Performance of serum C-reactive protein as a screening test for smear-negative tuberculosis in an ambulatory high HIV prevalence population

Douglas Wilson, Motasim Badri, Gary Maartens, Douglas Wilson, Motasim Badri, Gary Maartens

Abstract

Background: Delayed diagnosis has contributed to the high mortality of sputum smear-negative tuberculosis (SNTB) in high HIV prevalence countries. New diagnostic strategies for SNTB are urgently needed. C-reactive protein (CRP) is a non-specific inflammatory protein that is usually elevated in patients with tuberculosis, but its role in the diagnosis of tuberculosis is uncertain.

Methodology/principal findings: To determine the diagnostic utility of CRP we prospectively evaluated the performance of CRP as a screening test for SNTB in symptomatic ambulatory tuberculosis suspects followed up for 8 weeks in KwaZulu-Natal, South Africa. Confirmed tuberculosis was defined as positive culture or acid-fast bacilli with granulomata on histology, and possible tuberculosis as documented response to antitubercular therapy. The CRP quotient was defined as a multiple of the upper limit of normal of the serum CRP result. Three hundred and sixty four participants fulfilled entry criteria: 135 (37%) with confirmed tuberculosis, 114 (39%) with possible tuberculosis, and 115 (24%) without tuberculosis. The median CRP quotient was 15.4 (IQR 7.2; 23.3) in the confirmed tuberculosis group, 5.8 (IQR 1.4; 16.0) in the group with possible tuberculosis, and 0.7 (IQR 0.2; 2.2) in the group without tuberculosis (p<0.0001). The CRP quotient above the upper limit of normal had sensitivity 0.98 (95% CI 0.94; 0.99), specificity 0.59 (95% CI 0.50; 0.68), positive predictive value 0.74 (95% CI 0.67; 0.80), negative predictive value 0.96 (95% CI 0.88; 0.99), and diagnostic odds ratio 63.7 (95% CI 19.1; 212.0) in the confirmed tuberculosis group compared with the group without tuberculosis. Higher CRP quotients improved specificity at the expense of sensitivity.

Significance: In high HIV prevalence settings a normal CRP could be a useful test in combination with clinical evaluation to rule out tuberculosis in ambulatory patients. Point-of-care CRP should be further evaluated in primary care clinics.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Participant flow chart and final…
Figure 1. Participant flow chart and final diagnosis.
* Reasons for exclusion (n) Not able to attend for regular review - determined during screening visit (28) No active symptoms (17) Alternative medical diagnosis made at screening (14) Karnofsky Score

Figure 2. Receiver operating curves and sensitivity/specificity…

Figure 2. Receiver operating curves and sensitivity/specificity decision plots.

A and B comparing participants with…

Figure 2. Receiver operating curves and sensitivity/specificity decision plots.
A and B comparing participants with confirmed tuberculosis vs. those with no tuberculosis (n = 250); C and D combined confirmed and possible tuberculosis vs. those with no tuberculosis (n = 364); and E and F confirmed tuberculosis vs. those with possible tuberculosis and no tuberculosis.
Figure 2. Receiver operating curves and sensitivity/specificity…
Figure 2. Receiver operating curves and sensitivity/specificity decision plots.
A and B comparing participants with confirmed tuberculosis vs. those with no tuberculosis (n = 250); C and D combined confirmed and possible tuberculosis vs. those with no tuberculosis (n = 364); and E and F confirmed tuberculosis vs. those with possible tuberculosis and no tuberculosis.

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