Does treating low density malaria infections reduce malaria transmission?

治疗低密度疟疾感染是否可以减少疟疾传播？

• 批准号: 10574796
• 负责人: Jessica Lin
• 金额: $ 7.78万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-06 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10574796
• 关键词: Acute; Adult; Africa South of the Sahara; African; Age; Anopheles gambiae; Antimalarials; Area; Area Under Curve; Biological Assay; Bite; California; Child; Chronic; Clinical; Comparison arm; Consensus; Costs and Benefits; Culicidae; Data; Detection; Diagnostic; Disease; Dryness; Fever; Funding; Health; Human; Individual; Infection; Interruption; Intervention; Malaria; Malaria Diagnostic; Measures; Modeling; Molecular; Monoclonal Antibodies; Parasites; Participant; Periodicals; Pharmaceutical Preparations; Policies; Policy Maker; Prevalence; Preventive treatment; Primaquine; Randomized; Residual state; Role; Rural; Sampling; San Francisco; School-Age Population; Schools; Science; Seasons; Skin; Symptoms; Tanzania; Target Populations; Testing; Time; Translating; United States National Institutes of Health; Universities; Work; age group; arm; artemether; benflumetol; cohort; density; feeding; human old age (65+); infection rate; malaria infection; malaria transmission; molecular diagnostics; point of care; rapid test; success; transmission process; treatment arm; vaccine distribution

ABSTRACT Evidence is now robust that asymptomatic carriers contribute to the bulk of malaria transmission in Sub- Saharan Africa, where 95% of the global malaria burden resides. This is true in both high and low transmission settings. In areas where malaria control efforts have achieved some success and transmission has declined, it may be hard to make further progress without interventions targeting the asymptomatic infectious reservoir. We have worked in rural Bagamoyo district in coastal Tanzania since 2018, characterizing the asymptomatic reservoir and performing mosquito feeding studies to better understand human-to-mosquito transmission from low density malaria infections (LMI). This work has involved direct skin feeding assays to measure the infectivity of > 500 children and adults to Anopheles gambiae, with ongoing analyses examining the relationship of gametocytemia and other covariates to the likelihood of transmission (infectiousness) and mosquito infection rates. Now, in conjunction with the University of California San Francisco and the Ifakara Health Institute, we have the opportunity to leverage this data to understand how treatment of LMI through periodic active case detection in children can lead to a reduction in gametocyte carriage and the infectious reservoir. The “Low-density malaria infection (LMI) trial among children in Tanzania” (U01AI155315, PI: Hsiang and Olotu) will assess whether treating LMI in children results in clinical benefits on long-term health. Over two years, 200 children in Bagamoyo district randomized to undergo malaria active case detection with molecular testing (ACDm) will be screened 3 times each year (during biannual transmission peaks and at end of second peak) using an ultrasensitive PCR, and receive antimalarial therapy if positive. They will also be followed monthly and treated if they present with fever and are positive on a rapid test, as per standard passive case detection (PCD). In the comparator arm, 200 children will receive PCD only. In this proposed project, we will measure gametocytemia from monthly surveillance samples to determine the effects of proactive treatment of LMI on gametocyte prevalence and gametocyte AUC (area under the curve) in each study arm (Aim 1). Since reductions in gametocyte carriage will variably translate into reduced transmissibility across individuals based on factors such as age, symptom status, and seasonality, we will use data from our Bagamoyo skin feed cohort to model how reductions in gametocytemia translates to a reduction in human-to-mosquito transmission in both study arms (Aim 2). We hypothesize that active case detection of LMI will reduce gametocyte carriage and days of infectiousness in children to a greater extent than that achieved by PCD alone. The proposed work will quantify the potential transmission-reducing benefit of using ultrasensitive diagnostics to actively detect and treat LMI in African children. Findings will be important to policymakers and advance the science behind efforts to interrupt transmission and achieve malaria elimination.

摘要 现在有确凿的证据表明，无症状携带者是亚非州疟疾传播的主要原因。 撒哈拉非洲，全球疟疾负担的95%居住在那里。在高传输和低传输中都是如此 设置。在疟疾控制工作取得一些成功和传播下降的地区， 如果不针对无症状的感染性宿主进行干预，可能很难取得进一步的进展。 自2018年以来，我们一直在坦桑尼亚沿海的巴加莫约农村地区工作，描述了没有症状的 并进行蚊子喂食研究，以更好地了解人与蚊子之间的传播 低密度疟疾感染(LMI)。这项工作涉及到直接皮肤喂养试验来测量 500名儿童和成人对冈比亚按蚊的传染性，正在进行的分析检查 配子细胞症和其他协变量与传播可能性(传染性)和 蚊子感染率。现在，与加州大学旧金山分校和Ifakara 健康研究所，我们有机会利用这些数据来了解LMI是如何通过 在儿童中定期发现活动性病例可以导致配子携带减少和传染性 水库。坦桑尼亚儿童低密度疟疾感染(LMI)试验(U01AI155315，Pi：Hsiang 和Olotu)将评估治疗儿童LMI是否对长期健康产生临床好处。超过两个人 年，巴加莫约区200名儿童随机接受疟疾活动性病例分子检测 检测(ACDM)每年将进行3次筛查(在两年一次的传播高峰期和第二秒结束时 使用超灵敏的聚合酶链式反应)，如果阳性则接受抗疟疾治疗。他们也将被跟踪 每月一次，如果他们出现发烧，并根据标准被动病例快速检测呈阳性，则接受治疗 检测(PCD)。在对照ARM中，200名儿童将仅接受PCD。在这个拟议的项目中，我们将 从每月监测样本中测量配子细胞症，以确定积极治疗的效果 LMI对每个研究组配子体患病率和配子体AUC(曲线下面积)的影响(目标1)。自.以来 配子体携带量的减少将可变地转化为个体间传播率的降低 关于年龄、症状状态和季节性等因素，我们将使用来自Bagamoyo皮肤饲料的数据 模拟配子细胞症的减少如何转化为人与蚊子传播的减少的队列 在两个学习臂(目标2)。我们假设LMI的活跃病例检测将减少配子体携带 儿童的传染性天数比单独使用PCD的程度更大。拟议中的工作 将量化使用超灵敏诊断技术主动检测和减少传播的潜在好处 治疗非洲儿童的LMI。研究结果将对政策制定者和推动努力背后的科学具有重要意义 阻断传播，实现消灭疟疾。