SummaryBackgroundThere is a need to identify scalable tuberculosis screening strategies among high burden populations. The WHO has identified a non-sputum-based triage test as a development priority.MethodsWe performed a diagnostic accuracy study of point-of-care C-reactive protein (CRP) and Xpert-MTB-Host-Response (Xpert-MTB-HR) assays in the context of a mass screening program for tuberculosis in two prisons in Brazil. Incarcerated individuals irrespective of symptoms were screened by sputum Xpert-MTB/RIF and sputum culture. CRP was quantified in serum by a point-of-care assay (iChroma-II) and a 3-gene expression score was quantified from whole blood using the Xpert-MTB-HR cartridge. We evaluated receiver operating characteristic area under the curve (AUC) and assessed specificity at 90% sensitivity and sensitivity at 70% specificity, consistent with WHO target product profile (TPP) benchmarks.FindingsTwo hundred controls controls and 100 culture- or Xpert-positive tuberculosis cases were included. Half of tuberculosis cases and 11% of controls reported any tuberculosis symptoms. AUC for CRP was 0.79 (95% CI: 0.73-0.84) and for Xpert-MTB-HR was 0.84 (95% CI: 0.79-0.89). At 90% sensitivity, Xpert-MTB-HR had significantly higher specificity (53.0%, 95% CI: 45.0-69.0%) than CRP (28.1%, 95% CI: 20.2-41.8%) (p=0.003). Among individuals with medium or high sputum Xpert semi-quantitative load, sensitivity (at 70% specificity) of CRP (90.3%, 95% CI: 74.2-98.0) and Xpert-MTB-HR (96.8%, 95% CI: 83.3-99.9%) was higher.InterpretationFor active case finding in this high tuberculosis-burden setting, CRP and Xpert-MTB-HR did not meet TPP benchmarks for a triage test. However, Xpert-MTB-HR was highly sensitive in detecting individuals with medium or high sputum bacillary burden.FundingNational Institutes of Health (R01 AI130058 and R01 AI149620) and Brazilian National Council for Scientific and Technological Development (CNPq-404182/2019-4). Xpert-MTB-HR cartridges were provided by Cepheid.
Point-of-care C-reactive protein-based tuberculosis screening for people living with HIV: a diagnostic accuracy study
