Vanderbilt University and Vanderbilt Medical Center work with local and international partners to advance the field of tuberculosis research. Specific fields of research include:
One-third of the world’s population harbors latent M. tuberculosis infection, which can subsequently emerge as an airborne and transmittable disease. Reducing the human reservoir of infection through early detection, treatment and prevention efforts are vital to reducing the global burden of TB. Vanderbilt has been working closely with the Centers for Disease Control and Prevention, the Tennessee Department of Health and Metro Nashville Public Health Department to better prevent and treat TB infection among populations locally and internationally.
- TBTC Study 37, ASTEROID (Assessment of the Safety, Tolerability, and Effectiveness of Rifapentine given Daily for LTBI); Nashville, TN; PI – Timothy Sterling; CDC
- Patient-centered intervention to prevent TB among children less than 5 years old; Peru; PI – Larissa Otero (Peru); NIH K43TW011137
- Immune-mediated adverse drug reactions to HIV and TB treatments in South Africa: predict, prevent and improve long-term outcomes (IMARI SA study); South Africa; PIs - Elizabeth Phillips, Graeme Meintjes (South Africa); NIH R01AI152183
- TB Treatment and Prevention at the Metro Nashville Public Health TB Clinic
- Tuberculosis Trials Consortium (TBTC); Peru; PIs – Timothy Sterling, April Pettit; CDC
- Tuberculosis Epidemiology Studies Consortium (TBESC); Nashville, TN; PIs – April Pettit, Timothy Sterling; CDC
- Characterizing the impact of HIV disease severity in prediction models for tuberculosis treatment outcomes; Nashville, TN; PI – Lauren Peetluk; NIH F31AI152614
Drug-resistant strains of M. tuberculosis are becoming more common, particularly in developing countries. Multidrug-resistant TB (MDR-TB), defined as resistance to at least isoniazid and rifampin, and extensively drug-resistant TB (XDR-TB), defined as MDR-TB strains that are also resistant to fluoroquinolones and second-line injectable agents, are a growing concern. Researchers at Vanderbilt, with collaborators in Tennessee as well as Lima, Peru and Cape Town and Durban, South Africa, study resistance to fluoroquinolones, widely used for the treatment of bacterial infections, and how it may affect the diagnosis and treatment of TB.
- Predictors of Resistance Emergence Evaluation in MDR-TB Patients on Treatment (PRE-EMPT); India and Brazil; PIs – Robert Horsburgh (BU), Timothy Sterling; NIH R01AI134430
- Poor Treatment Response and Outcomes in Bedaquiline-Based Treatment Regimens for Drug-Resistant Tuberculosis in South Africa; PI – Yuri van der Heijden; NIH R01AI158605
- Mechanisms of Quinolone Resistance; Nashville, TN; PI – Neil Osheroff; VA Grant
- Fluoroquinolones and Efflux-Mediated Cross Resistance in HIV-related TB; Nashville, TN; PI – Timothy Sterling
- Mechanisms of antibiotic resistance development in bacterial pathogens; Nashville, TN; PI - Houra Merrikh; NIH R01AI127422
- Fluoroquinolone resistance in patients with multidrug-resistant tuberculosis; South Africa; PI – Yuri van der Heijden; NIH K08AI106420
TB is closely linked to HIV; HIV has been a key contributor to the TB epidemic. People with living with M. tuberculosis and HIV are significantly more likely to develop TB than people who are HIV-negative. To control TB in high HIV-prevalence settings, it is imperative to coordinate efforts for TB and HIV control. Vanderbilt collaborates with international organizations and population-based cohorts to reduce the burden of TB among people living with HIV and reduce the burden of HIV among persons with TB.
- International Epidemiologic Databases to Evaluate AIDS (IeDEA), NIH
- Caribbean, Central, and South America network for HIV Epidemiology (CCASAnet); Argentina, Brazil, Chile, Haiti, Honduras, Mexico, Peru; PIs – Catherine McGowan, Stephany Duda, Pedro Cahn (Argentina); NIH U01AI069923
- The North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD); Nashville, TN; PIs – Richard Moore (JHU), Keri Althoff (JHU), Timothy Sterling (VUMC Site PI); NIH U01AI069918
- Predictors of treatment toxicity, failure, and relapse in HIV-related tuberculosis; Brazil; PIs – Timothy Sterling, Valeria Rolla (Brazil); NIH R01AI120790
- Regional Prospective Observational Research for Tuberculosis (RePORT)- South Africa; PIs – Mark Hatherill (South Africa), Timothy Sterling; CRDF Global
- Avante: Towards Epidemic Control, improving TB/HIV diagnosis and care in Mozambique; PI – Bill Wester; CDC/PEPFAR
- Immune activation and dysglycemia in tuberculosis patients with and without HIV; South Africa; PIs – Yuri van der Heijden, John Koethe, Al Leslie (South Africa); CRDF Global
- Statistical methods for correlated outcome and covariate errors in studies of HIV/AIDS; South America and East Africa; PI – Bryan Shepherd; NIH R01AI131771
- The Antiretroviral Therapy Cohort Collaboration (ART-CC); North America and Europe; PI – Jonathan Sterne, Timothy Sterling; NIH U01AA026209
- International Epidemiologic Databases to Evaluate AIDS (IeDEA), NIH
Understanding how TB develops in the body is key to developing novel approaches to combating this disease. Researchers at Vanderbilt along with international collaborators have been working on improving our understanding of the mechanisms behind M. tuberculosis transmission and pathogenesis.
- Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil; PIs – Timothy Sterling, Bruno Andrade (Brazil); NIH U01AI069923
- RePORT International Coordinating Center (RICC); PIs – Jerrod Ellner (Rutgers), Timothy Sterling; CRDF Global
- Epidemiologic, immunologic, and genetic predictors and mechanisms of incipient, sub-clinical, and active TB in HIV-infected and -uninfected close TB contacts; Brazil; PIs – Timothy Sterling, Bruno Andrade (Brazil), Thomas Hawn (UW); NIH R01AI147765
- Characterization of Genomics and Metabolomics among Individuals Highly-Exposed, but resistant to Mtb Infection; PIs - Neel Gandhi (Emory); NIH R01AI139406
- Macrophage immunogenetics and incipient tuberculosis in Brazil; Brazil; PIs – Thomas Hawn (UW), Timothy Sterling, Bruno Andrade (Brazil); CRDF Global
- Molecular analysis of the adaptive immune response to tuberculosis; Nashville, TN; PI – Spyros Kalams; NIH R21AI127129
- Towards a global TB biomarker: Comparison of small transcriptomic signatures to predict, diagnose and monitor TB disease; Brazil, South Africa; PIs – Bruno Andrade (Brazil), Timothy Sterling, Mbandi Kimbung; CRDF Global
- Prospective profiling of eicosanoid and inflammatory balance in TB-diabetes; Brazil; PIs – Timothy Sterling, Bruno Andrade (Brazil), John Koethe, Henrique Serezani; CRDF Global
Rapid and accurate diagnosis is critical for timely initiation of TB treatment, but many people with TB (or TB symptoms) do not have access to adequate initial diagnosis. New tools and diagnostics are needed that can accurately diagnosis TB disease and be utilized in settings across the globe.
- A 100-fold more sensitive TB diagnostic based on magnetic concentration and "coffee ring" formation; PIs – David Wright and Rick Haselton; NIH R01AI135937
- Novel urine lipoarabinomannan (LAM) test; Brazil; PIs - David Wright, Micaella Jorge, Valeria Rolla, Adriano Gomes
- Sputum PCR-based test (Truenat) for the diagnosis of TB; Brazil; PIs – Afranio Kritski (Brazil)
- Urine TB diagnostic by amplicon reconstruction for PCR detection of DNA fragments; PI – Rick Haselton; NIH R21AI152497
The VTC aims to train the next generation of TB scientists, enabling them to succeed in their research and academic goals, and provide opportunities for TB training.
- HIV-Associated Tuberculosis Training Program (HATTP); South Africa; PIs – Graeme Meintjes (South Africa), David Haas; NIH D43TW010559
- Mentoring Investigators in HIV and Tuberculosis Therapeutics Research; Nashville, TN; PI – Kelly Dooley; NIH K24AI150349
- Vanderbilt SCHolars in HIV and Heart, Lung, Blood, and Sleep ReSearch (V-SCHoLARS); Nashville, TN; PIs – Matthew Freiberg, John Koethe; NIH K12HL143956
- Vanderbilt Infection Pathogenesis and Epidemiology Research Training Program (VIPER); Nashville, TN; PIs – Spyros Kalams; NIH T32AI007474
- Centers for AIDS Research (CFAR); Nashville, TN; PIs – Simon Mallal, David Haas; NIH P30AI110527
Improving existing treatment and therapy options by utilizing expertise in the pharmacology of anti-TB drugs; through the use of PK/PD analysis to optimize treatment regimens; and the exploration of safety and PK in people living with HIV, children and pregnant women.
- Second Generation InSTIs for the Treatment of HIV-1 in patients with TB co-infection on Rifampicin-based Treatment in KwaZulu Natal, South Africa; South Africa; PIs - Naidoo, Anushka, Kelly Dooley; NIH R01AI152142
- Innovative PK/PD approaches to optimize TBM treatment in children (TBM-KIDS trial); Baltimore, MD; PI - Kelly Dooley; NIH R01HD074944
- Phase 2 Study of PA-824 for Treatment of Pulmonary Tuberculosis IND 117472; Baltimore, MD; PI - Kelly Dooley; FDA R01FD004794
- Ph2a Study: Rifampin, Meropenem, Augmentin for Tuberculosis (COMRADE trial) IND 129159; Baltimore, MD; PI - Kelly Dooley; FDA R01FD005724