Global health initiatives to reduce malaria morbidity in school-aged children
Keywords:Absenteeism, Artemesinin Combination Therapy, Cognitive Impairment, Intermittent Protective Treatment, Rapid Diagnostic Testing, Seasonal Malaria Chemoprophylaxis, Teachers
Aim: To review global initiatives to reduce the burden of disease from malaria on school-aged children. The focus is on approaches with potential to reduce mortality and morbidity, improve the health and ability of children to attend school, avoid malaria impacting their potential academic achievement, and minimize the risk of short- and long-term cognitive impairment.
Methods: Literature searches using defined terms related to malaria and education, and a scoping review of the key literature selected, to provide a narrative summary of the challenges and potential solutions identified.
Results: There is robust evidence that school-aged children are particularly vulnerable to malaria, and need special measures to protect them; calls are widespread for better diagnostic approaches and program innovation because of current levels of malaria-related morbidity and mortality. School-based programs that educate children broadly on causation, prevention and care required can improve access to timely diagnosis and treatment; however, currently national malaria control interventions do not specifically target school-age children. The literature describes intervention strategies that include seasonal chemoprophylaxis, intermittent protective treatment and antimalarial therapy linked to mass drug administration for neglected tropical diseases. Recently, a community participatory intervention model based on WHO-endorsed diagnostic and treatment principles has taught teachers to screen all children sick at school using rapid point-of-care diagnostic testing and treat promptly with Artemesinin combination therapy; morbidity and absenteeism are significantly reduced. There is no consensus on the optimal intervention strategy; approaches will need to vary, but evidence of ‘what works and why’ exists to guide constructive implementation measures in each endemic region.Conclusion: Malaria exemplifies how health inequity negatively impacts a child’s health and ability to benefit from education, yet simple and effective school-based approaches exist that positively impact morbidity, provide access to WHO-endorsed diagnosis and treatment, are applicable worldwide and can increase the capacity of children to learn.
Abba, K., Deeks, J. J., Olliaro, P. L., Naing, C. M., Jackson, S. M., Takwoingi, Y., et al. (2011). Rapid diagnostic tests for diagnosing uncomplicated P. falciparum malaria in endemic countries. Cochrane database of systematic reviews, (7).
Afenyadu, G. Y., Agyepong, I. A., Barnish, G., & Adjei, S. (2005). Improving access to early treatment of malaria: a trial with primary school teachers as care providers. Tropical Medicine & International Health, 10(10), 1065-1072.
Agyepong, I. A., Sewankambo, N., Binagwaho, A., Coll-Seck, A. M., Corrah, T., Ezeh, A., et al. (2017). The path to longer and healthier lives for all Africans by 2030: the Lancet Commission on the future of health in sub-Saharan Africa. The Lancet, 390(10114), 2803-2859.
Airhihenbuwa, C. O., Makoni, S., Iwelunmor, J., & Munodawafa, D. (2014). Sociocultural infrastructure: communicating identity and health in Africa. Journal of health Communication, 19(1), 1-5.
Akweongo, P., Agyei-Baffour, P., Sudhakar, M., Simwaka, B. N., Konaté, A. T., Adongo, P. B., et al. (2011). Feasibility and acceptability of ACT for the community case management of malaria in urban settings in five African sites. Malaria journal, 10(1), 240.
Amexo, M., Tolhurst, R., Barnish, G., & Bates, I. (2004). Malaria misdiagnosis: effects on the poor and vulnerable. The Lancet, 364(9448), 1896-1898.
Ayi, I., Nonaka, D., Adjovu, J. K., Hanafusa, S., Jimba, M., Bosompem, K. M., et al. (2010). School-based participatory health education for malaria control in Ghana: engaging children as health messengers. Malaria journal, 9(1), 98.
Barger, B., Maiga, H., Traore, O. B., Tekete, M., Tembine, I., Dara, A., et al. (2009). Intermittent preventive treatment using artemisinin‐based combination therapy reduces malaria morbidity among school‐aged children in Mali. Tropical Medicine & International Health, 14(7), 784-791.
Bell, D., Fleurent, A. E., Hegg, M. C., Boomgard, J. D., & McConnico, C. C. (2016). Development of new malaria diagnostics: matching performance and need. Malaria journal, 15(1), 406.
Benjamin, J., Moore, B., Lee, S. T., Senn, M., Griffin, S., Lautu, D., et al. (2012). Artemisinin-naphthoquine combination therapy for uncomplicated pediatric malaria: a tolerability, safety, and preliminary efficacy study. Antimicrobial agents and chemotherapy, 56(5), 2465-2471.
Birbeck, G. L., Molyneux, M. E., Kaplan, P. W., Seydel, K. B., Chimalizeni, Y. F., Kawaza, K., & Taylor, T. E. (2010). Blantyre Malaria Project Epilepsy Study (BMPES) of neurological outcomes in retinopathy-positive paediatric cerebral malaria survivors: a prospective cohort study. The Lancet Neurology, 9(12), 1173-1181.
Boivin, M. J., Bangirana, P., Byarugaba, J., Opoka, R. O., Idro, R., Jurek, A. M., & John, C. C. (2007). Cognitive impairment after cerebral malaria in children: a prospective study. Pediatrics, 119(2), e360-e366.
Brooker, S., Kabatereine, N. B., Fleming, F., & Devlin, N. (2008). Cost and cost-effectiveness of nationwide school-based helminth control in Uganda: intra-country variation and effects of scaling-up. Health policy and planning, 23(1), 24-35.
Bundy, D. A. P., Lwin, S., Osika, J. S., McLaughlin, J., & Pannenborg, C. O. (2000). What should schools do about malaria?. Parasitology Today, 16(5), 181-182.
Cairns, M., Roca-Feltrer, A., Garske, T., Wilson, A. L., Diallo, D., Milligan, P. J., ... & Greenwood, B. M. (2012). Estimating the potential public health impact of seasonal malaria chemoprevention in African children. Nature communications, 3(1), 1-9.
Chandramohan, D., Webster, J., Smith, L., Awine, T., Owusu‐Agyei, S., & Carneiro, I. (2007). Is the Expanded Programme on Immunisation the most appropriate delivery system for intermittent preventive treatment of malaria in West Africa?. Tropical Medicine & International Health, 12(6), 743-750.
Clarke, S. E., Jukes, M. C., Njagi, J. K., Khasakhala, L., Cundill, B., Otido, J., et al. (2008). Effect of intermittent preventive treatment of malaria on health and education in schoolchildren: a cluster-randomised, double-blind, placebo-controlled trial. The Lancet, 372(9633), 127-138.
Clarke, S. E., Rouhani, S., Diarra, S., Saye, R., Bamadio, M., Jones, R., et al. (2017). 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 global health, 2(2), e000182.
Cohee, L. M., Chilombe, M., Ngwira, A., Jemu, S. K., Mathanga, D. P., & Laufer, M. K. (2018). Pilot study of the addition of mass treatment for malaria to existing school-based programs to treat neglected tropical diseases. The American journal of tropical medicine and hygiene, 98(1), 95-99.
Cohen, J. M., Woolsey, A. M., Sabot, O. J., Gething, P. W., Tatem, A. J., & Moonen, B. (2012). Optimizing investments in malaria treatment and diagnosis. Science, 338(6107), 612-614.
Counihan, H., Harvey, S. A., Sekeseke-Chinyama, M., Hamainza, B., Banda, R., Malambo, T., et al. (2012). Community health workers use malaria rapid diagnostic tests (RDTs) safely and accurately: results of a longitudinal study in Zambia. The American journal of tropical medicine and hygiene, 87(1), 57-63.
De Silva, P. M., & Marshall, J. M. (2012). Factors contributing to urban malaria transmission in sub-Saharan Africa: a systematic review. Journal of tropical medicine, 2012. doi:10.1155/2012/819563
Dicko, A., Sagara, I., Sissoko, M. S., Guindo, O., Diallo, A. I., Kone, M., et al. (2008). Impact of intermittent preventive treatment with sulphadoxine-pyrimethamine targeting the transmission season on the incidence of clinical malaria in children in Mali. Malaria journal, 7(1), 123.
Dondorp, A. M., Nosten, F., Yi, P., Das, D., Phyo, A. P., Tarning, J., et al. (2009). Artemisinin resistance in Plasmodium falciparum malaria. New England Journal of Medicine, 361(5), 455-467.
Drake, T. L., Okello, G., Njagi, K., Halliday, K. E., Jukes, M. C., Mangham, L., & Brooker, S. (2011). Cost analysis of school-based intermittent screening and treatment of malaria in Kenya. Malaria Journal, 10(1), 273.
Fernando, S. D., Gunawardena, D. M., Bandara, M. R. S. S., De Silva, D., Carter, R., Mendis, K. N., & Wickremasinghe, A. R. (2003)a. The impact of repeated malaria attacks on the school performance of children. The American journal of tropical medicine and hygiene, 69(6), 582-588.
Fernando, D., Wickremasinghe, R., Mendis, K. N., & Wickremasinghe, A. R. (2003)b. Cognitive performance at school entry of children living in malaria-endemic areas of Sri Lanka. Transactions of the Royal Society of Tropical Medicine and Hygiene, 97(2), 161-165.
Fernando, D., De Silva, D., Carter, R., Mendis, K. N., & Wickremasinghe, R. (2006). A randomized, double-blind, placebo-controlled, clinical trial of the impact of malaria prevention on the educational attainment of school children. The American journal of tropical medicine and hygiene, 74(3), 386-393.
Fernando, S. D., Rodrigo, C., & Rajapakse, S. (2010). The 'hidden' burden of malaria: cognitive impairment following infection. Malaria journal, 9(1), 366.
Greenwood, B. (2006). Intermittent preventive treatment–a new approach to the prevention of malaria in children in areas with seasonal malaria transmission. Tropical medicine & international health, 11(7), 983-991.
Halliday, K. E., Okello, G., Turner, E. L., Njagi, K., Mcharo, C., Kengo, J., et al. (2014). Impact of intermittent screening and treatment for malaria among school children in Kenya: a cluster randomized trial. The World Bank.
Holding, P. A., & Snow, R. W. (2001). Impact of Plasmodium falciparum malaria on performance and learning: review of the evidence. The American journal of tropical medicine and hygiene, 64(1_suppl), 68-75.
Hotez, P. J., Molyneux, D. H., Fenwick, A., Kumaresan, J., Sachs, S. E., Sachs, J. D., & Savioli, L. (2007). Control of neglected tropical diseases. New England Journal of Medicine, 357(10), 1018-1027.
Houngbedji, C. A., Prisca, B. N., Hürlimann, E., Yapi, R. B., Silué, K. D., Soro, G., et al. (2015). Disparities of Plasmodium falciparum infection, malaria-related morbidity and access to malaria prevention and treatment among school-aged children: a national cross-sectional survey in Côte d’Ivoire. Malaria journal, 14(1), 7.
International Artemisinin Study Group. (2004). Artesunate combinations for treatment of malaria: meta-analysis. The Lancet, 363(9402), 9-17.
Jukes, M. C., Pinder, M., Grigorenko, E. L., Smith, H. B., Walraven, G., Bariau, E. M., et al. (2006). Long-term impact of malaria chemoprophylaxis on cognitive abilities and educational attainment: follow-up of a controlled trial. PLoS clinical trials, 1(4), e9.
Källander, K., Nsungwa-Sabiiti, J., & Peterson, S. (2004). Symptom overlap for malaria and pneumonia—policy implications for home management strategies. Acta tropica, 90(2), 211-214.
Kihara, M., Carter, J. A., & Newton, C. R. (2006). The effect of Plasmodium falciparum on cognition: a systematic review. Tropical Medicine & International Health, 11(4), 386-397.
Koukounari, A., Estambale, B. B., Njagi, J. K., Cundill, B., Ajanga, A., Crudder, C., et al. (2008). Relationships between anaemia and parasitic infections in Kenyan schoolchildren: a Bayesian hierarchical modelling approach. International journal for parasitology, 38(14), 1663-1671.
Kyabayinze, D. J., Asiimwe, C., Nakanjako, D., Nabakooza, J., Counihan, H., & Tibenderana, J. K. (2010). Use of RDTs to improve malaria diagnosis and fever case management at primary health care facilities in Uganda. Malaria journal, 9(1), 200.
Lalloo, D. G., Olukoya, P., & Olliaro, P. (2006). Malaria in adolescence: burden of disease, consequences, and opportunities for intervention. The Lancet Infectious Diseases, 6(12), 780-793.
Lasker, R. D., & Weiss, E. S. (2003). Broadening participation in community problem solving: a multidisciplinary model to support collaborative practice and research. Journal of Urban Health, 80(1), 14-47.
Laxminarayan, R., Chow, J., & Shahid-Salles, S. A. (2006). Intervention cost-effectiveness: overview of main messages. In: Disease Control Priorities in Developing Countries. 2nd edition. The International Bank for Reconstruction and Development/The World Bank. Oxford University Press. 35-86
Leighton, C., & Foster, R. (1993). Economic impacts of malaria in Kenya and Nigeria. Bethesda: Abt Associates.
Macnab, A. (2013). The Stellenbosch consensus statement on health promoting schools. Global health promotion, 20(1), 78-81.
Macnab, A. J., Stewart, D., & Gagnon, F. A. (2014)a. Health promoting schools: initiatives in Africa. Health education, 114(4), 246-59.
Macnab, A. J., Gagnon, F. A., & Stewart, D. (2014)b. Health promoting schools: consensus, strategies, and potential. Health Education,114 (3), 170-185.
Macnab, A. J., Mukisa, R., Mutabazi, S., & Steed, R. (2016). Malaria in Uganda: School-based rapid diagnostic testing and treatment. Int J Epidemiol, 45(6), 1759-1762.
Macnab, A.J. (2020). School-based initiatives to reduce malaria morbidity and promote academic achievement in children. In: ‘Health in Transition: Translating DOHaD Science to Improve Future Health in Africa.’ Eds. Macnab A.J, Daar A, Pauw C. STIAS Book Series. Stellenbosch University Press.
Magnussen, P., Ndawi, B., Sheshe, A. K., Byskov, J., & Mbwana, K. (2001). Malaria diagnosis and treatment administered by teachers in primary schools in Tanzania. Tropical Medicine & International Health, 6(4), 273-279.
Marmot, M., Friel, S., Bell, R., Houweling, T. A., Taylor, S., & Commission on Social Determinants of Health. (2008). Closing the gap in a generation: health equity through action on the social determinants of health. The lancet, 372(9650), 1661-1669.
Matangila, J. R., Mitashi, P., da Luz, R. A. I., Lutumba, P. T., & Van Geertruyden, J. P. (2015). Efficacy and safety of intermittent preventive treatment for malaria in schoolchildren: a systematic review. Malaria journal, 14(1), 450.
Mbonye, A. K., Magnussen, P., Lal, S., Hansen, K. S., Cundill, B., Chandler, C., & Clarke, S. E. (2015). A cluster randomised trial introducing rapid diagnostic tests into registered drug shops in Uganda: impact on appropriate treatment of malaria. PLoS one, 10(7).
Mphwatiwa, T., Witek-McManus, S., Mtali, A., Okello, G., Nguluwe, P., Chatsika, H., et al. (2017). School-based diagnosis and treatment of malaria by teachers using rapid diagnostic tests and artemisinin-based combination therapy: experiences and perceptions of users and implementers of the Learner Treatment Kit, southern Malawi. Malaria journal, 16(1), 318.
Mutabingwa, T. K. (2005). Artemisinin-based combination therapies (ACTs): best hope for malaria treatment but inaccessible to the needy!. Acta tropica, 95(3), 305-315.
Nankabirwa, J., Brooker, S. J., Clarke, S. E., Fernando, D., Gitonga, C. W., Schellenberg, D., & Greenwood, B. (2014)a. Malaria in school‐age children in Africa: an increasingly important challenge. Tropical Medicine & International Health, 19(11), 1294-1309.
Nankabirwa, J. I., Wandera, B., Amuge, P., Kiwanuka, N., Dorsey, G., Rosenthal, P. J., et al. (2014)b. Impact of intermittent preventive treatment with dihydroartemisinin-piperaquine on malaria in Ugandan schoolchildren: a randomized, placebo-controlled trial. Clinical Infectious Diseases, 58(10), 1404-1412.
Nonaka, D., Kobayashi, J., Jimba, M., Vilaysouk, B., Tsukamoto, K., Kano, S., et al. (2008). Malaria education from school to community in Oudomxay province, Lao PDR. Parasitology International, 57(1), 76-82.
Okello, G., Ndegwa, S. N., Halliday, K. E., Hanson, K., Brooker, S. J., & Jones, C. (2012). Local perceptions of intermittent screening and treatment for malaria in school children on the south coast of Kenya. Malaria journal, 11(1), 185.
Opoku, E. C., Olsen, A., Browne, E., Hodgson, A., Awoonor-Williams, J. K., Yelifari, L., et al. (2016). Impact of combined intermittent preventive treatment of malaria and helminths on anaemia, sustained attention, and recall in Northern Ghanaian schoolchildren. Global health action, 9(1), 32197.
Pasha, O., Del Rosso, J., Mukaka, M., & Marsh, D. (2003). The effect of providing fansidar (sulfadoxine-pyrimethamine) in schools on mortality in school-age children in Malawi. The Lancet, 361(9357), 577-578.
Rennie, W., Phetsouvanh, R., Lupisan, S., Vanisaveth, V., Hongvanthong, B., Phompida, S., et al. (2007). Minimising human error in malaria rapid diagnosis: clarity of written instructions and health worker performance. Transactions of the Royal Society of Tropical Medicine and Hygiene, 101(1), 9-18.
Rutebemberwa, E., Kallander, K., Tomson, G., Peterson, S., & Pariyo, G. (2009). Determinants of delay in care‐seeking for febrile children in eastern Uganda. Tropical Medicine & International Health, 14(4), 472-479.
Sabot, O. J., Mwita, A., Cohen, J. M., Ipuge, Y., Gordon, M., Bishop, D., et al. (2009). Piloting the global subsidy: the impact of subsidized artemisinin-based combination therapies distributed through private drug shops in rural Tanzania. PLoS One, 4(9).
Sachs, J., & Malaney, P. (2002). The economic and social burden of malaria. Nature, 415(6872), 680-685.
Shillcutt, S., Morel, C., Goodman, C., Coleman, P., Bell, D., Whitty, C. J., & Mills, A. (2008). Cost-effectiveness of malaria diagnostic methods in sub-Saharan Africa in an era of combination therapy. Bulletin of the World Health Organization, 86, 101-110.
Simba, D. O., Warsame, M., Kakoko, D., Mrango, Z., Tomson, G., Premji, Z., & Petzold, M. (2010). Who gets prompt access to artemisinin-based combination therapy? A prospective community-based study in children from rural Kilosa, Tanzania. PLoS One, 5(8).
Simovska, V., & Carlsson, M. (2012). Health‐promoting changes with children as agents: findings from a multiple case study research. Health Education,112(3), 292-304.
Simwaka, B. N., Simwaka, K., & Bello, G. (2009). Retrospective analysis of a school-based malaria treatment programme demonstrates a positive impact on health and education outcomes in Mangochi district, Malawi. Journal of development effectiveness, 1(4), 492-506.
St Leger, L. (2001). Schools, health literacy and public health: possibilities and challenges. Health promotion international, 16(2), 197-205.
Tang, K. C., Nutbeam, D., Aldinger, C., St Leger, L., Bundy, D., Hoffmann, A. M., et al. (2009). Schools for health, education and development: a call for action. Health promotion international, 24(1), 68-77.
Temperley, M., Mueller, D. H., Njagi, J. K., Akhwale, W., Clarke, S. E., Jukes, M. C., et al. (2008). Costs and cost-effectiveness of delivering intermittent preventive treatment through schools in western Kenya. Malaria Journal, 7(1), 196.
Thera, M. A., Kone, A. K., Tangara, B., Diarra, E., Niare, S., Dembele, A., et al. (2018). School-aged children based seasonal malaria chemoprevention using artesunate-amodiaquine in Mali. Parasite epidemiology and control, 3(2), 96-105.
Thiam, S., Thior, M., Faye, B., Ndiop, M., Diouf, M. L., Diouf, M. B., et al. (2011). Major reduction in anti-malarial drug consumption in Senegal after nation-wide introduction of malaria rapid diagnostic tests. PloS one, 6(4).
Thuilliez, J., Sissoko, M. S., Toure, O. B., Kamate, P., Berthélemy, J. C., & Doumbo, O. K. (2010). Malaria and primary education in Mali: a longitudinal study in the village of Doneguebougou. Social science & medicine, 71(2), 324-334.
Tipke, M., Louis, V. R., Yé, M., De Allegri, M., Beiersmann, C., Sié, A., et al. (2009). Access to malaria treatment in young children of rural Burkina Faso. Malaria Journal, 8(1), 266.
Viner, R. M., Ozer, E. M., Denny, S., Marmot, M., Resnick, M., Fatusi, A., & Currie, C. (2012). Adolescence and the social determinants of health. The lancet, 379(9826), 1641-1652.
Visser, T., Bruxvoort, K., Maloney, K., Leslie, T., Barat, L. M., Allan, R., ... & Cohen, J. L. (2017). Introducing malaria rapid diagnostic tests in private medicine retail outlets: a systematic literature review. PloS one, 12(3).
Vitor-Silva, S., Reyes-Lecca, R. C., Pinheiro, T. R., & Lacerda, M. V. (2009). Malaria is associated with poor school performance in an endemic area of the Brazilian Amazon. Malaria Journal, 8(1), 230.
Von Seidlein, L. (2014). The failure of screening and treating as a malaria elimination strategy. PLoS medicine, 11(1).
Walldorf, J. A., Cohee, L. M., Coalson, J. E., Bauleni, A., Nkanaunena, K., Kapito-Tembo, A., et al. (2015). School-age children are a reservoir of malaria infection in Malawi. PloS one, 10(7).
White, N. J. (2005). Intermittent presumptive treatment for malaria. PLoS Medicine, 2(1).
Whitty, C. J., Chandler, C., Ansah, E., Leslie, T., & Staedke, S. G. (2008). Deployment of ACT antimalarials for treatment of malaria: challenges and opportunities. Malaria journal, 7(1), S7.
Wilson, A. L. (2011). A systematic review and meta-analysis of the efficacy and safety of intermittent preventive treatment of malaria in children (IPTc). PloS one, 6(2).
Witek-McManus, S., Mathanga, D. P., Verney, A., Mtali, A., Ali, D., Sande, J., et al. (2015). Design, implementation and evaluation of a training programme for school teachers in the use of malaria rapid diagnostic tests as part of a basic first aid kit in southern Malawi. BMC public health, 15(1), 904.
Wongsrichanalai, C., Barcus, M. J., Muth, S., Sutamihardja, A., & Wernsdorfer, W. H. (2007). A review of malaria diagnostic tools: microscopy and rapid diagnostic test (RDT). The American journal of tropical medicine and hygiene, 77(6_Suppl), 119-127.
World Health Organization. (1992) Malaria: A training guide for district health workers on malaria control in tropical Africa, Part 1. Learner’s guide. World Health Organization, Regional Office for Africa, Brazzaville.
World Health Organization. (1993). Implementation of the global malaria control strategy: report of a WHO Study Group on the Implementation of the Global Plan of Action for Malaria Control 1993. World Health Organization.
World Health Organization Commission on Social Determinants of Health. (2008). Closing the gap in a generation: Health equity through action on the social determinants of health: Commission on Social Determinants of Health final report. World Health Organization.
World Health Organization. (2011). Malaria rapid diagnostic test performance: results of WHO product testing of malaria RDTs: round 3 (2010-2011). World Health Organization.
World Health Organization. (2012). Seasonal Malaria Chemoprevention (SMC) for Plasmodium falciparum malaria control in highly seasonal transmission areas of the Sahel sub-region in Africa. Geneva, World Health Organization.
World Health Organization. (2013)a. What is a health promoting school? Geneva, World Health Organization.
World Health Organization. (2013)b. Schistosomiasis: progress report 2001-2011, strategic plan 2012-2020. Geneva, World Health Organization.
World Health Organization (2015) World Malaria Report 2015. Geneva, World Health Organization.
GHMJ (Global Health Management Journal) is an open-access journal following Creative Commons License Deed – Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) which allow users to copy and redistribute the material in any medium or format with one condition--appropriate credit is given to the journal. Author(s) must sign a Copyright Transfer Agreement Form prior to the publication to enable the journal to disseminate your work to the fullest extent. Each author(s) agree to transfer all copyrights of this work to the GHMJ (Global Health Management Journal). The author(s) however, explicitly reserve all proprietary rights other than copyright, such as patent rights, as stated in the Copyright Transfer Agreement Form.