Houben Rein M G J, Veeken Lara D, Schwalb Alvaro, Grint Daniel J, Wasserman Sean, van Crevel Reinout, Horton Katherine C
TB Modelling Group, TB Centre, LSHTM, London, UK.
Department of Infectious Disease Epidemiology, LSHTM, London, UK.
medRxiv. 2025 Sep 19:2025.09.18.25335917. doi: 10.1101/2025.09.18.25335917.
Community-wide screening is a crucial strategy to end tuberculosis (TB), but a common concern is potential harm from overtreatment following false positive diagnoses. However, current reference standards determining test performance have limitations, with implications for prevalence thresholds and treatment decisions for community-wide screening.
We estimated coverage of community-wide screening at a prevalence threshold of 0.5% (current global standard), 0.25%, and 0.1% for adult pulmonary TB. We considered test performance for Xpert Ultra against different reference standards (sputum culture, plus clinical evaluation, plus disease progression within two years). Potential harm was estimated through disability adjusted life years (DALYs) incurred or averted by treatment. We report net specificity, positive predictive value (PPV), the ratio of false positives to true positives, and DALYs averted for (non-)treatment based on different reference standards.
A lower threshold would increase screening coverage from the current 42% to 84% (0.25% threshold) and 89% (0.1% threshold) of the global TB burden. In a population of 100,000 with 0.5% prevalence, specificity was 99.5% for community screening, but increased to 99.7% using disease progression as reference standard, with PPV increasing from 45 to 66%. In addition, estimated harm of withholding appropriate treatment was approximately 1,200 times higher compared to providing inappropriate treatment, with treatment initiation after a positive Xpert Ultra increasing overall DALYs averted (median 5,977 versus 3,750).
The benefit of TB treatment following a positive molecular test in community-wide screening likely outweighs the harm associated with possible overtreatment, supporting expanding coverage of simplified community-wide screening.
全社区筛查是终结结核病（TB）的关键策略，但一个普遍担忧是假阳性诊断后过度治疗可能带来的危害。然而，当前确定检测性能的参考标准存在局限性，这对全社区筛查的患病率阈值和治疗决策产生影响。
我们估计了成人肺结核患病率阈值为0.5%（当前全球标准）、0.25%和0.1%时全社区筛查的覆盖率。我们考虑了Xpert Ultra针对不同参考标准（痰培养、临床评估以及两年内疾病进展情况）的检测性能。通过治疗所产生或避免的伤残调整生命年（DALYs）来估计潜在危害。我们报告了基于不同参考标准的净特异性、阳性预测值（PPV）、假阳性与真阳性的比率以及（未）治疗所避免的DALYs。
较低的阈值将使筛查覆盖率从当前的42%提高到全球结核病负担的84%（阈值为0.25%）和89%（阈值为0.1%）。在患病率为0.5%的10万人群中，社区筛查的特异性为99.5%，但以疾病进展为参考标准时增加到99.7%，PPV从45%增加到66%。此外，与提供不适当治疗相比， withhold适当治疗的估计危害高出约1200倍，Xpert Ultra检测呈阳性后开始治疗可使总体避免的DALYs增加（中位数为5977对3750）。
在全社区筛查中分子检测呈阳性后进行结核病治疗的益处可能超过与可能的过度治疗相关的危害，这支持扩大简化全社区筛查的覆盖范围。
