New insights into the spread of resistance to artemisinin and its analogues

Abstract

ABSTRACT: Plasmodium falciparum, the causative agent of malaria, has been developing resistance to several drugs worldwide for more than five decades. Initially, resistance was against drugs such as chloroquine, pyrimethamine, sulfadoxine, mefloquine and quinine. Research studies are now reporting parasites with resistance to the most effective and novel drug used against malaria infection worldwide, namely artemisinin. For this reason, the first-line treatment strategy of artemisinin-based combination therapy is becoming unsuccessful in areas where drug resistance is highly prevalent. The increase in artemisinin-resistant P. falciparum strains has threatened international efforts to eliminate malarial infections and to reduce the disease burden. 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 polymorphisms within the Kelch 13 gene of the parasite and is related to significantly upregulated resistance signalling pathways; thus, the pro-oxidant action of artemisinins can be antagonised. New strategies are required to halt the spread of artemisinin-resistant malarial parasites.

Keywords

• Artemisinin
• Plasmodium falciparum
• Malaria
• Resistance
• Kelch 13 mutation