Severe Plasmodium falciparum Malaria Complicated by Post-artemisinin Delayed Hemolysis in a Non-immune Pediatric Returning Traveler

Severe Plasmodium falciparum malaria remains a major cause of morbidity in children, particularly among non-immune travelers. Intravenous artesunate is the treatment of choice for severe malaria due to its rapid parasite clearance and improved safety profile. However, post-artemisinin delayed hemolysis (PADH) is increasingly recognized as a delayed adverse effect, typically occurring seven to 30 days after treatment. Recognition of PADH is crucial to avoid misdiagnosis, guide monitoring, and ensure timely intervention. A previously healthy nine-year-old boy presented with severe P. falciparum malaria following travel to Tanzania. He developed multiorgan dysfunction, including thrombocytopenia, acute kidney injury, hepatic dysfunction, and hypoxemic pneumonia, and was treated in the pediatric intensive care unit with intravenous artesunate followed by oral artemether-lumefantrine. After clinical improvement and parasite clearance, he was discharged. Ten days after treatment initiation, he re-presented with pallor, jaundice, and dark urine. Laboratory evaluation demonstrated hemoglobin decline, indirect hyperbilirubinemia, elevated lactate dehydrogenase (LDH), reticulocytosis, low haptoglobin, and absence of parasitemia - confirming PADH. He required admission and transfusion of packed red blood cells, with subsequent full hematological recovery. This case highlights PADH as an important delayed complication of artesunate therapy in non-immune pediatric travelers. Early recognition, structured post-treatment monitoring, and clear differentiation from malaria recrudescence are essential to guide management. This case reinforces the need for follow-up hemolysis testing seven to 30 days after treatment, particularly in patients with high initial parasitemia. This case report describes a child with severe falciparum malaria successfully treated with intravenous artesunate who subsequently developed PADH. It illustrates the biphasic course of artemisinin therapy - initial parasite clearance followed by delayed hemolysis - underscoring the need for post-discharge monitoring.