title: Efficacy and safety of artemisinin combination therapy (ACT) for non-falciparum malaria: a systematic review.
abstract: BACKGROUND
  Artemisinin combination therapy (ACT) is recommended as first-line treatment for uncomplicated Plasmodium falciparum malaria, whereas chloroquine is still commonly used for the treatment of non-falciparum species (Plasmodium vivax, Plasmodium ovale and Plasmodium malariae). A more simplified, more uniform treatment approach across all malaria species is worthwhile to be considered both in endemic areas and for malaria as an imported condition alike.
  
  
  METHODS
  A PROSPERO-registered systematic review to determine the efficacy and safety of ACT for the treatment of non-falciparum malaria was conducted, following PRISMA guidelines. Without language restrictions, Medline/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, Biosis Previews and the African Index Medicus were searched for studies published up to November 2014.
  
  
  RESULTS
  The literature search identified 986 reports; 40 publications were found eligible for inclusion, all of them on non-falciparum malaria in endemic areas. Most evidence was available for P. vivax (n = 35). Five clinical trials in total were identified evaluating ACT for P. ovale, P. malariae and Plasmodium knowlesi. Most ACT presentations have high efficacy against P. vivax parasites; artemisinin-based combinations have shorter parasite and fever clearance times compared to chloroquine. ACT is as effective as chloroquine in preventing recurrent parasitaemia before day 28. Artemisinin-based combinations with long half-lives show significantly fewer recurrent parasitaemia up to day 63. The limited evidence available supports both the use of chloroquine and an ACT for P. ovale and P. malariae. ACT seems to be preferable for optimal treatment of P. knowlesi.
  
  
  CONCLUSIONS
  ACT is at least equivalent to chloroquine in effectively treating non-falciparum malaria. These findings may facilitate development of simplified protocols for treating all forms of malaria with ACT, including returning travellers. Obtaining comprehensive efficacy and safety data on ACT use for non-falciparum species particularly for P. ovale, P. malariae and P. knowlesi should be a research priority.
  
  
  BACKGROUND
  CRD42014009103.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Visser
authors.forename: Rosanne W
authors.initials: RW
authors.lastname: Wieten
authors.forename: Daniëlle
authors.initials: D
authors.lastname: Kroon
authors.forename: Ingeborg M
authors.initials: IM
authors.lastname: Nagel
authors.forename: Sabine
authors.initials: S
authors.lastname: Bélard
authors.forename: Michèle
authors.initials: M
authors.lastname: van Vugt
authors.affiliation: Department of Infectious Diseases, Division of Internal Medicine, Center of Tropical Medicine and Travel Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, PO Box 22700, 1100 DE Amsterdam, The Netherlands. m.p.grobusch@amc.uva.nl.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Grobusch
mesh_terms: D000962:Antimalarials / Q000009:adverse effects* / Q000627:therapeutic use*; D037621:Artemisinins / Q000009:adverse effects* / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D037621:Artemisinins; C031327:artemisinin