Predictive value of interferon-gamma release assays for postpartum active tuberculosis in HIV-1-infected women

Jonnalagadda, Sasi; Brown, Elizabeth Levine; Lohman-Payne, Barbara; Wamalwa, Dalton; Farquhar, Carey; John‐Stewart, Grace

doi:10.5588/ijtld.13.0239

Cited by 7 publications

(6 citation statements)

References 17 publications

(26 reference statements)

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“…Our findings suggest that TST underestimates the burden of LTBI in pregnancy, and that QGIT has high sensitivity for predicting postpartum TB, similar to a report in Kenyan women (6). Countries that already perform targeted screening or are considering integrating LTBI screening into antenatal programs may benefit from using the IGRA in addition to or instead of TST.…”

Section: Discussionsupporting

confidence: 67%

Quantitative IFN-γ and IL-2 Response Associated with Latent Tuberculosis Test Discordance in HIV-infected Pregnant Women

Mathad

Bhosale

Balasubramanian

et al. 2016

Am J Respir Crit Care Med

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Rationale: Pregnant women with latent tuberculosis infection (LTBI) are at high risk for development of TB, especially if infected with HIV.Objectives: To assess the performance of LTBI tests in pregnant and postpartum women infected with HIV, investigate the immunology behind discordance in pregnancy, and explore the implications for the development of postpartum TB.Methods: We screened pregnant women in their second/third trimester and at delivery for LTBI using the tuberculin skin test (TST) and IFN-g 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 rank sum 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, 0.25). When stratified by pregnancy versus delivery, 20% had IGRA 1 /TST 2 discordance at each time point. A positive IGRA was associated with known TB contact (odds ratio, 3.6; confidence interval, 1.2-11.1; P = 0.02). Compared with IGRA 1 /TST 1 , women with IGRA 1 /TST 2 discordance had significantly less IFN-g (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 TB, of which three had IGRA 1 /TST 2 discordance during pregnancy.Conclusions: Choice of LTBI test in pregnant women infected with HIV affects results. Pregnant women with IGRA 1 /TST 2 discordance had less IFN-g 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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Section: Discussionsupporting

confidence: 67%

Quantitative IFN-γ and IL-2 Response Associated with Latent Tuberculosis Test Discordance in HIV-infected Pregnant Women

Mathad

Bhosale

Balasubramanian

et al. 2016

Am J Respir Crit Care Med

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“…We also had limitations: by including only IGRA-positive women in our analysis we were unable to comment on conversions from negative to positive results from pregnancy to delivery or postpartum and progression to TB disease in IGRA negative women. In previous studies by our group and others, the risk of postpartum TB was highest in IGRA+ women( Jonnalagadda et al, 2010 , Jonnalagadda et al, 2013 , Mathad et al, 2016 ). Because we performed serial TSTs, the increase in TST positivity from pregnancy to delivery, especially in women with HIV, could reflect a boosting effect from the second TST placement.…”

Section: Discussionsupporting

confidence: 47%

Stages of pregnancy and HIV affect diagnosis of tuberculosis infection and Mycobacterium tuberculosis (MTB)-induced immune response: Findings from PRACHITi, a cohort study in Pune, India

Bhosale¹,

Alexander²,

Deshpande³

et al. 2021

International Journal of Infectious Diseases

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Background: Accurate tuberculosis infection (TBI) tests are critical for pregnant women, especially those with HIV, who have a high risk of TB disease. Methods: We enrolled interferon gamma release assay (IGRA)+ pregnant women with and without HIV in a longitudinal study, followed up at delivery and 6 months postpartum. Tuberculin skin test (TST) and IGRA were compared by HIV status at each timepoint. Results: Of 165 enrolled IGRA+ pregnant women: 35 (21%) had HIV and were on antiretroviral therapy with median CD4 of 476 (IQR 399–586). Compared to antepartum, significantly fewer women remained IGRA+ at delivery [HIV+ n=21/35 (62%, p=0.009); HIV− n=100/130 (77%, p=0.002)] and postpartum [HIV+ n=30/35 (87%, p=0.03); HIV− n=116/130 (89%, p=0.01)]. IGRA/TST discordance was high in pregnant women (HIV+: 51%; HIV−: 25%). Median IFN- γ was lowest for all women at delivery; significantly lower in women with HIV at all timepoints compared to women without HIV. TB incidence was 50/ 1000 person-years and 18/1000 person-years among women with and without HIV respectively. Conclusions: Pregnancy affects TBI test results and reduces IFN- γ response to M. tuberculosis stimulation. Despite adequate CD4 counts, women with HIV express less IFN- γ than women without HIV, which may explain the high TB incidence in postpartum women with HIV.

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“…Many of these 59 studies did not have the primary aim of assessing diagnostic accuracy. Many recorded few cases of active TB (often < 10) 22,[25][26][27][29][30][31][32][33][35][36][37][38]40,[42][43][44][45]47,48,50,51,[56][57][58][59][62][63][64][65][67][68][69][70][71][72][73][74][75]77,78 and/or were restricted to groups such as patients infected with HIV, 9,28,29,36,49,51,56,60,65,…”

Section: Diagnostic Performance Of Interferon Gamma Release Assays Fomentioning

confidence: 99%

“…Even among these studies, case numbers were sometimes low (see Table 1). In addition, several of the studies 29,31,32,35,36,52,56,62,72 did not explicitly state that prevalent cases were excluded, although the extent to which this may have affected their estimates was not always clear.…”

Section: Diagnostic Performance Of Interferon Gamma Release Assays Fomentioning

confidence: 99%

“…Within the subset of 18 studies, several compared the frequency of TB disease between IGRA-positive and IGRA-negative participants, consistently finding that rates, hazards or odds of TB were higher among the former (although CIs sometimes crossed the null value). Unadjusted estimates included a hazard ratio of 4.0 (95% CI 0.8 to 19.3), 36 odds ratio of 2.10 (95% CI 0.13 to 34.4) 35 and rate ratios of 8.5 (no CI given), 34 2.9 (95% CI 2.8 to 21. 41 Adjusted values included a hazard ratio of 2.0 (95% CI 1.2 to 3.3), after adjustment for BCG vaccination scar, maternal education and current/prior household TB contact, 54 and an odds ratio of 14.9 (95% CI 2.77 to 80.3), adjusted for the number of IGRA-positive contacts of the same index case, receipt of treatment and place of contact (household vs. other).…”

Section: Diagnostic Performance Of Interferon Gamma Release Assays Fomentioning

confidence: 99%

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Two interferon gamma release assays for predicting active tuberculosis: the UK PREDICT TB prognostic test study

Abubakar

Lalvani

Southern

et al. 2018

Health Technol Assess

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Background Despite a recent decline in the annual incidence of tuberculosis (TB) in the UK, rates remain higher than in most Western European countries. The detection and treatment of latent TB infection (LTBI) is an essential component of the UK TB control programme. Objectives To assess the prognostic value and cost-effectiveness of the current two interferon gamma release assays (IGRAs) compared with the standard tuberculin skin test (TST) for predicting active TB among untreated individuals at increased risk of TB: (1) contacts of active TB cases and (2) new entrants to the UK from high-TB-burden countries. Design A prospective cohort study and economic analysis. Participants and setting Participants were recruited in TB clinics, general practices and community settings. Contacts of active TB cases and migrants who were born in high-TB-burden countries arriving in the UK were eligible to take part if they were aged ≥ 16 years. Main outcome measures Outcomes include incidence rate ratios comparing the incidence of active TB in those participants with a positive test result and those with a negative test result for each assay, and combination of tests and the cost per quality-adjusted life-year (QALY) for each screening strategy. Results A total of 10,045 participants were recruited between May 2010 and July 2015. Among 9610 evaluable participants, 97 (1.0%) developed active TB. For the primary analysis, all test data were available for 6380 participants, with 77 participants developing active TB. A positive result for TSTa (positive if induration is ≥ 5 mm) was a significantly poorer predictor of progression to active TB than a positive result for any of the other tests. Compared with TSTb [positive if induration is ≥ 6 mm without prior bacillus Calmette–Guérin (BCG) alone, T-SPOT®.TB (Oxford Immunotec Ltd, Oxford, UK), TSTa + T-SPOT.TB, TSTa + IGRA and the three combination strategies including TSTb were significantly superior predictors of progression. Compared with the T-SPOT.TB test alone, TSTa + T-SPOT.TB, TSTb + QuantiFERON® TB Gold In-Tube (QFT-GIT; QIAGEN GmbH, Hilden, Germany) and TSTb + IGRA were significantly superior predictors of progression and, compared with QFT-GIT alone, T-SPOT.TB, TSTa + T-SPOT.TB, TSTa + QFT-GIT, TSTa + IGRA, TSTb + T-SPOT.TB, TSTb + QFT-GIT and TSTb + IGRA were significantly superior predictors of progression. When evaluating the negative predictive performance of tests and strategies, negative results for TSTa + QFT-GIT were significantly poorer predictors of non-progression than negative results for TSTa, T-SPOT.TB and TSTa + IGRA. The most cost-effective LTBI testing strategies are the dual-testing strategies. The cost and QALY differences between the LTBI testing strategies were small; in particular, QFT-GIT, TSTb + T-SPOT.TB and TSTb + QFT-GIT had very similar incremental net benefit estimates. Conclusion This study found modest differences between tests, or combinations of tests, in identifying individuals who would go on to develop active TB. However, a two-step approach that combined TSTb with an IGRA was the most cost-effective testing option. Implications for practice and future research The two-step TSTb strategy, which stratified the TST by prior BCG vaccination followed by an IGRA, was the most cost-effective approach. The limited ability of current tests to predict who will progress limits the clinical utility of tests. The implications of these results for the NHS England/Public Health England national TB screening programme for migrants should be investigated. Study registration This study is registered as NCT01162265. Funding The National Institute for Health Research Health Technology Assessment programme.

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Predictive value of interferon-gamma release assays for postpartum active tuberculosis in HIV-1-infected women

Cited by 7 publications

References 17 publications

Quantitative IFN-γ and IL-2 Response Associated with Latent Tuberculosis Test Discordance in HIV-infected Pregnant Women

Quantitative IFN-γ and IL-2 Response Associated with Latent Tuberculosis Test Discordance in HIV-infected Pregnant Women

Stages of pregnancy and HIV affect diagnosis of tuberculosis infection and Mycobacterium tuberculosis (MTB)-induced immune response: Findings from PRACHITi, a cohort study in Pune, India

Two interferon gamma release assays for predicting active tuberculosis: the UK PREDICT TB prognostic test study

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