title: Molecular markers for chloroquine-resistant Plasmodium falciparum malaria in Thailand and Laos.
abstract: Chloroquine-resistant Plasmodium falciparum is well documented in Thailand. Laos, however, continues to use chloroquine (CQ) as the first-line therapy for the treatment of P. falciparum malaria. The objective of the present study was to determine the prevalence, in these two areas, of the cg2, pfmdr1 and pfcrt allelic types that have previously been associated with CQ resistance. Isolates of P. falciparum were collected from participants in ongoing treatment studies conducted in Thailand (near the Thai-Cambodian border) and in Laos (Vang Vieng district). The pfmdr1 and pfcrt alleles were characterized by PCR-RFLP and mutations in cg2 were characterized by PCR and single-stranded-conformation-polymorphism (SSCP) electrophoresis. Eight (32%) of the 25 Laotian isolates but only one (4%) of the 25 Thai isolates were found to contain the pfmdr1 mutation N86Y (P = 0.02). In contrast, the cg2 polymorphisms previously associated with CQ resistance were present in only 10 of the isolates from Laos but 24 of those from Thailand (40% v. 96%; P < 0.001). All the samples from both countries contained the pfcrt K76T mutant allele reported to confer resistance to CQ. The results may indicate that drug pressure for the maintenance of the pfmdr1 and cg2 alleles varies in intensity in the Thai and Laotian study areas, probably reflecting differences in the national malaria-treatment policies of Thailand and Laos.
authors.affiliation: Tropical Disease Unit, Division of Infectious Diseases, Department of Medicine, University of Toronto, Canada.
authors.forename: A C
authors.initials: AC
authors.lastname: Labbé
authors.forename: P
authors.initials: P
authors.lastname: Bualombai
authors.forename: D R
authors.initials: DR
authors.lastname: Pillai
authors.forename: K J
authors.initials: KJ
authors.lastname: Zhong
authors.forename: V
authors.initials: V
authors.lastname: Vanisaveth
authors.forename: B
authors.initials: B
authors.lastname: Hongvanthong
authors.forename: S
authors.initials: S
authors.lastname: Looareesuwan
authors.forename: K C
authors.initials: KC
authors.lastname: Kain
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics; D005819:Genetic Markers; D006801:Humans; D007812:Laos; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology*; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D015800:Protozoan Proteins / Q000235:genetics; D013785:Thailand
chemical_list: D018528:ATP-Binding Cassette Transporters; D000962:Antimalarials; C109422:CG2 protein, Plasmodium falciparum; D005819:Genetic Markers; D015800:Protozoan Proteins; C059987:mdr gene protein, Plasmodium; D002738:Chloroquine