Four-gene Pan-African Blood Signature Predicts Progression to Tuberculosis

Suliman S, Thompson E, Sutherland J, et al. Am J Respir Crit Care Med. 2018 Apr 6. [Epub ahead of print] [CrossRef] [PubMed]

Contacts of tuberculosis (TB) patients constitute an important target population for preventative measures as they are at high risk of infection with Mycobacterium tuberculosis but only 5-10% progress to develop TB during their lifetime. progression to disease. In a case-control study HIV-negative African cohort of exposed household contacts, the authors employed RNA sequencing, polymerase chain reaction (PCR) and the Pair Ratio algorithm in a training/test set approach. Overall, 79 progressors, who developed tuberculosis between 3 and 24 months following exposure, and 328 matched non-progressors, who remained healthy during 24 months of follow-up, were investigated. A four-transcript signature (RISK4), derived from samples in a South African and Gambian training set, predicted progression up to two years before onset of disease in blinded test set samples from South Africa, The Gambia and Ethiopia with little population-associated variability and also validated on an external cohort of South African adolescents with latent Mycobacterium tuberculosis infection. By contrast, published diagnostic or prognostic tuberculosis signatures predicted on samples from some but not all 3 countries, indicating site-specific variability. Post-hoc meta-analysis identified a single gene pair, C1QC/TRAV27, that would consistently predict TB progression in household contacts from multiple African sites but not in infected adolescents without known recent exposure events.  This simple whole blood-based PCR test predicts tuberculosis in household contacts from diverse African populations, with potential for implementation in national TB contact investigation programs.