Origin and Spread of Evolving Artemisinin-Resistant Plasmodium falciparum Malarial Parasites in Southeast Asia

In this review, we provide an epidemiological history of the emergence and ongoing spread of evolving Plasmodium falciparum artemisinin resistance (ARTR). Southeast Asia has been the focal point for emergence and spread of multiple antimalarial drug resistance phenomena, and is once again for evolving ARTR, also known as the "delayed clearance phenotype" (DCP). The five countries most impacted, Cambodia, Thailand, Myanmar, Laos, and Vietnam, each have complex histories of antimalarial drug use over many decades, which have in part molded the use of various artemisinin combination therapies (ACTs) within each country. We catalog the use of ACTs, evolving loss of ACT efficacy, and the frequency of pfk13 mutations (mutations associated with ARTR) in the Greater Mekong Subregion and map the historical spread of ARTR/DCP parasites. These data should assist improved surveillance and deployment of next-generation ACTs.