Efficacy and Safety of Intravenous Artesunate in Children With Severe Imported Malaria.

Abstract

To the Editors: We read with interest the article by Bélard et al1 on intravenous artesunate (ivA) use for imported severe malaria in children. IvA was a highly efficacious treatment in this cohort of children, treated outside malaria-endemic region. Despite the absence of severe side effects, the authors reported posttreatment hemolysis in about one-third of the patients.1 We retrospectively reviewed records of children with severe malaria treated with ivA between 2010 and 2018 at Meyer Children’s University Hospital, Florence, Italy. Malaria was considered severe according to the World Health Organization definition.2,3 Overall, 19 children of African origin with a median age of 5 [interquartile range (IQR) 2–8] years were enrolled (Table 1). All children had Plasmodium falciparum malaria, whereas coinfection with Plasmodium vivax was detected in a child. At admission, median parasitemia was 3% (IQR 2–8).TABLE 1.: General Characteristic of the Enrolled ChildrenIvA was administered with a median of 4 (IQR 3–5) doses. The dosage used was 2.4 mg/kg in the majority of children (n = 12, 63.2%) and 3 mg/kg the remaining ones (n = 7, 36.8%). IvA was administrated every 12 hours for the first 3 doses and, therefore, once daily. IvA was associated with intravenous quinine in all children, who received a median of 6 (IQR 3–11) doses. Moreover, 13 children (68.4%) received a full oral course of dihydroartemisinin/piperaquine, 4 children (21.1%) artemether/lumefantrine and 1 (5.3%) had oral quinine. Parasite clearance was reached after a median of 72 (IQR 48–96) hours after treatment starting. All children had a full recovery and were discharged from hospital after a median of 6 (IQR 5–8) days. No treatment side effects were reported in our population, with the exception of a case of mild posttreatment hemolysis. This was in a 6 years old child who had posttreatment hemolysis not requiring blood transfusion 8 days after ivA treatment start. He had Plasmodium falciparum malaria with baseline parasitemia of 23%. Our data confirm the efficacy of ivA in children with severe imported malaria outside malaria-endemic regions. In fact, a full recover without sequelae was obtained in all the children treated with ivA during the study period. Moreover, ivA has been confirmed to be safe in our population. In fact, no side effects were reported in our study, with the exception of one case of mild posttreatment hemolysis. The lower rate (0.05% vs. 30%) of posttreatment hemolysis in our study could be explained by the lower median parasitemia at admission (3% vs. 9.5%). In our patients, ivA was associated with intravenous quinine, as ivA has not been licensed in Europe with no good manufacturing practice-conform product available. Therefore, the sole use of ivA, despite known to be effective and safe, is at present administered off-label. Interestingly, this association was well tolerated and did not demonstrate higher rate of side effects. The main limitations of our study are the retrospective analysis of data and the limited number of children enrolled. Larger multicentric studies are needed to better understand safety and efficacy of imported severe malaria treatment in children. Elisabetta Venturini, MD, PhDDivision of Pediatric Infectious Disease, Anna Meyer Children’s University Hospital, Florence, Italy Lorenzo Zammarchi, MD, PhDDepartment of Experimental and Clinical Medicine, University of Florence, Referral Center for Tropical Diseases of Tuscany, Infectious and Tropical Diseases Unit, Careggi University Hospital, Florence, Italy Leila Bianchi, MDDivision of Pediatric Infectious Disease, Anna Meyer Children’s University Hospital, Florence, Italy Carlotta Montagnani, MD, PhDDivision of Pediatric Infectious Disease, Anna Meyer Children’s University Hospital, Florence, Italy Chiara Tersigni, MDDepartment of Health Sciences, University of Florence, Florence, Italy Barbara Bortone, MDDivision of Pediatric Infectious Disease, Anna Meyer Children’s University Hospital, Florence, Italy Elena Chiappini, MD, PhDDivision of Pediatric Infectious Disease, Anna Meyer Children’s University Hospital, Department of Health Sciences, University of Florence, Florence, Italy Luisa Galli, MDDivision of Pediatric Infectious Disease, Anna Meyer Children’s University Hospital, Department of Health Sciences, University of Florence, Florence, Italy