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:
    10451977
  • 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

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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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:
    10590740
  • 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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