Assessment of community-level effects of intermittent preventive treatment for malaria in schoolchildren in Jinja, Uganda (START-IPT trial): a cluster-randomised trial

Sarah G Staedke, Catherine Maiteki-Sebuguzi, Andrea M Rehman, Simon P Kigozi, Samuel Gonahasa, Jaffer Okiring, Steve W Lindsay, Moses R Kamya, Clare I R Chandler, Grant Dorsey, Chris Drakeley, Sarah G Staedke, Catherine Maiteki-Sebuguzi, Andrea M Rehman, Simon P Kigozi, Samuel Gonahasa, Jaffer Okiring, Steve W Lindsay, Moses R Kamya, Clare I R Chandler, Grant Dorsey, Chris Drakeley

Abstract

Background: Intermittent preventive treatment (IPT) is a well established malaria control intervention. Evidence that delivering IPT to schoolchildren could provide community-level benefits is limited. We did a cluster-randomised controlled trial to assess the effect of IPT of primary schoolchildren with dihydroartemisinin-piperaquine (DP) on indicators of malaria transmission in the community, in Jinja, Uganda.

Methods: We included 84 clusters, each comprising one primary school and the 100 closest available households. The clusters were randomly assigned 1:1 to receive IPT with DP or standard care (control) by restricted randomisation to ensure balance by geography and school type. Children in intervention schools received IPT monthly for up to six rounds (June to December, 2014). We did cross-sectional community surveys in randomly selected households at baseline and in January to April, 2015, during which we measured participants' temperatures and obtained finger-prick blood smears for measurement of parasite prevalence by microscopy. We also did entomological surveys 1 night per month in households from 20 randomly selected IPT and 20 control clusters. The primary trial outcome was parasite prevalence in the final community survey. The primary entomological survey outcome was the annual entomological inoculation rate (aEIR) from July, 2014, to April, 2015. This trial is registered at ClinicalTrials.gov, number NCT02009215.

Findings: Among 23 280 students registered in the 42 intervention schools, 10 079 (43%) aged 5-20 years were enrolled and received at least one dose of DP. 9286 (92%) of 10 079 received at least one full course of DP (three doses). Community-level parasite prevalence was lower in the intervention clusters than in the control clusters (19% vs 23%, adjusted risk ratio 0·85, 95% CI 0·73-1·00, p=0·05). The aEIR was lower in the intervention group than in the control group, but not significantly so (10·1 vs 15·2 infective bites per person, adjusted incidence rate ratio 0·80, 95% CI 0·36-1·80, p=0·59).

Interpretation: IPT of schoolchildren with DP might have a positive effect on community-level malaria indicators and be operationally feasible. Studies with greater IPT coverage are needed.

Funding: UK Medical Research Council, UK Department for International Development, and Wellcome Trust.

Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Figures

Figure 1
Figure 1
Map of study area The study included 84 clusters, each including one primary school and the closest available 100 surrounding households. IPT=intermittent preventive treatment.
Figure 2
Figure 2
Trial profile IPT=intermittent preventive treatment. DP=dihydroartemisinin-piperaquine. AL=artemether-lumefantrine. *One household was excluded and replaced with a newly recruited household.

References

    1. WHO . World Health Organization; Geneva: 2016. World malaria report 2016.
    1. Greenwood B, Koram K. Malaria control in Africa: progress but still much to do. Lancet. 2014;383:1703–1704.
    1. Kamya MR, Arinaitwe E, Wanzira H. Malaria transmission, infection, and disease at three sites with varied transmission intensity in Uganda: implications for malaria control. Am J Trop Med Hyg. 2015;92:903–912.
    1. Katureebe A, Zinszer K, Arinaitwe E. Measures of malaria burden after long-lasting insecticidal net distribution and indoor residual spraying at three sites in Uganda: a prospective observational study. PLoS Med. 2016;13:e1002167.
    1. Raouf S, Mpimbaza A, Kigozi R. Resurgence of malaria following discontinuation of indoor residual spraying of insecticide in a previously high transmission intensity area of Uganda. Clin Infect Dis. 2017;65:453–460.
    1. Nankabirwa J, Brooker SJ, Clarke SE. Malaria in school-age children in Africa: an increasingly important challenge. Trop Med Int Health. 2014;19:1294–1309.
    1. Matangila JR, Mitashi P, Inocencio da Luz RA, Lutumba PT, Van Geertruyden JP. Efficacy and safety of intermittent preventive treatment for malaria in schoolchildren: a systematic review. Malar J. 2015;14:450.
    1. Opoku EC, Olsen A, Browne E. Impact of combined intermittent preventive treatment of malaria and helminths on anaemia, sustained attention, and recall in Northern Ghanaian schoolchildren. Glob Health Action. 2016;9:32197.
    1. Clarke S, Rouhani S, Diarra S. Impact of a malaria intervention package in schools on Plasmodium infection, anaemia and cognitive function in schoolchildren in Mali: a pragmatic cluster-randomised trial. BMJ Glob Health. 2017;2:e000182.
    1. Matangila JR, Doua JY, Mitashi P, da Luz RI, Lutumba P, Van Geertruyden JP. Efficacy and safety of intermittent preventive treatment in schoolchildren with sulfadoxine/pyrimethamine (SP) and SP plus piperaquine in Democratic Republic of the Congo: a randomised controlled trial. Int J Antimicrob Agents. 2017;49:339–347.
    1. Goncalves BP, Kapulu M, Sawa P. Examining the human infectious reservoir for Plasmodium falciparum malaria in areas of differing transmission intensity. Nat Commun. 2017;8:1133.
    1. Gutman J, Kovacs S, Dorsey G, Stergachis A, Ter Kuile FO. Safety, tolerability, and efficacy of repeated doses of dihydroartemisinin-piperaquine for prevention and treatment of malaria: a systematic review and meta-analysis. Lancet Infect Dis. 2017;17:184–193.
    1. Kilama M, Smith DL, Hutchinson R. Estimating the annual entomological inoculation rate for Plasmodium falciparum transmitted by Anopheles gambiae s.l. using three sampling methods in three sites in Uganda. Malar J. 2014;13:111.
    1. WHO . World Health Organization; Geneva: 2011. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity.
    1. Nankabirwa JI, Yeka A, Arinaitwe E. Estimating malaria parasite prevalence from community surveys in Uganda: a comparison of microscopy, rapid diagnostic tests and polymerase chain reaction. Malar J. 2015;14:528.
    1. Hayes R, Bennett S. Simple sample size calculations for cluster-randomized trials. Int J Epidemiol. 1999;28:319–326.
    1. Griffin JT, Hollingsworth TD, Okell LC. Reducing Plasmodium falciparum malaria transmission in Africa: a model-based evaluation of intervention strategies. PLoS Med. 2010;7:e1000324.
    1. Newby G, Hwang J, Koita K. Review of mass drug administration for malaria and its operational challenges. Am J Trop Med Hyg. 2015;93:125–134.
    1. WHO . World Health Organization; Geneva: 2015. Mass drug administration, mass screening and treatment and focal screening and treatment for malaria: WHO Evidence Review Group meeting report.
    1. Eisele TP, Bennett A, Silumbe K. Short-term impact of mass drug administration with dihydroartemisinin plus piperaquine on malaria in southern province Zambia: a cluster-randomized controlled trial. J Infect Dis. 2016;214:1831–1839.
    1. Brady OJ, Slater HC, Pemberton-Ross P. Role of mass drug administration in elimination of Plasmodium falciparum malaria: a consensus modelling study. Lancet Glob Health. 2017;5:e680–e687.
    1. Cheah PY, White NJ. Antimalarial mass drug administration: ethical considerations. Int Health. 2016;8:235–238.
    1. Tiono AB, Ouedraogo A, Ogutu B. A controlled, parallel, cluster-randomized trial of community-wide screening and treatment of asymptomatic carriers of Plasmodium falciparum in Burkina Faso. Malar J. 2013;12:79.
    1. Larsen DA, Bennett A, Silumbe K. Population-wide malaria testing and treatment with rapid diagnostic tests and artemether-lumefantrine in southern Zambia: a community randomized step-wedge control trial design. Am J Trop Med Hyg. 2015;92:913–921.
    1. Cisse B, Ba EH, Sokhna C. Effectiveness of seasonal malaria chemoprevention in children under ten years of age in Senegal: a stepped-wedge cluster-randomised trial. PLoS Med. 2016;13:e1002175.
    1. Okello G, Jones C, Bonareri M. Challenges for consent and community engagement in the conduct of cluster randomized trial among school children in low income settings: experiences from Kenya. Trials. 2013;14:142.
    1. Geissler PW, Pool R. Editorial: popular concerns about medical research projects in sub-Saharan Africa—a critical voice in debates about medical research ethics. Trop Med Int Health. 2006;11:975–982.
    1. Cohee LM, Chilombe M, Ngwira A, Jemu SK, Mathanga DP, Laufer MK. Pilot study of the addition of mass treatment for malaria to existing school-based programs to treat neglected tropical diseases. Am J Trop Med Hyg. 2018;98:95–99.
    1. Schneider P, Schoone G, Schallig H. Quantification of Plasmodium falciparum gametocytes in differential stages of development by quantitative nucleic acid sequence-based amplification. Mol Biochem Parasitol. 2004;137:35–41.
    1. Clarke SE, Jukes MC, Njagi JK. Effect of intermittent preventive treatment of malaria on health and education in schoolchildren: a cluster-randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:127–138.
    1. Pullan RL, Gitonga C, Mwandawiro C, Snow RW, Brooker SJ. Estimating the relative contribution of parasitic infections and nutrition for anaemia among school-aged children in Kenya: a subnational geostatistical analysis. BMJ Open. 2013;3:e001936.
    1. Uganda Bureau of Statistics . Macro International; Calverton, MD: 2007. Uganda demographic and health survey, 2006.

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