title: Recovery of chloroquine sensitivity and low prevalence of the Plasmodium falciparum chloroquine resistance transporter gene mutation K76T following the discontinuance of chloroquine use in Malawi.
abstract: In 1993, Malawi stopped treating patients with chloroquine for Plasmodium falciparum malaria because of a high treatment failure rate (58%). In 1998, the in vitro resistance rate to chloroquine was 3% in the Salima District of Malawi; in 2000, the in vivo resistance rate was 9%. We assayed two genetic mutations implicated in chloroquine resistance (N86Y in the P. falciparum multiple drug resistance gene 1 and K76T in the P. falciparum chloroquine resistance transporter gene) in 82 P. falciparum isolates collected during studies in 1998 and 2000. The prevalence of N86Y remained similar to that in neighboring African countries that continued to use chloroquine. In contrast, the prevalence of K76T was substantially lower than in neighboring countries, decreasing significantly from 17% in 1998 to 2% in 2000 (P < 0.02). However, neither mutation was significantly associated with in vivo or in vitro resistance (P > 0.29). Withdrawal of the use of chloroquine appears to have resulted in the recovery of chloroquine efficacy and a reduction in the prevalence of K76T. However, other polymorphisms are also expected to contribute to resistance.
authors.affiliation: Department of International Affairs and Tropical Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan. hiro-tm@research.twmu.ac.jp
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Mita
authors.forename: Akira
authors.initials: A
authors.lastname: Kaneko
authors.forename: J Koji
authors.initials: JK
authors.lastname: Lum
authors.forename: Bwijo
authors.initials: B
authors.lastname: Bwijo
authors.forename: Miho
authors.initials: M
authors.lastname: Takechi
authors.forename: Innocent L
authors.initials: IL
authors.lastname: Zungu
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tsukahara
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tanabe
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Kobayakawa
authors.forename: Anders
authors.initials: A
authors.lastname: Björkman
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000293:Adolescent; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000494:pharmacology* / Q000627:therapeutic use; D004351:Drug Resistance / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008295:Malawi; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D017354:Point Mutation; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics
chemical_list: D018528:ATP-Binding Cassette Transporters; D000962:Antimalarials; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; C059987:mdr gene protein, Plasmodium; D002738:Chloroquine