Completed Projects

Host biomarkers for investigating the spectrum of M. tuberculosis infection

Background: Evaluation of cytokines and chemokines that distinguish active TB, including extrapulmonary TB, from latent Mtb infection. Using archived, cryopreserved PBMC samples collected by Dr. Bruno Andrade in Salvador, Brazil, we are evaluating the performance of our candidate biomarkers in individuals with varying degrees of severity of Mtb infection and disease, including LTBI, sub-clinical TB and ATB; the latter will include both pulmonary and extrapulmonary disease. We will also assess our biomarkers in samples derived from individuals with presumptive TB (symptomatic or asymptomatic) for whom diagnostic tests were negative for TB.
Primary aims: Evaluate the performance of T cell biomarkers for diagnosing TB across the spectrum of Mtb infection in HIV-uninfected and HIV-infected individuals.
Current status: A paper describing our results was published in CID (please refer to Publications).
Principal Investigators (Consortium PIs): Jyothi Rengarajan, Ph.D., Bruno Andrade, M.D., Ph.D.

Prospective profiling of eicosanoid and inflammatory balance in TB-diabetes – CRDF Global

Background: This study utilize specimens only from Salvador site in Brazil and South Africa. Associations between the eicosanoid balance and TB clinical outcomes were further demonstrated in patients with pulmonary TB in an exploratory study from our group. A longitudinal multi-site study simultaneously quantifying several eicosanoids is needed to evaluate whether eicosanoid balance reflects TB disease activity and if/how this balance is influenced by HIV and/or DM.
Primary aims: To define the clinical characteristics of individuals with TB and/or DM and/or HIV in Brazil and South Africa; To determine whether co-morbid DM is associated with qualitatively or quantitatively distinct eicosanoid profiles in patients with TB and/or TB-HIV; and to determine whether co-morbid DM is associated with qualitative or quantitative differences in the resolution of perturbed eicosanoid profile during and after ATT in patients with TB and/or TB-HIV.
Current status: After obtaining the protocol approval by the IRBs from South Africa, Brazil, and Vanderbilt University Medical Center (VUMC), the study sites finalized patient recruitment. We also established a Materials Transfer Agreement (MTA) that allowed shipment of biospecimens from Brazil and South Africa to Vanderbilt. An export permit was also required to ship the specimens from South Africa to VUMC. In addition, the SOPs of the laboratory assays were also finalized. The lipidomic assays were completed, plasma specimens from cohort A (TB patients with or without diabetes) were successfully shipped from South Africa to Brazil for the Luminex assays. Results were presented during international meetings and papers were published. Additional manuscripts are also ongoing. Please refer to our Publications page.
Principal Investigators (Consortium PIs): Bruno Andrade, M.D., Ph.D., Timothy Sterling, M.D., Henrique Serezani, Ph.D., John Koethe, M.D., Ginger Milne, M.S.C.I., Alisdair Leslie, Ph.D.

Cross-RePORT TB-Diabetes transcriptomic signatures – CRDF Global

Background:Evaluation of transcriptomic signatures in persons with TB, TB/DM. This study was in collaboration with sites in India and South Africa. This study utilized specimens from the Salvador, Bahia site.
Primary aims:This project used peripheral blood samples collected in RNA storage tubes by the RePORT studies in Brazil, South Africa and India. Samples were used for RNA sequencing to investigate the transcriptomic profile of TB patients with and without comorbid diabetes.
Current status:RNA samples extracted from participants´ specimens in Brazil were sent to India for the transcriptomic analysis. Results from the Brazilian samples were generated together with South African and Indian samples. A manuscript is under review and accepted for publication. Please refer to our Publications page.
Principal Investigators:Hardy Kornfeld, M.D., Bruno Andrade, M.D., Ph.D., Amita Gupta, M.D.

Validation of transcriptional signature to predict active TB disease among advanced HIV patients – CRDF Global

Background: Evaluation of transcriptomic signatures in advanced HIV, and TB/HIV. This is in collaboration with RePORT-India. This study used specimens only from the INI and FMT Brazil sites.
Primary aims: To conduct testing and validation of the 15-gene signature to predict active TB disease among advanced HIV patients with CD4 <100 cells/ul; and to assess and compare the cytokine/chemokine signature that may be predictive for active TB among advanced TB-HIV and HIV patients in India and Brazil.
Current status: IRB approvals in Brazil were received and all patients were recruited. Samples were collected and stored. Luminex assays were complete and a paper was published. Additional manuscripts are planned. Please refer to our Publications page.
Principal Investigators (Consortium PIs):

Valeria Rolla, MD, PhD, Marcelo Cordeiro dos Santos, MD, PhD, Padmini Salgame, PhD, Vidya Mave, MD, MPH, Amita Gupta, MD, Bruno Andrade, MD, PhD.