Parenteral
artesunate, a first-line treatment for severe
malaria in several countries, is associated with increased survival and has a better safety profile compared with parenteral
quinine or
quinidine. However, parenteral
artesunate has been associated with delayed
hemolysis, leading to concerns about
drug toxicity. Postartemisinin delayed
hemolysis (PADH) can occur 1-3 weeks after initiation of treatment with
artemisinin-based
antimalarials such as
artesunate and is characterized by a decline in
hemoglobin levels amid
hemolysis. CDC conducted a literature review and identified 18 cases of PADH since 2012, mostly in European travelers. In addition,
malaria case reports were reviewed retrospectively, and active surveillance was implemented in the United States, identifying two additional PADH cases, for a total of 20. A few patients with PADH required
blood transfusions, but among patients where complete follow-up information was available, all made a full recovery. Results from this review suggest that PADH occurs because of delayed clearance of once-infected erythrocytes, probably as a result of a pharmacologic effect of parenteral
artesunate and not
drug-related toxicity. Therefore, parenteral
artesunate can still be considered a safe treatment for severe
malaria and should remain an option for its treatment.