Plasmodium falciparum: correlation of in vivo resistance to chloroquine and antifolates with genetic polymorphisms in isolates from the south of Lao PDR
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Plasmodium falciparum: correlation of in vivo resistance to chloroquine and antifolates with genetic polymorphisms in isolates from the south of Lao PDR. / Berens, Nicole; Schwöbel, Babett; Jordan, Sabine; Vanisaveth, Viengsay; Phetsouvanh, Rattanaxay; Christophel, Eva-Maria; Phompida, Samlane; Jelinek, Tomas.
in: TROP MED INT HEALTH, Jahrgang 8, Nr. 9, 09.2003, S. 775-82.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Plasmodium falciparum: correlation of in vivo resistance to chloroquine and antifolates with genetic polymorphisms in isolates from the south of Lao PDR
AU - Berens, Nicole
AU - Schwöbel, Babett
AU - Jordan, Sabine
AU - Vanisaveth, Viengsay
AU - Phetsouvanh, Rattanaxay
AU - Christophel, Eva-Maria
AU - Phompida, Samlane
AU - Jelinek, Tomas
PY - 2003/9
Y1 - 2003/9
N2 - Levels of drug resistance of Plasmodium falciparum strains against antimalarials have increased in Laos. In several studies, chloroquine (CQ) resistance has been associated with point mutations in the Pfcrt and pfmdr genes, and sulphadoxine/pyrimethamine (S/P) resistance with point mutations in the genes of dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS). We combined a study of these molecular markers with an in vivo antimalarial drug sensitivity study in Attapeu province in the south of Lao PDR. We treated 100 patients with either CQ, S/P or a combination of both. In the CQ group, Pfcrt mutations showed a very high sensitivity (100%) but a low specificity (12.5%) to predict resistance. The combination of mutations in the Pfcrt and pfmdr genes was highly specific and had a positive predictive value of 100%. Mutations in the DHPS gene showed a high correlation with the development of resistance. The prevalence of mutations in the DHFR gene, especially codon 108 Asn, was predictive with high sensitivity (100%) but low specificity. Isolates derived from patients treated with a combination of both drugs showed a high correlation between the mutation in codon 437 of DHPS gene and in vivo-resistance (odds ratio 16.00, CI). The study provides evidence for the existence of antimalarial drug resistance in the south of Lao PDR, and offers a molecular method to predict resistance.
AB - Levels of drug resistance of Plasmodium falciparum strains against antimalarials have increased in Laos. In several studies, chloroquine (CQ) resistance has been associated with point mutations in the Pfcrt and pfmdr genes, and sulphadoxine/pyrimethamine (S/P) resistance with point mutations in the genes of dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS). We combined a study of these molecular markers with an in vivo antimalarial drug sensitivity study in Attapeu province in the south of Lao PDR. We treated 100 patients with either CQ, S/P or a combination of both. In the CQ group, Pfcrt mutations showed a very high sensitivity (100%) but a low specificity (12.5%) to predict resistance. The combination of mutations in the Pfcrt and pfmdr genes was highly specific and had a positive predictive value of 100%. Mutations in the DHPS gene showed a high correlation with the development of resistance. The prevalence of mutations in the DHFR gene, especially codon 108 Asn, was predictive with high sensitivity (100%) but low specificity. Isolates derived from patients treated with a combination of both drugs showed a high correlation between the mutation in codon 437 of DHPS gene and in vivo-resistance (odds ratio 16.00, CI). The study provides evidence for the existence of antimalarial drug resistance in the south of Lao PDR, and offers a molecular method to predict resistance.
KW - Adolescent
KW - Adult
KW - Aged
KW - Animals
KW - Antimalarials/therapeutic use
KW - Child
KW - Child, Preschool
KW - Chloroquine/therapeutic use
KW - Drug Combinations
KW - Drug Resistance
KW - Drug Therapy, Combination
KW - Folic Acid Antagonists/therapeutic use
KW - Humans
KW - Infant
KW - Laos
KW - Malaria, Falciparum/drug therapy
KW - Middle Aged
KW - Mutation/genetics
KW - Plasmodium falciparum/drug effects
KW - Polymorphism, Genetic/genetics
KW - Pyrimethamine/therapeutic use
KW - Sensitivity and Specificity
KW - Sulfadoxine/therapeutic use
U2 - 10.1046/j.1365-3156.2003.01099.x
DO - 10.1046/j.1365-3156.2003.01099.x
M3 - SCORING: Journal article
C2 - 12950663
VL - 8
SP - 775
EP - 782
JO - TROP MED INT HEALTH
JF - TROP MED INT HEALTH
SN - 1360-2276
IS - 9
ER -
