Identification of incipient tuberculosis in household contacts. The relevance of tuberculosis exposure scores and contact investigations.

Abstract Background The goal of tuberculosis elimination put forward in the End TB Strategy prioritizes diagnosis and treatment of incipient TB, recently defined by key stakeholders as an “asymptomatic, early pre-clinical disease during which pathology evolves” . Regarded as indicative of a high risk of TB progression, considerable efforts have been made to identify incipient TB through exploration of biomarkers. The present study aimed to evaluate simple scoring systems for TB exposure as screening tools for incipient TB in a contact investigation (CI) setting of low HIV-prevalence. Methods Nested within a large prospective study in household contacts (HHCs) of smear positive pulmonary TB cases in South-India conducted 2010-2012, we assessed 1) the association between the Tuberculosis Contact Score (TCS) and the Infectivity Score with established tools for Mycobacterium tuberculosis (Mtb) infection corrected for established TB risk factors and 2) the capability of the TB exposure scores to identify incipient TB defined by Mtb- culture positivity in sputum or gastric aspirate (subjects <5 years) specimen. Results Of 525 HHCs, 29 were Mtb -culture positive and 96.6% of these asymptomatic. The TCS and the Infectivity Score associated with positive Tuberculin Skin Test and QuantiFeron TB-Gold In-tube assay (QFT) results in multivariate analyses (TCS: OR TST 1.16, 95%CI: 1.01, 1.33; OR QFT 1.33 95%CI: 1.16, 1.51. Infectivity Score: OR TST 1.39, 95%CI: 1.10, 1.76; OR QFT 1.41 95%CI: 1.16, 1.71). The Infectivity Score showed a moderate capability to identify incipient TB (AUC of 0.61, 95%CI: 0.52, 0.70). Conclusion Although our results did not identify an easily applicable screening tool for incipient TB, the present study indicates that focusing on TB-related symptoms in CI settings may be of limited value for early identification of HHCs with high risk for TB progression, one of the goals of the End TB Strategy.