P. falciparum and Its Molecular Markers of Resistance to Antimalarial Drugs

Abstract

The use of molecular markers of resistance to monitor the emergence, and the spread of parasite resistance to antimalarial drugs is a very effective way of monitoring antimalarial drug resistance. The identification and validation of molecular markers have boosted our confidence in using these tools to monitor resistance. For example, P. falciparum chloroquine resistance transporter (PfCRT), P. falciparum multidrug resistance protein 1 (PfMDR1), P. falciparum multidrug kelch 13 (pfk13), have been identified as molecular markers of resistance to chloroquine, lumefantrine, and artemisinin respectively. The mechanism of resistance to antimalarial drugs is mostly by; (1) undergoing mutations in the parasite genome, leading to expelling the drug from the digestive vacuole, or (2) loss of binding affinity between the drug and its target. Increased copy number in the pfmdr1 gene also leads to resistance to antimalarial drugs. The major cause of the widespread chloroquine and sulfadoxine-pyrimethamine resistance globally is the spread of parasites resistant to these drugs from Southeast Asia to Africa, the Pacific, and South America. Only a few mutations in the parasite genome lead to resistance to chloroquine and sulfadoxine-pyrimethamine arising from indigenous parasites in Africa, Pacific, and South America.