A molecular epidemiologic study of point mutations for pyrimethamine-sulfadoxine resistance of Plasmodium falciparum isolates from Lao PDR.
To understand the current condition of pyrimethamine-sulfadoxine (PS) resistant falciparum malaria in Lao PDR, the frequency of point mutations in dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes of Plasmodium falciparum were examined in 50 blood samples collected from the patients with P. falciparum infection in Southern Lao PDR. Point mutations in 5 codons of the DHFR gene, which is known to be related to pyrimethamine resistance, were detected in 15 out of the 50 samples (30%). Among the 15 samples, 10 samples showed a double mutation of codons 59 and 108 (Cys59Arg with Ser108Asn). In the remaining 5 samples, an additional mutation was observed in codon 51 (Asn51 lle), providing a triple mutation of codons 51, 59 and 108. On the other hand, point mutations in the 4 codons of DHPS gene related to sulfadoxine resistance were observed only in 2 samples (4.0%), namely in codon 437 (Ala437Gly). Only one sample showed mutations in both DHFR and DHPS genes. From the results, it should be considered that the frequency of PS resistant malaria is still low in Lao PDR. Continuous monitoring for the PS resistant malaria, however, is necessary because of the increasing use of PS in this country.
Toma
Hiromu
H
Division of Tropical Parasitology, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan. htoma@med.u-ryukyu.ac.jp
Imada
Yumi
Y
Vannachone
Bouakham
B
Miyagi
Mio
M
Kobayashi
Jun
J
Uechi
Gen-Ichiro
G
Pethuvang
Rattanasay
R
Manivong
Khemphavanh
K
Phompida
Samlane
S
Sato
Yoshiya
Y
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D003062:Codon; D004094:Dihydropteroate Synthase / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics*; D006801:Humans; D007812:Laos; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D017720:Molecular Epidemiology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011739:Pyrimethamine / Q000494:pharmacology*; D013413:Sulfadoxine / Q000494:pharmacology*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
D000962:Antimalarials; D003062:Codon; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine