title: Artesunate versus quinine in the treatment of severe imported malaria: comparative analysis of adverse events focussing on delayed haemolysis.
abstract: BACKGROUND
  Severe malaria is a potentially life-threatening infectious disease. It has been conclusively shown that artesunate compared to quinine is superior in antiparasitic efficacy and in lowering mortality showing a better short-term safety profile. Regarding longer-term effects, reports of delayed haemolysis after parenteral artesunate for severe malaria in returning travellers have been published recently. So far, delayed haemolysis has not been described after the use of parenteral quinine.
  
  
  METHODS
  In this retrospective study, all patients treated for severe malaria at the University Medical Centre Hamburg-Eppendorf were included between 2006 and 2012. The primary endpoint was the proportion of delayed haemolysis in patients treated with quinine versus those who received artesunate. As secondary endpoint, the proportion of any adverse event was assessed.
  
  
  RESULTS
  A total of 36 patients with severe malaria were included in the analysis. Of these, 16 patients contributed sufficient data to assess the endpoint delayed haemolysis. Twelve were treated primarily with intravenous quinine - with four patients having received intrarectal artesunate as an adjunct treatment - and five patients were treated primarily with artesunate. Five cases of delayed haemolysis could be detected - two in patients treated with quinine and intrarectal artesunate and three in patients treated with artesunate. No case of delayed haemolysis was detected in patients treated with quinine alone.While adverse events observed in patients treated with artesunate were limited to delayed haemolysis (three patients, 60%) and temporary deterioration in renal function (three patients, 60%), patients treated with quinine showed a more diverse picture of side effects with 22 patients (71%) experiencing at least one adverse event. The most common adverse events after quinine were hearing disturbances (12 patients, 37%), hypoglycaemia (10 patients, 32%) and cardiotoxicity (three patients, 14%).
  
  
  CONCLUSIONS
  This study provides further evidence on delayed haemolysis after artesunate and underlines the importance of a standardized follow-up of patients treated with artesunate for severe malaria.
authors.affiliation: Department of Internal Medicine, Section Tropical Medicine University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Thierry
authors.initials: T
authors.lastname: Rolling
authors.forename: Dominic
authors.initials: D
authors.lastname: Wichmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Schmiedel
authors.forename: Gerd D
authors.initials: GD
authors.lastname: Burchard
authors.forename: Stefan
authors.initials: S
authors.lastname: Kluge
authors.forename: Jakob P
authors.initials: JP
authors.lastname: Cramer
mesh_terms: D000328:Adult; D000743:Anemia, Hemolytic / Q000139:chemically induced / Q000453:epidemiology*; D000962:Antimalarials / Q000009:adverse effects* / Q000627:therapeutic use; D037621:Artemisinins / Q000009:adverse effects* / Q000627:therapeutic use; D000077332:Artesunate; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D005260:Female; D005858:Germany / Q000453:epidemiology; D063426:Human Migration; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011803:Quinine / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; D011803:Quinine