[Monitoring the chemoresistance of Plasmodium falciparum malaria in Yopougon (Abidjan): in vivo study of chloroquine sensitivity and evaluation of pyrimethamine resistance following the analysis of point mutation in the dihydrofolate reductase gene].
A major endemic in Côte d'Ivoire, malaria is the first cause of hospital admissions and mortality in tropical Africa. The decrease of morbidity and mortality depends on early diagnosis and relevant treatment. This situation is hampered by an emerging resistance of P. falciparum to usual drugs such as chloroquine and sulfadoxine-pyrimethamine. In recognition of this problem, we established a monitoring system in the north of Abidjan (Yopougon) in order to better analyse P. falciparum resistance. The molecular basis of P. falciparum resistance to pyrimethamine is associated with point mutations in the dihydrofolate reductase (dhfr) gene. The presence of a wild-type codon 108-ser is defined by the presence of an Alu1 restriction site. A single base change resulting in the change of amino acid from 108-Ser to 108-Asn or 108-Thr results in the appearance of a Bsr1 or a Scrf1 restriction site respectively. In response to these needs, 42 children aged 6 to 59 months were enrolled in the study by using tests of therapeutic efficacy of chloroquine (14-day in vivo test of WHO). Before treatment, infected blood samples were stored at   20  C until P. falciparum DNA extraction. The results of the in vivo sensitivity of chloroquine showed 84.3% of plasmodic rate, 97.7 % of P. falciparum against 2.3% of P. malariae. However, 78.6% of adequate clinical response (ACR) was obtained and 21.4% of early therapeutic failure (ETF). At the end of the study, clearance of parasitemia and fever was obtained but the gametocytic rate was 4.8%. More, RFLP studies of amplified DNA fragment revealed that P. falciparum from 12 children (44.5%) had point mutation in the codon 108 of the dhfr gene. The mutation of these isolates was based on the change of amino-acid from 108-Ser to 108-Asn. Moreover, 51.8% of isolates were of the wild type. In conclusion, our results showed that chloroquine resistance is a reality in Abidjan just like anywhere else in West Africa. However, the number of isolates which had point mutation in the dhfr gene suggested that the future approach must be the study of possible correlation between the in vivo sulfadoxine-pyrimethamine test and point mutations in the dihydrofolate reductase and in the dihydropteroate synthase gene of P. falciparum from Côte d'Ivoire.
Djaman
Allico Joseph
AJ
Laboratoire de microbiologie, Institut national de santé publique and Laboratoire de pharmacodynamie-biochimie, UFR bioscience, Université de Cocody, Abidjan, Côte d'Ivoire. djamanj@hotmail.com
Basco
Léonardo K
LK
Mazabraud
André
A
D000818:Animals; D002675:Child, Preschool; D002738:Chloroquine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003062:Codon / Q000235:genetics; D007560:Cote d'Ivoire; D016054:DNA, Protozoan / Q000032:analysis; D004094:Dihydropteroate Synthase / Q000235:genetics; D004338:Drug Combinations; D004351:Drug Resistance; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D017354:Point Mutation; D011739:Pyrimethamine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013413:Sulfadoxine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D013997:Time Factors
D003062:Codon; D016054:DNA, Protozoan; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine