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

Betânia M F Nogueira; Francys Rangel; Alice M S Andrade; Evangeline Ann Daniel; Marina C Figueiredo; Cody Staats; Valeria C Rolla; Afrânio L Kritski; Marcelo Cordeiro-Santos; Amita Gupta; Luke Elizabeth Hanna; Timothy R Sterling; Mariana Araújo-Pereira; Bruno B Andrade; RePORT Brazil and RePORT India Consortia

doi:10.1093/infdis/jiae642

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

J Infect Dis. 2025 Jan 7:jiae642. doi: 10.1093/infdis/jiae642. Online ahead of print.

Authors

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 Figueiredo⁹, Cody Staats⁹, Valeria C Rolla¹⁰, Afrânio L Kritski¹¹, Marcelo Cordeiro-Santos^{12

13

14}, Amita Gupta¹⁵, Luke Elizabeth Hanna⁷, Timothy R Sterling⁹, Mariana Araújo-Pereira^{3

5

6}, Bruno B Andrade^{1

3

4

5

6}; RePORT Brazil and RePORT India Consortia

Collaborators

RePORT Brazil and RePORT India Consortia:
Elze Leite, Eduardo Gama, Allyson Guimarães Costa, Bruna da Costa Oliveira Lima, Amanda Araújo da Costa, Hilary Vansell

Affiliations

¹ Programa de Pós-graduação em Ciências da Saúde, Universidade Federal da Bahia, Salvador, Brazil.
² Departamento de Infectologia, Instituto Couto Maia, Salvador, Brazil.
³ Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil.
⁴ Curso de Medicina, Escola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador, Brazil.
⁵ Laboratório de Pesquisa Clínica e Translacional, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil.
⁶ Instituto de Pesquisa Clínica e Translacional, Medicina Zarns, Clariens Educação, Salvador, Brazil.
⁷ National Institute for Research in Tuberculosis, Indian Council of Medical Research (ICMR), Chennai, India.
⁸ University of Madras, Chennai, India.
⁹ Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, USA.
¹⁰ Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
¹¹ Programa Acadêmico de Tuberculose da Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
¹² Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil.
¹³ Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus, Brazil.
¹⁴ Faculdade de Medicina, Universidade Nilton Lins, Manaus, Brazil.
¹⁵ Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

PMID: 39763217
DOI: 10.1093/infdis/jiae642

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 non-progressors by sex, age, and exposure duration. Twenty-nine cytokines were measured by Luminex in 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 non-progressors from India. IL-8, IL-10, and CCL3 levels predicted incident tuberculosis (AUC: 0.75) in two years with sensitivity and specificity higher than 80%, in both cohorts. This signature predicted tuberculosis progression in close contacts meeting WHO goals.

Keywords: Biomarker Prediction; Cytokine; Quantiferon; Tuberculosis.

© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].