title: Correlation of in vivo-resistance to chloroquine and allelic polymorphisms in Plasmodium falciparum isolates from Uganda.
abstract: The efficacy of chloroquine in the treatment of uncomplicated falciparum malaria in Africa is heavily compromised by high levels of drug resistance. The occurrence of active site mutations in the Plasmodium falciparum multi drug resistance-gene 1 (pfmdr1) has been associated with development of resistance to chloroquine. This study investigates the occurrence of several mutations at codons 86, 1042 and 1246 of the pfmdr1-gene in infected blood samples taken from Ugandan children before treatment with chloroquine and their relationship to clinical and parasitological resistance. Even though a clear association of CQR to one certain pfmdr1 single point mutation could not be substantiated, the frequency of resistance was consistently higher for samples revealing any of the mutations than among wild type samples, and 90% of the clinically resistant samples did present a mutation. Thus detection of these allelic pfmdr1 polymorphisms is not a decisive factor for prediction of clinical chloroquine resistance, but an interplay of the different mutations with unknown cofactors is to be assumed and the possible role of other genetic alterations remains to be investigated.
authors.affiliation: Department of Infectious Diseases and Tropical Medicine, University of Munich, Munich, Germany.
authors.forename: T P
authors.initials: TP
authors.lastname: Flüeck
authors.forename: T
authors.initials: T
authors.lastname: Jelinek
authors.forename: A H
authors.initials: AH
authors.lastname: Kilian
authors.forename: I S
authors.initials: IS
authors.lastname: Adagu
authors.forename: G
authors.initials: G
authors.lastname: Kabagambe
authors.forename: F
authors.initials: F
authors.lastname: Sonnenburg
authors.forename: D C
authors.initials: DC
authors.lastname: Warhurst
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000483:Alleles; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002738:Chloroquine / Q000494:pharmacology* / Q000627:therapeutic use; D004351:Drug Resistance / Q000235:genetics; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D017354:Point Mutation; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics*; D014454:Uganda
chemical_list: D018528:ATP-Binding Cassette Transporters; D000962:Antimalarials; D015800:Protozoan Proteins; C059987:mdr gene protein, Plasmodium; D002738:Chloroquine