Abstract
BackgroundOptions for intervention against Mycobacterium tuberculosis infection are limited by the diagnostic tools available. The Purified Protein Derivative (PPD) skin test is thought to be non-specific, especially in tropical settings. We compared the PPD skin test with an ELISPOT test in The Gambia.Methodology/Principal FindingsHousehold contacts over six months of age of sputum smear positive TB cases and community controls were recruited. They underwent a PPD skin test and an ELISPOT test for the T cell response to PPD and ESAT-6/CFP10 antigens. Responsiveness to M. tuberculosis exposure was analysed according to sleeping proximity to an index case using logistic regression. 615 household contacts and 105 community controls were recruited. All three tests assessed increased significantly in positivity with increasing M. tuberculosis exposure, the PPD skin test most dramatically (OR 15.7; 95% CI 6.6–35.3). While the PPD skin test positivity continued to trend downwards in the community with increasing distance from a known case (61.9% to 14.3%), the PPD and ESAT-6/CFP-10 ELISPOT positivity did not. The PPD skin test was more in agreement with ESAT-6/CFP-10 ELISPOT (75%, p = 0.01) than the PPD ELISPOT (53%, p<0.0001). With increasing M. tuberculosis exposure, the proportion of ESAT-6/CFP-10 positive contacts who were PPD skin test positive increased (p<0.0001), and the proportion of ESAT-6/CFP-10 negative contacts that were PPD skin test negative decreased (p<0.0001); the converse did not occur.Conclusions/SignificanceThe PPD skin test has surprisingly high specificity for M. tuberculosis infection from recent exposure in The Gambia. In this setting, anti-tuberculous prophylaxis in PPD skin test positive individuals should be revisited.
Highlights
Tuberculosis (TB) causes approximately 2 million deaths per year globally;[1] 98% of these occur in low-income countries.[2]
Using an ex vivo ELISPOT assay that measures the precise IFN-c T cell response to stimulatory antigens after an overnight incubation period, we identified that two M. tuberculosis antigens, ESAT-6 (6kDa early secreted antigenic target) and CFP-10 (10-kDA culture fitrate protein) which are not found in BCG or many environmental mycobacteria, together offered improved specificity over Purified Protein Derivative (PPD) in the diagnosis of M. tuberculosis infection
The percentage of volunteers positive increased significantly from the community to the bedroom of a known TB index case for all three tests, most markedly for the PPD skin test and none of the tests was confounded by the presence of a BCG scar when introduced into the logistic regression model
Summary
Tuberculosis (TB) causes approximately 2 million deaths per year globally;[1] 98% of these occur in low-income countries.[2]. The Purified Protein Derivative (PPD) skin test is thought to be non-specific, especially in tropical settings. Household contacts over six months of age of sputum smear positive TB cases and community controls were recruited. They underwent a PPD skin test and an ELISPOT test for the T cell response to PPD and ESAT-6/CFP10 antigens. The PPD skin test has surprisingly high specificity for M. tuberculosis infection from recent exposure in The Gambia. In this setting, anti-tuberculous prophylaxis in PPD skin test positive individuals should be revisited
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
