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Artemisinin resistance or tolerance in human malaria patients
Authors:Jerapan Krungkrai  Waranya Imprasittichai  Sumintra Otjungreed  Sawirasagee Pongsabut  Sudaratana R Krungkrai
Institution:1. Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand;2. Unit of Biochemistry, Department of Medical Science, Faculty of Science, Rangsit University, Patumthani 12000, Thailand
Abstract:Malaria is a major cause of morbidity and mortality in the developing world. This situation is mainly due to emergence of resistance to most antimalarial drugs currently available. Artemisinin-based combination treatments are now first-line drugs for Plasmodium falciparum (P. falciparum) malaria. Artemisinin (qinghaosu) and its derivatives are the most rapid acting and efficacious antimalarial drugs. This review highlights most recent investigations into the emergence of artemisinin resistance in falciparum malaria patients on the Thai-Cambodian border, a historical epicenter for multidrug resistance spread spanning over 50 years. The study presents the first evidence that highlights the parasites reduced susceptibility to artemisinin treatment by prolonged parasite-clearance times, raising considerable concern on resistance development. Although the exact mechanism of action remains unresolved, development of resistance was proposed based from both in vitro experiments and human patients. Lines of evidence suggested that the parasites in the patients are in dormant forms, presumably tolerate to the drug pressure. The World Health Organization has launched for prevention and/or containment of the artemisinin-resistant malaria parasites. Taken together, the emergence of artemisinin resistance to the most potent antidote for falciparum malaria, poses a serious threat to global malaria control and prompts renewed efforts for urgent development of new antimalarial weapons.
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