Effect of intermittent preventive treatment of malaria on health and education in schoolchildren: a cluster-randomised, double-blind, placebo-controlled trial

Lancet. 2008 Jul 12;372(9633):127-138. doi: 10.1016/S0140-6736(08)61034-X.

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.

Findings: 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.

Interpretation: 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Amodiaquine / administration & dosage*
  • Amodiaquine / therapeutic use*
  • Anemia / epidemiology
  • Anemia / etiology
  • Anemia / prevention & control*
  • Animals
  • Antimalarials / administration & dosage
  • Antimalarials / therapeutic use*
  • Child
  • Child, Preschool
  • Cluster Analysis
  • Cognition / drug effects
  • Cross-Sectional Studies
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Combinations
  • Feces / parasitology
  • Female
  • Humans
  • Kenya / epidemiology
  • Malaria, Falciparum / complications
  • Malaria, Falciparum / epidemiology
  • Malaria, Falciparum / prevention & control*
  • Male
  • Plasmodium falciparum
  • Prevalence
  • Pyrimethamine / administration & dosage
  • Pyrimethamine / therapeutic use*
  • Sulfadoxine / administration & dosage
  • Sulfadoxine / therapeutic use*

Substances

  • Antimalarials
  • Drug Combinations
  • Amodiaquine
  • fanasil, pyrimethamine drug combination
  • Sulfadoxine
  • Pyrimethamine

Associated data

  • ClinicalTrials.gov/NCT00142246