Adjunctive Ivermectin Mass Drug Administration for Malaria Elimination: A cluster randomized trial

这项试验将首次调查在季节性低传播环境下，在大规模给药(MDA)中加入伊维菌素(IVM)和有效的抗疟疾药物(如双氢青蒿素-哌喹(DP))以减少疟疾传播的影响。在一项以群组为基础的随机社区试验中，将把添加剂IVM丙二醛与仅含DP的丙二醛(在疟疾传播高峰期(7-9月)每天治疗3天)与疟疾控制的标准方案干预措施(长效杀虫蚊帐和孕期间歇预防性治疗(IPTp))进行比较。主要结果指标将是以人群为基础的恶性疟原虫(疟疾感染)流行率(使用超敏感的聚合酶链式反应测试估计)和冈比亚按蚊(疟疾媒介)存活率(使用解剖按蚊卵巢估计的胎次来衡量)。将包括关于丙二醛覆盖率、干预的可接受性和可行性的数据以及成本效益分析。我们在比贾戈·S群岛建立了实地基础设施(包括训练有素的实地昆虫学家和实地实验室技术人员)，并详细说明了疟疾和其他被忽视的热带病以及岛屿上病媒种群造成的疾病负担的最新基线数据。这种“天然实验室”的岛屿环境提供了一个无与伦比的机会，可以使用综合的丙二醛策略，通过调查输入感染的影响(通过扩展的基于社区的CDSAT(病例检测筛查和治疗)干预，我们将在两个手臂中包括)，使用血液中的血清(免疫)标志物来定义传播动力学和估计昆虫学接种率(EIR)，并随着时间的推移监测IVM丙二醛对受限媒介种群的影响，从而了解传播及其阻断。

This trial will be the first to investigate the impact of adding ivermectin (IVM) to mass drug administration (MDA) with an efficacious antimalarial (eg dihydroartemisinin-piperaquine (DP)) to reduce malaria transmission in a seasonal low-transmission setting. Additive IVM MDA will be compared to DP-only MDA (with treatment daily for three days during the three months of peak malaria transmission (July-September)) in combination with standard programmatic interventions for malaria control (long-lasting insecticidal nets (LLIN) and intermittent preventative treatment in pregnancy (IPTp)) in a cluster-randomized community-based trial. Primary outcome measures will be population-based Plasmodium falciparum (malaria infection) prevalence (estimated using ultra-sensitive PCR tests) and Anopheles gambiae (malaria vector) survival (measured using parity estimated by dissection of Anopheles ovaries). Data on MDA coverage, acceptability and feasibility of the intervention and a cost-effectiveness analysis will be included. We have established field infrastructure on the Bijagós Archipelago (including trained field entomologists and field laboratory technicians) and have detailed recent baseline data on the burden of disease caused by malaria and other neglected tropical diseases (NTDs) and vector populations on the islands. This 'natural laboratory' island setting provides an unparalleled opportunity to understand transmission and its interruption using a combined MDA strategy through investigating the impact of imported infections (through an expanded community-based CDSAT (case detection screen and treat) intervention which we will include in both arms), using serological (immune) markers in the blood to define transmission dynamics and estimate entomological inoculation rate (EIR) and monitoring the effect of IVM MDA on confined vector populations over time.