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

Siân E Clarke, Matthew Ch Jukes, J Kiambo Njagi, Lincoln Khasakhala, Bonnie Cundill, Julius Otido, Christopher Crudder, Benson Ba Estambale, Simon Brooker, Siân E Clarke, Matthew Ch Jukes, J Kiambo Njagi, Lincoln Khasakhala, Bonnie Cundill, Julius Otido, Christopher Crudder, Benson Ba Estambale, Simon Brooker

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.

Figures

Figure 1
Figure 1
Trial profile ITT=intention-to-treat. PP=per-protocol.
Figure 2
Figure 2
Distribution of haemoglobin concentrations among children, according to treatment (intention-to-treat population) Individual-level data are presented; distribution does not take into account the clustering of children within schools.

References

    1. Snow R, Marsh K. The consequences of reducing transmission of Plasmodium falciparum infection in Africa. Adv Parasitol. 2002;52:235–264.
    1. Bloland PB, Boriga DA, Ruebush TK. Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission II. Descriptive epidemiology of malaria infection and disease among children. Am J Trop Med Hyg. 1999;60:641–648.
    1. Clarke SE, Brooker S, Njagi JK. Malaria morbidity amongst schoolchildren living in two areas of contrasting transmission in western Kenya. Am J Trop Med Hyg. 2004;71:732–738.
    1. Kurtzhals JA, Addae MM, Akanmori BD. Anaemia caused by asymptomatic Plasmodium falciparum infection in semi-immune African schoolchildren. Trans R Soc Trop Med Hyg. 1999;93:623–627.
    1. Holding PA, Snow RW. Impact of Plasmodium falciparum malaria on performance and learning: review of the evidence. Am J Trop Med Hyg. 2001;64(suppl 1–2):68–75.
    1. Lalloo DG, Olukoya P, Olliaro P. Malaria in adolescence: burden of disease, consequences, and opportunities for intervention. Lancet Infect Dis. 2006;6:780–793.
    1. Bundy DA, Lwin S, Osika JS, McLaughlin J, Pannenborg CO. What should schools do about malaria? Parasitol Today. 2000;16:181–182.
    1. Brooker S, Guyatt H, Omumbo J, Shretta R, Drake L, Ouma J. Situation analysis of malaria in school-aged children in Kenya: what can be done? Parasitol Today. 2000;16:183–186.
    1. Brooker S, Clarke SE, Snow RW, Bundy DA. Malaria in African schoolchildren: options for control. Trans R Soc Trop Med Hyg. 2008;102:304–305.
    1. Greenwood BM. Malaria chemoprophylaxis in endemic regions. In: Targett GAT, editor. Malaria: waiting for the vaccine. John Wiley & Sons; Chichester: 1991. pp. 83–104.
    1. Geerligs PD, Brabin BJ, Eggelte TA. Analysis of the effects of malaria chemoprophylaxis in children on haematological responses, morbidity and mortality. Bull World Health Organ. 2003;81:205–216.
    1. Colbourne MJ. The effect of malaria suppression in a group of Accra school children. Trans R Soc Trop Med Hyg. 1955;49:356–369.
    1. Fernando SD, Gunawardena DM, Bandara MR. The impact of repeated malaria attacks on the school performance of children. Am J Trop Med Hyg. 2003;69:582–588.
    1. Fernando SD, De Silva D, Carter R, Mendis KN, Wickremasinghe R. A randomized, double-blind, placebo-controlled, clinical trial of the impact of malaria prevention on the educational attainment of school children. Am J Trop Med Hyg. 2006;74:386–393.
    1. Greenwood BM. The use of antimalarial drugs to prevent malaria in the population of malaria-endemic areas. Am J Trop Med Hyg. 2004;70:1–7.
    1. Beier JC, Oster CN, Onyango FK. Plasmodium falciparum incidence relative to entomological inoculation rates at a site proposed for testing malaria vaccines in western Kenya. Am J Trop Med Hyg. 1994;50:529–536.
    1. Brooker S, Miguel EA, Waswa P. The potential of rapid screening methods for Schistosoma mansoni in western Kenya. Ann Trop Med Parasitol. 2001;95:343–351.
    1. Manly T, Robertson IH, Anderson V, Nimmo-Smith I. Test of Everyday Attention for Children: TEA-Ch. Thames Valley Test Company; Bury St Edmunds: 1999.
    1. McCarney SB. Early Childhood Attention Deficit Disorders Evaluation Scale. Hawthorne Educational Services Inc; Columbia, MO: 1995.
    1. Hayes RJ, Bennett S. Simple sample size calculations for cluster-randomized trials. Int J Epidemiol. 1999;28:319–326.
    1. Bennett S, Parpia T, Hayes R, Cousens S. Methods for the analysis of incidence rates in cluster randomized trials. Int J Epidemiol. 2002;31:839–846.
    1. Leenstra T, Phillips-Howard PA, Kariuki SK. Permethrin-treated bed nets in the prevention of malaria and anemia in adolescent schoolgirls in western Kenya. Am J Trop Med Hyg. 2003;68(suppl 4):S86–S93.
    1. Stephenson LS, Latham MC, Kinoti SN, Kurz KM, Brigham H. Single dose metrifonate or praziquantel treatment in Kenyan children. I. Effects on Schistosoma haematobium, hookworm, hemoglobin levels, splenomegaly, and hepatomegaly. Am J Trop Med Hyg. 1989;41:436–444.
    1. Beasley NM, Tomkins AM, Hall A. The impact of population level deworming on the hemoglobin levels of schoolchildren in Tanga, Tanzania. Trop Med Int Health. 1999;4:744–750.
    1. Gulani A, Nagpal J, Osmond C, Sachdev HP. Effect of administration of intestinal anthelmintic drugs on haemoglobin: systematic review of randomised controlled trials. BMJ. 2007;334:1095.
    1. Hall A, Roschnik N, Ouattara F. A randomised trial in Mali of the effectiveness of weekly iron supplements given by teachers on the haemoglobin concentrations of schoolchildren. Public Health Nutr. 2002;5:413–418.
    1. Longfils P, Heang UK, Soeng H, Sinuon M. Weekly iron and folic acid supplementation as a tool to reduce anemia among primary school children in Cambodia. Nutr Rev. 2005;63:39–45.
    1. Hettiarachchi M, Liyanage C, Wickremasinghe R, Hilmers DC, Abrams SA. The efficacy of micronutrient supplementation in reducing the prevalence of anaemia and deficiencies of zinc and iron among adolescents in Sri Lanka. Eur J Clin Nutr. 2007 published online May 16.
    1. Risonar MG, Tengco LW, Rayco-Solon P, Solon FS. The effect of a school-based weekly iron supplementation delivery system among anemic schoolchildren in the Philippines. Eur J Clin Nutr. 2007 published online May 30.
    1. Menendez C, Fleming AF, Alonso PL. Malaria-related anaemia. Parasitol Today. 2000;16:469–476.
    1. White NJ. Intermittent preventive treatment for malaria. PLoS Med. 2005;2:e3.
    1. Kihara M, Carter JA, Newton C. The effect of Plasmodium falciparum on cognition: a systematic review. Trop Med Int Health. 2006;11:386–397.
    1. Jukes MC, Pinder M, Grigorenko EL. Long-term impact of malaria chemoprophylaxis on cognitive abilities and educational attainment: follow-up of a controlled trial. PLoS Clin Trials. 2006;1:e19.
    1. Grantham-McGregor S, Ani C. A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr. 2001;131(suppl 2):649S–666S.
    1. Soemantri AG, Pollitt E, Kim I. Iron deficiency anaemia and educational achievement. Am J Clin Nutr. 1985;42:1221–1228.
    1. Jukes MC, Drake LJ, Bundy DA. School health, nutrition and education for all: levelling the playing field. CABI Publishing; Wallingford, UK: 2007.
    1. Bundy DA, Shaeffer S, Jukes M. School based health and nutrition programs. In: Jamison D, Breman JG, Measham AR, editors. Disease control priorities in developing countries. 2nd edn. The World Bank and Oxford University Press; New York, USA: 2006. pp. 1091–1108.
    1. Brooker S, Akhwale W, Pullan R. Epidemiology of plasmodium-helminth co-infection in Africa: populations at risk, potential impact on anemia and prospects for combining control. Am J Trop Med Hyg. 2007;77(suppl 6):88–98.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner