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Antimalarial drug resistance is the major challenge in the treatment of malaria all over the world. Plasmodium species are the parasite that causes malaria. Plasmodium falciparum is the most prevalent species found in sub-Saharan Africa that records the highest infections and death caused by malaria worldwide. Resistance to P. falciparum is caused by mutations in some target genes of the parasite, which includes Plasmodium falciparum: Na+/ H+ exchanger (Pfnhe-1), chloroquine resistance transporter (Pfcrt), dihydropteroate synthase (Pfdhps), dihydrofolate reductase (Pfdhfr), multidrug resistance 1 gene (Pfmdr1), cytochrome b, multidrug resistance-associated protein 1 (Pfmrp1), cg2 (Pfcg2), Ca2+ ATPase (PfATPase6) and kelch 13 gene. Most of these mutations are single nucleotide polymorphisms and has led to the decrease in susceptibility of some drugs like chloroquine, quinine, mefloquine, amodiaquine, sulphadoxine/pyrimethamine, lumefantrine and artemisinins in the treatment of malaria. The aim of this review was to survey on the existing antimalarial drug resistance in endemic areas of Africa and suggests a way forward in combating drug-resistant malaria in this region.