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. 2025 Sep 15;232(3):567-572.
doi: 10.1093/infdis/jiae642.

Predictive Markers of Incident Tuberculosis in Close Contacts in Brazil and India

Betânia M F Nogueira  1   2   3   4 , Francys Rangel  3   5   6 , Alice M S Andrade  3   5   6 , Evangeline Ann Daniel  7   8 , Marina C Figueiredo  9 , Cody Staats  9 , Valeria C Rolla  10 , Afrânio L Kritski  11 , Marcelo Cordeiro-Santos  12   13   14 , Amita Gupta  15 , Luke Elizabeth Hanna  7 , Timothy R Sterling  9 , Mariana Araújo-Pereira  3   5   6 , Bruno B Andrade  1   3   4   5   6
Affiliations

Predictive Markers of Incident Tuberculosis in Close Contacts in Brazil and India

Betânia M F Nogueira et al. J Infect Dis. .

Abstract

There are insufficient predictors of progression to tuberculosis among contacts. A case-control study within RePORT-Brazil matched 20 QuantiFERON-positive progressors and 40 nonprogressors by sex, age, and exposure duration. Twentynine cytokines were measured using a Luminex assay with QuantiFERON-TB Gold Plus supernatants collected at baseline and evaluated using machine learning for tuberculosis prediction. The same markers were evaluated in 8 QuantiFERON-positive progressors and 12 nonprogressors from India. Interleukin 8, interleukin 10, and CCL3 levels predicted incident tuberculosis (area under the receiver operating characteristic curve, 0.75) in 2 years with sensitivity and specificity >80%, in both cohorts. This signature predicted tuberculosis progression in close contacts meeting World Health Organization goals.

Keywords: Brazil; India; QuantiFERON; biomarker prediction; cytokine; multicentric study; tuberculosis.

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Conflict of interest statement

Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Identification and Validation of an Immune Signature Predicting TB Progression. (A) The MDI plot ranks the importance of cytokines and chemokines in distinguishing progressors from non-progressors. CCL3, IL-8, IL-10, and IFN-γ are highlighted as the most important variables with a MDI greater than 1. (B) Violin plots display the distribution of these cytokine levels (log-transformed) in the Brazilian cohort, comparing TB progressors and non-progressors. The ROC curve demonstrates the predictive power of the combined IL-8, IL-10, and CCL3 model in the Brazilian cohort. (C) Evaluation of the immune signature in an independent Indian cohort. Violin plots display the distribution of the same cytokines, showing a similar pattern of differential expression and ROC metrics between progressors and non-progressors if compared to Brazil. Parenthetical ranges in C represent 95% confidence intervals. Abbreviations: AUC, area under the receiver operating characteristic curve; CCL2 and CCL3, chemokine (C-C motif) ligand 2 and 3; CXCL10, chemokine (CXC motif) ligand 10; EGF, epidermal growth factor; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN, interferon; IL-8 (etc), interleukin 8 (etc); MDI, mean decrease in impurities; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor.
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