MECHANISMS OF DRUG RESISTANCE IN Plasmodium falciparum
Prevention, treatment and control of malaria mainly depends on the utilisation of synthetic drugs, unfortunately the parasites have developed resistance to almost all recommended drugs. Therefore, the aim of this paper was to review the state of knowledge on various resistance mechanism developed by Plasmodium falciparum. Antimalarial resistance is driven by a range of mechanisms, including molecular, genetic, and evolutionary factors. For Chloroquine, beside some basic molecular mutations, the parasite tends to divert the drug to enter the parasite’s food vacuole rather than its specific target organelles of action. High-level resistance to Pyrimethamine is caused by mutations in the DHFR gene, particularly at codons 108, 59, 51, and 164, leading to variations such as Ser108Asn, Cys59Arg, Asn51Ile, and Ile164Leu. Mutations in the DHPS gene that reduce the effectiveness of Sulfadoxine include codon changes such as A437G/K540E and A437G/A581G. Mutations in the Kelch13 (K13) propeller domain are linked to slower parasite clearance, where C580Y mutation is the most common but several other mutations in or near the K13 region, such as N458Y, Y493H, R539T, and I543T are also attributed to artemisinin resistance. Anti-malarial drugs resistance surveillance should be strategically adopted in all malaria endemic region to monitor the emergence of resistance.
Keywords: Plasmodium falciparum, Resistance, Mutations, Quinoloine, Antifolate, Artemisinin
