Delayed Hemolysis After Treatment With Parenteral Artesunate in African Children With Severe Malaria—A Double-center Prospective Study

BACKGROUND Parenteral artesunate is recommended as first-line therapy for severe malaria. While its efficacy is firmly established, data on safety are still incomplete. Delayed hemolysis has been described in hyperparasitemic nonimmune travelers, but it is unknown if African children are equally at risk. METHODS Children aged 6 to 120 months with severe malaria were followed up after treatment with parenteral artesunate in Lambarene, Gabon, and Kumasi, Ghana. The primary outcome was incidence of delayed hemolysis on day 14. RESULTS In total, 72 children contributed complete data sets necessary for primary outcome assessment. Delayed hemolysis was detected in 5 children (7%), with 1 child reaching a nadir in hemoglobin of 2.8 g/dL. Patients with delayed hemolysis had higher parasite counts on admission (geometric mean parasite densities (GMPD) 306 968/µL vs 92 642/µL, P = .028) and were younger (median age: 24 months vs 43 months, P = .046) than the rest of the cohort. No correlation with sickle cell trait or glucose-6-phosphate-dehydrogenase deficiency was observed. CONCLUSIONS Delayed hemolysis is a frequent and relevant complication in hyperparasitemic African children treated with parenteral artesunate for severe malaria. Physicians should be aware of this complication and consider prolonged follow-up. CLINICAL TRIALS REGISTRATION Pan-African Clinical Trials Registry: PACTR201102000277177 (www.pactr.org).