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

这项试验将首次调查在大规模给药（MDA）中加入伊维菌素（IVM）和有效的抗疟药物（如双氢青蒿素-哌喹（DP））对在季节性低传播环境中减少疟疾传播的影响。在一项以社区为基础的聚类随机试验中，将对添加性IVM丙二醛（在疟疾传播高峰的三个月（7 - 9月）每天治疗3天）与仅使用dp丙二醛(结合标准的疟疾控制规划干预措施（长效杀虫蚊帐（LLIN）和妊娠期间歇性预防治疗（IPTp））进行比较。主要结局指标将是基于人群的恶性疟原虫（疟疾感染）患病率（使用超灵敏PCR检测估计）和冈比亚按蚊（疟疾病媒）存活率（使用解剖按蚊卵巢估计的胎次来测量）。将包括关于MDA覆盖范围、干预措施的可接受性和可行性以及成本效益分析的数据。我们在Bijagós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），并详细掌握了关于疟疾和其他被忽视的热带病造成的疾病负担以及岛屿上病媒种群的最新基线数据。这种“自然实验室”岛屿环境提供了一个无与伦比的机会，可以通过调查输入性感染的影响（通过扩大的基于社区的CDSAT（病例检测和治疗）干预措施，我们将在两组中纳入），利用MDA联合战略了解传播及其中断。利用血液中的血清学（免疫）标记物确定传播动态，估计昆虫学接种率（EIR），并监测IVM MDA对受限病媒种群的影响。

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.