title: Chlorproguanil-dapsone versus sulfadoxine-pyrimethamine for sequential episodes of uncomplicated falciparum malaria in Kenya and Malawi: a randomised clinical trial.
abstract: BACKGROUND
  Chlorproguanil-dapsone exerts lower resistance pressure on Plasmodium falciparum than does sulfadoxine-pyrimethamine, but is rapidly eliminated. We aimed to find out whether chlorproguanil-dapsone results in a higher retreatment rate for malaria than sulfadoxine-pyrimethamine.
  
  
  METHODS
  In a randomised trial of paediatric outpatients with uncomplicated falciparum malaria, patients received either chlorproguanil-dapsone or sulfadoxine-pyrimethamine and were followed up for up to 1 year. Sites were in Kenya (n=410) and Malawi (n=500). We used per-protocol analysis to assess the primary outcome of annual malaria incidence.
  
  
  RESULTS
  Drop-outs were 117 of 410 (28.5%) in Kenya, and 342 of 500 (68.4%) in Malawi. Follow-up was for a median of 338 days (IQR 128-360) and 342 days (152-359) in Kilifi (chlorproguanil-dapsone and sulfadoxine-pyrimethamine, respectively), and for 120 days (33-281) and 84 days (26-224) in Blantyre. Mean annual malaria incidence was 2.5 versus 2.1 in Kenya (relative risk 1.16, 95% CI 0.98-1.37), and 2.2 versus 2.8 in Malawi (0.77, 0.63-0.94). 4.3% versus 12.8%, and 5.4% versus 20.1%, of patients were withdrawn for treatment failure in Kenya and Malawi, respectively. In Kenya haemoglobin concentration of 50 g/L or less caused exit in 6.9% of chlorproguanil-dapsone patients and 1.5% of sulfadoxine-pyrimethamine patients, but most anaemia occurred before re-treatment. In Malawi only one patient exited because of anaemia.
  
  
  CONCLUSIONS
  Despite the rapid elimination of chlorproguanil-dapsone, children treated with this drug did not have a higher incidence of malaria episodes than those treated with sulfadoxine-pyrimethamine. Treatment failure was more common with sulfadoxine-pyrimethamine. Cause of anaemia in Kenya was probably not adverse reaction to chlorproguanil-dapsone, but this observation requires further study.
authors.affiliation: Centre for Geographical Medicine, Kenya Medical Research Institute, Kilifi, Kenya.
authors.forename: J
authors.initials: J
authors.lastname: Sulo
authors.forename: P
authors.initials: P
authors.lastname: Chimpeni
authors.forename: J
authors.initials: J
authors.lastname: Hatcher
authors.forename: J G
authors.initials: JG
authors.lastname: Kublin
authors.forename: C V
authors.initials: CV
authors.lastname: Plowe
authors.forename: M E
authors.initials: ME
authors.lastname: Molyneux
authors.forename: K
authors.initials: K
authors.lastname: Marsh
authors.forename: T E
authors.initials: TE
authors.lastname: Taylor
authors.forename: W M
authors.initials: WM
authors.lastname: Watkins
authors.forename: P A
authors.initials: PA
authors.lastname: Winstanley
mesh_terms: D000962:Antimalarials / Q000009:adverse effects*; D002423:Cause of Death; D002675:Child, Preschool; D003622:Dapsone / Q000008:administration & dosage* / Q000009:adverse effects; D003906:Developing Countries; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D006452:Hemoglobinometry; D006801:Humans; D007223:Infant; D007630:Kenya; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D008295:Malawi; D008297:Male; D002727:Proguanil / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D011739:Pyrimethamine / Q000009:adverse effects*; D012008:Recurrence; D019233:Retreatment; D013413:Sulfadoxine / Q000009:adverse effects*; D015996:Survival Rate
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; C007030:chlorproguanil; D003622:Dapsone; D002727:Proguanil; D011739:Pyrimethamine