title: Artesunate to treat severe malaria in travellers: review of efficacy and safety and practical implications.
abstract: BACKGROUND
  Artesunate (AS) is the WHO first-line treatment of severe malaria in endemic countries, in adults and children. However, despite solid evidence that AS is safe and more effective than quinine in endemic areas, its deployment in non-endemic areas has been slow, due in part to the absence of a full good manufacturing practice (GMP) qualification (although prequalification has been granted in 2010). Prospective comparative trials were not conducted in travellers, but several retrospective studies and case reports are providing insights into the efficacy and safety of AS in imported severe malaria.
  
  
  METHODS
  We performed a systematic review on AS use in non-endemic areas for the treatment of imported severe malaria, using the Prisma method for bibliographic reports. Post-AS delayed haemolysis (PADH) was defined by delayed haemolytic episodes occurring 7-30 days after treatment initiation. We summarized prescription guidelines and generated answers to frequently asked questions regarding the use of AS in travellers with severe malaria.
  
  
  RESULTS
  We analysed 12 retrospectives and 1 prospective study as well as 7 case reports of AS treatment in 624 travellers. Of 574 patients with reported outcome, 23 died (4%). No death was attributed to AS toxicity. Non-haematological side effects were uncommon and mainly included mild hepatitis, neurological, renal, cutaneous and cardiac manifestations. PADH occurred in 15% of the treated patients. No death or sequelae were reported. Overall blood transfusion was administered in 50% of travellers with PADH.
  
  
  CONCLUSIONS
  AS is highly efficacious in travellers with severe malaria. The frequency of PADH supports the need of weekly follow-up of haematological parameters during 1 month. Full GMP qualification for the drug and rapid approval by drug agencies is warranted, backed by clear recommendations for optimal use.
authors.affiliation: Université Sorbonne Paris Cité, Université Paris Descartes, Inserm, INTS, Unité Biologie Intégrée du Globule Rouge, Laboratoire d'Excellence GR-Ex, Paris, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Roussel
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Service des Maladies Infectieuses et Tropicales, Paris, France.|Sorbonne Université, Université Pierre et Marie Curie, faculté de médecine Pitié-Salpêtrière, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Caumes
authors.affiliation: Sorbonne Université, Université Pierre et Marie Curie, faculté de médecine Pitié-Salpêtrière, Paris, France.|Centre National de Référence du Paludisme - Site Pitié-Salpêtrière, Paris, France.|Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Service de parasitologie, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Thellier
authors.affiliation: Université Sorbonne Paris Cité, Université Paris Descartes, Inserm, INTS, Unité Biologie Intégrée du Globule Rouge, Laboratoire d'Excellence GR-Ex, Paris, France.
authors.forename: Papa Alioune
authors.initials: PA
authors.lastname: Ndour
authors.affiliation: Université Sorbonne Paris Cité, Université Paris Descartes, Inserm, INTS, Unité Biologie Intégrée du Globule Rouge, Laboratoire d'Excellence GR-Ex, Paris, France.
authors.forename: Pierre A
authors.initials: PA
authors.lastname: Buffet
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Service des Maladies Infectieuses et Tropicales, Paris, France.|Sorbonne Université, Université Pierre et Marie Curie, faculté de médecine Pitié-Salpêtrière, Paris, France.|Centre National de Référence du Paludisme - Site Pitié-Salpêtrière, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Jauréguiberry
mesh_terms: D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D012189:Retrospective Studies; D014195:Travel
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate
keywords: Artesunate; anaemia; imported malaria; post-artesunate delayed haemolysis; travellers