Diagnostic value of molecular markers in chloroquine-resistant falciparum malaria in Southern Mauritania
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Diagnostic value of molecular markers in chloroquine-resistant falciparum malaria in Southern Mauritania. / Jelinek, T; Infectious Diseases and Tropical Medicine, University of Munich, Department; Infectious Diseases and Tropical Medicine, University of Munich, Department; Infectious Diseases and Tropical Medicine, University of Munich, Department; Infectious Diseases and Tropical Medicine, University of Munich, Department; Infectious Diseases and Tropical Medicine, University of Munich, Department; Infectious Diseases and Tropical Medicine, University of Munich, Department; Infectious Diseases and Tropical Medicine, University of Munich, Department; Infectious Diseases and Tropical Medicine, University of Munich, Department.
in: AM J TROP MED HYG, Jahrgang 67, Nr. 5, 11.2002, S. 449-53.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Diagnostic value of molecular markers in chloroquine-resistant falciparum malaria in Southern Mauritania
AU - Jelinek, T
AU - Infectious Diseases and Tropical Medicine, University of Munich, Department
AU - Infectious Diseases and Tropical Medicine, University of Munich, Department
AU - Infectious Diseases and Tropical Medicine, University of Munich, Department
AU - Infectious Diseases and Tropical Medicine, University of Munich, Department
AU - Infectious Diseases and Tropical Medicine, University of Munich, Department
AU - Infectious Diseases and Tropical Medicine, University of Munich, Department
AU - Infectious Diseases and Tropical Medicine, University of Munich, Department
AU - Infectious Diseases and Tropical Medicine, University of Munich, Department
PY - 2002/11
Y1 - 2002/11
N2 - 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.
AB - 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.
KW - Adult
KW - Animals
KW - Antimalarials/pharmacology
KW - Child
KW - Chloroquine/pharmacology
KW - Drug Combinations
KW - Drug Resistance/genetics
KW - Female
KW - Genetic Markers/genetics
KW - Humans
KW - Malaria, Falciparum/diagnosis
KW - Male
KW - Mauritania/epidemiology
KW - Mutation
KW - Odds Ratio
KW - Plasmodium falciparum/drug effects
KW - Polymorphism, Genetic/genetics
KW - Pyrimethamine/pharmacology
KW - Sensitivity and Specificity
KW - Sulfadoxine/pharmacology
U2 - 10.4269/ajtmh.2002.67.449
DO - 10.4269/ajtmh.2002.67.449
M3 - SCORING: Journal article
C2 - 12479542
VL - 67
SP - 449
EP - 453
JO - AM J TROP MED HYG
JF - AM J TROP MED HYG
SN - 0002-9637
IS - 5
ER -
