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
- 来源:
- 关键词:AddressAftercareAliquotAnimalsBiological AssayBloodBlood specimenChagas DiseaseClinicalClinical TrialsCollectionCommunicable DiseasesConflict (Psychology)DNADataDetectionDevelopmentDiagnosisDiagnosticDiscriminationDiseaseEnrollmentFrequenciesFutureGoalsHumanImmune responseIndividualInfectionLatin AmericaMacacaMacaca mulattaMeasurementMeasuresMedicineMethodsMuscleOutcomeOutcome StudyParasitesParticipantPatternPharmaceutical PreparationsPloidiesPopulationProtocols documentationResearchSamplingSerology testSpecimenTechniquesTestingTherapeuticTimeTreatment EfficacyTreatment outcomeTrypanosoma cruziUnited StatesVariantWorkbasecandidate selectionchronic infectioncomparativecostcurative treatmentsdrug candidatedrug developmentexperimental studyimprovednonhuman primatenovel therapeuticspreventresearch clinical testingscreeningseropositivesuccesstooltransmission process
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.
抽象的
原生动物寄生虫克氏锥虫的感染通常可以得到控制,但通常不会被宿主免疫消除
回应。在人类和许多其他宿主中,这种持续感染最终会导致已知的肌肉组织损伤
如恰加斯病。尽管存在几种部分有效的药物来治疗感染,但据估计只有约 1%
感染者接受治疗。现有药物更广泛使用的主要障碍是开发更好的药物
查加斯病的治疗方法,以及确定哪些人将从治疗中受益以及治疗的成功
对这些个体的治疗,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血清学检测来实现的,这些检测是可靠的
用于检测之前的暴露情况,但提供有关感染是否活跃的有限信息。该项目的目标是
验证和改进基于 PCR 的克氏锥虫感染治愈测试。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 的 PCR 检测方案。
克鲁兹感染通常使用非常有限的(有时只有一份)血液样本并从中提取一份进行分析
样本。然而,抗 T 试验中的受试者。 cruzi 药物通常在治疗后多次(4-6)次出血,并且 1-3 次
将等分试样提交至 PCR,通常在取血和等分试样之间产生不同的结果。所依据的假设
拟议的工作是通过血液中寄生虫 DNA 的 PCR 确定感染检测可以通过增加
血液采样,包括采集的血液样本数量以及通过 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得到检验,这些恒河猴将被重复采样
延长的时间范围(1 年)和更有限的时间范围(1 个月),最多可筛选 200 份 DNA
每个出血点进行 PCR。使用寄生虫或寄生虫 DNA 掺入的血液进行平行研究,我们可以解释
受感染动物的血液寄生虫水平及其在数月或数年内的变化。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入组方案
在此类试验结束时进行明确的测试,明确衡量治疗效果。这些工具将确保
候选抗 T 蛋白的未来临床试验。 cruzi 药物将提供确凿的结果。
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:
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:
9754759 - 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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