Impact of intermittent screening and treatment for malaria among school children in Kenya: a cluster randomised trial

Katherine E Halliday, George Okello, Elizabeth L Turner, Kiambo Njagi, Carlos Mcharo, Juddy Kengo, Elizabeth Allen, Margaret M Dubeck, Matthew C H Jukes, Simon J Brooker, Katherine E Halliday, George Okello, Elizabeth L Turner, Kiambo Njagi, Carlos Mcharo, Juddy Kengo, Elizabeth Allen, Margaret M Dubeck, Matthew C H Jukes, Simon J Brooker

Abstract

Background: Improving the health of school-aged children can yield substantial benefits for cognitive development and educational achievement. However, there is limited experimental evidence of the benefits of alternative school-based malaria interventions or how the impacts of interventions vary according to intensity of malaria transmission. We investigated the effect of intermittent screening and treatment (IST) for malaria on the health and education of school children in an area of low to moderate malaria transmission.

Methods and findings: A cluster randomised trial was implemented with 5,233 children in 101 government primary schools on the south coast of Kenya in 2010-2012. The intervention was delivered to children randomly selected from classes 1 and 5 who were followed up for 24 months. Once a school term, children were screened by public health workers using malaria rapid diagnostic tests (RDTs), and children (with or without malaria symptoms) found to be RDT-positive were treated with a six dose regimen of artemether-lumefantrine (AL). Given the nature of the intervention, the trial was not blinded. The primary outcomes were anaemia and sustained attention. Secondary outcomes were malaria parasitaemia and educational achievement. Data were analysed on an intention-to-treat basis. During the intervention period, an average of 88.3% children in intervention schools were screened at each round, of whom 17.5% were RDT-positive. 80.3% of children in the control and 80.2% in the intervention group were followed-up at 24 months. No impact of the malaria IST intervention was observed for prevalence of anaemia at either 12 or 24 months (adjusted risk ratio [Adj.RR]: 1.03, 95% CI 0.93-1.13, p = 0.621 and Adj.RR: 1.00, 95% CI 0.90-1.11, p = 0.953) respectively, or on prevalence of P. falciparum infection or scores of classroom attention. No effect of IST was observed on educational achievement in the older class, but an apparent negative effect was seen on spelling scores in the younger class at 9 and 24 months and on arithmetic scores at 24 months.

Conclusion: In this setting in Kenya, IST as implemented in this study is not effective in improving the health or education of school children. Possible reasons for the absence of an impact are the marked geographical heterogeneity in transmission, the rapid rate of reinfection following AL treatment, the variable reliability of RDTs, and the relative contribution of malaria to the aetiology of anaemia in this setting.

Trial registration: www.ClinicalTrials.gov NCT00878007.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1. Map of the study area…
Figure 1. Map of the study area and schools.
Schools assigned to the IST intervention are shown in blue and schools assigned to the control group are shown in yellow. Insert shows the location of the study site in Kenya.
Figure 2. Study design diagram.
Figure 2. Study design diagram.
This figure depicts the randomisation procedures.
Figure 3. Trial profile.
Figure 3. Trial profile.
The flow of children and clusters in the 50 control 51 IST intervention groups at all assessment points throughout the two-year study period. FU1 indicates follow-up 1 and FU2 indicates follow-up 2. Cluster size is presented as mean (SD) [min, max].

References

    1. O'Meara WP, Mangeni JN, Steketee R, Greenwood B (2010) Changes in the burden of malaria in sub-Saharan Africa. Lancet Infect Dis 10: 545–555.
    1. Ceesay SJ, Casals-Pascual C, Nwakanma DC, Walther M, Gomez-Escobar N, et al. (2010) Continued decline of malaria in The Gambia with implications for elimination. PLoS ONE 5: e12242 doi:
    1. Kalayjian BC, Malhotra I, Mungai PL, Holding PA, King CH (2013) Marked decline in malaria prevalence among pregnant women and their offspring from 1996 to 2010 on the South Kenyan coast. Am J Trop Med Hyg 89: 1129–1134.
    1. Ceesay SJ, Casals-Pascual C, Erskine J, Anya SE, Duah NO, et al. (2008) Changes in malaria indices between 1999 and 2007 in The Gambia: a retrospective analysis. Lancet 372: 1545–1554.
    1. O'Meara WP, Bejon P, Mwangi TW, Okiro EA, Peshu N, et al. (2008) Effect of a fall in malaria transmission on morbidity and mortality in Kilifi, Kenya. Lancet 372: 1555–1562.
    1. Greenwood BM (2008) Control to elimination: implications for malaria research. Trends Parasitol 24: 449–454.
    1. Smith DL, Guerra CA, Snow RW, Hay SI (2007) Standardizing estimates of the Plasmodium falciparum parasite rate. Malar J 6: 131.
    1. Brooker S, Kolaczinski JH, Gitonga CW, Noor AM, Snow RW (2009) The use of schools for malaria surveillance and programme evaluation in Africa. Malar J 8: 231.
    1. Brooker S, Guyatt H, Omumbo J, Shretta R, Drake L, et al. (2000) Situation analysis of malaria in school-aged children in Kenya - what can be done? Parasitol Today 16: 183–186.
    1. Japan International Cooperation Agency (JICA) (2012) Basic education sector analysis report: Kenya. Tokyo: JICA.
    1. Kurtzhals JA, Addae MM, Akanmori BD, Dunyo S, Koram KA, et al. (1999) Anaemia caused by asymptomatic Plasmodium falciparum infection in semi-immune African schoolchildren. Trans R Soc Trop Med Hyg 93: 623–627.
    1. Menendez C, Fleming AF, Alonso PL (2000) Malaria-related anaemia. Parasitol Today 16: 469–476.
    1. Fernando D, Wickremasinghe R, Mendis KN, Wickremasinghe AR (2003) Cognitive performance at school entry of children living in malaria-endemic areas of Sri Lanka. Trans R Soc Trop Med Hyg 97: 161–165.
    1. Kihara M, Carter JA, Newton CRJC (2006) The effect of Plasmodium falciparum on cognition: a systematic review. Trop Med Int Health 11: 386–397.
    1. Fernando SD, Rodrigo C, Rajapakse S (2010) The ‘hidden’ burden of malaria: cognitive impairment following infection. Malar J 9: 366.
    1. Nankabirwa J, Wandera B, Kiwanuka N, Staedke SG, Kamya MR, et al. (2013) Asymptomatic Plasmodium infection and cognition among primary schoolchildren in a high malaria transmission setting in Uganda. Am J Trop Med Hyg 88: 1102–1108.
    1. Al Serouri AW, Grantham-McGregor SM, Greenwood B, Costello A (2000) Impact of asymptomatic malaria parasitaemia on cognitive function and school achievement of schoolchildren in the Yemen Republic. Parasitology 121: 337–345.
    1. Fernando D, de Silva D, Carter R, Mendis KN, Wickremasinghe R (2006) 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 74: 386–393.
    1. Moonen B, Cohen JM, Snow RW, Slutsker L, Drakeley C, et al. (2010) Operational strategies to achieve and maintain malaria elimination. Lancet 376: 1592–1603.
    1. Bousema T, Griffin JT, Sauerwein RW, Smith DL, Churcher TS, et al. (2012) Hitting hotspots: spatial targeting of malaria for control and elimination. PLoS Med 9: e1001165 doi:
    1. Githeko AK, Brandling-Bennett AD, Beier M, Atieli F, Owaga M, et al. (1992) The reservoir of Plasmodium falciparum malaria in a holoendemic area of western Kenya. Trans R Soc Trop Med Hyg 86: 355–358.
    1. Bousema JT, Gouagna LC, Drakeley CJ, Meutstege AM, Okech BA, et al. (2004) Plasmodium falciparum gametocyte carriage in asymptomatic children in western Kenya. Malar J 3: 18.
    1. Brooker S (2009) Malaria control in schools: a toolkit on effective education sector responses to malaria in Africa. Washington (D.C.): The World Bank
    1. Clarke SE, Jukes MCH, Njagi JK, Khasakhala L, Cundill B, et al. (2008) Effect of intermittent preventive treatment of malaria on health and education in schoolchildren: a cluster-randomised, double-blind, placebo-controlled trial. Lancet 372: 127–138.
    1. Barger B, Maiga H, Traore OB, Tekete M, Tembine I, et al. (2009) Intermittent preventive treatment using artemisinin-based combination therapy reduces malaria morbidity among school-aged children in Mali. Trop Med Int Health 14: 784–791.
    1. Griffin JT, Hollingsworth TD, Okell LC, Churcher TS, White M, et al. (2010) Reducing Plasmodium falciparum malaria transmission in Africa: a model-based evaluation of intervention strategies. PLoS Med 7: e1000324 doi:
    1. Kern SE, Tiono AB, Makanga M, Gbadoe AD, Premji Z, et al. (2011) Community screening and treatment of asymptomatic carriers of Plasmodium falciparum with artemether-lumefantrine to reduce malaria disease burden: a modelling and simulation analysis. Malar J 10: 210.
    1. Tagbor H, Bruce J, Agbo M, Greenwood B, Chandramohan D (2010) Intermittent screening and treatment versus intermittent preventive treatment of malaria in pregnancy: a randomised controlled non-inferiority trial. PLoS ONE 5: e14425 doi:
    1. Tiono AB, Ouedraogo A, Ogutu B, Diarra A, Coulibaly S, et al. (2013) A controlled, parallel, cluster-randomized trial of community-wide screening and treatment of asymptomatic carriers of Plasmodium falciparum in Burkina Faso. Malar J 12: 79.
    1. Brooker S, Okello G, Njagi K, Dubeck MM, Halliday KE, et al. (2010) Improving educational achievement and anaemia of school children: design of a cluster randomised trial of school-based malaria prevention and enhanced literacy instruction in Kenya. Trials 11: 93.
    1. Snow RW, Schellenberg JR, Peshu N, Forster D, Newton CR, et al. (1993) Periodicity and space-time clustering of severe childhood malaria on the coast of Kenya. Trans R Soc Trop Med Hyg 87: 386–390.
    1. Mbogo CM, Mwangangi JM, Nzovu J, Gu W, Yan G, et al. (2003) Spatial and temporal heterogeneity of Anopheles mosquitoes and Plasmodium falciparum transmission along the Kenyan coast. Am J Trop Med Hyg 68: 734–742.
    1. Mwangangi JM, Mbogo CM, Orindi BO, Muturi EJ, Midega JT, et al. (2013) Shifts in malaria vector species composition and transmission dynamics along the Kenyan coast over the past 20 years. Malar J 12: 13.
    1. Bustinduy AL, Thomas CL, Fiutem JJ, Parraga IM, Mungai PL, et al. (2011) Measuring fitness of Kenyan children with polyparasitic infections using the 20-meter shuttle run test as a morbidity metric. PLoS Negl Trop Dis 5: e1213 doi:
    1. Halliday KE, Karanja P, Turner EL, Okello G, Njagi K, et al. (2012) Plasmodium falciparum, anaemia and cognitive and educational performance among school children in an area of moderate malaria transmission: baseline results of a cluster randomized trial on the coast of Kenya. Trop Med Int Health 17: 532–549.
    1. Dubeck MM, Jukes MCH, Okello G (2012) Early primary literacy instruction in Kenya. Comparative Education Review 56: 48–68.
    1. Martinez EZ, Louzada-Neto F, Derchain SFM, Achcar JA, Gontijo RC, et al. (2008) Bayesian estimation of performance measures of cervical cancer screening tests in the presence of covariates and absence of a gold standard. Cancer Inform 6: 33–46.
    1. Division of Malaria Control Ministry of Public Health and Sanitation (2009) National Malaria Strategy 2009–2017. Nairobi: Kenya NMCP.
    1. Manly T, Robertson IH, Anderson V, Nimmo-Smith I (1999) Test of everyday attention for children: TEA-Ch. Bury St Edmunds, UK: Thames Valley Test Company.
    1. Luria AR (1966) Higher cortical functions in man. New York: Basic Books.
    1. Invernizzi M, Sullivan A, Meier J, Swank L (2004) PALS: phonological awareness literacy screening. Charlottesville (Virginia): University of Virginia.
    1. Benoist B, McLean E, Egli I, Cogswell M (2008) Worldwide prevalence of anaemia 1993–2003: WHO global database on anaemia. Geneva: WHO.
    1. Filmer D, Pritchett LH (2001) Estimating wealth effects without expenditure data–or tears: an application to educational enrollments in states of India. Demography 38: 115–132.
    1. WHO (2007) Anthroplus: growth reference 5–19 years. WHO, editor. Geneva: WHO.
    1. Hayes RJ, Moulton LH (2009) Cluster randomised trials. Hall C, editor. London: CRC Press.
    1. Bundy D (2011) Rethinking school health: a key component of education for all. Washington (D.C.): World Bank.
    1. Okello G, Jones C, Bonareri M, Ndegwa SN, McHaro C, et al. (2013) Challenges for consent and community engagement in the conduct of cluster randomized trial among school children in low income settings: experiences from Kenya. Trials 14: 142.
    1. Bejon P, Warimwe G, Mackintosh CL, Mackinnon MJ, Kinyanjui SM, et al. (2009) Analysis of immunity to febrile malaria in children that distinguishes immunity from lack of exposure. Infect Immun 77: 1917–1923.
    1. Bousema T, Kreuels B, Gosling R (2011) Adjusting for heterogeneity of malaria transmission in longitudinal studies. J Infect Dis 204: 1–3.
    1. Sowunmi A, Gbotosho GO, Happi CT, Adedeji AA, Fehintola FA, et al. (2007) Therapeutic efficacy and effects of artemether-lumefantrine and amodiaquine-sulfalene-pyrimethamine on gametocyte carriage in children with uncomplicated Plasmodium falciparum malaria in southwestern Nigeria. Am J Trop Med Hyg 77: 235–241.
    1. Woodring JV, Ogutu B, Schnabel D, Waitumbi JN, Olsen CH, et al. (2010) Evaluation of recurrent parasitemia after artemether-lumefantrine treatment for uncomplicated malaria in children in western Kenya. Am J Trop Med Hyg 83: 458–464.
    1. Nambozi M, Van Geertruyden J-P, Hachizovu S, Chaponda M, Mukwamataba D, et al. (2011) Safety and efficacy of dihydroartemisinin-piperaquine versus artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Zambian children. Malar J 10: 50.
    1. Nankabirwa J, Cundill B, Clarke S, Kabatereine N, Rosenthal PJ, et al. (2010) Efficacy, safety, and tolerability of three regimens for prevention of malaria: a randomized, placebo-controlled trial in Ugandan schoolchildren. PLoS ONE 5: e13438 doi:
    1. Ochola LB, Vounatsou P, Smith T, Mabaso MLH, Newton CRJC (2006) The reliability of diagnostic techniques in the diagnosis and management of malaria in the absence of a gold standard. Lancet Infect Dis 6: 582–588.
    1. Speybroeck N, Praet N, Claes F, Van Hong N, Torres K, et al. (2011) True versus apparent malaria infection prevalence: the contribution of a Bayesian approach. PLoS ONE 6: e16705 doi:
    1. Gonçalves L, Subtil A, de Oliveira MR, do Rosário V, Lee P-W, et al. (2012) Bayesian latent class models in malaria diagnosis. PLoS ONE 7: e40633 doi:
    1. Okell LC, Ghani AC, Lyons E, Drakeley CJ (2009) Submicroscopic infection in Plasmodium falciparum-endemic populations: a systematic review and meta-analysis. J Infect Dis 200: 1509–1517.
    1. Okell LC, Bousema T, Griffin JT, Ouédraogo AL, Ghani AC, et al. (2012) Factors determining the occurrence of submicroscopic malaria infections and their relevance for control. Nat Commun 3: 1237.
    1. Dinko B, Oguike MC, Larbi JA, Bousema JT, Sutherland CJ (2013) Persistent detection of Plasmodium falciparum, P. malariae, P. ovale curtisi and P. ovale wallikeri after ACT treatment of asymptomatic Ghanaian school-children. Int J Parasitol 3: 45–50.
    1. Okello G, Ndegwa SN, Halliday KE, Hanson K, Brooker SJ, et al. (2012) Local perceptions of intermittent screening and treatment for malaria in school children on the south coast of Kenya. Malar J 11: 185.
    1. Drake TL, Okello G, Njagi K, Halliday KE, Jukes MC, et al. (2011) Cost analysis of school-based intermittent screening and treatment of malaria in Kenya. Malar J 10: 273.
    1. Piola P, Fogg C, Bajunirwe F, Biraro S, Grandesso F, et al. (2005) Supervised versus unsupervised intake of six-dose artemether-lumefantrine for treatment of acute, uncomplicated Plasmodium falciparum malaria in Mbarara, Uganda: a randomised trial. Lancet 365: 1467–1473.
    1. Borrmann S, Sasi P, Mwai L, Bashraheil M, Abdallah A, et al. (2011) Declining responsiveness of Plasmodium falciparum infections to artemisinin-based combination treatments on the Kenyan coast. PLoS ONE 6: e26005 doi:
    1. Agarwal A, McMorrow M, Onyango P, Otieno K, Odero C, et al. (2013) A randomized trial of artemether-lumefantrine and dihydroartemisinin-piperaquine in the treatment of uncomplicated malaria among children in western Kenya. Malar J 12: 254.
    1. National Coordination Agency for Population and Development (2005) Kwale District Strategic Plan 2005–2010 for implementation of the National Population Poilcy for Sustainable Development. Nairobi: National Coordination Agency for Population and Development. 1–55 p.
    1. Kenya Food Security Steering Group (2012) The 2011/12 Short Rains Season Assessment Report. Nairobi: Kenya Food Security Steering Group. 1–42 p.
    1. Pullan RL, Gitonga C, Mwandawiro C, Snow RW, Brooker SJ (2013) Estimating the relative contribution of parasitic infections and nutrition for anaemia among school-aged children in Kenya: a subnational geostatistical analysis. BMJ Open 3.
    1. Smith LA, Jones C, Adjei RO, Antwi GD, Afrah NA, et al. (2010) Intermittent screening and treatment versus intermittent preventive treatment of malaria in pregnancy: user acceptability. Malar J 9: 18.
    1. Hamadani JD, Fuchs GJ, Osendarp SJ, Khatun F, Huda SN, et al. (2001) Randomized controlled trial of the effect of zinc supplementation on the mental development of Bangladeshi infants. Am J Clin Nutr 74: 381–386.
    1. Heyneman SP, Loxley WA (1983) The effect of primary-school quality on academic achievement across twenty-nine high- and low-income countries. Ajs 88: 1162–1194.
    1. Bhargava A, Jukes M, Ngorosho D, Khilma C, Bundy DA (2005) Modeling the effects of health status and the educational infrastructure on the cognitive development of Tanzanian schoolchildren. Am J Hum Biol 17: 280–292.
    1. Takem EN, Affara M, Amambua-Ngwa A, Okebe J, Ceesay SJ, et al. (2013) Detecting foci of malaria transmission with school surveys: a pilot study in the Gambia. PLoS ONE 8: e67108 doi:
    1. Gitonga CW, Karanja PN, Kihara J, Mwanje M, Juma E, et al. (2010) Implementing school malaria surveys in Kenya: towards a national surveillance system. Malar J 9: 306.
    1. Ashton RA, Kefyalew T, Tesfaye G, Pullan RL, Yadeta D, et al. (2011) School-based surveys of malaria in Oromia Regional State, Ethiopia: a rapid survey method for malaria in low transmission settings. Malar J 10: 25.
    1. Stevenson J, Stresman G, Gitonga CW, Gillig J, Owaga C, et al. (2013) Reliability of school surveys in estimating geographic variation in malaria transmission in the Western Kenyan highlands. PLoS ONE 8: e77641 doi:

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