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

Abstract

Background Systematic screening for active pulmonary tuberculosis (TB) is recommended for high-risk populations however the lack of an accurate, simple, and low-cost screening test that can be used in high burden areas is a major obstacle to its implementation. We evaluated whether C-reactive protein (CRP) possesses the necessary test characteristics to screen individuals for active pulmonary TB. Methods We performed a systematic review and meta-analysis of studies evaluating the diagnostic accuracy of CRP (cut-point of 10 mg/L) for pulmonary TB. We searched four databases for eligible articles published before January 31, 2015 and extracted data for individual studies. We synthesized data separately for outpatient and inpatient studies and generated pooled summary estimates (95% CI) for sensitivity and specificity using random-effects meta-analysis. We performed pre-specified subgroup analyses to determine pooled summary estimates of CRP for diagnosis-seeking vs. screening populations and for patients with and without HIV infection. Findings We identified nine unique studies enrolling 1723 patients from the outpatient and inpatient setting. In the outpatient setting, CRP had high sensitivity (93%, 95% CI: 85–97) and moderate specificity (62%, 95% CI: 42–79) for active pulmonary TB. CRP was just as sensitive and specific for active pulmonary TB among patients with confirmed HIV-infection. Among hospitalized patients, specificity of CRP was poor (21%, 95% CI: 6–52). Interpretation CRP shows considerable promise as a tool to facilitate systematic screening for active TB, even among PLHIV. CRP-based TB screening should now be studied in other high-risk groups to determine the full impact of this simple and low-cost test.

Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV

“…CRP has been more extensively evaluated. Sensitivity has been consistently high while specificity has varied with the population being studied (range 6–52% in inpatient studies and 58–81% in ambulatory screening studies [ 31 ]). Our study is among the first to evaluate all five of these biomarkers, and the previous studies support that the biomarkers identified here can be expected to have higher specificity in the context of TB screening in ambulatory settings, where patients without TB are less likely to have other illnesses resulting in systemic inflammation.…”

“…Previous studies have analyzed the accuracy of individual inflammatory markers such as C-reactive protein (CRP) and cytokines/chemokines such as interferon gamma (INF-γ), interferon gamma-induced protein (IP-10), monokine induced by interferon-γ (MIG), interleukin 6 (IL-6), and interleukin 18 (IL-18) for diagnosing active TB [ 21 – 27 ]. Of these, CRP has shown the most promise as a potential TB screening tool with high (89%) sensitivity for active TB and variable specificity (generally higher among outpatients and lower among hospitalized patients) [ 10 , 22 , 28 – 31 ]. We hypothesized that a panel of inflammatory markers, cytokines and/or chemokines measured directly in blood samples would have higher diagnostic accuracy for TB than CRP alone.…”

Trends in C-Reactive Protein, D-Dimer, and Fibrinogen during Therapy for HIV-Associated Multidrug-Resistant Tuberculosis

“…9 C-reactive protein (CRP) is elevated in 93% of patients with HIV and TB coinfection at the time of diagnosis. 10 Once on therapy, studies of individuals without HIV coinfection and with drug-sensitive TB have shown reductions in CRP levels to be associated with increased 2-month culture conversion rates and less need for treatment extension. [11][12][13][14] Fibrinogen has also been shown to be elevated in HIV/TB coinfected patients 15,16 and to normalize within the first 2 months of therapy.…”

Evaluation of tuberculosis treatment response with serial C-reactive protein measurements

“…Serum or whole blood CRP concentrations are widely used in routine clinical practice and can be measured using affordable point-of-care (POC) devices. Utility of both laboratory and POC CRP testing has been shown when screening tuberculosis suspects in Africa [22–25], with elevated levels in >90% of HIV infected individuals at time of tuberculosis diagnosis [25]. Reductions in CRP concentration after two months on antituberculosis therapy have been described in tuberculosis patients in South Africa, the Gambia, and Brazil [18,26–28].…”