Minimally Invasive Tissues Sampling to Evaluate HIV-associated Meningitis in Zambia

赞比亚通过微创组织取样评估艾滋病毒相关脑膜炎

基本信息

批准号：
10536463
负责人：
Omar Khalik Siddiqi
金额：
$ 47.22万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
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：
2022-06-15 至 2027-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10536463
关键词：
Address Adult Africa South of the Sahara African Area Automobile Driving Autopsy Biological Assay Biological Markers Biopsy Specimen Brain Burial Caring Central Nervous System Infections Cerebrospinal Fluid Cessation of life Clinical Clinical Management Collection Core Biopsy Country Diagnosis Diagnostic Etiology Evaluation Family Fellowship Future Goals HIV HIV Seropositivity HIV diagnosis Histologic Histology Hour Incidence Infection Inpatients Investigation Knowledge Laboratories Lipids Measures Meningeal Tuberculosis Meningitis Metagenomics Methods Microbiology Molecular Mycobacterium tuberculosis Neuraxis Organ Organism Outcome Pathologist Pathology Patient-Focused Outcomes Patients Polymerase Chain Reaction Population Preparation Prevalence Rapid diagnostics Religious Belief Research Resource-limited setting Role Sampling Services Site Specificity Spinal Puncture Symptoms Taboo Testing Time Tissue Sample Tissues Training Zambia brain tissue co-infection comorbidity diagnostic biomarker diagnostic strategy doctoral student improved improved outcome innovation insight lateral flow assay lipidomics lipoarabinomannan low and middle-income countries minimally invasive molecular diagnostics mortality mycobactins neuropathology next generation sequencing pathogen point of care point-of-care diagnostics portability prevent programs public health relevance screening treatment strategy uptake

项目摘要

There is an urgent need to establish the etiology and improve diagnostics of HIV-associated meningitis in countries like Zambia given the high rates of mortality. A lack of post-mortem studies in low and middle-income countries prevents in-depth studies on tissue from confirmed meningitis patients. Central nervous system (CNS) co-infection frequently occurs in HIV-associated meningitis, but no study has investigated its impact on mortality. Tuberculous meningitis (TBM), one of the most common causes of HIV-associated meningitis, lacks a sensitive cerebrospinal fluid (CSF) lateral flow assay to serve as a simple point of care diagnostic. The best candidate lipid biomarker for a point of care assay has not been established. Best practices and expertise for CSF and brain tissue handling, processing, and analyses are also lacking in many sub- Saharan African countries. Our long-term goal is to establish causes of mortality, optimal diagnostic biomarkers, and laboratory expertise to improve outcomes of HIV-associated meningitis. We will test the following set of specific aims: Aim 1) Establish comprehensive etiologies of HIV-associated meningitis Aim 2) To improve CSF diagnostics for patients with HIV-associated meningitis in resource-limited settings, we will explore more optimal candidate CSF lipid biomarkers to diagnose TBM. Aim 3) Strengthen laboratory services to improve the diagnosis of meningitis The approach is innovative, because it systematically uses post-mortem tissue from an endemic setting to evaluate HIV-associated meningitis. The proposed research is significant because it allows us to establish etiologies and diagnostic biomarkers in HIV-associated meningitis while improving the laboratory capability in Zambia to diagnose CNS infections. These findings will have an important impact on the clinical management of meningitis and provide specific evidence to guide empiric treatment of patients in the future.

迫切需要确定艾滋病毒相关的病因并改进诊断赞比亚等国家的脑膜炎死亡率很高。缺乏尸检研究在低收入和中等收入国家，阻碍了对确诊脑膜炎组织的深入研究患者。中枢神经系统 (CNS) 合并感染常发生在 HIV 相关人群中脑膜炎，但没有研究调查其对死亡率的影响。结核性脑膜炎（TBM），缺乏敏感的脑脊液是导致 HIV 相关脑膜炎的最常见原因之一脑脊液（CSF）侧流检测可作为简单的护理诊断。最佳人选用于即时检测的脂质生物标志物尚未建立。最佳实践和专业知识脑脊液和脑组织的处理、处理和分析在许多子领域也缺乏撒哈拉非洲国家。我们的长期目标是确定死亡原因、最佳治疗方案诊断生物标志物和实验室专业知识，以改善艾滋病毒相关的结果脑膜炎。我们将测试以下一组具体目标：目标 1) 建立 HIV 相关脑膜炎的全面病因学目标 2) 改善对艾滋病毒相关脑膜炎患者的脑脊液诊断在资源有限的情况下，我们将探索更优化的候选脑脊液脂质生物标志物诊断TBM。目标 3) 加强实验室服务以改善脑膜炎的诊断这种方法是创新的，因为它系统地使用了地方病的死后组织评估艾滋病毒相关脑膜炎的环境。拟议的研究意义重大，因为它使我们能够建立 HIV 相关脑膜炎的病因学和诊断生物标志物，同时提高赞比亚诊断中枢神经系统感染的实验室能力。这些发现将有对脑膜炎的临床治疗产生重要影响并提供具体证据指导患者今后的经验性治疗。