Performance of Serum C-Reactive Protein as a Screening Test for Smear-Negative Tuberculosis in an Ambulatory High HIV Prevalence Population

PLoS One. 2011 Jan 10; Volume 6, Number 1: e15248 Wilson, D., Badri, M., Maartens, G.

Delayed diagnosis has contributed to the high mortality of sputum smear-negative TB (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 TB, but its role in the diagnosis of TB is uncertain. To determine the diagnostic utility of CRP the researchers prospectively evaluated the performance of CRP as a screening test for SNTB in symptomatic ambulatory TB suspects followed up for 8 weeks in KwaZulu-Natal, South Africa. Confirmed TB was defined as positive culture or acid-fast bacilli with granulomata on histology, and possible TB 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 TB, 114 (39%) with possible TB, and 115 (24%) without TB. The median CRP quotient was 15.4 (IQR 7.2; 23.3) in the confirmed TB group, 5.8 (IQR 1.4; 16.0) in the group with possible TB, and 0.7 (IQR 0.2; 2.2) in the group without TB (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 TB group compared with the group without TB. Higher CRP quotients improved specificity at the expense of sensitivity. In high HIV prevalence settings, a normal CRP could be a useful test in combination with clinical evaluation to rule out TB in ambulatory patients. Point-of-care CRP should be further evaluated in primary care clinics