#11: Post-malarial Hemolysis is Rare in Malawian Children with Cerebral Malaria

Abstract

Background In severe malaria, artesunate decreases mortality compared to quinine. Artesunate’s introduction into clinical use in malaria-endemic areas revealed a unique adverse effect: severe hemolysis appearing several weeks after treatment completion. Though initial reports of post-artesunate hemolysis (PAH) were gathered from adult returning travelers, studies of African children revealed that PAH was less common in this semi-immune population. There are no published studies establishing the incidence and severity of PAH in several severe malarial syndromes in African children, including cerebral malaria (CM). We determined the incidence and severity of post-treatment hemolysis in Malawian children surviving CM by analyzing hospital and follow-up data from a long-standing study of CM pathogenesis. Methods Children aged 6 months to 14 years admitted to Queen Elizabeth Central Hospital (Blantyre, Malawi) with a clinical diagnosis of CM were enrolled in a retrospective cohort study. Children admitted before 2014 and treated with quinine (n=258) were compared to those admitted in 2014 and after and treated with artesunate (n=235). Hematocrit and parasite density were obtained at admission and every 6 hours until parasite clearance. The last hematocrit obtained during hospitalization was compared with the one-month post-hospitalization hematocrit value. Results The overall rate of a post-hospitalization decrease in hematocrit in children surviving CM was 5.3% (4.7% for quinine, 5.8% for artesunate, p value for difference= 0.582); no patients with a hematocrit decrease were symptomatic; none required transfusion. Of the 26 children with a decrease in hematocrit at one month after hospitalization, 23.1% had evidence of a new malaria infection. When children treated with quinine and artesunate were combined, a higher hematocrit on admission, lower quantitative histidine rich protein 2 level, and splenomegaly were independently associated with a post-treatment decrease in hematocrit. Conclusions In African survivors of CM, post-treatment hemolysis is rare, mild, and unassociated with the antimalarial treatment received.