Pharmacology and Toxicology

The development of chloroquine as an antimalarial drug and the

subsequent evolution of drug resistant Plasmodium strains had major impacts on global public health in the 20th century. In P. falciparum, the cause of the most lethal human malaria, chloroquine resistance is linked to multiple mutations in PfCRT, a protein that likely functions as a transporter in the parasite's digestive vacuole membrane. Rapid diagnostic assays for PfCRT mutations are already employed as surveillance tools for drug resistance. Saudi Arabia is still considered by WHO to be in the zone of chloroquine-sensitive countries. However, several reports have been published demonstrating cases with CO resistance. Sporadic cases

have been reported as well as one large scale study demonstrated 12.4% resistance. However, all these reports were based on treatment failure (in vivo) rather than in vitro or molecular bases. Recent evidence suggests a crucial role for a point mutation in the P. falciparum chloroquine resistance transporter (pfcrt) gene on chromosome 7 in conferring CQ resistance In this study we detected mutation in the K76 codon in three cases out of 60 (5%) using ApoI restriction enzyme. Although the percentage of drug resistance is not quite disturbing, but it could represent the possible establishment of chloroquine-resistant P. falciparum in Saudi Arabia, or the

beginning of the spread of resistant strains by labors coming from countries with established resistance to this country. Also, cross-border importation of resistant strains from neighboring countries such as Yemen needs to be considered. In vivo tests need to be conducted in parallel with the molecular markers to estimate more precisely the actual prevalence of resistance. Validation of molecular markers is therefore urgently required and needs strong collaborative partnerships between sub regional and regional

networks.