Establishing the Feasibility of using daily Dried Blood Spots (DBS) to study the Natural History of Low-density Asymptomatic Malaria Infection to Inform Malaria Elimination

建立利用每日干血斑 (DBS) 研究低密度无症状疟疾感染自然史的可行性，为消除疟疾提供信息

• 批准号: 10116276
• 负责人: Sean C Murphy
• 金额: $ 18.53万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10116276
• 关键词: Address; Adult; Aliquot; Area; Blood; Blood specimen; Child; Clinic; Collection; Communities; Consumption; Country; Data; Diagnostic; Diagnostic tests; Failure; Feasibility Studies; Future; Goals; HIV-1; Healthcare; Home; Human; Individual; Infection; Intervention; Investigation; Kinetics; Laboratories; Length; Logistics; Malaria; Measures; Messenger RNA; Methods; Microscopic; Monitor; Natural History; Parasites; Participant; Patients; Pharmaceutical Preparations; Plasmodium; Plasmodium falciparum; Polymerase Chain Reaction; Population; Protocols documentation; Public Health; Quantitative Reverse Transcriptase PCR; Rapid diagnostics; Research; Reverse Transcription; Ribosomal RNA; Risk; Sampling; Site; Spottings; Standardization; Symptoms; Techniques; Technology; Testing; Time; Travel; Uganda; Variant; Venous; Vietnam; Visit; cost; cost effective; density; design; experience; feasibility testing; follow-up; insight; malaria infection; malaria transmission; minimally invasive; molecular diagnostics; sample collection; tool; transmission process

ABSTRACT There are a significant number of low-density Plasmodium infections in endemic populations, and the proportion of this type of infection appears to increase with decreasing transmission intensity. However, most studies to date have assessed these infections at a single time point or at infrequent time points, which offers little to no information on the dynamics of these infections and their possible contribution to malaria transmission. Recent data suggest that asymptomatic parasite densities may be much more dynamic than previously known. The goal of this project is to demonstrate the feasibility and quality of daily dried blood spot (DBS) sampling in order to quantify parasite and gametocyte density kinetics of low-density asymptomatic Plasmodium falciparum infections to better understand their possible contribution to malaria transmission by studying the natural history of such infections in a population experiencing intermediate transmission. We will measure the proportion of subjects who successfully collect daily DBS over a 28-day period, and quantify the quality of the samples collected over time. Ultrasensitive quantitative reverse transcription PCR for P. falciparum 18S rRNA and gametocyte mRNA will be combined to cost-effectively identify infected participants and then deconvolute daily samples to illustrate the parasite density kinetics. If successful, the results from this study will offer a technique to further study the dynamics of low-density parasite carriage and be generalizable to other malaria-endemic countries confronting the public health problem of asymptomatic malaria for malaria control and elimination.

摘要 在地方性人群中有相当数量的低密度疟原虫感染， 这类感染的比例似乎随着传播强度的降低而增加。但大多数 迄今为止的研究已经在单个时间点或不常见的时间点评估了这些感染， 关于这些感染的动态及其对疟疾的可能贡献的信息很少或没有 传输最近的数据表明，无症状的寄生虫密度可能比 以前知道的。本项目的目标是论证日干血斑的可行性和质量 (DBS)采样，以量化低密度无症状的寄生虫和配子体密度动力学 恶性疟原虫感染，以更好地了解其对疟疾传播的可能贡献， 在经历中间传播的人群中研究这种感染的自然史。我们将 测量在28天内成功收集每日DBS的受试者比例，并量化 随着时间的推移收集的样品的质量。超灵敏定量逆转录PCR检测P. 将恶性疟原虫18S rRNA和配子体mRNA结合起来，以经济有效地识别受感染的参与者 然后解卷积每日样本以说明寄生虫密度动力学。如果成功， 本研究为进一步研究低密度寄生虫携带动力学提供了技术手段， 可推广到面临无症状疟疾患者公共卫生问题的其他疟疾流行国家 为控制和消除疟疾而努力。

项目成果

Assessing the daily natural history of asymptomatic Plasmodium infections in adults and older children in Katakwi, Uganda: a longitudinal cohort study.

• DOI: 10.1016/s2666-5247(23)00262-8
• 发表时间: 2024-01
• 期刊: LANCET MICROBE
• 影响因子: 38.2
• 作者: Hergott, Dianna E. B.;Owalla, Tonny J.;Staubus, Weston J.;Seilie, Annette M.;Chavtur, Chris;Balkus, Jennifer E.;Apio, Bernadette;Lema, Jimmy;Cemeri, Barbara;Akileng, Andrew;Chang, Ming;Egwang, Thomas G.;Murphy, Sean C.
• 通讯作者: Murphy, Sean C.

Feasibility of community at-home dried blood spot collection combined with pooled reverse transcription PCR as a viable and convenient method for malaria epidemiology studies.

社区在家干血点收集的可行性与汇总逆转录PCR相结合，作为疟疾流行病学研究的可行且方便的方法。

• DOI: 10.1186/s12936-022-04239-x
• 发表时间: 2022-07-14
• 期刊: MALARIA JOURNAL
• 影响因子: 3
• 作者: Hergott, Dianna E. B.;Owalla, Tonny J.;Balkus, Jennifer E.;Apio, Bernadette;Lema, Jimmy;Cemeri, Barbara;Akileng, Andrew;Seilie, Annette M.;Chavtur, Chris;Staubus, Weston;Chang, Ming;Egwang, Thomas G.;Murphy, Sean C.
• 通讯作者: Murphy, Sean C.

Rethinking detection of pre-existing and intervening Plasmodium infections in malaria clinical trials.

• DOI: 10.3389/fimmu.2022.1003452
• 发表时间: 2022
• 期刊: Frontiers in immunology
• 影响因子: 7.3