title: [Limits of the efficacy of chloroquine and sulfadoxine-pyrimethamine in Northern Abidjan (Cote d'Ivoire): Combined in vivo and in vitro studies].
abstract: Antimalarial drug resistance in endemic malaria zones is first detected in vitro; when it reaches a certain threshold, it becomes perceptible and is expressed in therapeutic failure among subjects only slightly or not at all immune. This work conducted in northern Abidjan (Cote d'Ivoire) studied children with uncomplicated malaria, who were followed for 14 days (during the year 2000) in accordance with the WHO protocol for surveillance of antimalarial drug resistance. Concomitantly, the Plasmodium falciparum isolates were cultured in the presence of variable concentrations of chloroquine, pyrimethamine and quinine during in vitro chemosensitivity tests. The RPMI 1640 used as medium for the pyrimethamine did not contain PABA (para-amino benzoic acid) or folic acid. In all, 114 in vitro tests were completed, 33 to chloroquine, 32 to pyrimethamine, and 49 to quinine. Therapeutic efficacy was tested in 65 patients: 33 to chloroquine and 32 to sulfadoxine-pyrimethamine (SP). The results found 36% of the isolates were chloroquine-resistant (CQ-R) and 33% of the patients treated with chloroquine did not respond adequately (therapeutic failure, TF). The 12 CQ-R isolates corresponded to 11 TF subjects and 1 patient with adequate clinical and parasitological response. The concordance between the two tests was good (kappa=0.93). For pyrimethamine, 37.5% of the isolates were resistant (PYR-R), and 37.5% of patients responded adequately to SP. The 12 PYR-R isolates were from 12 TF subjects, so that kappa=1.0, when pyrimethamine resistance is defined as IC50 > 2,000 nM. Because of the elevated rate of chloroquine resistance, the national antimalaria program has recommended since July 2003 that amodiaquine be used as a first-line drug, to replace chloroquine. The relatively elevated number of TF with SP are a source of concern, because it is used in Yopougon (Abidjan). Additional studies to assess the prevalence of resistance to this combination in other areas of Abidjan city (Cote d' Ivoire) would be useful.
authors.affiliation: Unité de parasitologie, Laboratoire de microbiologie de l'Institut national de santé publique (Abidjan), BP V 47 Abidjan Laboratoire de pharmacodynamie-biochimique, UFR Biosciences, Université de Cocody, Abidjan, Côte d'Ivoire. djamanj@hotmail.com
authors.forename: Joseph
authors.initials: J
authors.lastname: Djaman
authors.forename: Stéphane
authors.initials: S
authors.lastname: Abouanou
authors.forename: Leonardo
authors.initials: L
authors.lastname: Basco
authors.forename: Moussa
authors.initials: M
authors.lastname: Koné
mesh_terms: D000655:Amodiaquine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D002675:Child, Preschool; D002738:Chloroquine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D007560:Cote d'Ivoire; D003470:Culture Media; D003627:Data Interpretation, Statistical; D004338:Drug Combinations; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007231:Infant, Newborn; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000517:prevention & control; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects*; D015995:Prevalence; D011739:Pyrimethamine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D011803:Quinine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013413:Sulfadoxine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D000962:Antimalarials; D003470:Culture Media; D004338:Drug Combinations; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D011803:Quinine; D011739:Pyrimethamine