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

• 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
• 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

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.

目前迫切需要确定艾滋病毒相关性肺炎的病因并改进诊断方法。 由于死亡率很高，赞比亚等国家的脑膜炎发病率很高。缺乏尸检研究 在低收入和中等收入国家， 患者中枢神经系统（CNS）合并感染经常发生在HIV相关的 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）， 艾滋病毒相关脑膜炎的最常见原因之一，缺乏敏感的脑脊液 液体（CSF）侧流测定用作简单的护理点诊断。最佳人选 尚未建立用于护理点测定的脂质生物标志物。最佳做法和专门知识 对于CSF和脑组织的处理、加工和分析， 撒哈拉非洲国家。我们的长期目标是确定死亡原因， 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 脑膜炎我们将测试以下一组具体目标： 目的1）建立HIV相关脑膜炎的综合病因学 目的2）提高对HIV相关脑膜炎患者的CSF诊断， 在资源有限的情况下，我们将探索更佳的候选CSF脂质生物标志物， 诊断TBM。 目的3）加强化验服务，提高脑膜炎的诊断水平 这种方法是创新的，因为它系统地使用了一种流行病的死后组织， 以评估HIV相关脑膜炎。这项研究意义重大，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， 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 对脑膜炎的临床管理产生重要影响，并提供具体证据， 指导今后患者的经验性治疗。