Surprisingly high specificity of the PPD skin test for M. tuberculosis infection from recent exposure in The Gambia

Abstract

Background: Options 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 findings: 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. 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/significance: 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.

Figure 1. Study profile.

Figure 2

Percent positive for each test by exposure category. A. PPD ELISPOT positive and percent PPD skin test positive for those with a result for both tests (n = 691). PPD ELISPOT positivity is represented according to a predetermined 10 spot cut-off (PPD ELISPOT 10) as well as an alternative 5 spot cut-off (PPD ELISPOT 5). PPD skin test positivity is represented according to a predetermined 10 mm induration cut-off as well as 2 alternative cutoffs: 5 mm and 15 mm. B. ESAT-6/CFP-10 ELISPOT positivity represented according to a predetermined 10 spot cut-off (EC ELISPOT 10) as well as an alternative 5 spot cut-off (EC ELISPOT 5).

Figure 3

Scaled rectangular diagrams showing relative proportions of TB case contacts who are PPD skin test positive and/or ELISPOT test result positive in relation to each other. The sizes of the boxes are proportional to the relative number of individuals they represent and the numbers represent numbers of individuals. A. PPD ELISPOT and ESAT-6/CFP-10 (EC) ELISPOT (n = 720) B. PPD ELISPOT and PPD skin test (n = 691) C. ESAT-6/CFP-10 ELISPOT and PPD skin test (n = 691)

Figure 4

Comparison of PPD skin test and ESAT-6/CFP-10 (EC) ELISPOT test in relation to each other, expressed as percentages across exposure category by sleeping proximity to a TB case. A. Proportion of ESAT-6/CFP-10 positive who are PPD skin test positive (n = 215) B. Proportion of ESAT-6/CFP-10 negative who are PPD skin test negative (n = 476) C. Proportion of PPD skin test positive who are ESAT-6/CFP-10 positive (n = 228) D. Proportion of PPD skin test negative who are ESAT-6/CFP-10 negative (n = 463)