Post-artesunate Delayed Hemolysis in African Children With Severe Malaria: Incidence, Medical Impact and Prevention

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BACKGROUND: Post-artesunate delayed hemolysis (PADH) occurs in 7%-25% of adults with severe imported malaria. Whether it exists in African children is controversial. METHODS: In total, 351 children treated with artesunate were enrolled in a prospective severe malaria study in Benin. Clinical, epidemiological and biological data, plasma concentrations of antimalarials were captured or determined on admission then at 3, 5, 14, 21, and 28 days after starting treatment. PADH was defined by a >10% drop in hemoglobin level and/or a >10% rise in LDH concentrations beyond Day 5. RESULTS: Fourteen children (4%) died before D14. Although 10% of guardians declared administration of anti-malarial drugs before admission, 316/350 (90%) of children had measurable plasma levels of lumefantrine (n = 279), quinine (n = 104), sulfadoxine (n = 67), artemisinin (n = 28), chloroquine (n = 16), or other antimalarials (n = 9). PADH occurred in 76/332 children (22.9%). Levels of pitted red blood cells (RBC) were higher and recovery from anemia was slower in these children. Severe anemia and transfusion were more frequent between D14 and D28 in children with PADH compared to children without PADH (10.6% vs 0.4%, 9.8% vs 0%). During follow-up, children with PADH were more frequently hospitalized (11.1% vs 1.6%) and had more frequent infectious events (6.9% vs 0.4%) than children without PADH. Children who received 2 transfusions within 3 days post-admission had a lower incidence of PADH than untransfused children (12.5% vs 26.8%, P = .015). CONCLUSIONS: Despite widespread self-medication with antimalarials, PADH affects 23% of African children treated with artesunate for severe malaria, of whom more than 15% suffer from severe anemia and/or infectious events. Liberal early transfusion may be protective against PADH.