Abstract
BackgroundDelayed 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 FindingsTo 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.SignificanceIn 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.
Highlights
The HIV epidemic has substantially increased the incidence of tuberculosis, and especially smear-negative tuberculosis (SNTB), in high prevalence resource-limited settings [1,2,3]
Tuberculosis diagnosis One hundred and thirty five (37%) participants were classified as having confirmed tuberculosis (132 on culture and three on histology), and 114 (31%) had possible tuberculosis
The C-reactive protein (CRP) quotient above the upper limit of normal had sensitivity 0.98, specificity 0.59, positive predictive value 0.74, negative predictive value 0.96, and diagnostic odds ratio 63.7 in the confirmed tuberculosis group compared with the group without tuberculosis (Table 2)
Summary
The HIV epidemic has substantially increased the incidence of tuberculosis, and especially smear-negative tuberculosis (SNTB), in high prevalence resource-limited settings [1,2,3]. C-reactive protein (CRP) is a non-specific acute phase serum protein that is elevated in HIV seropositive and seronegative patients with tuberculosis [8,9,10,11,12,13,14,15]. The diagnostic utility of CRP in smear-negative tuberculosis suspects in a high HIV prevalence setting is unknown. Delayed diagnosis has contributed to the high mortality of sputum smear-negative tuberculosis (SNTB) in high HIV prevalence countries. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
