Adaptive immunity is essential in preventing recrudescence of Plasmodium yoelii malaria parasites after artesunate treatment.

Artemisinin-based antimalarials, such as artesunate (ART), alone or in combination, are the mainstay of the therapy against malaria caused by Plasmodium falciparum. However, the emergence and spread of artemisinin resistance threatens the future success of its global malaria eradication. Although much of the reported artemisinin resistance can be attributed to mutations intrinsic to the parasite, a significant proportion of treatment failures are thought to be due to other factors such as the host's immune system. Exactly how the immune system participates in the clearance and elimination of malaria parasites during ART treatment is unknown. Here, we show that a developing primary immune response, involving both B and CD4+ T cells, is necessary for the complete elimination but not initial clearance, of Plasmodium yoelii YM parasites in mice treated with ART. Our study uncovers a dynamic interplay between ART and host adaptive immunity in Plasmodium sp. elimination.