Identifying CMV Retinitis as a Reversible Cause of Vision Loss in Persons with HIV-associated Meningitis

确定 CMV 视网膜炎是 HIV 相关脑膜炎患者视力丧失的可逆原因

• 批准号: 10752843
• 负责人: Simon Arunga
• 金额: $ 31.59万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10752843
• 关键词: Acquired Immunodeficiency Syndrome; Africa; Africa South of the Sahara; Blindness; Caring; Cells; Cellular Phone; Central Nervous System Infections; Collaborations; Cryopreservation; Cryptococcal Meningitis; Cryptococcus; Cytomegalovirus; Cytomegalovirus Retinitis; DNA; Detection; Development; Diagnosis; Diagnostic; Disease; Disease Marker; Early treatment; Equipment; Evaluation; Eye; Eye diseases; Fundus photography; Ganciclovir; General Hospitals; Grant; Guidelines; HIV; HIV/AIDS; Health; Hospitalization; Hospitals; Image; Image Enhancement; Imaging technology; Incidence; Individual; Infection; Internal Medicine; Logistic Regressions; Measures; Meningeal Tuberculosis; Meningitis; Meningoencephalitis; Microbiology; Minnesota; Mycobacterium tuberculosis; Neurologic; Ophthalmologist; Ophthalmology; Opportunistic Infections; Organ; Patients; Persons; Pharmaceutical Preparations; Physicians; Plasma; Play; Population; Populations at Risk; Prevalence; Research; Resource-limited setting; Retina; Retinitis; Risk; Risk Factors; Role; Secure; Sensitivity and Specificity; Severities; Site; Survivors; Symptoms; Technical Expertise; Technology; Time; Training; Uganda; Universities; Viral Load result; Viremia; Virus; Vision; Visual; Visual impairment; Vitreous humor; adjudication; clinical examination; combat; design; diagnostic accuracy; experience; fundus imaging; high risk; high risk population; improved; institutional capacity; interest; low and middle-income countries; mortality; novel; opportunistic pathogen; portability; prevent; retinal imaging; routine care; standard of care; teleophthalmology; viral detection

Project Summary Vision loss is common in persons diagnosed with advanced HIV disease (CD4<200 cells/L) presenting with central nervous system (CNS) infections, such as cryptococcal or TB meningitis. The prevalence of cytomegalovirus (CMV) retinitis as a reversible cause of vision loss and the relationship of end-organ eye disease and CMV viremia is poorly characterized in Africa. Our long term objective is to develop improved guidelines and institutional capacity for ophthalmologic care relevant to low and middle income countries with high burdens of HIV/AIDS. The specific objective of this R21 project is to determine the prevalence of CMV retinitis in Ugandans living with AIDS who are hospitalized with symptoms of meningitis. The project is designed to determine if new smartphone technology could expand the reach of high quality ophthalmologic evaluations in these settings. We additionally want to assess if detectable virus in different compartments of the body could predict the development or severity of CMV end-organ disease in the eye. Specific Aim 1. Determine the prevalence of CMV retinitis in hospitalized persons with HIV-associated meningitis using mobile non-mydriatic fundus imaging by general physicians and compare the diagnostic accuracy to trained ophthalmologist examinations.  We hypothesize undetected CMV retinitis accounts for a proportion of the vision impairment seen in persons with HIV-associated meningitis that is otherwise thought irreversible. Using tele-ophthalmology- based non-mydriatic fundus imaging, general hospital physicians will be able to accurately screen and detect CMV retinitis with non-inferior accuracy as compared to trained ophthalmologists in Ugandans with HIV-associated meningitis. Specific Aim 2. Determine how baseline plasma CMV DNA concentrations correlate with CMV retinitis diagnosis made by either clinical exam or vitreous humor virus detection (in deceased patients only).  We hypothesize detectable CMV DNA in baseline plasma predicts the presence of CMV retinitis and correlates with CMV DNA in vitreous humor, which is a marker of disease activity/severity. Overall, this project will improve our understanding of the prevalence of CMV retinitis in our population and promote future research to combat reversible causes of vision loss in persons with HIV-associated meningitis. We also aim to deepen and expand the collaborative research capacity among ophthalmology, internal medicine, and microbiology departments at research sites throughout Uganda.

项目概要 视力丧失在被诊断患有晚期 HIV 疾病（CD4<200 个细胞/μL）的患者中很常见 患有中枢神经系统 (CNS) 感染，例如隐球菌或结核性脑膜炎。 巨细胞病毒（CMV）视网膜炎作为视力丧失的可逆原因及其与眼终末器官的关系 疾病和 CMV 病毒血症在非洲的特征尚不明确，我们的长期目标是开发改进的方法。 与低收入和中等收入国家相关的眼科护理指南和机构能力 艾滋病毒/艾滋病的沉重负担。 该 R21 项目的具体目标是确定乌干达人中 CMV 视网膜炎的患病率 该项目旨在确定因脑膜炎症状而住院的艾滋病患者是否是新的。 智能手机技术可以扩大这些环境中高质量眼科评估的范围。 我们还想评估身体不同部位中可检测到的病毒是否可以预测 眼睛 CMV 终末器官疾病的发展或严重程度。 具体目标 1. 确定 HIV 相关住院患者中 CMV 视网膜炎的患病率 全科医生使用移动式免散瞳眼底成像技术对脑膜炎进行了比较 经过培训的眼科医生检查的诊断准确性。  我们发现 CMV 视网膜炎占视力障碍的一部分 患有艾滋病相关脑膜炎的人，否则被认为是不可逆转的。 基于免散瞳眼底成像，综合医院医生将能够准确筛查和 与乌干达训练有素的眼科医生相比，检测 CMV 视网膜炎的准确性不低 艾滋病毒相关脑膜炎。 具体目标 2. 确定基线血浆 CMV DNA 浓度与 CMV 视网膜炎的相关性 通过临床检查或玻璃体液病毒检测（仅限已故患者）做出诊断。  我们在基线血浆中捕获了可检测到的 CMV DNA，预测了 CMV 视网膜炎的存在，并且 与玻璃体液中的 CMV DNA 相关，玻璃体液是疾病活动/严重程度的标志。 总体而言，该项目将提高我们对人群中 CMV 视网膜炎患病率的了解，并 促进未来的研究，以对抗艾滋病毒相关脑膜炎患者视力丧失的可逆性原因。 我们还旨在深化和扩大眼科、内科之间的合作研究能力 乌干达各地研究地点的医学和微生物学部门。