini kit. RFLP-PCR for the detection of the CQ-resistant T76 and sensitive K76 genotype was carried out. Twenty-five samples were shown to have the point mutation in pfcrt whereas the remaining samples were classified as CQ-sensitive (wild-type). In view of the fact that CQ is the first line anti-malarial drug in Malaysia, this finding could be an important indication that treatment with CQ may no longer be effective in the future.
Herbal Medicine Research Center, Institute for Medical Research, Kuala Lumpur, Malaysia.
Nor Azrina
NA
Norahmad
Noor Rain
NR
Abdullah
Norhayati
N
Yaccob
Jenarun
J
Jelip
Jiloris F
JF
Dony
Khairul Faiz
KF
Ruslan
Lokman Hakim
LH
Sulaiman
Hasidah Mohd
HM
Sidek
Harald
H
Noedl
Zakiah
Z
Ismail
D000962:Antimalarials / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics; D017125:Genes, Protozoan / Q000235:genetics*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000235:genetics* / Q000469:parasitology; D008296:Malaysia; D026901:Membrane Transport Proteins / Q000235:genetics*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D009154:Mutation; D010963:Plasmodium falciparum / Q000235:genetics* / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D015995:Prevalence; D015800:Protozoan Proteins / Q000235:genetics*
D000962:Antimalarials; D002738:Chloroquine; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; C416369:PfCRT protein, Plasmodium falciparum