• Ifedayo M Adetifa, Martin O C Ota, David J Jeffries, Moses D Lugos, Abdulrahman S Hammond, Nicholas J Battersby, Patrick K Owiafe, Simon D Donkor, Martin Antonio, Hannah B Ibanga, Roger H Brookes, Peter Aka, Robert Walton, Richard A Adegbola, and Philip C Hill.
• Medical Research Council Unit, The Gambia, Fajara, P.O. Box 273, Banjul, The Gambia. iadetifa@mrc.gm.
• Am. J. Respir. Crit. Care Med. 2013 Feb 15; 187 (4): 439-45.

RationaleBiomarkers that can be used to evaluate new interventions against latent tuberculosis infection (LTBI) and predict reactivation TB disease are urgently required.ObjectivesTo evaluate ESAT-6 and CFP-10 (EC) IFN-γ ELISPOT as a biomarker for treatment efficacy in LTBI.MethodsThis was a randomized, blinded, and placebo-controlled trial of INH in EC ELISPOT and Mantoux test positive participants.Measurements And Main ResultsParticipants received a 6-month course of 900 mg INH twice weekly or a matching placebo. INH acetylator genotypes were determined and urine tested for INH metabolites to confirm adherence. The proportion of positive responders for CFP-10 and ESAT-6 between treatment arms was compared using mixed effects logistic regression models. A Tweedie (compound Poisson) model was fitted to allow for zero inflation and overdispersion of quantitative response. The proportions of EC ELISPOT-positive subjects reduced over time (P < 0.001) but did not differ by study arm (P = 0.36). Median spot-forming units for ESAT-6 and CFP-10 also declined significantly with time (P < 0.001) but did not differ by study arm (P = 0.74 and 0.71, respectively). There was no evidence of an interaction between acetylator status and INH treatment with respect to ELISPOT results over time.ConclusionsIn contacts with LTBI, INH therapy plays no role in observed decreases in Mycobacterium tuberculosis antigen-specific T-cell responses over time. IFN-γ ELISPOT is probably not a useful biomarker of treatment efficacy in LTBI. Clinical trial registered with www.clinicaltrials.gov (NCT 00130325).

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