Adriana Weinberg1, Lisa Aaron2, Grace Montepiedra2, Timothy R Sterling3, Renee Browning4, Blandina Mmbaga5, Tichaona Vhembo6, Shilpa Naik7, Enid Kabugho8, Gaerolwe Masheto9, Savita Pahwa10, Jyoti S Mathad11, Sylvia M LaCourse12, Katie McCarthy13, Sarah Bradford13, Gerhard Theron14, Diane Costello15, Bonnie Zimmer16, Marie F Pierre17, Kamunkhwala Gausi18, Paolo Denti18, David W Haas3, Amita Gupta19. 1. Department of Pediatrics, Medicine and Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. 2. Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA. 3. Vanderbilt Tuberculosis Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA. 4. Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. 5. Kilimanjaro Christian Medical Centre (KCMC) Moshi, Tanzania. 6. University of Zimbabwe College of Health Sciences Clinical Trials Research Centre (UZCHS-CTRC), Harare, Zimbabwe. 7. Department of Obstetrics and Gynaecology, BJGMC, Pune, India. 8. Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda. 9. Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana, and Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA. 10. Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida, USA. 11. Department of Medicine, Center for Global Health, Weill Cornell Medicine, New York, New York, USA. 12. Department of Medicine, University of Washington, Seattle, Washington, USA. 13. FHI 360, Durham, North Carolina, USA. 14. FAM-CRU CRS, Department of Obstetrics and Gynaecology, Stellenbosch University, Cape Town, South Africa. 15. University of California Los Angeles, Los Angeles, California, USA. 16. Frontier Science Foundation, Amherst, New York, USA. 17. Les Centres GHESKIO, Port-au-Prince, Haïti. 18. Division of Clinical Pharmacology, University of Cape Town, Cape Town, South Africa. 19. Departments of Medicine and International Health, Johns Hopkins University, Baltimore, Maryland, USA.
Abstract
BACKGROUND: Pregnancy is accompanied by immune suppression. We hypothesized that Mycobacterium tuberculosis-specific inflammatory responses used to identify latent tuberculosis infection (LTBI) lose positivity during pregnancy. We also hypothesized that isoniazid preventive therapy (IPT) may revert LTBI diagnoses because of its sterilizing activity. METHODS: 944 women with human immunodeficiency virus infection (HIV) participating in a randomized, double-blind, placebo-controlled study comparing 28 weeks of IPT antepartum versus postpartum, were tested by QuantiFERON-gold-in-tube (QGIT) antepartum and by QGIT and tuberculin skin test (TST) at delivery and postpartum. Serial QGIT positivity was assessed by logistic regression using generalized estimating equations. RESULTS: From entry to delivery, 68 (24%) of 284 QGIT-positive women reverted to QGIT-negative or indeterminate. Of these, 42 (62%) recovered QGIT positivity postpartum. The loss of QGIT positivity during pregnancy was explained by decreased interferon gamma (IFNγ) production in response to TB antigen and/or mitogen. At delivery, LTBI was identified by QGIT in 205 women and by TST in 113 women. Corresponding numbers postpartum were 229 and 122 women. QGIT and TST kappa agreement coefficients were 0.4 and 0.5, respectively. Among QGIT-positive women antepartum or at delivery, 34 (12%) reverted to QGIT-negative after IPT. There were no differences between women who initiated IPT antepartum or postpartum. CONCLUSIONS: Decreased IFNγ responses in pregnancy reduced QGIT positivity, suggesting that this test cannot reliably rule out LTBI during pregnancy. TST was less affected by pregnancy, but had lower positivity compared to QGIT at all time points. IPT was associated with loss of QGIT positivity, the potential clinical consequences of which need to be investigated.
BACKGROUND: Pregnancy is accompanied by immune suppression. We hypothesized that Mycobacterium tuberculosis-specific inflammatory responses used to identify latent tuberculosis infection (LTBI) lose positivity during pregnancy. We also hypothesized that isoniazid preventive therapy (IPT) may revert LTBI diagnoses because of its sterilizing activity. METHODS: 944 women with human immunodeficiency virus infection (HIV) participating in a randomized, double-blind, placebo-controlled study comparing 28 weeks of IPT antepartum versus postpartum, were tested by QuantiFERON-gold-in-tube (QGIT) antepartum and by QGIT and tuberculin skin test (TST) at delivery and postpartum. Serial QGIT positivity was assessed by logistic regression using generalized estimating equations. RESULTS: From entry to delivery, 68 (24%) of 284 QGIT-positive women reverted to QGIT-negative or indeterminate. Of these, 42 (62%) recovered QGIT positivity postpartum. The loss of QGIT positivity during pregnancy was explained by decreased interferon gamma (IFNγ) production in response to TB antigen and/or mitogen. At delivery, LTBI was identified by QGIT in 205 women and by TST in 113 women. Corresponding numbers postpartum were 229 and 122 women. QGIT and TST kappa agreement coefficients were 0.4 and 0.5, respectively. Among QGIT-positive women antepartum or at delivery, 34 (12%) reverted to QGIT-negative after IPT. There were no differences between women who initiated IPT antepartum or postpartum. CONCLUSIONS: Decreased IFNγ responses in pregnancy reduced QGIT positivity, suggesting that this test cannot reliably rule out LTBI during pregnancy. TST was less affected by pregnancy, but had lower positivity compared to QGIT at all time points. IPT was associated with loss of QGIT positivity, the potential clinical consequences of which need to be investigated.
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