title: Evidence basis for antimalarial policy change in Sierra Leone: five in vivo efficacy studies of chloroquine, sulphadoxine-pyrimethamine and amodiaquine.
abstract: OBJECTIVE
  To provide nationally relevant information on the antimalarial efficacy of chloroquine (CQ), sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ) in Sierra Leone, with a view to updating antimalarial policy in the country.
  
  
  METHODS
  Between October 2002 and May 2003, standard WHO methodology for in vivo efficacy assessment was used in five sites to study the therapeutic response of 6-59 months old uncomplicated Plasmodium falciparum malaria cases treated with CQ (n = 247), SP (n = 353) or AQ (n = 434). Follow-up was of 28 days, with polymerase chain reaction genotyping to distinguish late recrudescences from re-infections.
  
  
  RESULTS
  Overall 85.3% of patients reached an analysable endpoint. CQ failure proportions were very high, ranging from 39.5% (95% CI: 25.0-55.6) in Kabala to 78.8% (65.3-88.9) in Kailahun. Early failures under CQ were frequent. SP efficacy was also disappointing, with failure from 23.2% (13.9-34.9) in Kabala to 46.1% (35.4-57.0) in Kailahun. AQ resistance was more moderate, ranging from 5.4% (1.8-12.1) in Makeni to 29.8% (20.3-40.8) in Kailahun, with almost no early failures. AQ also provided more rapid fever and parasite clearance.
  
  
  CONCLUSIONS
  In a consensus meeting organized by the Ministry of Health and Sanitation, and based on these findings, artesunate (AS) + AQ and artemether-lumefantrine (Coartemtrade mark) were identified as the only options to rapidly replace CQ. The choice fell on AS + AQ because of expected high efficacy, lower cost in a blister presentation, and the absence of safety data on artemether-lumefantrine in pregnancy. Donor support is required to support this policy change. Throughout Africa, as SP resistance increases, these two regimens are probably the only options available while newer combinations are developed. Efficacy studies should focus on testing AQ and AS + AQ.
authors.affiliation: Epicentre, 8 rue Saint-Sabin, 75011 Paris, France. francesco.checchi@lshtm.ac.uk
authors.forename: Francesco
authors.initials: F
authors.lastname: Checchi
authors.forename: Paul
authors.initials: P
authors.lastname: Roddy
authors.forename: Sarian
authors.initials: S
authors.lastname: Kamara
authors.forename: Arthur
authors.initials: A
authors.lastname: Williams
authors.forename: Guy
authors.initials: G
authors.lastname: Morineau
authors.forename: Abdul Rahman
authors.initials: AR
authors.lastname: Wurie
authors.forename: Bona
authors.initials: B
authors.lastname: Hora
authors.forename: Nadine de
authors.initials: Nd
authors.lastname: Lamotte
authors.forename: Tim
authors.initials: T
authors.lastname: Baerwaldt
authors.forename: Annette
authors.initials: A
authors.lastname: Heinzelmann
authors.forename: Alison
authors.initials: A
authors.lastname: Danks
authors.forename: Loretxu
authors.initials: L
authors.lastname: Pinoges
authors.forename: Aggrey
authors.initials: A
authors.lastname: Oloo
authors.forename: Rémy
authors.initials: R
authors.lastname: Durand
authors.forename: Lisa
authors.initials: L
authors.lastname: Ranford-Cartwright
authors.forename: Martin
authors.initials: M
authors.lastname: Smet
mesh_terms: D000655:Amodiaquine / Q000627:therapeutic use; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D002675:Child, Preschool; D002738:Chloroquine / Q000627:therapeutic use; D003906:Developing Countries; D004338:Drug Combinations; D004351:Drug Resistance; D019317:Evidence-Based Medicine; D005260:Female; D006291:Health Policy; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects; D011739:Pyrimethamine / Q000627:therapeutic use; D012807:Sierra Leone; D013413:Sulfadoxine / Q000627:therapeutic use; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine