Pregnancy Differentially Impacts Performance of Latent Tuberculosis Diagnostics in a High-Burden Setting

Jyoti S Mathad,Renu Bharadwaj,Amita Gupta,Kavita Chopade,Prasad Deshpande,Daniel Fitzgerald,Ramesh Bhosale,Savita Kanade,Nikhil Gupte,Marshall J Glesby,Vandana Kulkarni,Vidya Mave,Ashwini Nangude,Nishi Suryavanshi,Pradeep Sambarey,Vikrant Sangar,Richard Van Zyl-Smit

doi:10.1371/journal.pone.0092308

Abstract

BackgroundTargeted screening for latent TB infection (LTBI) in vulnerable populations is a recommended TB control strategy. Pregnant women are at high risk for developing TB and likely to access healthcare, making pregnancy an important screening opportunity in developing countries. The sensitivity of the widely-used tuberculin skin test (TST), however, may be reduced during pregnancy.MethodsWe performed a cross-sectional study comparing the TST with the QuantiFERON Gold In-tube (QGIT) in 401 HIV-negative women presenting antepartum (n = 154), at delivery (n = 148), or postpartum (n = 99) to a government hospital in Pune, India. A subset of 60 women enrolled during pregnancy was followed longitudinally and received both tests at all three stages of pregnancy.ResultsThe QGIT returned significantly more positive results than the TST. Of the 401 women in the cross-sectional study, 150 (37%) had a positive QGIT, compared to 59 (14%) for the TST (p<0.005). Forty-nine (12%) did not have their TST read. Of 356 who had both results available, 46 (13%) were concordant positive, 91 (25%) were discordant (12 (3%) TST+/QGIT-; 79 (22%) TST−/QGIT+), and 206 (57%) concordant negative. Comparison by stage of pregnancy revealed that QGIT percent positivity remained stable between antepartum and delivery, unlike TST results (QGIT 31–32% vs TST 11–17%). Median IFN-γ concentration was lower at delivery than in antepartum or postpartum (1.66 vs 2.65 vs 8.99 IU/mL, p = 0.001). During postpartum, both tests had significantly increased positives (QGIT 31% vs 32% vs 52%, p = 0.01; TST 17% vs 11% vs 25%, p<0.005). The same trends were observed in the longitudinal subset.ConclusionsTiming and choice of LTBI test during pregnancy impact results. QGIT was more stable and more closely approximated the LTBI prevalence in India. But pregnancy stage clearly affects both tests, raising important questions about how the complex immune changes brought on by pregnancy may impact LTBI screening.

Highlights

800 million women carry latent Mycobacterium tuberculosis infection (LTBI), and 3 million develop active TB disease every year
The objectives of our study were to examine how pregnancy impacts the performance of latent TB infection (LTBI) diagnostics and to establish the concordance of the QuantiFERON TB Gold In-tube Test (QGIT), an interferon gamma release assay (IGRA), with the TST during pregnancy and the postpartum period in a TB-endemic country
One antepartum woman reported a personal history of TB and one postpartum woman had received isoniazid preventive therapy (IPT) in the past

Summary

Introduction

800 million women carry latent Mycobacterium tuberculosis infection (LTBI), and 3 million develop active TB disease every year. TB disproportionately affects women between the ages of 15 and 45 [1], when they are most likely to become pregnant. The disease is twice as likely to reactivate postpartum than at any other time in a woman’s life [2]. A woman whose LTBI reactivates during pregnancy has a high risk of death, prenatal complications and poor fetal outcomes[3,4,5]. The challenge is identifying pregnant women carrying the infection. Targeted screening for latent TB infection (LTBI) in vulnerable populations is a recommended TB control strategy. Pregnant women are at high risk for developing TB and likely to access healthcare, making pregnancy an important screening opportunity in developing countries. The sensitivity of the widely-used tuberculin skin test (TST), may be reduced during pregnancy

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