title: Increased incidence of cycloguanil resistance in malaria cases entering France from Africa, determined as point mutations in the parasites' dihydrofolate-reductase genes.
abstract: The incidence of cycloguanil resistance in 501 Plasmodium falciparum isolates from individuals entering France from Africa was estimated by a method based on PCR-restriction-fragment-length polymorphisms. None of the subjects had taken antifol prophylaxis. Annual incidence of the resistance, detected as a point mutation at codon 108 in the parasite's dihydrofolate-reductase gene, increased from 19.8% in 1995 to 43.6% in 1997 (P < 0.001). The proportion of isolates found to be susceptible (i.e. wild-type) among travellers returning from the African countries known as Group 2 in France (i.e. Burkina Faso, Côte d'Ivoire, Gambia, Ghana, Guinea, Liberia, Madagascar, Mali, Mauritania, Niger, Senegal, Sierra Leone, Tchad and Togo) was reasonably high (62.9%) and much higher than in the other subjects returning from other identifiable countries in Africa (35.3%). The antimalarial prophylaxis recommended in France to those travelling to Group-2 countries, chloroquine-proguanil, therefore still seems reasonable, although cycloguanil resistance may seriously undermine the efficacy of this drug combination in the future.
authors.affiliation: Centre National de Référence pour la Chimiosensibilité du Paludisme, Hôpital Bichat-Claude Bernard, Paris, France. rjdurand@club-internet
authors.forename: R
authors.initials: R
authors.lastname: Durand
authors.forename: J P
authors.initials: JP
authors.lastname: di Piazza
authors.forename: C
authors.initials: C
authors.lastname: Longuet
authors.forename: Y
authors.initials: Y
authors.lastname: Sécardin
authors.forename: J
authors.initials: J
authors.lastname: Clain
authors.forename: J
authors.initials: J
authors.lastname: le Bras
mesh_terms: D000349:Africa; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D004351:Drug Resistance; D005493:Folic Acid Antagonists / Q000627:therapeutic use; D005602:France; D017125:Genes, Protozoan; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D010963:Plasmodium falciparum / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D002727:Proguanil; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*; D014227:Triazines / Q000627:therapeutic use*
chemical_list: D000962:Antimalarials; D005493:Folic Acid Antagonists; D014227:Triazines; C026009:cycloguanil; D013762:Tetrahydrofolate Dehydrogenase; D002727:Proguanil