[Mechanisms and epidemiology of resistances to antimalarials].
Drug resistant malaria is mostly due to Plasmodium falciparum, a species highly prevalent in tropical Africa, Amazonia and South-East Asia and responsible for severe involvement of fever or anemia prompting more than a million death per year. Resistance originate from chromosomic mutations. Antimetabolite-resistant mutants (pyrimethamine and proguanil) are highly prevalent in Asia, America and East Africa. One to 3 point mutations on the dihydrofolate-reductase gene, the target enzyme, give moderate to high level of resistance. Molecular biology furnishes sensitive tools for population-based studies of resistance to these compounds. Four-aminoquinolines resistant mutants (chloroquine and amodiaquine) were encountered more than 10 years after a huge amount of these drugs has been sold. The level of resistance varies among parasites isolates populations. Impaired uptake of the drug by the parasite vacuole is a common characteristic of resistant strains. This phenotype is poorly correlated with PfMDR1 gene mutations on chromosome 5 but is strongly associated with a particular RFLP profile on chromosome 7. Amino-alcohol resistant falciparum malaria is scarce (quinine, mefloquine, halofantrine) and supposed to be associated with impaired uptake of the drug by the parasite, the mechanism of which is still unclear. In each of these three antimalarial drugs groups, the highly resistant level to a peticular compound, the highly prevalence of cross resistance of the malaria isolate. An established and strong drug pressure probably explains the multi-chemoresistance encoutered in South-East Asia and forests of South America. In Africa, frequent genetic recombinations in Plasmodium originates from a high level of malaria transmission, and falciparum chloroquine-resistance prevalence seems to stabilize at an equal level as chloroquine-sensitive malaria.
Le Bras
J
J
Centre National de Référence de la Chimiosensibilité du Paludisme, Hôpital Bichat-Claude-Bernard, Paris.
Basco
L K
LK
de Pécoulas
P E
PE
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance / Q000502:physiology; D018432:Drug Resistance, Multiple; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology; D017720:Molecular Epidemiology; D010963:Plasmodium falciparum / Q000187:drug effects; D011739:Pyrimethamine / Q000494:pharmacology
D000962:Antimalarials; D002738:Chloroquine; D011739:Pyrimethamine
Mécanismes et épidémiologie des résistances aux antipaludiques.