Screening performance of C-reactive protein for active pulmonary tuberculosis in HIV-positive patients: A systematic review with a meta-analysis

Background Tuberculosis (TB) is the leading infectious cause of mortality worldwide. In the last years, resistant strains of the etiological agent, Mycobacterium tuberculosis , have emerged, thus demanding more triage tests to identify active pulmonary TB (PTB) patients and to evaluate their disease severity. Therefore, acute-phase reaction serum tests are required for monitoring TB patients, among WHO symptom screening recommendations. C-reactive protein (CRP) is a non-specific inflammatory biomarker that has been recently proposed for TB screening and can be quantitatively analyzed through cost-effective point-of-care assays. A previous meta-analysis found CRP to be highly sensitive and moderately specific for active PTB with confirmed HIV infection. Methods We performed a meta-analysis update of diagnostic tests, pooling sensitivities, and specificities in order to assess the accuracy of CRP as a potential test for the screening of HIV-associated PTB in outpatients. We searched MEDLINE, Web of Science, and SCOPUS for eligible articles before 19 October 2021. Results We identified 13 eligible studies with HIV-positive patients with PTB. At a CRP threshold of 10 mg/L, CRP pooled sensitivity was 87% (76%-93%) and pooled specificity was 67% (49%-81%), with an area under the curve (AUC) of 0.858. Using a CRP threshold of 8 mg/L, pooled sensitivity was 82% (72%-89%) and pooled specificity was 82% (67%-92%), with an AUC of 0.879. We found that CRP has a high sensitivity in the screening of PTB in HIV-positive outpatients, consistent with findings reported previously. Conclusions Regardless of pooled specificity, better results were found using the CRP threshold of 8 mg/L as a test screening of PTB, meeting the need of further approaching specific TB diagnostic methods and reducing resource consumption.