Mind the clinic-community gap: how concerned should we be about false positive test results in mass tuberculosis screening?

Community-wide screening for bacteriologically confirmed pulmonary tuberculosis may reduce tuberculosis burden, although concerns of overtreatment remain because of false positive diagnoses due to subpar specificity of current bacteriological tests for screening. Our review and data analysis shows that clinic-based test specificity estimates of Xpert against culture underestimate performance in communities, both for Xpert MTB/RIF (community=99.8% vs clinic=98.4%) and Xpert Ultra (community=99.4% vs clinic=95.6%), reducing the presumed false positivity of sputum Xpert using culture as reference by 86.8% and 85.4%, respectively, as compared to clinic-based specificity estimates. These findings support large-scale evaluation of community-wide screening for tuberculosis.