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Intravenous Artesunate for Imported Severe Malaria in Children Treated in Four Tertiary Care Centers in Germany

A Retrospective Study

Bélard, Sabine MD*,†; Brand, Judith MD*; Schulze-Sturm, Ulf MD; Janda, Ales MD§; von Both, Ulrich MD; Tacoli, Costanza Phd; Alberer, Martin MD**; Kempf, Caroline MD††; Stegemann, Miriam S. MD‡‡; Krüger, Renate MD*; Varnholt, Verena MD*; Blohm, Martin MD; Reiter, Karl MD§§; Zoller, Thomas MD‡‡; Suttorp, Norbert MD‡‡; Mall, Marcus MD*,†; von Bernuth, Horst PhD*,¶¶,‖‖; Gratopp, Alexander MD*; Hübner, Johannes MD; Hufnagel, Markus MD§; Kobbe, Robin MD; Kurth, Florian MD‡‡

The Pediatric Infectious Disease Journal: November 2019 - Volume 38 - Issue 11 - p e295–e300
doi: 10.1097/INF.0000000000002417
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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.

From the *Department of Paediatric Pulmonology, Immunology and Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany

Berlin Institute of Health, Berlin, Germany

Department of Paediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

§Division of Paediatric Infectious Diseases and Rheumatology, Department of Paediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany

Division Paediatric Infectious Diseases, Dr. von Hauner Children’s Hospital, University Hospital, Ludwig Maximilians University, Munich, Germany

Institute of Tropical Medicine and International Health, Charité - Universitätsmedizin Berlin, Berlin, Germany

**Division of Infectious Diseases and Tropical Medicine, University Hospital, LMU Munich, Munich, Germany

††Department of Paediatric Gastroenterology, Nephrology and Metabolic Disorders, Charité- Universitätsmedizin Berlin, Berlin, Germany

‡‡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

§§Division of Paediatric Intensive Care, Dr. von Hauner Children’s Hospital, University Hospital, Ludwig Maximilians University, Munich, Germany

¶¶Labor Berlin, Immunology, Berlin, Germany

‖‖Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Accepted for publication June 6, 2019.

There was no project-specific funding. S.B. is currently a participant in the BIH-Charité Clinician Scientist Program funded by Charité - Universitätsmedizin Berlin and the Berlin Institute of Health.

The authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.pidj.com).

Address for correspondence: Sabine Bélard, MD, Department of Paediatric Pulmonology, Immunology and Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany. E-mail: sabine.belard@charite.de.

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