title: Susceptibility of Plasmodium falciparum in vitro to chloroquine, mefloquine, quinine and sulfadoxine/pyrimethamine in Somalia: relationships between the responses to the different drugs.
abstract: The susceptibilities of Plasmodium falciparum to chloroquine, mefloquine, quinine and sulfadoxine/pyrimethamine were investigated in Mogadishu in 1988, after chloroquine resistance had spread widely in Somalia. Possible correlations of the responses to these drugs were also investigated. Standard World Health Organization in vitro micro-tests were performed. Of 76 isolates tested for chloroquine susceptibility, 58 (76%) were resistant to the drug with mean EC50 and EC99 values of 1.06 x 10(-6) mol/litre and 10.44 x 10(-6) mol/litre of blood, respectively, indicating a high prevalence and degree of resistance. In contrast, all isolates tested were inhibited by mefloquine 3.2 x 10(-6) mol/litre of blood, quinine at 2.56 x (-6) mol/litre of blood-medium mixture, and sulfadoxine/pyrimethamine at 6.0/0.075 x 10(-6) mol/litre of blood-medium mixture, indicating full sensitivity to these 3 drugs. However, a significant positive correlation was found between responses to quinine and chloroquine and between those to quinine and mefloquine; the responses to chloroquine and mefloquine were not correlated. The results may suggest that sites responsible for the correlation are shared between quinine and chloroquine but not essentially between chloroquine and mefloquine. Thus the evolution of chloroquine resistance together with increased use of quinine treatment of P. falciparum may increase the risks of development of quinine resistance, whereas the development of mefloquine resistance would not be triggered by chloroquine resistance.
authors.affiliation: Department of Morphology and Pathology, Faculty of Medicine, Somali National University, Mogadishu.
authors.forename: M
authors.initials: M
authors.lastname: Warsame
authors.forename: W H
authors.initials: WH
authors.lastname: Wernsdorfer
authors.forename: D
authors.initials: D
authors.lastname: Payne
authors.forename: A
authors.initials: A
authors.lastname: Björkman
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D015767:Mefloquine / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects*; D011739:Pyrimethamine / Q000494:pharmacology; D011803:Quinine / Q000494:pharmacology; D012998:Somalia; D013413:Sulfadoxine / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D013413:Sulfadoxine; D002738:Chloroquine; D011803:Quinine; D015767:Mefloquine; D011739:Pyrimethamine