ARTICLE: Quantitative IFN-γ,IL-2 Response and Latent Tuberculosis Test Discordance in HIV-infected Pregnant Women

AUTHORS: Jyoti S Mathad, Ramesh Bhosale, Usha Balasubramanian, Savita Kanade, Vidya Mave, Nishi Suryavanshi, Nikhil Gupte, Samir Joshi, Ajay Chandanwale, Kathryn M Dupnik, Vandana Kulkarni, Prasad Deshpande, Daniel W Fitzgerald and Amita Gupta

JOURNAL: Am J Respir Crit Care Med. 2016 Jan 14. [Epub ahead of print]


RATIONALE: Pregnant women with latent TB infection (LTBI) are at high risk for development of tuberculosis, especially if HIV-infected.

OBJECTIVES: To assess the performance of LTBI tests in HIV-infected pregnant and postpartum women, investigate immunology behind discordance in pregnancy, and explore the implications for the development of postpartum tuberculosis.

METHODS: We screened pregnant women in their 2nd/3rd trimester and at delivery for LTBI using the tuberculin skin test (TST) and interferon gamma release assay (IGRA) (QuantiFERON® Gold). A subset of antepartum women had longitudinal testing, with repeat testing at delivery and postpartum and additional cytokines measured from the IGRA supernatant. The kappa statistic and Wilcoxon ranksum test were used to determine agreement and comparison of cytokine concentrations, respectively.

MEASUREMENTS AND MAIN RESULTS: Of 252 enrolled, 71 (28%) women had a positive IGRA but only 27 (10%) had a positive TST (p<0.005). There was 75% agreement (kappa of 0.25). When stratified by pregnancy vs. delivery, 20% had IGRA+/TST- discordance at each timepoint. A positive IGRA was associated with known TB contact (OR 3.6, CI 1.2-11.1, p=0.02). Compared to IGRA+/TST+, women with IGRA+/TST- discordance produced significantly less IFN-γ (1.85 vs 3.48 IU/mL, p=0.02) and IL-2 (46.17 vs 84.03 pg/mL, p=0.01). Five developed postpartum tuberculosis, of which three had IGRA+/TST- discordance during pregnancy.

CONCLUSIONS: Choice of LTBI test in HIV-infected pregnant women affects results. Pregnant women with IGRA+/TST- discordance produce less IFN-γ and IL-2 than those with concordant positive results and may represent an especially high-risk subset for the development of active TB postpartum.

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