Reactive household-based self-administered treatment against residual malaria transmission: a cluster randomised trial

由于采取了长效驱虫蚊帐和室内滞留喷洒等预防性干预措施以及及时有效的治疗，过去十年来，包括撒哈拉以南非洲一些国家在内的一些国家的疟疾负担大幅下降。然而，目前的干预措施无法中断由（可能）巨大和隐藏的人类感染库维持的传播，这意味着一部分人携带疟疾感染而没有任何症状。后者没有生病，但它们仍然可以感染蚊子媒介，一旦感染，就会感染其他个体。已经提出了几种方法来处理人类感染宿主，包括对整个人群进行有效治疗（大规模药物给药），对受感染个体进行一般或靶向筛查和治疗。它们都需要卫生系统作出重大努力，排除了当地社区的积极参与，而且就筛查和治疗方法而言，实地诊断测试的敏感性不足以检测出所有受感染者。我们提出了一种新的方法，在卫生设施中诊断的临床疟疾病例被认为是疟疾感染者可能聚集的指标病例。因此，干预措施将包括向疟疾患者（或儿童的父母/监护人）提供足够剂量的双氢青蒿素-哌喹，这是冈比亚的二线治疗，以系统地治疗家庭所有成员，即：反应性家庭自我管理治疗（RHOST）。卫生工作人员将通过电话与常驻村卫生工作者联系，跟踪治疗情况，村卫生工作者将在疗程结束后几天检查所有家庭成员是否按正确剂量服用。村卫生工作者还将评估并记录任何不良事件。在实施的第一年，将通过开展形成性研究来优化干预措施，这些研究将提供足够的信息，以使RHOST适应当地情况，同时积极吸引当地社区参与。形成性研究将（i）提供与RHOST有关的基线数据;（ii）通过基于社区的参与性方法，为RHOST制定和测试健康信息、教育和交流（IEC）信息和战略;（iii）监测和评估IEC信息和战略，使RHOST不断适应当地情况。在这一阶段之后，将实施一项适合当地情况的RHOST，并评价其对人类疟疾感染宿主的影响。主要结果将是在干预后的第二个传播季节结束时，通过分子方法确定所有年龄组的疟疾感染率。将评估对当地卫生系统的影响，例如抗疟药物的库存和流动，以及对卫生工作人员活动的影响。经济评估将使用试验结果指标来估计干预措施的增量成本和成本效益。试验将在冈比亚的北岸西部地区进行，从海岸一直延伸到法拉芬尼镇，因为预防性干预的覆盖率很高，疟疾流行率很低。在干预村，将实施RHOST，而在控制村，除了国家疟疾控制方案实施的标准控制措施和卫生设施提供的常规临床护理外，将不进行额外的干预。该试验将在32个中等规模（400- 800人）村庄实施，其中16个为干预组，16个为对照组，这将提供足够的把握度来检测两个研究组之间的显著差异。

Thanks to preventive interventions such as long-lasting insecticidal bed nets and indoor residual spraying, and prompt and efficacious treatments, the malaria burden has decreased substantially over the last decade in several countries, including some in sub-Saharan Africa. Nevertheless, current interventions are unable to interrupt transmission which is maintained by a (probably) large and hidden human reservoir of infection, meaning a proportion of individuals carrying a malaria infection without any symptom. The latter are not sick but they can still infect mosquito vectors that, once infectious, infect other individuals. Several approaches have been proposed to deal with the human reservoir of infection and include the administration of an efficacious treatment to the whole population (mass drug administration), general or targeted screening and treatment of infected individuals. They all require major efforts by the health system, exclude the active participation of the local communities, and, for the screening and treatment approaches the field-based diagnostic tests are not sufficiently sensitive to detect all infected individuals. We propose a novel approach in which clinical malaria cases diagnosed in health facilities are considered index cases around which malaria-infected individuals are probably clustered. Therefore, the intervention will consist in providing to malaria patients (or the parent/guardian in case of children) sufficient doses of dihydroartemisinin-piperaquine, the second line treatment in The Gambia, to systematically treat all members of the household, i .e. reactive household-based self-administered treatment (RHOST). Health staff will follow the treatment by liaising via telephone with the resident village health worker, who will check a few days after completion of the treatment course whether this has been taken at the correct dosage by all household members. The village health worker will also assess for and document any adverse events. The intervention will be optimized by carrying out, during the first year of its implementation, formative research that will provide sufficient information to adapt RHOST to the local context and, at the same time, actively engage local communities. Formative research will (i) provide baseline data relevant to RHOST; (ii) develop and test health Information, Education and Communication (IEC) messages and strategies for RHOST through a community-based and participatory approach; (iii) monitor and evaluate IEC messages and strategies for the continuous adaptation of RHOST to the local context. This phase will be followed by the implementation of a locally adapted RHOST and the evaluation of its impact on the human reservoir of malaria infection. The primary outcome will be the prevalence of malaria infection determined by molecular methods in all age groups at the end of the second transmission season following the intervention. The impact on the local health system, e.g. stock and flow of antimalarial medication, impact on the activities of the health workforce, will be assessed. The economic evaluation will estimate the incremental cost and cost-effectiveness of the intervention using the trial outcome measures.The trial will be carried out in The Gambia, in the North Bank West Region, stretching from the coast up to the town of Farafenni, as the coverage of preventive intervention is high and malaria prevalence low. In intervention villages, RHOST will be implemented while in the control villages there will be no additional intervention besides the standard control measures implemented by the National Malaria Control Program and routine clinical care provided by health facilities. The trial will be implemented in 32 moderate sized (400- 800 persons) villages, 16 in the intervention and 16 in the control arm, which will provide sufficient power to detect a significant difference between the 2 study arms.