Short report: lack of prediction of amodiaquine efficacy in treating Plasmodium falciparum malaria by in vitro tests.
Amodiaquine (AQ) is currently a major candidate for new antimalarial combinations, although in vivo and in vitro tests have been rarely simultaneously investigated. The efficacy of AQ was assessed at the dose of 30 mg/kg in treating Plasmodium falciparum malaria attacks in 74 children from southeast Gabon, and the in vitro activity of monodesethylamodiaquine (MdAQ), the main metabolite of AQ, was measured against P. falciparum parasites isolated from these children. Treatment failures were observed in 40.5% of the children, while 5.4% of the isolates showed in vitro resistance to MdAQ. No relationship was observed between in vivo and in vitro susceptibility. The in vitro activities of MdAQ and chloroquine were correlated. The reasons for such disparities between in vivo and in vitro AQ activities are discussed and the issue of the validity of in vitro tests to measure AQ efficacy is raised.
Aubouy
Agnes
A
Centre International de Recherches Médicales de Franceville, Unité de Parasitologie Médicale, Franceville, Gabon, France.
Mayombo
Justice
J
Keundjian
Annick
A
Bakary
Mohamed
M
Le Bras
Jacques
J
Deloron
Philippe
P
D000655:Amodiaquine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use*; D000962:Antimalarials / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance / Q000235:genetics; D005681:Gabon; D006801:Humans; D066298:In Vitro Techniques; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000235:genetics; D021261:Parasitic Sensitivity Tests / Q000379:methods; D011237:Predictive Value of Tests; D016896:Treatment Outcome
D000962:Antimalarials; D000655:Amodiaquine; C047386:desethylamodiaquine