GH11-005, Uganda: Operational Research for cryptococcal antigen screening to improve ART survival

GH11-005，乌干达：用于提高 ART 存活率的隐球菌抗原筛查的操作研究

• 批准号: 8703027
• 负责人: David Bisagaya Meya
• 金额: $ 48.53万
• 依托单位: INFECTIOUS DISEASES INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8703027
• 关键词: GH11; 005; Uganda; Operational; Research

Cryptococcal meningitis (CM) is a leading cause of death in AIDS patients in the developing world, responsible for up to 500,000 deaths each year in sub-Saharan Africa alone. In Uganda, cryptococcosis accounts for 30% of mortality in AIDS patients after starting ART. Many of these cases of CM may be preventable. Routine screening for sub-clinical infection, using a simple blood test (cryptococcal antigen or CRAG) in patients presenting to ART programmes, can identify which patients are at risk of developing CM. If identified, these persons could be given "pre-emptive" anti- fungal treatment to prevent development of overt meningitis and death. Our research team has demonstrated in a study of 311 persons with advanced HIV-infection in Kampala, Uganda, that such a screen and treat strategy would be highly cost-effective, at an estimated $21 per quality-adjusted life year (QALY) saved. We know that ART alone is insufficient to prevent the development of CM in patients with sub-clinical infection, and antifungal therapy is required. Yet, the optimal pre-emptive anti-fungal treatment dose and duration necessary to prevent CM in patients with sub-clinical infection have yet to be established. We propose to investigate how practical and effective CRAG screening and targeted pre-emptive fluconazole treatment would be in the operational setting of patients entering ART treatment programmes in Kampala City Council clinics in Uganda. In addition, a new point-of-care CRAG screening test will be evaluated in parallel with the currently used test. In the planned study, 1000 patients will be screened for cryptococcal antigenemia prior to starting ART. Those with a positive result will receive pre-emptive short course oral fluconazole therapy to treat sub-clinical cryptococcosis and determine if this is effective at preventing CM. All patients will then be started on standard ART and followed for 6 months to determine their overall outcome and incidence of clinical CM compared to historical cohort controls. The cost-effectiveness of the intervention with pre- emptive fluconazole therapy will be analyzed. The results of this operational research would be widely applicable to other regions in sub-Saharan Africa and could lead to improved public policies to prevent CM.

隐球菌脑膜炎（CM）是发展中国家艾滋病患者死亡的主要原因， 仅在撒哈拉以南非洲，每年就有50万人死于疟疾。在乌干达， 隐球菌病占艾滋病患者开始抗逆转录病毒治疗后死亡率的30%。 CM是可以预防的。常规筛查亚临床感染，使用简单的血液 测试（隐球菌抗原或CRAG）的患者提出的艺术计划，可以确定 患者有发生CM的风险。如果被发现，这些人可能会被给予“先发制人”的反 真菌治疗，以防止发展明显的脑膜炎和死亡。 我们的研究小组在一项对311名晚期艾滋病毒感染者的研究中证明， 乌干达的坎帕拉，这样的筛查和治疗策略将是非常具有成本效益的， 估计每质量调整生命年（QALY）节省21美元。我们知道单靠抗逆转录病毒疗法是不够的 预防亚临床感染患者发生CM，抗真菌治疗是 必需的.然而，预防真菌感染所需的最佳预防性抗真菌治疗剂量和持续时间 亚临床感染患者的CM尚未确定。 我们建议研究如何实用和有效的CRAG筛选和有针对性的先发制人 氟康唑治疗将在进入ART治疗的患者的手术环境中进行 在乌干达的坎帕拉市理事会诊所开展的方案。此外，新的床旁CRAG 筛选试验将与目前使用的试验平行评价。在计划的研究中，1000 在开始ART之前，将对患者进行隐球菌抗原血症筛查。 结果将接受前瞻性短程口服氟康唑治疗亚临床 隐球菌病，并确定这是否是有效的预防CM。所有患者将开始 标准ART并随访6个月，以确定其总体结局和临床 CM与历史队列对照相比。预处理干预的成本效益 并对氟康唑的积极治疗进行分析。这项业务研究的结果将是 广泛适用于撒哈拉以南非洲其他地区，并可导致公共政策的改善 预防CM。