New Insights into the Spread of Resistance to Artemisinin and its Analogues

Abstract The causative agent of malaria, Plasmodium falciparum, has been developing resistance to several drugs worldwide since more than five decades. Initially, resistance was toward drugs such as chloroquine, pyrimethamine, sulfadoxine, mefloquine, and quinine. Research studies are now reporting the resistance of parasites to the most effective and novel drug used against malaria infection worldwide, that is, artemisinin; for this reason, the first-line treatment strategy, including artemisinin combination therapy, is becoming unsuccessful in areas where drug resistance is highly prevalent. The increase in the artemisinin-resistant strains of P. falciparum has threatened international efforts to eliminate malaria infections and reduce disease burden. The detection of several phenotypes that display artemisinin resistance, specification of basic genetic factors, the discovery of molecular pathways, and evaluation of its clinical outcome are possible by the current series of research on genomics and transcriptomic levels in Asia and Africa. In artemisinin resistance, slow parasite clearance among malaria-infected patients and enhanced in vitro survival of parasites occurs at the early ring stage. This resistance is due to single nucleotide polymorphism within the Kelch 13 gene of the parasite and is related to the significantly upregulated signaling pathway; thus, the pro-oxidant action of artemisinins can be antagonized. New strategies are required to halt the spread of artemisinin-resistant malarial parasites.