Phased Implementation of a Public Health Programme: Cryptococcal Screening and Treatment in South Africa

公共卫生计划的分阶段实施：南非的隐球菌筛查和治疗

• 批准号: 9232071
• 负责人: David R Boulware
• 金额: $ 57.82万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9232071
• 关键词: AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Adult; Africa; Africa South of the Sahara; Antifungal Agents; Antifungal Therapy; Antigens; Blood; Blood Tests; Brain; CD4 Lymphocyte Count; Caring; Case Fatality Rates; Cause of Death; Cells; Cessation of life; Clinic; Clinical; Collaborations; Communicable Diseases; Comorbidity; Consensus; Continuity of Patient Care; Cost Savings; Cost effectiveness research; Costs and Benefits; Cryptococcal Meningitis; Cryptococcus; Cryptococcus neoformans infection; Custom; Diagnosis; Evaluation; Failure; Fluconazole; Guidelines; HIV; HIV Infections; HIV therapy; Health system; Healthcare Systems; Hospitalization; Incidence; Individual; Infection; Institutes; Intervention; Measures; Meningitis; Methods; Morbidity - disease rate; Mycoses; Patient Care; Patients; Persons; Pharmaceutical Preparations; Phase; Pilot Projects; Plasma; Prevalence; Prevention; Program Evaluation; Provider; Province; Public Health; Quality-Adjusted Life Years; Randomized Clinical Trials; Reflex action; Research; Resources; Risk; Risk Factors; Serum; Services; South Africa; South African; Specimen; Spinal Puncture; Testing; Treatment Failure; Uganda; antiretroviral therapy; base; cohort; cost effective; cost effectiveness; design; follow-up; high risk; improved; mortality; national surveillance; peripheral blood; prevent; programs; public health relevance; routine care; screening; surveillance data; treatment program; tv watching; uptake

 DESCRIPTION (provided by applicant): Cryptococcal meningitis is a leading cause of death among persons with AIDS in the resource-limited settings, responsible for approximately 20% of deaths in HIV treatment programs in Africa. Many of these deaths are preventable. Despite the aggressive roll out of ART in South Africa, the incidence of cryptococcal meningitis has only slightly decreased by 10- 15% per the National Institute of Communicable Diseases (NICD) national surveillance. Cryptococcus remains the most common cause of meningitis among adults in South Africa. Recent research has shown that routine screening for sub-clinical early infection among asymptomatic patients presenting to ART programs using a simple blood test (cryptococcal antigen or CRAG) can identify which patients are at high risk of developing meningitis or death. The prevalence of this detectable sub-clinical cryptococcal infection is 4.1% among South Africans with CD4<100. If identified, these asymptomatic persons can be given "preemptive" anti-fungal fluconazole therapy to prevent meningitis and/or death. Our research collaboration has demonstrated that such a screening strategy would be highly cost-effective, at an estimated <$10 per quality-adjusted life year (QALY) saved. In South Africa, such a CRAG screening would be cost-saving overall to the healthcare system and result in better survival. Based on our team's previous cost-effectiveness research, South Africa has included CRAG screening of HIV-infected persons with CD4<100 cells/mcL as part of their 2015 National HIV Treatment Guidelines, yet broad implementation has not yet occurred. We propose to implement CRAG screening using lab-based reflex testing of leftover plasma specimens in persons with CD4<100 cells/mcL. We will implement at CD4 testing labs across South Africa using a stepped wedge design phased implementation in order to assess the public health impact. First, we will determine if implementation of CRAG screening using lab- based reflex testing provides better uptake as compared with provider initiated testing in HIV- infected persons with CD4<100 cells/mcL(Aim 1). Second, we will implement an enhanced metrics and evaluation surveillance cohort to determine the barriers for care of CrAg+ preemptive therapy and determine those at high risk of treatment failure for 6 month cryptococcal-free survival (Aim 2). Lastly, we will determine if customization of care with target lumbar punctures based of CrAg titer >1:160 will improve 6-month survival and decrease the current 25% failure rate (i.e. meningitis or death) with current WHO recommended CrAg+ preemptive therapy (Aim 3).

 描述（由申请人提供）：隐球菌性脑膜炎是资源有限地区艾滋病患者死亡的主要原因，约占非洲艾滋病毒治疗项目死亡人数的 20%。其中许多死亡是可以预防的。尽管南非大力推广 ART，但根据国家传染病研究所 (NICD) 的国家监测，隐球菌性脑膜炎的发病率仅略有下降 10-15%。隐球菌仍然是南非成年人脑膜炎的最常见原因。 最近的研究表明，使用简单的血液检测（隐球菌抗原或 CRAG）对接受 ART 计划的无症状患者进行亚临床早期感染的常规筛查，可以识别哪些患者患脑膜炎或死亡的风险较高。在 CD4<100 的南非人中，这种可检测到的亚临床隐球菌感染的患病率为 4.1%。如果确诊，可以对这些无症状者进行“预防性”抗真菌氟康唑治疗，以预防脑膜炎和/或死亡。我们的研究合作已经证明，这种筛查策略具有很高的成本效益，估计每个质量调整生命年 (QALY) 可以节省 <10 美元。在南非，这样的 CRAG 筛查将为医疗保健系统节省总体成本，并带来更好的生存率。 根据我们团队之前的成本效益研究，南非已将 CD4<100 个细胞/mcL 的 HIV 感染者的 CRAG 筛查纳入其 2015 年国家 HIV 治疗指南，但尚未广泛实施。 我们建议使用基于实验室的反射测试对 CD4<100 个细胞/mcL 的人的剩余血浆样本进行 CRAG 筛查。我们将在南非各地的 CD4 测试实验室采用阶梯式楔形设计分阶段实施，以评估公共卫生影响。首先，我们将确定与提供者对 CD4<100 个细胞/mcL 的 HIV 感染者发起的测试相比，使用基于实验室的反射测试实施 CRAG 筛查是否能提供更好的吸收率（目标 1）。其次，我们将实施增强的指标和评估监测队列，以确定 CrAg+ 先发性治疗的障碍，并确定那些在 6 个月无隐球菌生存方面治疗失败的高风险人群（目标 2）。最后，我们将确定基于 CrAg 滴度 >1:160 的目标腰椎穿刺定制护理是否会提高 6 个月生存率，并降低当前 WHO 推荐的 CrAg+ 先发性治疗（目标 3）的 25% 失败率（即脑膜炎或死亡）。