Diagnostic value of molecular markers in chloroquine-resistant falciparum malaria in Southern Mauritania.
Despite its diminishing efficacy because of increased resistance, chloroquine remains the primary antimalarial agent in many endemic areas. Evidence is mounting that point mutations on the Pfcrt and possibly the Pfmdr1 genes are conferring plasmodial resistance to chloroquine. In 1998, atypically strong rainfalls led to an increased activity of falciparum malaria in Mauritania that affected non-endemic regions bordering the Saharan desert. An in vivo study on chloroqine resistance was combined with studies for molecular markers of drug resistance. Detection of Pfmdr1-76-tyrosine showed an increased odds ratio (2.91) for resistance (P = 0.0195). However, by use of this codon alone, sensitivity for detection of resistance was 60.6%, and specificity was 65.3%. In comparison, detection of the K76T mutation at Pfcrt showed a very high sensitivity (100%) while specificity remained relatively low (65.4%). For the combination of mutations on both genes, the odds ratio for detection of resistance increased to 5.31 (P = 0.0005). Here, sensitivity was again decreased to 60.6% while specificity increased to 76.9%. The results of this study suggest that detection of Pfcrt T76 can be applied for predicting chloroquine resistance in epidemiologic settings with sufficiently high sensitivity to make it an attractive alternative to time- and labor-consuming in vivo trials. Additional testing for Pfmdr Y76 provides increased specificity to this approach.
Jelinek
T
T
Department of Infectious Diseases and Tropical Medicine, University of Munich, Munich, Germany. jelinek@lrz.uni-muenchen.de
Aida
A O
AO
Peyerl-Hoffmann
G
G
Jordan
S
S
Mayor
A
A
Heuschkel
C
C
el Valy
A O
AO
von Sonnenburg
F
F
Christophel
E M
EM
D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002738:Chloroquine / Q000494:pharmacology* / Q000627:therapeutic use; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D016778:Malaria, Falciparum / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology*; D008297:Male; D008435:Mauritania / Q000453:epidemiology; D009154:Mutation; D016017:Odds Ratio; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D011739:Pyrimethamine / Q000494:pharmacology / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D013413:Sulfadoxine / Q000494:pharmacology / Q000627:therapeutic use
D000962:Antimalarials; D004338:Drug Combinations; D005819:Genetic Markers; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine