Diagnostic accuracy of C-reactive protein for active pulmonary tuberculosis: a meta-analysis

Abstract

Setting: Systematic screening for active pulmonary tuberculosis (PTB) is recommended for high-risk populations, including people living with the human immunodeficiency virus (PLHIV); however, currently recommended TB screening tools are inadequate for most high-burden settings.

Objective: To determine whether C-reactive protein (CRP) possesses the necessary test characteristics to screen individuals for active PTB.

Design: We performed a systematic review and meta-analysis of studies evaluating the diagnostic accuracy of CRP (10 mg/l cut-off point) for culture-positive PTB. Pooled diagnostic accuracy estimates were generated using random-effects meta-analysis for out-patients and in-patients, and for pre-specified subgroups based on HIV status and test indication.

Results: We identified nine unique studies enrolling 1793 adults from out-patient (five studies, 1121 patients) and in-patient settings (five studies, 672 patients), 72% of whom had confirmed HIV infection. Among out-patients, CRP had high sensitivity (93%, 95%CI 88-98) and moderate specificity (60%, 95%CI 40-75) for active PTB. Specificity was lowest among in-patients (21%, 95%CI 6-52) and highest among out-patients undergoing TB screening (range 58-81%). There was no difference in summary estimates by HIV status.

Conclusion: CRP, which is available as a simple, inexpensive and point-of-care test, can be used to screen PLHIV presenting for routine HIV/AIDS (acquired immune-deficiency syndrome) care for active TB.

Figures

Figure 1. Flow diagram of studies

Abbreviations: CRP (C-reactive protein); TB (tuberculosis). Legend: An updated search performed on October 20, 2015 to identify additional studies published between February 1, 2014 and January 31, 2015 yielded no additional eligible studies

Figure 2. Outpatient pulmonary tuberculosis study quality using the Quality Assessment of Diagnostic Studies (QUADAS-2) tool

A. Summary study quality. B. Individual study quality. *C-reactive protein evaluated as a screening test for pulmonary tuberculosis among people living with HIV †C-reactive protein evaluated as a diagnostic test for pulmonary tuberculosis among people with smear-negative sputa

Figure 2. Outpatient pulmonary tuberculosis study quality using the Quality Assessment of Diagnostic Studies (QUADAS-2) tool

A. Summary study quality. B. Individual study quality. *C-reactive protein evaluated as a screening test for pulmonary tuberculosis among people living with HIV †C-reactive protein evaluated as a diagnostic test for pulmonary tuberculosis among people with smear-negative sputa

Figure 3. Diagnostic accuracy of CRP for pulmonary tuberculosis among outpatients

A. Forest plot. B. Hierarchical summary receiver operating characteristics (HSROC) plot. Abbreviations: CRP (C-reactive protein) *CRP evaluated as a screening test for tuberculosis †CRP evaluated as a diagnostic test for symptomatic patients undergoing tuberculosis evaluation Pooled sensitivity 93% (95% CI: 85–97); test for heterogeneity I2 = 39%, p=0.16 Pooled specificity 62% (95% CI: 42–79); test for heterogeneity I2 = 96%, p<0.0001

Figure 3. Diagnostic accuracy of CRP for pulmonary tuberculosis among outpatients

A. Forest plot. B. Hierarchical summary receiver operating characteristics (HSROC) plot. Abbreviations: CRP (C-reactive protein) *CRP evaluated as a screening test for tuberculosis †CRP evaluated as a diagnostic test for symptomatic patients undergoing tuberculosis evaluation Pooled sensitivity 93% (95% CI: 85–97); test for heterogeneity I2 = 39%, p=0.16 Pooled specificity 62% (95% CI: 42–79); test for heterogeneity I2 = 96%, p<0.0001

Figure 4. Diagnostic accuracy of CRP for pulmonary tuberculosis among ambulatory patients with confirmed HIV infection

A. Forest plot B. Hierarchical summary receiver operating characteristics (HSROC) plot. Abbreviations: CRP (C-reactive protein) *CRP evaluated as a screening test for tuberculosis †CRP evaluated as a diagnostic test for symptomatic patients undergoing tuberculosis evaluation Pooled sensitivity 93% (95% CI: 85–97); test for heterogeneity I2 = 40%, p=0.16 Pooled specificity 64% (95% CI: 42–81); test for heterogeneity I2 = 96%, p<0.0001

Figure 4. Diagnostic accuracy of CRP for pulmonary tuberculosis among ambulatory patients with confirmed HIV infection

A. Forest plot B. Hierarchical summary receiver operating characteristics (HSROC) plot. Abbreviations: CRP (C-reactive protein) *CRP evaluated as a screening test for tuberculosis †CRP evaluated as a diagnostic test for symptomatic patients undergoing tuberculosis evaluation Pooled sensitivity 93% (95% CI: 85–97); test for heterogeneity I2 = 40%, p=0.16 Pooled specificity 64% (95% CI: 42–81); test for heterogeneity I2 = 96%, p<0.0001