Improving the efficiency of clinic-based active tuberculosis case finding: evaluation of point-of-care C-reactive protein-based triage testing in Vietnam.

提高临床活动性结核病病例发现的效率：越南基于 C 反应蛋白的护理点分类检测的评估。

• 批准号: 10117189
• 负责人: Christina Yoon
• 金额: $ 20.49万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-03 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10117189
• 关键词: Acute-Phase Proteins; Algorithms; Area; Biological Assay; Blood capillaries; Body Weight decreased; C-reactive protein; Centers for Disease Control and Prevention (U.S.); Cessation of life; Characteristics; Clinic; Clinical; Clinical Trials Unit; Communities; Consumption; Coughing; Country; Data; Detection; Diagnosis; Diagnostic; Enrollment; Evaluation; Family; Fever; Funding; Future; HIV; HIV Seronegativity; HIV Seropositivity; Health; Health Personnel; Incidence; Individual; Infection; Interleukin-6; Knowledge; Life; Measures; Mediating; Mission; Night Sweating; Outcome; Outpatients; Participant; Patient Selection; Patients; Performance; Predictive Value; Provider; Public Health; Recommendation; Research; Sensitivity and Specificity; Specificity; Study models; Symptoms; Testing; Triage; Tuberculosis; United States National Institutes of Health; Vietnam; Work; base; care seeking; case finding; cost; diagnostic accuracy; disability; improved; next generation; point of care; scale up; screening; tool; transmission process

PROJECT SUMMARY Passive case finding – which relies on healthcare workers to determine which patients should be referred for confirmatory TB testing – remains the predominant approach to TB case finding, resulting in missed or delayed TB diagnosis and ongoing TB transmission within families and communities. In order to achieve the End TB Strategy targets for a 95% reduction in TB deaths and a 90% reduction in TB incidence by 2035, immediate and rapid scale-up of clinic-based active case finding (ACF; provider-initiated symptom screening, followed by Xpert MTB/RIF [Xpert] confirmatory testing) is essential. However, the major barrier to ACF implementation is the low specificity of symptom screening, which makes ACF unaffordable for most high burden countries because the cost to test all symptomatic patients with Xpert testing would consume 20-80% of current TB spending. Thus, there is an urgent need to identify an effective triage test than can limit the proportion of symptomatic patients requiring Xpert testing to those with the highest likelihood of having active TB. The overall objective of this application is to determine whether a triage testing strategy based on C-reactive protein (CRP) levels, measured using a low cost ($2 per test) and rapid (results in 3 minutes) point-of-care (POC) assay could optimize selection of patients for confirmatory TB testing. The central hypothesis is that a TB screening algorithm inclusive of POC CRP triage testing will be more efficient than cough ≥2 weeks alone (currently recommended symptom screen) and will thereby enable the efficient use of more sensitive TB screening strategies (e.g., any TB symptom, any cough) to also improve ACF yield. The scientific premise for this hypothesis is based on our own work that identified POC CRP as the first test to meet the minimum sensitivity (≥90%) and specificity (≥70%) targets established by the WHO for an effective TB screening test among HIV-positive individuals. To test our hypothesis, the study will enroll 1200 HIV-negative outpatients with any TB symptom (cough, fever, night sweats, weight loss) from 4 clinics participating in the CDC-funded TB Trials Consortium (TBTC) Clinical Trials Unit (CTU) in Hanoi, Vietnam. Aim 1 will determine the sensitivity, specificity and predictive values of POC CRP (cut- point 10 mg/L) for culture-confirmed TB among patients who screen positive by 3 symptom-based screening strategies: any TB symptom, any cough and cough ≥2 weeks (current recommendation). Aim 2 will perform Xpert Ultra testing in all participants and will identify the optimal TB screening algorithm by comparing the diagnostic yield (proportion of all TB cases detected by Xpert Ultra) and efficiency (number needed to test using Xpert Ultra to detect one case of culture-confirmed TB) of 3 TB screening algorithms combining symptom screening with POC CRP triage testing to 3 TB screening algorithms without POC CRP triage testing (symptom screening alone), and to each other. This research is significant because it has the potential to identify a more efficient and more sensitive TB screening algorithm that would increase TB detection by facilitating efficient scale-up of ACF activities (systematic screening and Xpert Ultra testing) in Vietnam and other target countries. !

项目概要 被动病例发现——依靠医护人员来确定应转诊哪些患者 结核病确诊检测——仍然是发现结核病病例的主要方法，导致漏诊或延误 结核病诊断和家庭和社区内持续的结核病传播，以实现消灭结核病。 战略目标是到 2035 年立即将结核病死亡人数减少 95%，将结核病发病率减少 90% 快速扩大基于临床的主动病例发现（ACF；提供者发起的症状筛查，然后是 Xpert MTB/RIF [Xpert] 验证性测试）是必不可少的，但是 ACF 实施的主要障碍是较低。 症状筛查的特异性，这使得大多数高负担国家无力承担 ACF，因为 通过 Xpert 检测对所有有症状的患者进行检测的费用将占当前结核病支出的 20-80%。 迫切需要确定一种有效的分诊测试来限制有症状患者的比例 要求对最有可能患有活动性结核病的人进行 Xpert 检测 总体目标 应用程序是确定是否基于 C 反应蛋白 (CRP) 水平的分类测试策略，测量 使用低成本（每次测试 2 美元）和快速（3 分钟内出结果）即时检测 (POC) 检测可以优化选择 核心假设是包含 POC 的结核病筛查算法。 CRP 分类检测比单独咳嗽≥2 周更有效（目前推荐的症状筛查） 从而能够有效利用更敏感的结核病筛查策略（例如，任何结核病症状、任何结核病症状） 咳嗽）也可以提高 ACF 产量，这一假设的科学前提是基于我们自己的工作： 将 POC CRP 确定为第一个满足最低敏感性 (≥90%) 和特异性 (≥70%) 目标的测试 由世界卫生组织建立，用于在艾滋病毒阳性个体中进行有效的结核病筛查测试。 假设，该研究将招募 1200 名患有任何结核病症状（咳嗽、发烧、盗汗、 减肥）来自参与 CDC 资助的结核病试验联盟 (TBTC) 临床试验单位的 4 家诊所 （CTU）位于越南河内，目标 1 将确定 POC CRP（cut-）的敏感性、特异性和预测值。 点 10 mg/L）用于通过 3 项基于症状的筛查筛查呈阳性的患者中培养确诊的结核病 策略：任何结核病症状、任何咳嗽且咳嗽≥2 周（当前建议执行目标 2）。 Xpert Ultra 对所有参与者进行测试，并将通过比较 诊断率（Xpert Ultra 检测到的所有结核病例的比例）和效率（使用 Xpert Ultra 检测所需的数量） Xpert Ultra 检测 1 例培养确诊结核病）结合症状的 3 种结核病筛查算法 使用 POC CRP 分类测试进行筛查至 3 TB 筛查算法，无需 POC CRP 分类测试（症状 这项研究很重要，因为它有可能确定更多的信息。 高效且更灵敏的结核病筛查算法，可通过促进高效性来提高结核病检测率 在越南和其他目标国家扩大 ACF 活动（系统筛查和 Xpert Ultra 测试）。 ！