Optimizing blood PCR as test of cure in Chagas disease

优化血液 PCR 作为恰加斯病的治愈测试

基本信息

  • 批准号:
    10590740
  • 负责人:
  • 金额:
    $ 7.55万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-03-11 至 2024-02-29
  • 项目状态:
    已结题

项目摘要

Abstract Infection with the protozoan parasite Trypanosoma cruzi is generally controlled but often not eliminated by host immune responses. In humans and many other hosts, this persistent infection ultimately results in muscle tissue damage known as Chagas disease. Although several partially effective drugs exist to treat the infection, it is estimated that only ~1% of infected subjects receive treatment. The major impediment to the wider use of current drugs, the development of better therapeutics in Chagas disease, and the identification of those who would benefit from treatment and the success of treatment in those individuals, is the absence of reliable methods to definitively determine the presence or absence of infection. Diagnosis of possible infection is generally achieved using a combination of serological tests, which are reliable for detecting prior exposure but provide limited information on whether the infection is active. The goal of this project is to validate and improve PCR-based tests of cure for T. cruzi infection. The primary application of the results of this study will be to the more definitive evaluation of clinical trial outcomes. Current PCR-detection protocols for diagnosis of T. cruzi infection generally use a very limited (sometimes only one) blood sample and assay a single aliquot from that sample. However, subjects in trials of anti-T. cruzi drugs are generally bled multiple (4-6) times post-treatment and 1-3 aliquots are submitted to PCR, usually with variable results between bleeds and aliquots. The hypothesis underlying the proposed work is that definitive detection of infection via PCR of parasite DNA in blood can be achieved by increasing the sampling of blood, both the number of blood samples taken and the aliquots of that blood that are evaluated by PCR. This hypothesis will be tested in a group of naturally infected rhesus macaques who will be repeatedly sampled over both an extended time frame (1 year) and a more limited period (1 month) with up to 200 aliquots of DNA screened by PCR at each bleed point. Parallel studies using parasite- or parasite-DNA-spiked blood we allow interpretation of the blood parasite levels in the infected animals, and its variation, over months or years. The ultimate outcome of these studies is expected to be a dependable pre-enrollment protocol for participant selection for clinical drug trials and definitive tests at the conclusion of such trials that unequivocally measure treatment efficacy. Such tools will assure that future clinical trials of candidate anti-T. cruzi drugs will provide conclusive results.
摘要 原生动物寄生虫克氏锥虫的感染通常被控制,但通常不能通过宿主免疫消除。 应答在人类和许多其他宿主中,这种持续感染最终导致已知的肌肉组织损伤。 恰加斯病虽然存在几种部分有效的药物来治疗感染,但据估计, 受感染者接受治疗。目前的主要障碍是药物的更广泛使用,更好的开发 治疗南美锥虫病,并确定那些谁将受益于治疗和成功的 这些人的治疗,是缺乏可靠的方法来明确确定是否存在 感染可能感染的诊断通常是通过结合可靠的血清学检测来实现的 用于检测先前的暴露,但提供关于感染是否活跃的有限信息。这个项目的目标是 验证和改进基于PCR的T.克氏感染本研究结果的初步应用 将是对临床试验结果进行更明确的评估。目前用于诊断T. 克氏感染通常使用非常有限(有时仅一个)血液样品, sample.然而,在抗T. Cruzi药物通常在治疗后流血的多次(4-6次), 将等分试样进行PCR,通常在采血和等分试样之间具有可变的结果。这一假设的基础是 建议的工作是通过血液中寄生虫DNA的PCR确定性检测感染可以通过增加 血液采样,采集的血液样本数量和通过PCR评估的血液等分试样。 这一假设将在一组自然感染的恒河猴中进行测试,这些恒河猴将被反复采样, 延长的时间范围(1年)和更有限的时间(1个月),最多200份DNA等分试样, 每个出血点的PCR。使用寄生虫或寄生虫DNA加标血液的平行研究,我们可以解释 受感染动物血液中的寄生虫水平及其数月或数年的变化。这些的最终结果 研究预计将成为临床药物试验参与者选择的可靠预招募方案, 在这些试验结束时进行明确的测试,明确测量治疗效果。这些工具将确保 候选抗T的未来临床试验。cruzi药物将提供决定性的结果。

项目成果

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Rick L Tarleton其他文献

The importance of persistence and dormancy in emTrypanosoma cruzi/em infection and Chagas disease
克氏锥虫感染和恰加斯病中持续性和休眠的重要性
  • DOI:
    10.1016/j.mib.2025.102615
  • 发表时间:
    2025-08-01
  • 期刊:
  • 影响因子:
    7.500
  • 作者:
    Molly E Bunkofske;Fernando J Sanchez-Valdez;Rick L Tarleton
  • 通讯作者:
    Rick L Tarleton

Rick L Tarleton的其他文献

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{{ truncateString('Rick L Tarleton', 18)}}的其他基金

The activation of benzoxaborole prodrug AN15368, a clinical candidate for Chagas disease
苯并氧杂硼罗前药 AN15368 的激活,恰加斯病的临床候选药物
  • 批准号:
    10667721
  • 财政年份:
    2023
  • 资助金额:
    $ 7.55万
  • 项目类别:
Optimizing blood PCR as test of cure in Chagas disease
优化血液 PCR 作为恰加斯病的治愈测试
  • 批准号:
    10451977
  • 财政年份:
    2022
  • 资助金额:
    $ 7.55万
  • 项目类别:
Trypanosoma cruzi dormancy and its implications for therapeutic treatment
克氏锥虫休眠及其对治疗的影响
  • 批准号:
    10573204
  • 财政年份:
    2020
  • 资助金额:
    $ 7.55万
  • 项目类别:
Trypanosoma cruzi dormancy and its implications for therapeutic treatment
克氏锥虫休眠及其对治疗的影响
  • 批准号:
    10368984
  • 财政年份:
    2020
  • 资助金额:
    $ 7.55万
  • 项目类别:
Purchase of an imaging flow cytometer 2016
2016年购买成像流式细胞仪
  • 批准号:
    9273704
  • 财政年份:
    2017
  • 资助金额:
    $ 7.55万
  • 项目类别:
Mechanisms of persistence in Trypanosoma cruzi infection
克氏锥虫感染的持续机制
  • 批准号:
    9754759
  • 财政年份:
    2016
  • 资助金额:
    $ 7.55万
  • 项目类别:
Multiplex treatment outcomes test for Chagas disease
恰加斯病多重治疗结果测试
  • 批准号:
    9305839
  • 财政年份:
    2016
  • 资助金额:
    $ 7.55万
  • 项目类别:
Mechanisms of persistence in Trypanosoma cruzi infection
克氏锥虫感染的持续机制
  • 批准号:
    9237877
  • 财政年份:
    2016
  • 资助金额:
    $ 7.55万
  • 项目类别:
Mechanisms of persistence in Trypanosoma cruzi infection
克氏锥虫感染的持续机制
  • 批准号:
    9979735
  • 财政年份:
    2016
  • 资助金额:
    $ 7.55万
  • 项目类别:
Generation of reference genomes for Trypanosoma cruzi using PacBio sequencing
使用 PacBio 测序生成克氏锥虫参考基因组
  • 批准号:
    9251753
  • 财政年份:
    2016
  • 资助金额:
    $ 7.55万
  • 项目类别:

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生物样本暴露于解冻条件下的等分水平视觉指示器
  • 批准号:
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  • 财政年份:
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Aliquot-level visual indicators of biospecimen exposure to thawed conditions
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数字的解剖学和生理学-素数和等分和的统计-
  • 批准号:
    21K13772
  • 财政年份:
    2021
  • 资助金额:
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    Grant-in-Aid for Early-Career Scientists
Experimental Analysis of Aliquot Sequences
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  • 批准号:
    467312-2014
  • 财政年份:
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