Making an early diagnosis of talaromycosis - an approach to reduce morbidity and mortality in advanced HIV disease in Southeast Asia

对踝部真菌病进行早期诊断——一种降低东南亚晚期艾滋病毒发病率和死亡率的方法

基本信息

  • 批准号:
    9978703
  • 负责人:
  • 金额:
    $ 59.5万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-07-16 至 2024-06-30
  • 项目状态:
    已结题

项目摘要

Talaromyces marneffei (Tm) is one of seven dimorphic human fungal pathogens that cause substantial global morbidity and mortality in immunocompetent and immunocompromised individuals. Tm is endemic throughout Southeast Asia where it is a leading cause of death with an on-treatment mortality of 30% in people with advanced HIV disease. A critical barrier to reducing mortality is our inability to make an early diagnosis. The disease is insidious, and early symptoms are non-specific. Diagnosis relies on culturing the organism from clinical specimens which is only positive during advanced stage of disease and takes up to 14 days to identify. Consequently many patients die before a culture diagnosis is made. This project aims to reduce Tm mortality by introducing a novel sensitive antigen detection method and by testing an innovative concept that will enable early disease screening and treatment. We have preliminary data that a novel enzyme immunoassay (EIA) detecting a Tm-specific abundantly-released cell wall protein Mp1p is highly specific and is more sensitive than blood culture for Tm detection. This project will drive the translation of this new technology into improving patient care, testing its clinical utility as a rapid diagnostic test, and establishing a proof of concept that infection can be identified early during pre-clinical stage. This would create new opportunities for disease screening and prevention strategies. To do this, we will establish a cohort of febrile AIDS patients for the evaluation of diagnosis utility and will establish a cohort of asymptomatic AIDS patients starting HIV therapy for evaluation of early disease detection. We will test the following hypotheses: 1) the Mp1p EIA is at least 20% more sensitive than conventional cultures and reduces time to diagnosis; 2) Mp1p antigen precedes development of talaromycosis in asymptomatic patients and is associated with morbidity and all-cause mortality; 3) the Mp1p EIA has similar sensitivity and specificity in the urine compared to plasma/sera samples of patients. We have established a team of investigators from Duke University, University of Hong Kong, and Oxford University Clinical Research Unit and its partner hospitals in Vietnam with expertise and experience in the development and clinical evaluation of diagnostics. Upon completion of the project, we expect to provide robust data to support the integration of the Mp1p EIA into routine Tm diagnostic algorithm. Data generated from these studies have the potential to shift the current treatment paradigm from treating advanced disease to preventing disease development through a screen-and-treat approach. We expect our strategy will substantially impact disease burden.
马尔尼菲篮状菌(Talaromycesmarneffei,Tm)是七种二型人类真菌病原体之一, 免疫功能正常和免疫功能低下个体的全球发病率和死亡率。Tm是 在整个东南亚流行,是治疗期间死亡的主要死因 30%的晚期艾滋病患者降低死亡率的一个关键障碍是我们无法 做一个早期诊断。这种疾病是隐性的,早期症状是非特异性的。诊断 依赖于从仅在晚期呈阳性的临床标本中培养生物体 需要14天的时间来识别。因此,许多患者在培养前死亡。 作出诊断。该项目旨在通过引入一种新的敏感抗原来降低Tm死亡率 检测方法,并通过测试一个创新的概念,这将使早期疾病筛查, 治疗我们有初步数据表明,一种新型酶免疫分析(EIA)可以检测Tm特异性 大量释放的细胞壁蛋白Mp 1 p具有高度特异性,比血培养更敏感 用于Tm检测。该项目将推动这项新技术转化为改善患者 护理,测试其作为快速诊断测试的临床实用性,并建立感染 可以在临床前早期发现。这将为疾病创造新的机会 筛查和预防策略。为此,我们将建立一个发热艾滋病患者队列, 评估诊断效用,并将建立一个无症状艾滋病患者队列, HIV治疗对早期疾病检测的评价。我们将测试以下假设:1) Mp 1 p EIA比常规培养敏感至少20%,并缩短诊断时间; 2) mp 1 p抗原先于无症状患者的足癣病的发展,并与 发病率和全因死亡率; 3)Mp 1 p EIA在尿液中具有相似的敏感性和特异性 与患者的血浆/血清样本相比。我们从杜克大学成立了一个调查小组 香港大学、牛津大学临床研究部及其合作伙伴 越南医院在开发和临床评估方面的专业知识和经验, 诊断在项目完成后,我们预计将提供强大的数据,以支持整合 将Mp 1 p EIA引入常规Tm诊断算法。这些研究产生的数据具有 有可能将目前的治疗模式从治疗晚期疾病转变为预防疾病 通过筛选和治疗的方法进行开发。我们预计我们的战略将大大影响 疾病负担。

项目成果

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Thuy Le其他文献

Thuy Le的其他文献

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{{ truncateString('Thuy Le', 18)}}的其他基金

Tropical Medicine Research Center for Talaromycosis in Vietnam
越南踝部真菌病热带医学研究中心
  • 批准号:
    10444448
  • 财政年份:
    2022
  • 资助金额:
    $ 59.5万
  • 项目类别:
Tropical Medicine Research Center for Talaromycosis in Vietnam
越南踝部真菌病热带医学研究中心
  • 批准号:
    10598580
  • 财政年份:
    2022
  • 资助金额:
    $ 59.5万
  • 项目类别:
Mapping of the IgM and IgG antibody responses to Talaromyces marneffei infection in mice and humans - Deciphering acute from reactivated or latent infections
小鼠和人类对马尔尼菲踝节菌感染的 IgM 和 IgG 抗体反应图谱 - 区分急性感染和潜伏感染
  • 批准号:
    10327068
  • 财政年份:
    2021
  • 资助金额:
    $ 59.5万
  • 项目类别:
Mapping of the IgM and IgG antibody responses to Talaromyces marneffei infection in mice and humans - Deciphering acute from reactivated or latent infections
小鼠和人类对马尔尼菲踝节菌感染的 IgM 和 IgG 抗体反应图谱 - 区分急性感染和潜伏感染
  • 批准号:
    10436393
  • 财政年份:
    2021
  • 资助金额:
    $ 59.5万
  • 项目类别:
Making an early diagnosis of talaromycosis - an approach to reduce morbidity and mortality in advanced HIV disease in Southeast Asia
对踝部真菌病进行早期诊断——一种降低东南亚晚期艾滋病毒发病率和死亡率的方法
  • 批准号:
    10426172
  • 财政年份:
    2019
  • 资助金额:
    $ 59.5万
  • 项目类别:
Making an early diagnosis of talaromycosis - an approach to reduce morbidity and mortality in advanced HIV disease in Southeast Asia
对踝部真菌病进行早期诊断——一种降低东南亚晚期艾滋病毒发病率和死亡率的方法
  • 批准号:
    10190805
  • 财政年份:
    2019
  • 资助金额:
    $ 59.5万
  • 项目类别:
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