title: Plasmodium falciparum genotypes associated with chloroquine and amodiaquine resistance in Guinea-Bissau.
abstract: Chloroquine is the most commonly used antimalarial in Guinea-Bissau and high doses are routinely prescribed. Blood from 497 patients treated with different doses of chloroquine or amodiaquine were genotyped. Pfcrt and pfmdr1 polymorphisms were identified. Pfmsp2 analysis identified recrudescent infections. The pfcrt 72-76 haplotypes were CVIET and CVMNK. The pfcrt 76T prevalence was 23% at day 0 and 96%, 83% and 100% at recrudescence following treatment with 25 mg/kg and 50 mg/kg of chloroquine and 15 mg/kg of amodiaquine respectively. When treating pfcrt 76T carrying P. falciparum the efficacy of 50 mg/kg and 25 mg/kg of chloroquine was 78% and 34% respectively (P = 0.007). The genetic basis of chloroquine resistance is probably the same in Guinea-Bissau as in the rest of Africa. The low pfcrt 76T prevalence suggests that resistance to normal dose chloroquine does not confer a major advantage to falciparum in Bissau and could be a result of treatment with high-dose chloroquine.
authors.affiliation: Malaria Research Unit, Department of Infectious Diseases, Division of Medicine, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden. johan.ursing@ki.se
authors.forename: Johan
authors.initials: J
authors.lastname: Ursing
authors.forename: Poul-Erik
authors.initials: PE
authors.lastname: Kofoed
authors.forename: Amabelia
authors.initials: A
authors.lastname: Rodrigues
authors.forename: Lars
authors.initials: L
authors.lastname: Rombo
authors.forename: José Pedro
authors.initials: JP
authors.lastname: Gil
mesh_terms: D000293:Adolescent; D000655:Amodiaquine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000008:administration & dosage / Q000494:pharmacology; D004351:Drug Resistance; D005260:Female; D005838:Genotype; D006169:Guinea-Bissau; D006801:Humans; D015810:Linkage Disequilibrium; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D010963:Plasmodium falciparum / Q000145:classification / Q000187:drug effects / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D015800:Protozoan Proteins / Q000235:genetics*; D013997:Time Factors
chemical_list: D000655:Amodiaquine; D000962:Antimalarials; D002738:Chloroquine; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum