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Meta-Analysis
. 2021 May 22;21(1):467.
doi: 10.1186/s12879-021-06141-4.

Interferon-gamma release assay levels and risk of progression to active tuberculosis: a systematic review and dose-response meta-regression analysis

Jorge R Ledesma  1 , Jianing Ma  1 , Peng Zheng  1   2 , Jennifer M Ross  3   4 , Theo Vos  1   2 , Hmwe H Kyu  5   6
Affiliations
Meta-Analysis

Interferon-gamma release assay levels and risk of progression to active tuberculosis: a systematic review and dose-response meta-regression analysis

Jorge R Ledesma et al. BMC Infect Dis. .

Abstract

Background: Identifying and treating individuals with high risk of progression from latent tuberculosis infection to active tuberculosis (TB) disease is critical for eliminating the disease. We aimed to conduct a systematic review and meta-regression analysis to quantify the dose-response relationship between interferon-gamma release assay (IGRA) levels and the risk of progression to active TB.

Methods: We searched PubMed and Embase from 1 January 2001 to 10 May 2020 for longitudinal studies that reported the risk of progression from latent to active TB as a function of baseline IGRA values. We used a novel Bayesian meta-regression method to pool effect sizes from included studies and generate a continuous dose-response risk curve. Our modeling framework enabled us to incorporate random effects across studies, and include data with different IGRA ranges across studies. The quality of included studies were assessed using the Newcastle-Ottawa scale (NOS).

Results: We included 34 studies representing 581,956 person-years of follow-up with a total of 788 incident cases of TB in the meta-regression analysis. Higher levels of interferon-gamma were associated with increased risk of progression to active tuberculosis. In the dose-response curve, the risk increased sharply between interferon-gamma levels 0 and 5 IU/ml, after which the risk continued to increase moderately but at a slower pace until reaching about 15 IU/ml where the risk levels off. Compared to 0 IU/ml, the relative risk of progression to active TB among those with interferon-gamma levels of 0.35, 1, 5, 10, 15, and 20 IU/ml were: 1.64 (1.28-2.08), 2.90 (2.02-3.88), 11.38 (6.64-16.38), 19.00 (13.08-26.90), 21.82 (14.65-32.57), and 22.31 (15.43-33.00), respectively. The dose-response relationship remains consistent when limiting the analysis to studies that scored highest in the NOS.

Conclusion: The current practice of dichotomizing IGRA test results simplifies the TB infection disease continuum. Evaluating IGRA test results over a continuous scale could enable the identification of individuals at greatest risk of progression to active TB.

Keywords: Active tuberculosis; Dose-response meta-regression; IGRA; Latent tuberculosis.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart of study selection
Fig. 2
Fig. 2
Dose-response curve for the association between interferon gamma levels and risk of developing active tuberculosis
Fig. 3
Fig. 3
Sensitivity analysis results (excluding studies with NOS quality score < 5)
Fig. 4
Fig. 4
Subgroup analysis results: a comparing PLHIV with HIV-negative individuals, b comparing TB case contacts with primary analysis, c comparing migrants with primary analysis, d comparing healthcare workers with primary analysis, e comparing studies providing preventive treatment with studies not providing preventive treatment, f comparing adults with children
See this image and copyright information in PMC

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