Molecular surveillance of Plasmodium falciparum chloroquine resistance transporter variant T76 in Jazan area, Kingdom of Saudi Arabia.
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. 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. 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. The mutation in the K76 codon in 3 cases out of 60 (5%) using ApoI restriction enzyme was detected. Although the percentage of drug resistance was not quite disturbing, but represented the possible establishment of chloroquine-resistant P. falciparum in Saudi Arabia, or the beginning of resistant strains by labors coming from abroad. Cross-border importation of resistant strains from neighboring countries must be considered. In vivo tests must be conducted parallel with the molecular markers to estimate more precisely the actual prevalence of resistance. Validation of molecular markers is urgently required and needs strong collaborative partnerships between subregional and regional networks.
Department of Clinical Parasitology, Faculty of Medicine, Jazan University, National Center for Training and Research, Jazan, Kingdom of Saudi Arabia. hamdy57@hotmail.com
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Dawoud
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Ageely
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El Sheikh
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Heiba
D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D001483:Base Sequence; D002738:Chloroquine / Q000627:therapeutic use*; D016054:DNA, Protozoan / Q000032:analysis; D004351:Drug Resistance / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D026901:Membrane Transport Proteins / Q000235:genetics*; D021141:Nucleic Acid Amplification Techniques; D010963:Plasmodium falciparum / Q000187:drug effects*; D017354:Point Mutation / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics*; D012529:Saudi Arabia; D017211:Treatment Failure
D000962:Antimalarials; D016054:DNA, Protozoan; D005819:Genetic Markers; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine