Background Accessible, accurate screening tests are necessary to advance tuberculosis (TB) case finding and early detection in high-burden countries. Methods 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). Results 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]. Conclusions CAD4TB achieves TPP targets and outperforms Xpert HR and CRP. Combining screening tests further increased accuracy. Registration NCT04923958

中文翻译：

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前瞻性跨国队列中结核病筛查试验的诊断准确性：胸部 X 光检查与计算机辅助检测、Xpert TB 宿主反应和 C 反应蛋白


背景 在高负担国家，为了推进结核病 （TB） 病例的发现和早期发现，需要获得可及、准确的筛查检测。方法 我们在菲律宾、越南、南非、乌干达和印度的初级卫生中心前瞻性筛查了患有 ≥2 周咳嗽的成年人。参与者接受了胸部 X 光检查、Cepheid Xpert TB 宿主反应 （Xpert HR） 检测和床旁 C 反应蛋白 （CRP） 检测 （Boditech）。胸部 X 光图像使用计算机辅助检测算法 CAD4TB v7 处理。我们根据微生物学参考标准（痰液 Xpert Ultra，培养）评估了诊断准确性。选择最佳切点以最大限度地提高 90% 敏感性下的特异性。考虑了双测试筛查算法，使用 1） 连续阴性连续筛查 （阳性定义为任一测试阳性） 和 2） 连续阳性连续筛查 （阳性定义为两项测试均呈阳性）。结果在 2021 年 7 月至 2022 年 8 月期间，1,392 名疑似结核病参与者获得了有效的指标检测和参考标准结果，303 名 （22%） 确诊了结核病。在头对头比较中，CAD4TB v7 在 90% 的敏感性下显示出最高的特异性 （Xpert HR 为 70.3% vs. 65.1%，差异 95% CI 为 1.6-8.9;CRP 为 49.7%，差异 95% CI 为 17.0-24.3）。三种双测试筛选算法符合 WHO 目标产品概况 （TPP） 最低准确性阈值，并且比单独测试具有更高的准确性。在 90% 的敏感性下，Xpert HR-CAD4TB [序贯阴性] 的特异性为 79.6%，CRP-CAD4TB [序贯阴性] 为 75.9%，Xpert HR-CAD4TB [序贯阳性] 为 73.7%。结论 CAD4TB 达到 TPP 靶点，性能优于 Xpert HR 和 CRP。结合筛选测试可进一步提高准确性。注册NCT04923958