Increased risk of active tuberculosis during pregnancy and postpartum: a register-based cohort study in Sweden

Jonsson, Jerker; Kühlmann-Berenzon, Sharon; Berggren, Ingela; Bruchfeld, Judith

doi:10.1183/13993003.01886-2019

Cited by 65 publications

(52 citation statements)

References 18 publications

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“…those without this profile) at an increased risk of TB progression and would further support the idea of LTBI as a spectrum where subgroups of LTBI+ are protected from progression while others are not (9, 10). In addition, future studies would also need to determine whether this relationship of the systemic immune profile with TB progression is causal as it could partly explain the increased risk of Mtb progression during pregnancy and post-partum (15)(16)(17).…”

Section: Discussionmentioning

confidence: 99%

“…It is not currently known whether there is a difference in systemic inflammation between LTBI+ and LTBI− pregnant women, and how this might change by trimester of pregnancy. Furthermore, LTBI+ women have a higher risk of Mtb progression during pregnancy and post-partum, but the reasons are not clear (15)(16)(17). The immune profile during pregnancy, including the systemic inflammatory milieu, may inform on potential changes to immunity that increase susceptibility to TB disease during pregnancy.…”

Section: Introductionmentioning

confidence: 99%

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Systemic Inflammation in Pregnant Women With Latent Tuberculosis Infection

et al. 2021

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BackgroundRecent studies in adults have characterized differences in systemic inflammation between adults with and without latent tuberculosis infection (LTBI+ vs. LTBI−). Potential differences in systemic inflammation by LTBI status has not been assess in pregnant women.MethodsWe conducted a cohort study of 155 LTBI+ and 65 LTBI− pregnant women, stratified by HIV status, attending an antenatal clinic in Pune, India. LTBI status was assessed by interferon gamma release assay. Plasma was used to measure systemic inflammation markers using immunoassays: IFNβ, CRP, AGP, I-FABP, IFNγ, IL-1β, soluble CD14 (sCD14), sCD163, TNF, IL-6, IL-17a and IL-13. Linear regression models were fit to test the association of LTBI status with each inflammation marker. We also conducted an exploratory analysis using logistic regression to test the association of inflammatory markers with TB progression.ResultsStudy population was a median age of 23 (Interquartile range: 21–27), 28% undernourished (mid-upper arm circumference (MUAC) <23 cm), 12% were vegetarian, 10% with gestational diabetes and 32% with HIV. In multivariable models, LTBI+ women had significantly lower levels of third trimester AGP, IL1β, sCD163, IL-6 and IL-17a. Interestingly, in exploratory analysis, LTBI+ TB progressors had significantly higher levels of IL1β, IL-6 and IL-13 in multivariable models compared to LTBI+ non-progressors.ConclusionsOur data shows a distinct systemic immune profile in LTBI+ pregnant women compared to LTBI− women. Data from our exploratory analysis suggest that LTBI+ TB progressors do not have this immune profile, suggesting negative association of this profile with TB progression. If other studies confirm these differences by LTBI status and show a causal relationship with TB progression, this immune profile could identify subsets of LTBI+ pregnant women at high risk for TB progression and who can be targeted for preventative therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Systemic Inflammation in Pregnant Women With Latent Tuberculosis Infection

et al. 2021

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“…According to recent WHO reports, about one-quarter of the world's population is estimated to have LTBI and only 5-10% of these individuals eventually develop active TB (World Health Organization, 2019). However, the risk of developing active TB as a result of reactivation of the LTBI could substantially increase in the presence of several predisposing factors such as Human immunodeficiency virus (HIV) infection and pregnancy (World Health Organization, 2019;Jonsson et al, 2020). HIV infection diminishes the Th1 cell-mediated immune response Abbreviations: TB, tuberculosis; LTBI, latent tuberculosis infection; HIV, Human immunodeficiency virus; M. tuberculosis, Mycobacterium tuberculosis; CD, cluster of differentiation; IFN, interferon; BCG, Bacille Calmette-Guérin; TST, tuberculin skin test; ELISA, enzyme-linked immunosorbent assay; QFTGIT, QuantiFERON-TB Gold In-Tube; PPD, purified protein derivative; ESAT-6, Early secreted antigen target-6; CFP-10, Culture filtrate protein-10; IQR, interquartile range; CDC, Center for Disease Control and Prevention; WHO, World Health Organization. to M. tuberculosis, while pregnancy deepens this suppression of anti-mycobacterial responses in HIV-positive individuals (Birku et al, 2020;Amelio et al, 2019;Mofenson and Laughon, 2007).…”

Section: Introductionmentioning

confidence: 99%

Effect of pregnancy and HIV infection on detection of latent TB infection by Tuberculin Skin Test and QuantiFERON-TB Gold In-Tube assay among women living in a high TB and HIV burden setting

Birku

Desalegn

Kassa

et al. 2020

International Journal of Infectious Diseases

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To investigate the effect of pregnancy and Human immunodeficiency virus (HIV) infection on detection performances of tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube (QFTGIT) for the diagnosis of latent tuberculosis infection (LTBI) among women living in high TB and HIV endemic setting. Method: A cross-sectional study was conducted among women with and without pregnancy and HIV infection. Three-hundred twenty women were enrolled in this study and were diagnosed using TST and QFTGIT for the detection of LTBI.Results: Overall prevalence of LTBI among the enrolled women was 55.6%, 46.3% and 51.1% as determined by TST, QFTGIT and concordant TST/QFTGIT results, respectively. Our study revealed that pregnancy or HIV infection reduced the rate of detection of LTBI by TST and QFTGIT tests, with the utmost effect observed in HIV-positive pregnant women. Additionally, we observed that the concordance between TST and QFTGIT among women increased with the presence of pregnancy and/or HIV infection. A history of contact with TB patients was significantly associated with positivity of TST and QFTGIT. Conclusion: This study demonstrated that both pregnancy and HIV infection profoundly affected the detection performance of TST and QFTGIT, which may be associated with immunosuppression of antimycobacterial immunity in women with pregnancy and/or HIV infection.

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“…Multiple studies have demonstrated this increased risk of TB in PWWH, particularly postpartum [ 26 , 27 ]. Women without HIV also have an increased TB risk during pregnancy, and an even greater risk postpartum [ 28 , 29 ]. How pregnancy- and postpartum-induced biomarker changes affect immune activation pathways known to predict morbidity and mortality in HIV remains incompletely understood [ 30 ].…”

mentioning

confidence: 99%

Changes in Immune Activation During Pregnancy and the Postpartum Period in Treated HIV Infection

Schnittman

Byakwaga

Boum

et al. 2021

Open Forum Infectious Diseases

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Background Pregnant women with HIV (PWWH) have high postpartum morbidity and mortality from infections like tuberculosis. Immunologic changes during pregnancy and postpartum periods may contribute to these risks, particularly the immunoregulatory kynurenine pathway of tryptophan catabolism, which contributes to both HIV and tuberculosis pathogenesis and increases in the early postpartum. Methods Women with HIV initiating ART in the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort who were pregnant at enrollment or became pregnant during observation were studied (N=54). Plasma kynurenine/tryptophan (KT) ratio, sCD14, sCD163, sCD27, IP-10, D-dimer, IL-6, and I-FABP levels were assessed through the first year of ART and at 3-month intervals throughout pregnancy and one year postpartum. Biomarker changes were assessed with linear mixed models adjusted for ART duration. Hemoglobin concentration changes were used to estimate pregnancy-related changes in plasma volume. Results Median baseline CD4 was 134. D-dimer increased through the third trimester before returning to baseline postpartum while most other biomarkers declined significantly during pregnancy, beyond what would be expected from pregnancy-associated plasma volume expansion. IP-10 and sCD14 remained suppressed for at least 12 months postpartum. KT ratio was the only biomarker that increased above pre-pregnancy baseline in the postpartum (mean +30%, P<0.001) and remained higher than baseline for >9 months (P<0.045 for all timepoints). Conclusions Several immune activation markers decline during pregnancy and remain suppressed postpartum, but the kynurenine pathway of tryptophan catabolism increases above baseline for >9 months postpartum. The mechanisms underlying postpartum kynurenine pathway activity are incompletely understood, but may contribute to increased tuberculosis risk in this setting.

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Increased risk of active tuberculosis during pregnancy and postpartum: a register-based cohort study in Sweden

Cited by 65 publications

References 18 publications

Systemic Inflammation in Pregnant Women With Latent Tuberculosis Infection

Systemic Inflammation in Pregnant Women With Latent Tuberculosis Infection

Effect of pregnancy and HIV infection on detection of latent TB infection by Tuberculin Skin Test and QuantiFERON-TB Gold In-Tube assay among women living in a high TB and HIV burden setting

Changes in Immune Activation During Pregnancy and the Postpartum Period in Treated HIV Infection

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