The Impact of Sequestration on Artemisinin-Induced Parasite Clearance in Plasmodium falciparum Malaria in Africa.

This article investigates the impact of parasite sequestration on the in vivo efficacy of artemisinin treatment for Plasmodium falciparum malaria in northern Uganda, where artemisinin resistance is emerging. Using plasma levels of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) to estimate sequestered parasite biomass, the study found that in patients infected with PfKelch13 wild-type parasites, higher sequestration was significantly associated with delayed parasite clearance half-life after artemisinin monotherapy. This association was independent of peripheral parasitemia, parasite developmental stage, and posttreatment parasitemia surge. The findings suggest that sequestered mature parasites, which are not detected in peripheral blood, contribute to reduced artemisinin susceptibility and may influence malaria pathology and treatment outcomes, highlighting the need to consider sequestration in evaluating drug efficacy and resistance.