Performance of serum c-reactive protein as a screening test for smear-negative tuberculosis in an ambulatory high HIV prevalence population
Department of Medicine, Edendale Hospital, University of KwaZulu-Natal, Pietermaritzburg, KwaZulu-Natal, South Africa; Department of Medicine, University of Cape Town, Cape Town, South Africa; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa
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. © 2011 Wilson et al.
C reactive protein; tuberculostatic agent; C reactive protein; acid fast bacterium; adult; article; bacterium culture; controlled clinical trial; diagnostic test accuracy study; diagnostic value; drug response; female; follow up; granuloma; histopathology; human; Human immunodeficiency virus infection; human tissue; major clinical study; male; predictive value; prevalence; primary health care; prospective study; protein analysis; protein blood level; screening test; sensitivity and specificity; South Africa; sputum smear; tuberculosis; AIDS related complex; evaluation; hospital information system; Human immunodeficiency virus infection; mass screening; methodology; standard; tuberculosis; Bacilli (class); Adult; AIDS-Related Opportunistic Infections; C-Reactive Protein; Female; HIV Infections; Humans; Male; Mass Screening; Point-of-Care Systems; Predictive Value of Tests; Prevalence; Sensitivity and Specificity; South Africa; Tuberculosis