Roe, J;
Venturini, C;
Gupta, R;
Gurry, C;
Chain, BM;
Sun, Y;
Southern, J;
... Noursadeghi, M; + view all
(2020)
Blood transcriptomic stratification of short-term risk in contacts of tuberculosis.
Clinical Infectious Diseases
, 70
(5)
pp. 731-737.
10.1093/cid/ciz252.
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Abstract
Background: The highest risk of tuberculosis (TB) arises in the first few months after exposure. We reasoned that this risk reflects incipient disease among TB contacts. Blood transcriptional biomarkers of TB may predate clinical diagnosis, suggesting they offer improved sensitivity to detect subclinical incipient disease. Therefore, we sought to test the hypothesis that refined blood transcriptional biomarkers of active TB will improve stratification of short-term disease risk in TB contacts. // Methods: We combined analysis of previously published blood transcriptomic data with new data from a prospective HIV negative United Kingdom cohort of 333 TB contacts. We used stability selection as an alternative computational approach to identify an optimal signature for short-term risk of active TB, and evaluated its predictive value in independent cohorts. // Results: In a previously published HIV negative South African casecontrol study of patients with asymptomatic Mycobacterium tuberculosis infection, a novel three-gene transcriptional signature comprising BATF2, GBP5 and SCARF1 achieved a positive predictive value (PPV) of 23% for progression to active TB within 90 days. In a new UK cohort of 333 HIV negative TB contacts with a median follow up of 346 days, this signature achieved a PPV of 50% (95% confidence interval: 15.7-84.3) and NPV of 99.3% (97.599.9). By comparison, peripheral blood interferon gamma release assays in the same cohort achieved a PPV of 5.6% (2.1-11.8). // Conclusion: This blood transcriptional signature provides unprecedented opportunities to target therapy among TB contacts with greatest risk of incident disease.
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