In the early 2000s, artemisinin-based combination therapy (ACT) was introduced as first-line treatment for uncomplicated Plasmodium falciparum malaria in virtually all endemic countries. However, despite the well-known excellent tolerability of ACTs, hypersensitivity to artemisinin derivatives remains a repeatedly documented adverse drug reaction of still unknown frequency. The clinical features of an artemisinin-induced hypersensitivity reaction range from mild to life-threatening severity, and a significant number of cases may pass unnoticed. In this review, we discuss the medical importance of hypersensitivity to artemisinin derivatives and we review data on the presumed frequency and its potential underlying mechanisms. Furthermore, we advocate to make alternative non-artemisinin-based drugs available for patients who do not tolerate artemisinin derivatives and to continue investing in the development of novel non-artemisinin-based combination regimens.
