Focal mass drug administration (fMDA) to reduce Plasmodium vivax transmission, a pragmatic cluster randomized controlled trial in Peru

旨在减少间日疟原虫传播的集中集中药物管理（fMDA），这是秘鲁的一项实用整群随机对照试验

• 批准号: 10680477
• 负责人: Michelle Sang Hsiang
• 金额: $ 126.14万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-10 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10680477
• 关键词: Acceleration; Address; Adherence; Aftercare; Aminoquinolines; Antimalarials; Applied Research; Blood; Case Management; Chloroquine; Clinical; Communicable Diseases; Communities; Consent; Cost Measures; Country; Data; Detection; Diagnostic; Dose; Drug Targeting; Drug resistance; Effectiveness; Eligibility Determination; Family; Genetic Variation; Glucosephosphate Dehydrogenase; Glucosephosphate Dehydrogenase Deficiency; Half-Life; Health system; Hemolysis; Household; Incidence; Individual; Infection; Intervention; Life; Liver; Malaria; Mass Screening; Measures; Microscopy; Mission; National Institute of Allergy and Infectious Disease; Outcome; Peru; Pharmaceutical Preparations; Plasmodium falciparum; Plasmodium vivax; Policies; Population; Prevalence; Primaquine; Public Health; Randomized; Randomized, Controlled Trials; Recommendation; Relapse; Safety; Seasons; Serious Adverse Event; Seroprevalences; Testing; Vivax Malaria; adverse event risk; arm; asexual; burden of illness; comparative efficacy; comparison control; cost; cost effective; cost effectiveness; cost-effectiveness ratio; density; effectiveness evaluation; follow-up; high risk; improved; incremental cost-effectiveness; indexing; infection risk; member; meter; novel therapeutics; open label; pharmacovigilance; point of care testing; prevent; primary outcome; prophylactic; public health relevance; rapid test; risk minimization; secondary endpoint; secondary outcome; standard of care; tool; transmission blocking; transmission process; treatment arm; treatment effect; urban area; vector control

Project Summary/Abstract In most countries approaching elimination, Plasmodium vivax (Pv) represents an increasing proportion relative to P. falciparum (Pf). Mass drug administration (MDA), as a way target subpatent, asymptomatic infections, is recommended for P. falciparum elimination, but the recommendation does not extend to P. vivax given limited evidence, tools, and safety concerns. The objective of our study is to evaluate the long-term impact, safety, and cost-effectiveness of focal MDA (fMDA) for Pv transmission reduction. To test our hypothesis that fMDA, in addition to standard aggressive interventions, will safely reduce transmission, we propose a 3-year open-label CRCT in the low endemic setting of Loreto Region, Peru. Villages or clusters will be randomized to control or fMDA. The control arm will receive standard interventions (vector control, symptomatic case management, and active case detection of asymptomatic cases). The treatment arm will receive standard interventions plus fMDA, which will utilize a new drug for radical cure of P. vivax, tafenoquine, and a new quantitative glucose 6 phosphate dehydrogenase (G6PD) deficiency rapid test to support safe administration of tafenoquine. fMDA will be targeted to consenting and eligible high-risk villagers, defined as household members and neighbors of recent Pv index cases. fMDA will be conducted in 2 rounds per year, two months apart during the low malaria season, and over 3 years. Eligibility will be re-assessed each year, and prior to each fMDA round. Specific aims are to: 1) Determine the effectiveness of fMDA to reduce Pv transmission as measured in a primary outcome of incidence and secondary outcomes of infection prevalence, seroprevalence, and genetic diversity, 2) Evaluate the safety and tolerability of fMDA, and 3) Measure the cost-effectiveness of fMDA. To maximize

项目总结/摘要 在大多数接近消灭的国家，间日疟原虫（Pv）的比例相对 恶性疟原虫（Pf. falciparum）。大规模给药（MDA）作为一种靶向治疗隐性感染、无症状感染的方法， 推荐用于消除恶性疟原虫，但该建议不适用于间日疟原虫， 证据工具和安全问题我们研究的目的是评估长期影响，安全性， 和成本效益的局灶性MDA（fMDA）的PV传播减少。为了验证我们的假设， 除了标准的积极干预措施，将安全地减少传播，我们提出了一个3年的开放标签， 秘鲁洛雷托地区低流行环境中的CRCT。村庄或集群将被随机分配到对照组或 fMDA。对照组将接受标准干预措施（病媒控制、症状性病例管理和 无症状病例的主动病例检测）。治疗组将接受标准干预加fMDA， 它将利用根治间日疟原虫的新药他非诺喹和新的定量葡萄糖6 磷酸脱氢酶（G6 PD）缺乏快速测试，以支持他非诺喹的安全给药。fMDA 将针对同意和合格的高风险村民，定义为家庭成员和邻居， 最近的Pv指数病例。fMDA将每年进行两轮，在低疟疾期间间隔两个月 赛季，三年多。资格将每年重新评估，并在每一轮fMDA之前。具体 目的是：1）确定fMDA减少PV传播的有效性，如在初级 发病率结果和感染流行率、血清阳性率和遗传多样性的次要结果， 2)评价fMDA的安全性和耐受性; 3）衡量fMDA的成本效果。最大化