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Comparative Study
. 2014 Mar 21;9(3):e92308.
doi: 10.1371/journal.pone.0092308. eCollection 2014.

Pregnancy differentially impacts performance of latent tuberculosis diagnostics in a high-burden setting

Affiliations
Comparative Study

Pregnancy differentially impacts performance of latent tuberculosis diagnostics in a high-burden setting

Jyoti S Mathad et al. PLoS One. .

Abstract

Background: 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), however, may be reduced during pregnancy.

Methods: We 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.

Results: The 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.

Conclusions: Timing 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.

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Conflict of interest statement

Competing Interests: All authors have read and approved the revised manuscript, have met the criteria for authorship as established by the International Committee of Medical Journal Editors, and are able to verify the validity of the results reported. As stated previously, AG has received funding from the Gilead Foundation and the World Health Organization. JSM has received a travel grant from the Infectious Diseases Society of America. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. All other authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Cross-sectional comparison of TST and QGIT positivity by stage of pregnancya.
QGIT positivity was significantly higher than TST positivity at each stage of pregnancy. TST positivity was lowest during delivery and highest in postpartum women. QGIT positivity was stable during antepartum and delivery but was also higher in postpartum women. There was a trend towards a significant difference in TST positivity between antepartum versus delivery (p = 0.17) and antepartum versus postpartum (0.20), and a significant difference between delivery versus postpartum (0.009). There was no significant difference in QGIT positivity between antepartum versus delivery (p = 0.89), but there was a trend towards significance between antepartum versus postpartum (0.11) and a significant difference between delivery and postpartum (p = 0.02). aThe number of women who did not return for TST reading was 11 from antenatal, 5 from delivery and 29 from postpartum. Results shown here only include women with both TST and QGIT results. Abbreviations: QGIT =  QuantiFERON TB Gold In-tube Test; TST =  tuberculin skin test.
Figure 2
Figure 2. Longitudinal comparison of TST and QGIT positivity by stage of pregnancya.
QGIT positivity was higher than TST positivity at each stage of pregnancy, but only reached statistical significance at delivery. TST positivity was lowest during delivery and highest in postpartum women. QGIT positivity was also highest in postpartum women. aIncludes results for women who had TST and QGIT test results for at least 2 different visits: antepartum/delivery, delivery/postpartum, or antepartum/postpartum. Abbreviations: QGIT =  QuantiFERON TB Gold In-tube Test; TST =  tuberculin skin test.
Figure 3
Figure 3. Agreement between TST and QGIT decreases by stage of pregnancy.
Percent agreement and kappa were highest in antepartum women and lowest in postpartum women. Abbreviations: TST indicates tuberculin skin test, QGIT indicates QuantiFERON-TB Gold Test In-Tube.

References

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