title: Delayed hemolysis after treatment with parenteral artesunate in African children with severe malaria--a double-center prospective study.
abstract: BACKGROUND
  Parenteral artesunate is recommended as first-line therapy for severe malaria. While its efficacy is firmly established, data on safety are still incomplete. Delayed hemolysis has been described in hyperparasitemic nonimmune travelers, but it is unknown if African children are equally at risk.
  
  
  METHODS
  Children aged 6 to 120 months with severe malaria were followed up after treatment with parenteral artesunate in Lambaréné, Gabon, and Kumasi, Ghana. The primary outcome was incidence of delayed hemolysis on day 14.
  
  
  RESULTS
  In total, 72 children contributed complete data sets necessary for primary outcome assessment. Delayed hemolysis was detected in 5 children (7%), with 1 child reaching a nadir in hemoglobin of 2.8 g/dL. Patients with delayed hemolysis had higher parasite counts on admission (geometric mean parasite densities (GMPD) 306 968/µL vs 92 642/µL, P = .028) and were younger (median age: 24 months vs 43 months, P = .046) than the rest of the cohort. No correlation with sickle cell trait or glucose-6-phosphate-dehydrogenase deficiency was observed.
  
  
  CONCLUSIONS
  Delayed hemolysis is a frequent and relevant complication in hyperparasitemic African children treated with parenteral artesunate for severe malaria. Physicians should be aware of this complication and consider prolonged follow-up.
  
  
  BACKGROUND
  Pan-African Clinical Trials Registry: PACTR201102000277177 (www.pactr.org).
authors.affiliation: Department of Internal Medicine I, Section Tropical Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Department of Clinical Research, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany Centre de Recherches Médicales de Lambaréné, Gabon.
authors.forename: Thierry
authors.initials: T
authors.lastname: Rolling
authors.affiliation: School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
authors.forename: Tsiri
authors.initials: T
authors.lastname: Agbenyega
authors.affiliation: Centre de Recherches Médicales de Lambaréné, Gabon Institute of Tropical Medicine, University Medical Center Tübingen, Tübingen, Germany.
authors.forename: Saadou
authors.initials: S
authors.lastname: Issifou
authors.affiliation: Centre de Recherches Médicales de Lambaréné, Gabon Institute of Tropical Medicine, University Medical Center Tübingen, Tübingen, Germany.
authors.forename: Ayola Akim
authors.initials: AA
authors.lastname: Adegnika
authors.affiliation: School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana Paediatric Emergency Unit, Department of Child Health, Komfo Anokye Teaching Hospital, Kumasi, Ghana.
authors.forename: Justice
authors.initials: J
authors.lastname: Sylverken
authors.affiliation: Department of Internal Medicine I, Section Tropical Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Department of Clinical Research, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Spahlinger
authors.affiliation: School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana Paediatric Emergency Unit, Department of Child Health, Komfo Anokye Teaching Hospital, Kumasi, Ghana.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ansong
authors.affiliation: Centre de Recherches Médicales de Lambaréné, Gabon Institute of Tropical Medicine, University Medical Center Tübingen, Tübingen, Germany.
authors.forename: Sascha J Z
authors.initials: SJ
authors.lastname: Löhr
authors.affiliation: Department of Internal Medicine I, Section Tropical Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Department of Clinical Research, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Gerd D
authors.initials: GD
authors.lastname: Burchard
authors.affiliation: Infectious Disease Epidemiology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: May
authors.affiliation: Centre de Recherches Médicales de Lambaréné, Gabon Institute of Tropical Medicine, University Medical Center Tübingen, Tübingen, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Mordmüller
authors.affiliation: Centre de Recherches Médicales de Lambaréné, Gabon Institute of Tropical Medicine, University Medical Center Tübingen, Tübingen, Germany Centre for Infection and Immunity, Division of Clinical Sciences, St. George's, University of London, London, United Kingdom.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Krishna
authors.affiliation: Centre de Recherches Médicales de Lambaréné, Gabon Institute of Tropical Medicine, University Medical Center Tübingen, Tübingen, Germany.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
authors.affiliation: Department of Internal Medicine I, Section Tropical Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Department of Clinical Research, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Jakob P
authors.initials: JP
authors.lastname: Cramer
mesh_terms: D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D005681:Gabon / Q000453:epidemiology; D005869:Ghana / Q000453:epidemiology; D006461:Hemolysis; D006801:Humans; D007223:Infant; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D011446:Prospective Studies
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate
keywords: African children; Severe malaria; adverse events; artesunate; hemolysis