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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hiv相关的病因和改进诊断