| Author | Mendelsohn, Simon C. | |
| Author | Andrade, Bruno B. | |
| Author | Mbandi, Stanley Kimbung | |
| Author | Andrade, Alice M. S. | |
| Author | Muwanga, Vanessa M. | |
| Author | Figueiredo, Marina C. | |
| Author | Erasmus, Mzwandile | |
| Author | Rolla, Valeria C. | |
| Author | Thami, Prisca K. | |
| Author | Santos, Marcelo Cordeiro | |
| Author | Nicholson, Adam Penn | |
| Author | Kritski, Afranio L. | |
| Author | Hatherill, Mark | |
| Author | Sterling, Timothy R. | |
| Author | Scriba1, Thomas J. | |
| Access date | 2024-08-06T17:52:03Z | |
| Available date | 2024-08-06T17:52:03Z | |
| Document date | 2024 | |
| Citation | MENDELSOHN, Simon C. et al. Transcriptomic signatures of progression to tuberculosis disease among close contacts in Brazil. The Journal of Infectious Diseases, p. 1-11, 2024. | en_US |
| ISSN | 1537-6613 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/65269 | |
| Sponsorship | National Institutes of Health.
CRDF Global.
Ministério da Saúde, Brasil. Secretaria de Ciência e Tecnologia. Departamento de Ciência e Tecnologia. | en_US |
| Language | eng | en_US |
| Publisher | Oxford University Press | en_US |
| Rights | open access | en_US |
| Subject in Portuguese | Biomarcadores | en_US |
| Subject in Portuguese | Sangue | en_US |
| Subject in Portuguese | Prognóstico | en_US |
| Subject in Portuguese | Transcriptômico | en_US |
| Subject in Portuguese | Tuberculose | en_US |
| Title | Transcriptomic signatures of progression to tuberculosis disease among close contacts in Brazil | en_US |
| Type | Article | en_US |
| DOI | 10.1093/infdis/jiae237 | |
| Abstract | Background: Approximately 5% of people infected with Mycobacterium tuberculosis progress to tuberculosis (TB) disease without preventive therapy. There is a need for a prognostic test to identify those at highest risk of incident TB so that therapy can be targeted. We evaluated host blood transcriptomic signatures for progression to TB disease. Methods: Close contacts (≥4 hours of exposure per week) of adult patients with culture-confirmed pulmonary TB were enrolled in Brazil. Investigation for incident, microbiologically confirmed, or clinically diagnosed pulmonary or extrapulmonary TB disease through 24 months of follow-up was symptom triggered. Twenty previously validated blood TB transcriptomic signatures were measured at baseline by real-time quantitative polymerase chain reaction. Prognostic performance for incident TB was tested by receiver operating characteristic curve analysis at 6, 9, 12, and 24 months of follow-up. Results: Between June 2015 and June 2019, 1854 close contacts were enrolled. Twenty-five progressed to incident TB, of whom 13 had microbiologically confirmed disease. Baseline transcriptomic signature scores were measured in 1789 close contacts. Prognostic performance for all signatures was best within 6 months of diagnosis. Seven signatures (Gliddon4, Suliman4, Roe3, Roe1, Penn-Nicholson6, Francisco2, and Rajan5) met the minimum World Health Organization target product profile for a prognostic test through 6 months and 3 signatures (Gliddon4, Rajan5, and Duffy9) through 9 months. None met the target product profile threshold through ≥12 months of follow-up.
Conclusions: Blood transcriptomic signatures may be useful for predicting TB risk within 9 months of measurement among TB-exposed contacts to target preventive therapy administration. | en_US |
| Affilliation | South African Tuberculosis Vaccine Initiative. Institute of Infectious Disease and Molecular Medicine. Division of Immunology. Department of Pathology. University of Cape Town. Cape Town, South Africa. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisa Clínica e Translacional. Salvador, BA, Brasil. | en_US |
| Affilliation | South African Tuberculosis Vaccine Initiative. Institute of Infectious Disease and Molecular Medicine. Division of Immunology. Department of Pathology. University of Cape Town. Cape Town, South Africa. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisa Clínica e Translacional. Salvador, BA, Brasil. | en_US |
| Affilliation | South African Tuberculosis Vaccine Initiative. Institute of Infectious Disease and Molecular Medicine. Division of Immunology. Department of Pathology. University of Cape Town. Cape Town, South Africa. | en_US |
| Affilliation | Vanderbilt University Medical Center. Nashville, Tennessee. | en_US |
| Affilliation | South African Tuberculosis Vaccine Initiative. Institute of Infectious Disease and Molecular Medicine. Division of Immunology. Department of Pathology. University of Cape Town. Cape Town, South Africa. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Micobacterioses. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | South African Tuberculosis Vaccine Initiative. Institute of Infectious Disease and Molecular Medicine. Division of Immunology. Department of Pathology. University of Cape Town. Cape Town, South Africa. | en_US |
| Affilliation | Fundação de Medicina Tropical Doutor Heitor Vieira Dourado. Manaus, AM, Brasil. | en_US |
| Affilliation | South African Tuberculosis Vaccine Initiative. Institute of Infectious Disease and Molecular Medicine. Division of Immunology. Department of Pathology. University of Cape Town. Cape Town, South Africa / FIND. Geneva, Switzerland. | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Centro de Pesquisa em Tuberculose. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | South African Tuberculosis Vaccine Initiative. Institute of Infectious Disease and Molecular Medicine. Division of Immunology. Department of Pathology. University of Cape Town. Cape Town, South Africa. | en_US |
| Affilliation | Vanderbilt University Medical Center. Nashville, Tennessee. | en_US |
| Affilliation | South African Tuberculosis Vaccine Initiative. Institute of Infectious Disease and Molecular Medicine. Division of Immunology. Department of Pathology. University of Cape Town. Cape Town, South Africa. | en_US |
| Subject | Biomarkers | en_US |
| Subject | Blood | en_US |
| Subject | Prognostic | en_US |
| Subject | Transcriptomic | en_US |
| Subject | Tuberculosis | en_US |
| DeCS | Biomarcadores | en_US |
| DeCS | Sangue | en_US |
| DeCS | Prognóstico | en_US |
| DeCS | Análise da expressão gênica de célula única | en_US |
| DeCS | Tuberculose | en_US |
