Host blood-based biosignatures for subclinical TB: a prospective study of household contacts of adult pulmonary TB index cases in Southern India.

Identification of blood transcriptional biomarkers linked to different phases of tuberculosis. The discovery of a transcriptional signature that distinguishes subclinical TB from incipient TB at baseline could lead to tuberculosis interventions that combat the tuberculosis epidemic in the context of household contacts. All household contacts were followed up for one year. Samples were collected at 0, 2, 6, and 12 months. Some people go on to develop TB (Subclinical TB) whereas some others do not (Incipient TB). Household controls were carefully selected from the same incipient TB and sub-clinical TB families and age-matched to either incipient or subclinical TB cases. We used the same method as for the controls to pick the active TB cases in the adult index TB. In this study, for incipient TB baseline and 12 month or last available samples were selected, for sub-clinical TB baseline and culture-postive for Mtb time point samples or closely available time-point samples were selected, whereas for active TB and household controls baseline samples were selected and sent for RNA-sequencing. Within families/households of TB index cases, the present study aimed to i) identify differentially expressed transcriptional biomarkers associated with distinct stages of TB in samples acquired at baseline contact investigation. ii) identify transcriptional signatures with the ability to distinguish subclinical TB from incipient TB in samples acquired at baseline, iii) evaluate the performance of identified transcriptional signature(s) in active TB disease cases and asymptomatic household controls in samples acquired at baseline.