title: Effect of intermittent preventive treatment of malaria on health and education in schoolchildren: a cluster-randomised, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Malaria is a major cause of morbidity and mortality in early childhood, yet its consequences for health and education during the school-age years remain poorly understood. We examined the effect of intermittent preventive treatment (IPT) in reducing anaemia and improving classroom attention and educational achievement in semi-immune schoolchildren in an area of high perennial transmission.
  
  
  METHODS
  A stratified, cluster-randomised, double-blind, placebo-controlled trial of IPT was done in 30 primary schools in western Kenya. Schools were randomly assigned to treatment (sulfadoxine-pyrimethamine in combination with amodiaquine or dual placebo) by use of a computer-generated list. Children aged 5-18 years received three treatments at 4-month intervals (IPT n=3535, placebo n=3223). The primary endpoint was the prevalence of anaemia, defined as a haemoglobin concentration below 110 g/L. This outcome was assessed through cross-sectional surveys 12 months post-intervention. Analysis was by both intention to treat, excluding children with missing data, and per protocol. This study is registered with ClinicalTrials.gov, number NCT00142246.
  
  
  RESULTS
  2604 children in the IPT group and 2302 in the placebo group were included in the intention-to-treat analysis of the primary outcome; the main reason for exclusion was loss to follow-up. Prevalence of anaemia at 12 months averaged 6.3% in the IPT group and 12.6% in the placebo group (adjusted risk ratio 0.52, 95% CI 0.29-0.93; p=0.028). Significant improvements were also seen in two of the class-based tests of sustained attention, with a mean increase in code transmission test score of 6.05 (95% CI 2.83-9.27; p=0.0007) and counting sounds test score of 1.80 (0.19-3.41; p=0.03), compared with controls. No effect was shown for inattentive or hyperactive-compulsive behaviours or on educational achievement. The per-protocol analysis yielded similar results. 23 serious adverse events were reported within 28 days of any treatment (19 in the IPT group and four in the placebo group); the main side-effects were problems of balance, dizziness, feeling faint, nausea, and/or vomiting shortly after treatment.
  
  
  CONCLUSIONS
  IPT of malaria improves the health and cognitive ability of semi-immune schoolchildren. Effective malaria interventions could be a valuable addition to school health programmes.
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK. Electronic address: sian.clarke@lshtm.ac.uk.
authors.forename: Siân E
authors.initials: SE
authors.lastname: Clarke
authors.affiliation: Harvard University, Cambridge, MA, USA.
authors.forename: Matthew Ch
authors.initials: MC
authors.lastname: Jukes
authors.affiliation: Division of Malaria Control, Ministry of Health, Nairobi, Kenya.
authors.forename: J Kiambo
authors.initials: JK
authors.lastname: Njagi
authors.affiliation: African Mental Health Foundation, Nairobi, Kenya.
authors.forename: Lincoln
authors.initials: L
authors.lastname: Khasakhala
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Cundill
authors.affiliation: Institute of Tropical and Infectious Diseases, University of Nairobi, Kenya.
authors.forename: Julius
authors.initials: J
authors.lastname: Otido
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Crudder
authors.affiliation: Institute of Tropical and Infectious Diseases, University of Nairobi, Kenya.
authors.forename: Benson Ba
authors.initials: BB
authors.lastname: Estambale
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK; Malaria Public Health and Epidemiology Group, Centre for Geographic Medicine Research-Coast, KEMRI-Wellcome Trust Collaborative Programme, Nairobi, Kenya.
authors.forename: Simon
authors.initials: S
authors.lastname: Brooker
mesh_terms: D000293:Adolescent; D000655:Amodiaquine / Q000008:administration & dosage* / Q000627:therapeutic use*; D000740:Anemia / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D003071:Cognition / Q000187:drug effects; D003430:Cross-Sectional Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005243:Feces / Q000469:parasitology; D005260:Female; D006801:Humans; D007630:Kenya / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D008297:Male; D010963:Plasmodium falciparum; D015995:Prevalence; D011739:Pyrimethamine / Q000008:administration & dosage / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine