Identifying ELISPOT and Skin Test Cut-offs for Diagnosis of Mycobacterium Tuberculosis Infection in The Gambia

Abstract

SETTING: An urban area, The Gambia. OBJECTIVE: To identify ELISPOT and PPD skin test cut-offs, targeting sensitivity and specificity equivalence. DESIGN: Tuberculosis cases 15 years of age and their household contacts underwent ELISPOT, HIV and PPD skin tests. Cases and contacts sleeping in a different house were used to estimate sensitivity and specificity, providing two planes for estimating cut-offs. Specificity was adjusted for infection from previous exposure using a multivariate discrimination algorithm. RESULTS: The point on the line of intersection of the planes that maximised sensitivity and specificity equivalence occurred at 4 spots (95% confidence interval [CI] 3.5–5, multiplier 0) for CFP-10 and 5.5 spots (4.5–8, multiplier 0 for ESAT-6), yielding a sensitivity and specificity of 76% for both antigens. Combining ESAT-6 and CFP-10 using an ‘or’ statement yielded a maximum equivalence sensitivity and specificity of 76.5% at 6 spots for ESAT-6 and 11.5 spots for CFP-10. For the PPD skin test sensitivity and specificity, an equivalence of 78% occurred at 11 mm induration (9–13 mm). CONCLUSION: An ELISPOT cut-off for ESAT-6 or CFP- 10 could be set at 4–8 spot forming units (20–40 spots per million), with little benefit from combining the results. A cut-off of 9–13 mm for the PPD skin test is reasonable when comparing with the ELISPOT