School-based Treatment with ACT to Reduce Transmission: Evaluation of the community impact of intermittent preventive treatment for malaria in Uganda

尽管全球承诺控制疟疾，供资也大幅增加，但非洲的疟疾负担仍然很高。目前，疟疾控制的目标是五岁以下儿童和孕妇。学龄儿童仍然相对暴露，使他们面临患病和死亡的风险，并有可能将疟疾传播给社区其他成员。间歇性预防治疗（IPT），即不论感染状况如何，按预先确定的时间间隔给予抗疟疾治疗，已被证明对孕妇、婴儿和幼儿有益，并已成为一项重要的疟疾控制战略。在乌干达和非洲其他地方进行的初步研究表明，学龄儿童也受益于IPT，但IPT的社区效益和对疟疾传播的影响尚未得到证实。我们建议评估乌干达学龄儿童疟疾IPT对社区健康和疟疾传播指标的影响。我们将在卡农古区选择36所小学参与研究；18所学校将被随机分配接受IPT干预，18所学校将被分配到标准护理（不干预）。双氢青蒿素-哌喹（DP）是一种高效、长效的以青蒿素为基础的联合疗法，将向在干预学校上学的符合条件的儿童每学期提供一次（每年3次），为期一年。此外，根据国家指导方针，干预学校和标准护理学校的所有儿童都将每年接受驱虫治疗。将通过对社区、学童和蚊虫媒介的调查来衡量结果。社区和学校调查将在基线和第三轮（也是最后一轮）治疗后大约两个月进行。社区调查将包括一份家庭调查表和对所有家庭成员的实验室评价；将包括从36个分组中随机抽取的180户居民。在学校调查中，将从36所学校中随机抽取64名学生。在社区和学校调查中，将获得手指刺血样本，以评估疟疾寄生虫和测量血液计数（血红蛋白）。还将从36个群集中随机选择的8个家庭中收集蚊子。在研究期间，每所房屋将每月抽样一次。试验的主要结果将是社区中感染疟疾寄生虫的人口比例和昆虫学接种率（每年每人感染蚊子叮咬的估计数量）。我们还将确定感染疟疾寄生虫的学童的比例。一项定性研究将在主要试验的同时进行，以调查对IPT干预的看法，以及将干预纳入乌干达卫生服务和学校系统的潜在可行性。这项工作的结果将有助于为未来信息、教育和传播计划的设计提供信息，如果干预措施被规模化。我们还将进行数学建模，以确定干预措施在其他流行病学环境中的潜在影响。鉴于学龄儿童对社区疟疾传播的潜在贡献，以及基于学校的干预措施在操作上取得成功和可持续性的可能性，以学龄儿童为目标的IPT是否能够在人口层面上减少疟疾传播的问题具有高度相关性。这项试验将解决这个问题，并包括卫生服务研究和建模，以帮助指导未来的研究和干预措施的实施，并帮助制定乌干达和非洲其他地方的政策。

Despite global commitment to malaria control and substantial increases in funding, the burden of malaria in Africa remains high. Currently, malaria control is targeted at children under five years and pregnant women. School-aged children remain relatively uncovered leaving them at risk for illness and death, and with the potential to transmit malaria to other members of the community. Intermittent preventive treatment (IPT), administering antimalarial treatment at predefined intervals regardless of infection status, has been shown to benefit pregnant women, infants, and young children, and has become an important malaria control strategy. Initial studies conducted in Uganda and elsewhere in Africa suggest that school-aged children also benefit from IPT, but the community benefits of IPT and impact on malaria transmission are unproven. We propose to evaluate the impact of IPT for malaria in Ugandan schoolchildren on indicators of health and malaria transmission in the community. We will select 36 primary schools in Kanungu district to participate in the study; 18 schools will be randomly assigned to receive the IPT intervention, and 18 will be assigned to standard care (no intervention). Dihydroartemisinin-piperaquine (DP), a highly effective and long-acting, artemisinin-based combination therapy (ACT) will be provided to eligible children attending intervention schools once a term (3 times per year) for one year. In addition, all children in both the intervention and standard care schools will receive annual deworming, according to national guidelines.Outcomes will be measured using surveys of communities, schoolchildren, and mosquito vectors.Community and school surveys will be conducted at baseline and approximately two months after the third (and final) round of treatment. The community surveys will consist of a household questionnaire and a laboratory evaluation of all household members; 180 residents from randomly selected households from each of the 36 clusters will be included. For the school surveys, 64 randomly selected children from each of the 36 schools will be included. In both community and school surveys, a finger-prick blood sample will be obtained to evaluate for malaria parasites and to measure blood counts (haemoglobin). Mosquitos will also be collected from eight randomly selected households from each of the 36 clusters. Each house will be sampled once a month for the duration of the study. The primary outcomes for the trial will be the proportion of people that are infected with malaria parasites and the entomologic inoculation rate (estimated number of infective mosquito bites per person per year) in the community. We will also determine the proportion of schoolchildren that are infected with malaria parasites. A qualitative study will run alongside the main trial to investigate perceptions of the IPT intervention, and the potential feasibility of integrating the intervention into health service and school systems in Uganda. Results from this work will help to inform the design of future Information, Education, and Communication programmes if the intervention was taken to scale. We will also conduct mathematical modelling to determine the potential impact of the intervention in other epidemiological settings. Given the potential contribution by school-aged children to malaria transmission in the community, and the likelihood of operational success and sustainability of school-based interventions, the question of whether IPT targeted to schoolchildren could reduce malaria transmission at a population level is highly relevant. This trial will address that question, and includes health service research and modelling to help guide future research and implementation of the intervention, and help shape policies in Uganda and elsewhere in Africa.