Plasmodium falciparum resistance to piperaquine driven by PfCRT

The Articles by William Hamilton and colleagues1 and Rob van der Pluijm and colleagues2 illustrate the plummeting clinical efficacy of dihydroartemisinin–piperaquine as a first-line treatment for Plasmodium falciparum malaria in southeast Asia. To test for differences in parasite fitness between mutants, we used a competitive growth rate assay in which each parasite line was individually cocultured with an isogenic green fluorescent protein (GFP)-positive Dd2 line. The data support a key role for PfCRT mutations in driving the recent expansion of highly piperaquine-resistant parasites in southeast Asia and highlight the need for vigilance in screening for novel PfCRT mutations in other malaria-endemic regions, notably in Africa or South America where piperaquine use has been increasing.