Crowder Rebecca, Thangakunam Balamugesh, Andama Alfred, Christopher Devasahayam J, Dalay Victoria, Nwamba Welile, Kik Sandra V, Van Nguyen Dong, Nhung Nguyen Viet, Phillips Patrick P J, Ruhwald Morten, Theron Grant, Worodria William, Yu Charles, Nahid Payam, Cattamanchi Adithya, Gupta-Wright Ankur, Denkinger Claudia M
Center for Tuberculosis and Division of Pulmonary and Critical Care Medicine, University of California San Francisco, San Francisco, USA.
Christian Medical College, Vellore, India.
Clin Infect Dis. 2024 Nov 7. doi: 10.1093/cid/ciae549.
Accessible, accurate screening tests are necessary to advance tuberculosis (TB) case finding and early detection in high-burden countries.
We prospectively screened adults with ≥2 weeks of cough at primary health centers in the Philippines, Vietnam, South Africa, Uganda, and India. Participants received chest-X-ray, Cepheid Xpert TB Host Response (Xpert HR) testing, and point-of-care C-reactive protein (CRP) testing (Boditech). Chest-X-ray images were processed using CAD4TB v7, a computer-aided detection algorithm. We assessed diagnostic accuracy against a microbiologic reference standard (sputum Xpert Ultra, culture). Optimal cut-points were chosen to maximize specificity at 90% sensitivity. Two-test screening algorithms were considered, using 1) sequential negative serial screening (positive defined as positive on either test) and 2) sequential positive serial screening (positive defined as positive on both tests).
Between July 2021 and August 2022, 1,392 participants with presumptive TB had valid index tests and reference standard results, and 303 (22%) had confirmed TB. In head-to-head comparisons, CAD4TB v7 showed the highest specificity at 90% sensitivity (70.3% vs. 65.1% for Xpert HR, difference 95% CI 1.6 to 8.9; 49.7% for CRP, difference 95% CI 17.0 to 24.3). Three two-test screening algorithms met WHO target product profile (TPP) minimum accuracy thresholds and had higher accuracy than any test alone. At 90% sensitivity, the specificity was 79.6% for Xpert HR-CAD4TB [sequential negative], 75.9% for CRP-CAD4TB [sequential negative], and 73.7% for Xpert HR-CAD4TB [sequential positive].
CAD4TB achieves TPP targets and outperforms Xpert HR and CRP. Combining screening tests further increased accuracy.
NCT04923958.
在高负担国家，可及且准确的筛查测试对于推进结核病（TB）病例发现和早期检测至关重要。
我们在菲律宾、越南、南非、乌干达和印度的初级卫生中心对咳嗽≥2周的成年人进行前瞻性筛查。参与者接受胸部X光检查、赛沛Xpert TB宿主反应（Xpert HR）检测和即时C反应蛋白（CRP）检测（Boditech）。胸部X光图像使用CAD4TB v7（一种计算机辅助检测算法）进行处理。我们根据微生物学参考标准（痰Xpert Ultra、培养）评估诊断准确性。选择最佳切点以在90%灵敏度时最大化特异性。考虑了两种测试筛查算法，即1）序贯阴性串联筛查（阳性定义为任一测试呈阳性）和2）序贯阳性串联筛查（阳性定义为两项测试均呈阳性）。
在2021年7月至2022年8月期间，1392名疑似结核病参与者有有效的索引测试和参考标准结果，303人（22%）确诊为结核病。在直接比较中，CAD4TB v7在90%灵敏度时显示出最高的特异性（Xpert HR为70.3%，而Xpert HR为65.1%，差异9
