title: Plasmodium falciparum: correlation of in vivo resistance to chloroquine and antifolates with genetic polymorphisms in isolates from the south of Lao PDR.
abstract: Levels of drug resistance of Plasmodium falciparum strains against antimalarials have increased in Laos. In several studies, chloroquine (CQ) resistance has been associated with point mutations in the Pfcrt and pfmdr genes, and sulphadoxine/pyrimethamine (S/P) resistance with point mutations in the genes of dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS). We combined a study of these molecular markers with an in vivo antimalarial drug sensitivity study in Attapeu province in the south of Lao PDR. We treated 100 patients with either CQ, S/P or a combination of both. In the CQ group, Pfcrt mutations showed a very high sensitivity (100%) but a low specificity (12.5%) to predict resistance. The combination of mutations in the Pfcrt and pfmdr genes was highly specific and had a positive predictive value of 100%. Mutations in the DHPS gene showed a high correlation with the development of resistance. The prevalence of mutations in the DHFR gene, especially codon 108 Asn, was predictive with high sensitivity (100%) but low specificity. Isolates derived from patients treated with a combination of both drugs showed a high correlation between the mutation in codon 437 of DHPS gene and in vivo-resistance (odds ratio 16.00, CI). The study provides evidence for the existence of antimalarial drug resistance in the south of Lao PDR, and offers a molecular method to predict resistance.
authors.affiliation: Department of Infectious Diseases and Tropical Medicine, University of Munich, Munich, Germany. Nicole.berens@gmx.net
authors.forename: Nicole
authors.initials: N
authors.lastname: Berens
authors.forename: Babett
authors.initials: B
authors.lastname: Schwoebel
authors.forename: Sabine
authors.initials: S
authors.lastname: Jordan
authors.forename: Viengxay
authors.initials: V
authors.lastname: Vanisaveth
authors.forename: Rattanaxay
authors.initials: R
authors.lastname: Phetsouvanh
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Christophel
authors.forename: Samlane
authors.initials: S
authors.lastname: Phompida
authors.forename: Tomas
authors.initials: T
authors.lastname: Jelinek
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000627:therapeutic use*; D004338:Drug Combinations; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005493:Folic Acid Antagonists / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D007812:Laos; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D011739:Pyrimethamine / Q000627:therapeutic use*; D012680:Sensitivity and Specificity; D013413:Sulfadoxine / Q000627:therapeutic use*
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D005493:Folic Acid Antagonists; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine