Quantitative T Cell Assay Reflects Infectious Load of Mycobacterium Tuberculosis in an Endemic Case Contact Model

Abstract

Background. Currently, reliable efficacy markers for assessment of new interventions against tuberculosis (TB) are limited to disease and death. More precise measurement of the human immune response to Mycobacterium tuberculosis infection may be important. A qualitative enzyme-linked immunospot assay (ELISPOT) result for early secretory antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) offers improved specificity over the purified protein derivative (PPD) skin test reaction in the detection of M. tuberculosis infection. We evaluated the quantitative ELISPOT and PPD skin test responses to recent M. tuberculosis exposure. Methods. We studied quantitative PPD skin test and PPD ELISPOT results in 1052 healthy household contacts of index patients with cases of sputum smear–positive and culture-positive TB in The Gambia, according to a positive or negative ex vivo interferon g ELISPOT response to M. tuberculosis–specific antigens (ESAT-6/CFP-10). We then studied the quantitative PPD skin test and PPD ELISPOT results in patient contacts who had positive ESAT-6/CFP-10 results against a natural exposure gradient according to sleeping proximity to a patient with TB. Results. The number of positive results was significantly greater for both PPD skin test and PPD ELISPOT in ESAT-6/CFP-10–positive subjects, compared with others (P ! .0001). However, when quantitative PPD skin test and PPD ELISPOT results were compared in ESAT-6/CFP-10–positive subjects, only the ELISPOT count was sensitive to the exposure gradient, increasing significantly according to exposure (Pp.009). Conclusions. The quantitative ELISPOT response to PPD in specific-antigen–positive contacts of patients with TB reflects the infectious load of M. tuberculosis as a result of recent exposure. This finding offers new possibilities for assessment of the efficacy of new interventions, and adjustment should be made for it when relating the early immune response to progression to disease.