Background: Studies have demonstrated the safety and efficacy of intravenous artesunate (IVAS) for treatment of severe malaria in endemic and nonendemic countries. However, post-artesunate delayed hemolysis (PADH) is an increasingly recognized phenomenon after its administration. This study describes the prevalence and outcomes of PADH events among severe malaria cases treated with IVAS in the United States.
Methods: Patients diagnosed with severe malaria and treated with IVAS from April 2019 to July 2021 were included. Demographic, clinical, laboratory, therapeutic, and outcome measures were described using proportions, medians, and interquartile range. Patients reported to experience PADH were compared with those not reported to have PADH, and tests of significance were performed.
Results: Of 332 patients included in our analysis, 9 (2.7%) experienced PADH. The majority of infections in both groups were in non-Hispanic Black individuals. Parasite density (11.0% vs 8.0%), admission hemoglobin (11.0 g/dL vs 11.8 g/dL) were similar in the 2 groups. Total bilirubin levels at admission (4.7 mg/dL vs 2.2 mg/dL) and within 8 hours after completion of IVAS (2.6 mg/dL vs 1.2 mg/dL) were notably higher in PADH patients. Cumulative IVAS dose of >9.5 mg/kg and >3 doses of IVAS were risk factors for PADH. The majority (7 of 9) of PADH cases were diagnosed within 2 weeks after initiation of IVAS. Five patients (56%) required blood transfusions, and all recovered without sequelae.
Conclusions: PADH is an uncommon and self-limiting adverse event in many cases; weekly monitoring of hemoglobin and hemolytic markers may identify cases requiring intervention in a timely manner.
Keywords: adverse effects; intravenous artesunate; post-artesunate delayed hemolysis; safety; severe malaria.
Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.