Molecular epidemiology of malaria in Cameroon. XII. In vitro drug assays and molecular surveillance of chloroquine and proguanil resistance

• Published in: The American journal of tropical medicine and hygiene Vol. 67; no. 4; pp. 383 - 387
• Main Author: Basco, LK
• Format: Journal Article
• Language: English
• Published: Lawrence, KS ASTMH 01.10.2002; Allen Press
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimalarials - pharmacology; Antiparasitic agents; Biological and medical sciences; Cameroon - epidemiology; Child; chloroquine; Chloroquine - pharmacology; Culicidae; Drug Resistance - genetics; Freshwater; Human protozoal diseases; Humans; In Vitro Techniques; Infectious diseases; Malaria; Malaria, Falciparum - epidemiology; Malaria, Falciparum - parasitology; Medical sciences; Membrane Proteins - genetics; Membrane Transport Proteins; Molecular Epidemiology; Mutation; Parasitic diseases; Pharmacology. Drug treatments; Plasmodium falciparum; Plasmodium falciparum - drug effects; Plasmodium falciparum - genetics; Polymerase Chain Reaction; proguanil; Proguanil - pharmacology; Protozoal diseases; Protozoan Proteins; Tetrahydrofolate Dehydrogenase - genetics; Tropical medicine; Cameroon; Africa; Human; Drug; Antimalarial; Protozoal disease; Malaria; Drug susceptibility test; Chloroquine; Parasitosis; In vitro; Infection; Resistance; Biguanides; Proguanil; Parasiticid; Molecular epidemiology; Sanitary surveillance
• ISSN: 0002-9637; 1476-1645
• DOI: 10.4269/ajtmh.2002.67.383

Chloroquine-proguanil combination is one of the options for chemoprophylaxis. The rapid evolution of drug resistance status requires a constant upgrade of epidemiologic data. Due to various difficulties in conducting prospective clinical studies on the prophylactic efficacy of the drug combination, especially in highly chloroquine-resistant zones, in vitro drug sensitivity assays and specific molecular markers for chloroquine (Plasmodium falciparum chloroquine-resistance transporter, pfcrt) and cycloguanil (a biologically active metabolite of proguanil; dihydrofolate reductase, dhfr) resistance were evaluated as an alternative approach in this study. Of 116 isolates, 62 (53.4%) were doubly resistant in vitro to chloroquine (IC50 > or = 100 nM) and cycloguanil (IC50 > or = 15 nM). Likewise, 62 of 118 isolates (52.5%) carried both the mutant Thr-76 pfcrt allele and at least one dhfr mutant allele (1 with a single Asn-108 allele, 8 with double Arg-59 and Asn-108 mutations, and 53 with triple Ile-51, Arg-59, and Asn-108 mutations). The in vitro drug response corresponded with the presence or absence of key mutation(s) in the pfcrt and dhfr genes. These results suggest the high proportion of P. falciparum isolates in southern Cameroon that may not respond to chloroquine-proguanil combination.