The CryptoART Study: Decreasing mortality associated with initiation of antiretro

摘要 隐球菌病和结核病是导致患者死亡的主要原因， 撒哈拉以南地区的艾滋病毒/艾滋病，包括开始抗逆转录病毒治疗（ART）的患者。 尽管人们越来越努力地促进结核病患者的早期诊断， 开始ART，只有少数几个项目将注意力集中在早期 隐球菌病的诊断和治疗，以减少隐球菌病相关 发病率和死亡率。 隐球菌病的早期诊断可以通过有效筛查患者来实现 在开始ART之前，CD4计数较低（<100个细胞/mm 3）。 开发侧流试验（LFA），这是一种低成本的护理点试验， 需要昂贵的设备或高技能的实验室技术人员提供 在资源有限的环境中早期诊断隐球菌病的机会。 我们建议评估隐球菌病筛查计划的实施情况， 津巴布韦哈拉雷的一个大型公共艾滋病毒/抗逆转录病毒治疗中心。主要目的是 降低与ART启动相关的发病率和死亡率， 隐球菌病的发病率和死亡率。我们将测试LFA的性能 对照金标准（隐球菌抗原乳胶凝集试验、血液和CSF 培养），并确定其在全血（手指针刺）中的灵敏度和特异性， 尿我们还建议制定一个脑膜炎风险评分，可用于远程 设施，以确定在患者与阳性LFA测试，其中患者最大 隐球菌脑膜炎的风险，需要转移到资源更好的设施， 穿刺和静脉抗真菌治疗 成功实施这一筛选计划，通过使用低成本 干预措施有可能减少ART治疗中隐球菌病的发生 在撒哈拉以南非洲的项目。

ABSTRACT Cryptococcosis and tuberculosis are the leading causes of death in patients with HIV/AIDS in sub-Saharan, including patients initiating antiretroviral therapy (ART). Although there are increasing efforts to facilitate early diagnosis of TB in patients initiating ART, there are only a few programs that have focused attention on the early diagnosis and treatment of cryptococcal disease to decrease cryptococcosis associated morbidity and mortality. Early diagnosis of cryptococcal disease can be achieved by effectively screening patients with low CD4 counts (<100cells/mm3) prior to the initiation of ART. The recent development of the lateral flow assay (LFA), a low cost point of care test that does not require expensive equipment or a highly skilled laboratory technician provides an opportunity for early diagnosis of cryptococcal disease in resource limited settings. We propose to evaluate the implementation of a screening program for cryptococcosis at a large public HIV/ART treatment centre in Harare, Zimbabwe. The primary objective is to decrease morbidity and mortality associated with the initiation of ART by decreasing morbidity and mortality due to cryptococcosis. We will test the performance of the LFA against gold standards (cryptococcal antigen latex agglutination assays, blood and CSF cultures) and determine its sensitivity and specificity in whole blood (finger stick) and urine. We also propose to develop a meningitis risk score that can be used by remote facilities to identify among patients with a positive LFA test which patients are at greatest risk of cryptococcal meningitis and require transfer to better resourced facilities for spinal taps and intravenous antifungal therapy. The successful implementation of this screening program through the use of low cost interventions has the potential to decrease incident cryptococcosis in ART treatment programs in sub-Saharan Africa.