Sabine Bélard1,2, Judith Brand1, Ulf Schulze-Sturm3, Ales Janda4, Ulrich von Both5, Costanza Tacoli6, Martin Alberer7, Caroline Kempf8, Miriam S Stegemann9, Renate Krüger1, Verena Varnholt1, Martin Blohm3, Karl Reiter10, Thomas Zoller9, Norbert Suttorp9, Marcus Mall1,2, Horst von Bernuth1,11,12, Alexander Gratopp1, Johannes Hübner5, Markus Hufnagel4, Robin Kobbe3, Florian Kurth9. 1. From the Department of Paediatric Pulmonology, Immunology and Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany. 2. Berlin Institute of Health, Berlin, Germany. 3. Department of Paediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 4. Division of Paediatric Infectious Diseases and Rheumatology, Department of Paediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 5. Division Paediatric Infectious Diseases, Dr. von Hauner Children's Hospital, University Hospital, Ludwig Maximilians University, Munich, Germany. 6. Institute of Tropical Medicine and International Health, Charité - Universitätsmedizin Berlin, Berlin, Germany. 7. Division of Infectious Diseases and Tropical Medicine, University Hospital, LMU Munich, Munich, Germany. 8. Department of Paediatric Gastroenterology, Nephrology and Metabolic Disorders, Charité- Universitätsmedizin Berlin, Berlin, Germany. 9. Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. 10. Division of Paediatric Intensive Care, Dr. von Hauner Children's Hospital, University Hospital, Ludwig Maximilians University, Munich, Germany. 11. Labor Berlin, Immunology, Berlin, Germany. 12. Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Abstract
BACKGROUND: Intravenous artesunate (ivA) is the standard treatment for severe malaria. Data systematically evaluating the use of ivA in pediatric patients outside malaria-endemic regions are limited. The aim of this case series was to summarize efficacy and safety of ivA for imported severe malaria in children in Germany. METHODS: Our retrospective case series included pediatric patients with imported severe malaria treated with at least 1 dose of ivA (Artesun, Guilin Pharmaceutical; Shanghai, China) at 4 German tertiary care centers. Severe malaria was defined according to World Health Organization criteria. RESULTS: Between 2010 and 2018, 14 children with a median [interquartile range (IQR)] age of 6 (1;9.5) years were included. All children were of African descent. All but 2 patients had Plasmodium falciparum malaria; 1 child had P. vivax malaria and 1 child had P. falciparum and P. vivax co-infection. Median (IQR) parasitemia at admission in patients with P. falciparum was 9.5% (3;16.5). Patients were treated with 1-10 [median (IQR) 3 (3;4)] doses ivA. All but one patient received a full course of oral antimalarial treatment. Parasite clearance was achieved within 2-4 days, with the exception of 1 patient with prolonged clearance of peripheral parasitemia. Three patients experienced posttreatment hemolysis but none needed blood transfusion. Otherwise ivA was safe and well tolerated. CONCLUSIONS: ivA was highly efficacious in this pediatric cohort. We observed episodes of mild to moderate posttreatment hemolysis in approximately one-third of patients. The legal status and usage of potentially lifesaving ivA should be evaluated in Europe.
BACKGROUND: Intravenous artesunate (ivA) is the standard treatment for severe malaria. Data systematically evaluating the use of ivA in pediatric patients outside malaria-endemic regions are limited. The aim of this case series was to summarize efficacy and safety of ivA for imported severe malaria in children in Germany. METHODS: Our retrospective case series included pediatric patients with imported severe malaria treated with at least 1 dose of ivA (Artesun, Guilin Pharmaceutical; Shanghai, China) at 4 German tertiary care centers. Severe malaria was defined according to World Health Organization criteria. RESULTS: Between 2010 and 2018, 14 children with a median [interquartile range (IQR)] age of 6 (1;9.5) years were included. All children were of African descent. All but 2 patients had Plasmodium falciparum malaria; 1 child had P. vivax malaria and 1 child had P. falciparum and P. vivax co-infection. Median (IQR) parasitemia at admission in patients with P. falciparum was 9.5% (3;16.5). Patients were treated with 1-10 [median (IQR) 3 (3;4)] doses ivA. All but one patient received a full course of oral antimalarial treatment. Parasite clearance was achieved within 2-4 days, with the exception of 1 patient with prolonged clearance of peripheral parasitemia. Three patients experienced posttreatment hemolysis but none needed blood transfusion. Otherwise ivA was safe and well tolerated. CONCLUSIONS:ivA was highly efficacious in this pediatric cohort. We observed episodes of mild to moderate posttreatment hemolysis in approximately one-third of patients. The legal status and usage of potentially lifesaving ivA should be evaluated in Europe.