| Author | Gupte, Akshay N. | |
| Author | Kumar, Pavan | |
| Author | Pereira, Mariana Araújo | |
| Author | Kulkarni, Vandana | |
| Author | Paradkar, Mandar | |
| Author | Pradhan, Neeta | |
| Author | Menon, Pradeep | |
| Author | Darasini, Padmapriya | |
| Author | Hanna, Luke-Elizabeth | |
| Author | Shivakumar, Shri Vijay Bala Yogendra | |
| Author | Rockwood, Neesha | |
| Author | Bruyn, Elsa Du | |
| Author | Karyakarte, Rajesh | |
| Author | Gaikwad, Sanjay | |
| Author | Bollinger, Robert | |
| Author | Golub, Jonathan | |
| Author | Gupte, Nikhil | |
| Author | Viswanathan, Vijay | |
| Author | Wilkinson, Robert J. | |
| Author | Mave, Vidya | |
| Author | Babu, Subash | |
| Author | Kornfeld, Hardy | |
| Author | Andrade, Bruno B. | |
| Author | Gupta, Amita | |
| Access date | 2023-02-03T13:59:35Z | |
| Available date | 2023-02-03T13:59:35Z | |
| Document date | 2022 | |
| Citation | GUPTE, Akshay N. et al. Baseline IL-6 is a biomarker for unfavorable tuberculosis treatment outcomes: a multi-site discovery and validation study. European Respiratory Journal, v. 59, n. 4, p. 1-21, 2022. | en_US |
| ISSN | 1399-3003 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/56850 | |
| Sponsorship | Federal funds from the Government of India’s (GOI).
Department of Biotechnology (DBT).
The Indian Council of Medical Research (ICMR).
Tthe United States National Institutes of Health (NIH).
National Institute of Allergy and Infectious Diseases (NIAID).
Office of AIDS Research (OAR).
CRDF Global.
NIAID do NIH.
Wyncote Foundation.
Gilead Foundation.
Ujala Foundation.
Johns Hopkins University Center for AIDS Research.
National Institute Of Allergy And Infectious Diseases of the National Institutes of Health.
oordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).
Programa de Pesquisa Intramural da Fundação Oswaldo Cruz (FIOCRUZ).
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
The Francis Crick Institute.
Cancer Research UK.
Wellcome Trust.
The European and Developing Countries Clinical Trials Partnership.
The Foundation for the National Institutes of Health. | en_US |
| Language | eng | en_US |
| Publisher | European Respiratory Society | en_US |
| Rights | open access | en_US |
| Subject in Portuguese | Base IL-6 | en_US |
| Subject in Portuguese | Biomarcador | en_US |
| Subject in Portuguese | Tuberculose | en_US |
| Title | Baseline IL-6 is a biomarker for unfavorable tuberculosis treatment outcomes: a multi-site discovery and validation study | en_US |
| Type | Article | en_US |
| DOI | 10.1183/13993003.00905-2021. | |
| Abstract | Background: Biomarkers of unfavourable tuberculosis (TB) treatment outcomes are needed to accelerate new drug and regimen development. Whether plasma cytokine levels can predict unfavourable TB treatment outcomes is unclear. Methods: We identified and internally validated the association between 20 a priori selected plasma inflammatory markers and unfavourable treatment outcomes of failure, recurrence and all-cause mortality among adults with drug-sensitive pulmonary TB in India. We externally validated these findings in two independent cohorts of predominantly diabetic and HIV co-infected TB patients in India and South Africa, respectively. Results: Pre-treatment interferon-γ, interleukin (IL)-13 and IL-6 were associated with treatment failure in the discovery analysis. Internal validation confirmed higher pre-treatment IL-6 concentrations among failure cases compared with controls. External validation among predominantly diabetic TB patients found an association between pre-treatment IL-6 concentrations and subsequent recurrence and death. Similarly, external validation among predominantly HIV co-infected TB patients found an association between pre-treatment IL-6 concentrations and subsequent treatment failure and death. In a pooled analysis of 363 TB cases from the Indian and South African validation cohorts, high pre-treatment IL-6 concentrations were associated with higher risk of failure (adjusted OR (aOR) 2.16, 95% CI 1.08-4.33; p=0.02), recurrence (aOR 5.36, 95% CI 2.48-11.57; p<0.001) and death (aOR 4.62, 95% CI 1.95-10.95; p<0.001). Adding baseline IL-6 to a risk prediction model comprised of low body mass index, high smear grade and cavitation improved model performance by 15% (C-statistic 0.66 versus 0.76; p=0.02). Conclusions: Pre-treatment IL-6 is a biomarker for unfavourable TB treatment outcomes. Future studies should identify optimal IL-6 concentrations for point-of-care risk prediction. | en_US |
| Affilliation | Division of Infectious Diseases. Johns Hopkins University School of Medicine. Baltimore, USA / Center for Clinical Global Health Education. Johns Hopkins University School of Medicine. Baltimore, USA. | en_US |
| Affilliation | National Institute for Research in Tuberculosis. Chennai, India. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research, Salvador, Brazil /Universidade Federal da Bahia. Faculdade de Medicina, Salvador, BA, Brasil. | en_US |
| Affilliation | Center for Clinical Global Health Education. Johns Hopkins University School of Medicine. Baltimore, USA / Byramjee-Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site. Pune, India / Johns Hopkins India Private Limited. Pune, India. | en_US |
| Affilliation | Center for Clinical Global Health Education. Johns Hopkins University School of Medicine. Baltimore, USA / Byramjee-Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site. Pune, India / Johns Hopkins India Private Limited. Pune, India. | en_US |
| Affilliation | Center for Clinical Global Health Education. Johns Hopkins University School of Medicine. Baltimore, USA / Byramjee-Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site. Pune, India / Johns Hopkins India Private Limited. Pune, India. | en_US |
| Affilliation | National Institute for Research in Tuberculosis. Chennai, India. | en_US |
| Affilliation | National Institute for Research in Tuberculosis. Chennai, India. | en_US |
| Affilliation | National Institute for Research in Tuberculosis. Chennai, India. | en_US |
| Affilliation | Johns Hopkins India Private Limited. Pune, India. | en_US |
| Affilliation | Wellcome Centre for Infectious Disease Research in Africa. Institute of Infectious Disease and Molecular Medicine. University of Cape Town. Observatory. Cape Town, South Africa / Department of Microbiology. Faculty of Medicine. University of Colombo. Colombo, Sri Lanka / Department of Infectious Diseases. Imperial College London. United Kingdom. | en_US |
| Affilliation | Wellcome Centre for Infectious Disease Research in Africa. Institute of Infectious Disease and Molecular Medicine. University of Cape Town. Observatory. Cape Town, South Africa / Department of Infectious Diseases. University of Cape Town. Observatory. Cape Town, South Africa. | en_US |
| Affilliation | Department of Microbiology. Byramjee-Jeejeebhoy Government Medical College. Pune, India. | en_US |
| Affilliation | Department of Pulmonary Medicine. Byramjee-Jeejeebhoy Government Medical College. Pune, India. | en_US |
| Affilliation | Division of Infectious Diseases. Johns Hopkins University School of Medicine. Baltimore, USA / Center for Clinical Global Health Education. Johns Hopkins University School of Medicine. Baltimore, USA. | en_US |
| Affilliation | Division of Infectious Diseases. Johns Hopkins University School of Medicine. Baltimore, USA / Center for Tuberculosis Research. Johns Hopkins University. Baltimore, USA. | en_US |
| Affilliation | Division of Infectious Diseases. Johns Hopkins University School of Medicine. Baltimore, USA / Center for Clinical Global Health Education. Johns Hopkins University School of Medicine. Baltimore, USA. | en_US |
| Affilliation | Professor M. Viswanathan Diabetes Research Center. Chennai, India. | en_US |
| Affilliation | Wellcome Centre for Infectious Disease Research in Africa. Institute of Infectious Disease and Molecular Medicine. University of Cape Town. Observatory. Cape Town, South Africa / Department of Infectious Diseases. Imperial College London. United Kingdom / Department of Infectious Diseases. University of Cape Town. Observatory. Cape Town, South Africa / The Francis Crick Institute. 1 Midland Rd, London. | en_US |
| Affilliation | Division of Infectious Diseases. Johns Hopkins University School of Medicine. Baltimore, USA /Center for Clinical Global Health Education. Johns Hopkins University School of Medicine. Baltimore, USA. | en_US |
| Affilliation | National Institutes of Health. National Institute for Research in Tuberculosis. International Center for Excellence in Research. Chennai, India. | en_US |
| Affilliation | Division of Pulmonary Medicine. University of Massachusetts Medical School. Worcester, USA. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research, Salvador, BA, Brazil / Universidade Federal da Bahia. Faculdade de Medicina, Salvador, BA, Brasil. | en_US |
| Affilliation | Division of Infectious Diseases. Johns Hopkins University School of Medicine. Baltimore, USA /Center for Clinical Global Health Education. Johns Hopkins University School of Medicine. Baltimore, USA. | en_US |
| Subject | Base IL-6 | en_US |
| Subject | Biomarker | en_US |
| Subject | Tuberculosis | en_US |
| DeCS | Biomarcadores | en_US |
| DeCS | Tuberculose | en_US |
