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

项目概要/摘要 在大多数接近消除的国家，间日疟原虫 (Pv) 的比例相对不断增加 恶性疟原虫（Pf）。大规模药物管理（MDA）作为针对亚专利、无症状感染者的一种方式， 建议用于消除恶性疟原虫，但鉴于有限，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、 以及用于减少光伏传输的焦点 MDA (fMDA) 的成本效益。为了检验我们的假设，即 fMDA， 除了标准的积极干预措施外，为了安全地减少传播，我们提出了为期 3 年的开放标签 秘鲁洛雷托地区低流行环境下的 CRCT。村庄或集群将被随机分组​​以进行控制或 fMDA。控制臂将接受标准干预措施（病媒控制、症状病例管理和 主动发现无症状病例）。治疗组将接受标准干预措施加上 fMDA， 它将利用一种新药来根治间日疟原虫，他非诺喹和一种新的定量葡萄糖 6 磷酸脱氢酶 (G6PD) 缺乏症快速检测，支持他非诺喹的安全给药。丙二醛 将针对同意且符合条件的高风险村民，定义为家庭成员和邻居 最近的 Pv 指数案例。 fMDA 将每年进行 2 轮，在低疟疾期间间隔两个月 季节，并超过3年。每年都会在每轮 fMDA 之前重新评估资格。具体的 目标是： 1) 确定 fMDA 减少 Pv 传输（在一次测量中测量）的有效性 发病率结果和感染流行率、血清流行率和遗传多样性的次要结果， 2) 评估 fMDA 的安全性和耐受性，以及 3) 衡量 fMDA 的成本效益。最大化