Robert S Wallis, MD, FIDSA, FRCPE
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INFECTIOUS DISEASES
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TUBERCULOSIS DRUG DEVELOPMENT
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HOST-DIRECTED THERAPIES
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BIOMARKERS
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BACKGROUND
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I am a physician scientist with training in Internal Medicine and Infectious Diseases, and expertise in the development of biologics, vaccines, and small molecules. I hold academic appointments as Professor of Medicine at Vanderbilt and Case Western Reserve School of Medicine. I have published approximately 170 manuscripts, review articles, and book chapters, mainly in the areas of anti-infective drug development, biomarkers, and immunotherapy. My publication indices are summarized here at Google Scholar.
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My career shifted from academia to industry in 2004, when I led a successful bid by PPD, a contract research organization, to win what at the time was the largest contract in the history of the US NIAID, managing the international trials of its Division of AIDS. I came to Pfizer in 2008 as the Therapeutic Area Clinical Lead for Infectious Diseases, where my responsibilities included clinical development of a wide range of antibacterials, antivirals, antifungals, sepsis therapies, and therapeutic antibodies. I provided oversight of trial designs, development plans, and regulatory strategies. I also served as clinical lead for the development of sutezolid, an oxazolidinone antimicrobial for the treatment of tuberculosis. Pfizer completed the first study of sutezolid in TB patients.
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In 2014 I joined the Aurum Institute as Chief Science Officer, where I am responsible for developing Aurum's program of biomedical research on TB and HIV. Our projects have included studies of host-directed TB therapy funded by the Gates foundation, the German Ministry of Education and Research (BMBF), US NIH, the European Commission (Horizon 2020), and EDCTP. We also are studying individuals who have been heavily exposed to active TB cases but who have remained tuberculin skin test (TST) and IFNg (QFT) negative (funded by the Gates foundation and NIH). I also serve as a member of the editorial board of the Journal of Infectious Diseases and am a member of the external scientific advisory board of the German Center for Infection Research (DZIF).
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PUBLICATIONS
TCA metabolism regulates DNA hypermethylation in MTB immune tolerance. PNAS 2024
Adjunctive NAC and lung function in pulmonary tuberculosis. NEJM Evidence 2024
Perspectives from the 2nd International Post-Tuberculosis Symposium. IJTLD Open 2024
Repurposing N-acetylcysteine for non-acetaminophen induced acute liver failure. Transl Gastroenterol Hepatol 2024
Performance of spirometry at TB diagnosis. IJTLD 2023
Circulating biomarkers, FeNO and lung function in patients with HIV and tuberculosis. JID 2023
Lung function and collagen 1a levels during TB treatment. BMC Pulm Med 2023
IFN-γ independent markers of MTB exposure among SA gold miners. eBioMed 2023
A phase 2 open label trial of delpazolid regimens. Trials 2023
QFN TB Gold+ vs TB Gold in-tube for LTBI diagnosis in SA gold miners. Gates Open 2022
Quantitative Systems Pharmacology Modeling Framework of Autophagy in Tuberculosis. AAC 2022
Impact of N-acetylcysteine on tuberculosis: A systematic review. Antioxidants (Basel) 2022
Tuberculosis "Autoregression": A historical perspective. Am J Trop Med Hyg 2022
Assay Conversion. mSPHERE 2022
Host-directed immunotherapy of viral and bacterial infections: past, present and future. Nat Rev Immunol 2022
Resistance to MTB infection among highly TB exposed South African gold miners. PLOS One 2022
Lung and blood early biomarkers for host-directed tuberculosis therapies. PLoS One 2022
Lancet Glob Health 2021
Clinical standards for the assessment, management and rehabilitation of post-TB lung disease. IJTLD 2021
conversion. J Clin Invest 2021
Response in T2DM. Front Cell Infect Microbiol 2021
An ecological study of BCG vaccination and COVID-19 mortality. PLoS One 2021
Mycobacterial growth inhibition assay in diabetes mellitus. Frontiers in Cellular and Infection Microbiology 2021
Adjunctive host-directed therapies for pulmonary TB: a prospective, open-label, phase 2, randomised controlled trial.
Lancet Respir Med 2021
Pulmonary restriction predicts long-term pulmonary impairment in HIV+TB. BMC Pulm Med 2021
An ecological study of BCG vaccination and COVID-19 morbidity and mortality. PLoS One 2020
Post-TB lung health: Perspectives from the 1st international symposium. IJTLD 2020
Post-TB mortality and morbidity: valuing the hidden epidemic. Lancet Respir Med 2020 (preprint: here)
A common NLRC4 variant associates with inflammation and pulmonary function in HIV+ TB. Clin Infect Dis 2019
Declines in lung function after ART initiation in adults with HIV+TB. Clin Infect Dis 2019
Lung injury on ART in adults with HIV+TB. Clin Infect Dis 2019
BMC Pulm Med 2019
Nat Med 2019
18F-FDG PET/CT scan in the evaluation of host-directed adjunctive TB therapies (TB-HDT). AIDS 2018 (abstract)
Immunologic mechanisms of human resistance to MTB infection. Nature Rev Immunol 2018
Mycobactericidal activity of bedaquiline plus rifabutin or rifampin. PLoS ONE 2018
Pan-tuberculosis regimens: an argument for. Lancet Respir Med 2018
Application of a whole blood mycobacterial growth inhibition assay to study immunity against
Mycobacterium tuberculosis in a high tuberculosis burden population. PLoS ONE 2017
Methods for selecting regimen duration to prevent relapse in DS and DR-TB. IJTLD 2016
High dose rifampin, moxifloxacin, and SQ109: The PANACEA MAMS TB trial. Lancet ID 2016
Cardiac safety of XDR-TB regimens including bedaquiline, delamanid, and clofazimine. ERJ 2016
Vitamin D as adjunctive host-directed therapy in TB: A systematic review. Open Forum Infect Dis 2016
Safety and immunogenicity of rBCG AERAS-422 in healthy adults. eBioMedicine 2016
Activity of nitazoxanide and tizoxanide againt Mtb in vitro and whole blood culture. Tuberc 2016
Tuberculosis - Advances in drugs, regimens, HDT and biomarkers. Lancet Infect Dis 2016
Mathematical models of tuberculosis relapse and reactivation. Frontiers Microbiol 2016
Toward host-directed therapies for tuberculosis. Nature Rev Drug Discov 2015 (preprint: here)
Sputum culture conversion in new TB regimens. Lancet Respir Med 2015
Early biomarkers and regulatory innovation in MDR-TB. Clin Infect Dis 2015
Month 2 culture status and treatment duration as predictors of TB recurrence: Model validation and update.
PLoS ONE 2015
Advancing host-directed therapy for tuberculosis. Nature Rev Immunol 2015
Sputum culture conversion as a tuberculosis biomarker: A glass half empty or half full?
Lancet Respir Med 2015
Lack of a therapeutic role for IFNg in tuberculosis. J Infect Dis 2014
Corticosteroid effects on sputum culture in pulmonary tuberculosis. Open Forum Infect Dis 2014
Mycobactericidal activity of sutezolid (PNU-100480) in sputum (EBA) and blood (WBA) of TB patients.
PLoS ONE 2014
(PNU-101603) against intracellular Mtb in ex vivo whole blood cultures (WBA) of patients with
pulmonary tuberculosis. AAC 2014
Inhibition of mycobacterial growth in vitro following primary but not secondary vaccination with BCG.
Clin Vaccine Immunol 2013
Month 2 culture status and treatment duration as predictors of tuberculosis relapse risk in a meta-
regression model. PLoS ONE 2013
Tuberculosis biomarkers discovery: developments, needs, and challenges. Lancet Infect Dis 2013
Early bactericidal activity of new drug regimens for tuberculosis. Lancet 2013
Application of a stochastic modeling to assess the evolution of tuberculous and non-tuberculous
mycobacterial infection in patients treated with TNF inhibitors. PLoS ONE 2013
Sustainable Tuberculosis Drug Development. Clin Infect Dis 2012
Sterilizing activities of novel combinations lacking first- and second-line drugs in a murine model of
tuberculosis. Antimicrob Agents Chemother 2012
Rapid evaluation in whole blood culture of regimens for XDR-TB containing PNU-100480 (sutezolid),
TMC207, PA-824, SQ109, and pyrazinamide. PLoS One 2012
SQ109 and PNU-100480 interact to kill M. tuberculosis in vitro. J Antimicrob Chemother 2012
Biologics and infections: lessons from tumor necrosis factor blocking agents. Infect Dis Clin North Am 2011
Biomarker-assisted dose selection for safety and efficacy in early development of PNU-100480 for
tuberculosis. Antimicrob Agents Chemother 2011
Pulmonary infectious complications of tumor necrosis factor blockade. Infect Dis Clin North Am 2010
Pharmacokinetics and whole-blood bactericidal activity against Mycobacterium tuberculosis of single
doses of PNU-100480 in healthy volunteers. J Infect Dis 2010
The risk of tuberculosis related to tumour necrosis factor antagonist therapies: a TBNET consensus
statement. Eur Respir J 2010
Biomarkers and diagnostics for tuberculosis: progress, needs, and translation into practice. Lancet 2010
Biomarkers for tuberculosis disease activity, cure, and relapse: 2 month culture conversion.
Lancet Infect Dis 2010
Treatment of HIV-related inflammatory cerebral cryptococcoma with adalimumab. Clin Infect Dis 2010
Biomarkers of disease activity, cure, and relapse in tuberculosis. Clin Chest Med 2009
Advances in immunotherapy for tuberculosis treatment. Clin Chest Med 2009
Infectious complications of tumor necrosis factor blockade. Curr Opin Infect Dis 2009
Significance of early secreted antigenic target 6-specific T cell depletion after HIV-1 infection.
J Infect Dis 2009
Biomarkers for tuberculosis disease status and diagnosis. Curr Opin Pulm Med 2009
Adalimumab treatment of life-threatening tuberculosis. Clin Infect Dis 2009
Strain specificity of antimycobacterial immunity in whole blood culture after TB cure. Tuberculosis 2009
Biomarkers for tuberculosis disease activity, cure, and relapse. Lancet Infect Dis 2009
Mycobacterial disease attributable to tumor necrosis factor-alpha blockers. Clin Infect Dis 2008
Tumour necrosis factor antagonists: structure, function, and tuberculosis risks. Lancet Infect Dis 2008
Clin Infect Dis 2008
Mathematical modeling of the cause of TB during TNF blockade. Arthritis Rheum 2008
Acquired rifamycin resistance: pharmacology and biology. Expert Rev Anti Infect Ther 2008
Report of the expert consultation on immunotherapy of tuberculosis. WHO 2007
Bactericidal activity of OPC-67683 against drug-tolerant Mycobacterium tuberculosis. JAC 2007
Structural-functional relationships of TNF-alpha antagonists: next steps.
J Investig Dermatol Symp Proc 2007
Reactivation of latent tuberculosis by TNF blockade: the role of interferon gamma.
J Investig Dermatol Symp Proc 2007
Persistence, not resistance, is the cause of loss of isoniazid effect. J Infect Dis 2007
Corticosteroids and HIV infection: a review of experience. Curr Opin HIV AIDS 2007
Surrogate markers to assess new therapies for drug-resistant TB. Expert Rev Anti Infect Ther 2007
Here today--gone tomorrow: the case for transient acute tuberculosis infection. AJRCCM 2006
Tumor necrosis factor antagonists: different kinetics and/or mechanisms of action may explain
differences in the risk for developing granulomatous infection. Semin Arthritis Rheum 2006
Tumor-necrosis-factor blockers: differential effects on mycobacterial immunity. J Infect Dis 2006
Glutathione and growth inhibition of M tuberculosis in healthy and HIV infected subjects. AIDS Res Ther 2006
AIDS Res Hum Retroviruses 2005
Anti-tuberculosis treatment and infliximab. Respir Med 2005
Reconsidering adjuvant immunotherapy for tuberculosis. Clin Infect Dis 2005
Reactivation of latent granulomatous infections by infliximab. Clin Infect Dis 2005
Can EBA studies of rifapentine tell us how to prevent acquired rifamycin-resistant relapse?
Am J Respir Crit Care Med 2005
TNF and granuloma biology: explaining the differential infection risk of etanercept and infliximab.
Semin Arthritis Rheum 2005
Infect Immun 2005
Sutton's law. Int J Tuberc Lung Dis 2005
Immunoadjuvant prednisolone therapy for HIV-TB: a phase 2 clinical trial in Uganda. J Infect Dis 2005
Mechanisms of action of TNF antagonist and granulomatous infections. J Rheumatol 2004
Granulomatous infections due to tumor necrosis factor blockade & Correction. Clin Infect Dis 2004
whole-blood culture. Antimicrob Agents Chemother 2004
A study of the safety, immunology, virology, and microbiology of adjunctive etanercept in HIV-TB.
AIDS 2004
TB chemotherapy: antagonism between immunity and sterilization. Am J Respir Crit Care Med 2004
counts of 200 to 700 mm-3. J Acquir Immune Defic Syndr 2003
Whole blood bactericidal activity during treatment of pulmonary tuberculosis. J Infect Dis 2003
tuberculosis. Clin Diagn Lab Immunol 2002
Adult tuberculosis in the 21st century: pathogenesis, clinical features, and management.
Curr Opin Pulm Med 2001
A whole blood bactericidal assay for tuberculosis. J Infect Dis 2001
Inhibition of isoniazid-induced expression of Mycobacterium tuberculosis antigen 85 in sputum: A
potential surrogate marker in tuberculosis chemotherapy trials. Antimicrob Agents Chemother 2001
Opsonizing antibodies (IgG1) up-regulate monocyte proinflammatory cytokines tumour necrosis factor-
alpha (TNF-alpha) and IL-6 but not anti-inflammatory cytokine IL-10 in mycobacterial antigen-
stimulated monocytes-implications for pathogenesis. Clin Exp Immunol 2001
Predicting the outcome of therapy for pulmonary tuberculosis. Am J Respir Crit Care Med 2000
Randomized controlled trial of Mycobacterium vaccae immunotherapy in non-human immunodeficiency
virus-infected ugandan adults with newly diagnosed pulmonary tuberculosis. J Infect Dis 2000
PPD-specific IgG1 antibody subclass upregulate tumour necrosis factor expression in PPD-stimulated
monocytes: possible link with disease pathogenesis in tuberculosis. Clin Exp Immunol 2000
Enhanced production of recombinant Mycobacterium tuberculosis antigens in Escherichia coli by
replacement of low-usage codons. Infect Immun 2000
Depressed T-cell interferon-gamma responses in pulmonary tuberculosis: analysis of underlying
mechanisms and modulation with therapy. J Infect Dis 1999
Drug tolerance in Mycobacterium tuberculosis. Antimicrob Agents Chemother 1999
Instability of tuberculin and Candida skin test reactivity in HIV-infected Ugandans. AJRCCM 1998
Pentoxifylline in HIV-TB: safety at 4 years. J Infect Dis 1998
in pulmonary tuberculosis treatment. J Infect Dis 1998
Enhanced responses to Mycobacterium tuberculosis antigens by human alveolar lymphocytes during
active pulmonary tuberculosis. J Infect Dis 1998
Measurement of induced cytokines in AIDS clinical trials using whole blood: a preliminary report.
Clin Diagn Lab Immunol 1998
Proinflammatory cytokine and human immunodeficiency virus RNA levels during early Mycobacterium
avium complex bacteremia in advanced AIDS. J Infect Dis 1998
blood mononuclear cells from patients with Kaposi's sarcoma in Uganda. J Infect Dis 1997
Tuberculosis vaccines: how close to human testing? Tuber Lung Dis 1997
Examining a paradox in the pathogenesis of human pulmonary tuberculosis: immune activation and
suppression/anergy. Tuber Lung Dis 1997
Immune activation, allergic drug toxicity and mortality in HIV-positive tuberculosis. Tuber Lung Dis 1996
Pentoxifylline therapy in human immunodeficiency virus-seropositive persons with tuberculosis: a
randomized, controlled trial. J Infect Dis 1996
Induction of monocyte expression of tumor necrosis factor alpha by the 30-kD alpha antigen of
Mycobacterium tuberculosis and synergism with fibronectin. J Clin Invest 1996
Predictors of survival in human immunodeficiency virus-infected patients with pulmonary TB.
Am J Respir Crit Care Med 1996
New approaches to identification of antigens of Mycobacterium tuberculosis. Infect Agents Dis 1996
Guérin in purified protein derivative (PPD)-positive individuals. J Immunol 1995
Cytokines and tuberculosis. J Leukoc Biol 1994
Screening of a cosmid library of BCG in M smegmatis for novel T-cell stimulatory antigens.
Res Microbiol 1993
protein of Mycobacterium tuberculosis. Infect Immun 1993
Influence of tuberculosis on human immunodeficiency virus (HIV-1): enhanced cytokine expression and
elevated beta 2-microglobulin in HIV-1-associated tuberculosis. J Infect Dis 1993
Macrophages, mycobacteria and HIV: the role of cytokines in determining mycobacterial virulence and
regulating viral replication. Res Microbiol 1992
Duration of fever during treatment of infective endocarditis. Medicine (Baltimore) 1992
PROBIT: a computer program analysis. J Immunol Methods 1991
Human Mycobacterium tuberculosis-reactive CD4+ T-cell clones: heterogeneity in antigen recognition,
cytokine production, and cytotoxicity for mononuclear phagocytes. Infect Immun 1991
Direct mitogenic properties of interleukin-1. J Lab Clin Med 1991
T cell activation by mycobacterial antigens in inflammatory synovitis. Cell Immunol 1991
Human immune response to Mycobacterium tuberculosis antigens. Infect Immun 1991
Induction of interleukin 1 and TNF by mycobacterial proteins: the monocyte western blot.
Proc Natl Acad Sci USA 1990
Cell membrane is a major locus for UV B-induced alterations in accessory cells. J Clin Invest 1990
More on zidovudine and HIV-related thrombocytopenia. N Engl J Med 1989
Identification of antigens of M tuberculosis using human monoclonal antibodies. J Clin Invest 1989
Dyscoordinate expression of TNF-a by human blood monocytes and alveolar macrophages. ARRD 1989
Immunologic aspects of mycobacterial infections. Rev Infect Dis 1989
Expression of tumor necrosis factor in vitro by human mononuclear phagocytes stimulated with whole
Mycobacterium bovis BCG and mycobacterial antigens. Infect Immun 1988
The immunology of tuberculous pleurisy. Semin Respir Infect 1988
Tumor necrosis factor is the major monocyte product that increases complement receptor expression on
mature human neutrophils. Blood 1988
Clin Exp Immunol 1987
Testing for AIDS: more problems with predictive values. JAMA 1986
Direct stimulation of monocyte release of IL 1 by mycobacterial protein antigens. J Immunol 1986
Increased IL-1 production and monocyte suppressor cell activity associated with human TB. ARRD 1986
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BOOK CHAPTERS
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Immunology of SARS-CoV-2 Infection. In: Textbook of SARS-CoV-2 and COVID-19, Elsevier 2022
Advances in host-directed therapies against tuberculosis. Springer 2021
Antitubercular drug discovery and development. In Burger's Medicinal Chemistry 8th Edition, 2021
Clinical Immunology of Tuberculosis. In: Davies P (ed): Clinical Tuberculosis. London, CRC Press. 2014.
Assessment of whole blood bactericidal activity in the evaluation of new TB drugs. In: Donald PR, van
Helden (eds): Antituberculosis Chemotherapy. Progress in Respiratory Research. Basel, Karger. 2011
Immunotherapy of tuberculosis. In: Schaaf S and Zumla A (eds): Tuberculosis: A comprehensive clinical
reference. Saunders/Elsevier 2009.
Report of the joint TDR/EC expert consultation to evaluate the potential roles of biomarkers in the
management of HIV-infected and HIV-uninfected patients with tuberculosis. WHO, Geneva 2008.
Report of the expert consultation on immunotherapeutic interventions for tuberculosis.
WHO, Geneva, 2007.
Infectious complications of TNF blockade. Up To Date. 2006-17.
Surrogate markers of TB chemotherapy. In: Yew WW (ed): Tuberculosis Drug Development,
Nova Science Publishers 2006.
In vitro models to study immune control of intracellular M. tuberculosis infection.
In: S. Cole, K. Eisenach, D. McMurray and W. Jacobs (eds): Tuberculosis and the Tubercle
Bacillus. ASM Press, 2005..
Immunotherapy of tuberculosis and other mycobacterial infections. In Jacobson J,
Immunotherapy of infectious diseases, Humana Press, 2002.
Tuberculin and anergy panel skin testing. In Tan JS (ed): Expert's Guide to the Management of Common
Infectious Diseases. American College of Physicians, Philadelphia.
Immunology of M. tuberculosis and other mycobacteria. In: Chmel H (ed): Pulmonary Infections and
Immunity, Plenum Press, NY 1994.
Regulation of the immune response to M. tuberculosis, in Ayoub EM, Cassell GH, Branche WC, Henry TJ
(eds): Microbial determinants of virulence and host response. ASM Press, Washington, DC 1990.
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INVITED LECTURES
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NIH Workshop to Define Next-Generation TB-HDT, “Clinical Overview”, Bethesda, 2024
2nd Intl Virtual Conference on MTB R&D, “Oxidative Stress and Lung Injury in Tuberculosis”, 2024
2nd Intl PTLD Symposium, “Host-directed TB therapy”, Stellenbosch, 2023
SMA-TB Annual meeting, “Host-directed TB therapy”, Tbilisi, 2023
IUATLD NAR Annual Conf, “Host-directed TB therapy”, Vancouver, 2021
TB Pharm Workshop, “Host-directed TB therapy”, 2021
ECCMID, "TNF blockers and tuberculosis", Paris, 2020
IUATLD TB Science program, “Host-directed TB therapy”, Hyderabad, 2019
Gates foundation Grand Challenges meeting, “Host-directed TB therapy”, Addis Ababa, 2019
Int’l conf on post-TB Lung Disease, “Host-directed TB therapy”, Stellenbosch, 2019
Gordon Conf TB Drug Development, “Host-directed TB therapy”, Barcelona, 2019
FHI360, “Host-directed TB therapy”, Durham, 2019
HVTN national network meeting, “Host-directed TB therapy”, Washington DC, 2019
NIH workshop, “Host-directed TB therapy, Bethesda, 2019
Institute Merieux TB IVD program, “Pan-TB regimens: the argument pro”, Cape Town, 2019
EDCTP Forum, “Host-directed therapy for TB”, Lisbon, 2018
NIH workshop on TB meningitis, “Host-directed therapy for tuberculosis”, Rockville, 2017
FIDSSA Annual meeting, "21st Century development of pan-TB regimens", Cape Town, 2017
FDA workshop, "Predicting required duration of new TB regimens, Rockville, 2017
NIH workshop, "Host-directed therapy for CNS tuberculosis", Rockvill, 2017
UCT Lung Institute, "Host-directed therapy for M/XDR-TB", Cape Town, 2017
NIH/WGND workshop, "21st Century paths to oxazolidinone pan-TB regimens", Rockville, 2016
NIH/BMGF Workshop, "Resistance to TB infection in S African miners", Rockville, 2016
NIH Workshop, "Endpoints in TB HDT clinical trials", Rockville MD, 2016
Gates Grand Challenges, "Personalized treatment of tuberculosis", London UK, 2016
INTERTB, "Host directed therapy of tuberculosis", London UK, 2016
ATS, "Host directed therapy of tuberculosis", San Francisco CA, 2016
ICID, "Advancing treatment of MDR-TB" and session chair, Hyderabad India, 2016
Gates Grand Challenges, "Host-directed therapy for tuberculosis", Beijing China 2015
SIgN symposium, "Host-directed therapy for tuberculosis", Singapore 2015
K-RITH symposium, "Host-directed therapy for tuberculosis", Durban South Africa, 2014
WHO Task Force, "Advancing regimens for MDR-TB", Washington DC, 2014
NIH workshop, "Advancing host-directed therapy for tuberculosis", Rockville MD, 2014
PanACEA, "Development of sutezolid regimens for tuberculosis", Dakar Senegal, 2013
Aurum Institute, "Host-directed therapies for tuberculosis", Johannesburg South Africa, 2013
CURE-TB Symposium and ITRC Scientific Retreat, "Oxazolidinone regimens for MDR-TB" and “PK-PD of sutezolid intracellular mycobactericidal activity” Chengdu China 2013
Critical Path for TB Regimens Annual Workshop, "Development of sutezolid-containing TB regimens", Washington DC, 2013
TB pharmacology conference, "PK/PD modeling of sutezolid", Denver CO, 2013
Gordon Conference on TB Drug Development, “Two month culture status and treatment duration as predictors of relapse risk”, Lucca (Barga) Italy, 2013
UCL TB Day Program, “TB Biomarkers”, London UK, 2013
Int’l Meeting on Childhood TB, “TB Diagnostics and Biomarkers” and “TB Drug Development Today”, Padua Italy, 2013
32nd semi-annual CDC TBTC meeting, “Accelerating development of new TB regimens”, Atlanta GA, 2012
Asia REACH Roundtable Meeting, “Best practices for LTBI screening and treatment prior to anti-TNF treatment”, Hong Kong, 2012
WHO Task Force for the Introduction of New TB Drugs and Regimens, “Update on sutezolid”, Geneva Switzerland, 2012
EUROMEDNET-TB Biomarkers Workshop, “TB Biomarkers: A drug developer’s perspective”, Marrakech Morocco, 2012
5th International workshop on Clinical Pharmacology of Tuberculosis Drugs, “Oxazolidinones for Tuberculosis”, San Francisco, 2012
Gates Foundation Special Program on TB Translational Pharmacology, “Alternatives to EBA”, Washington DC, 2012
UC San Diego 3rd Global Symposium on IGRAs, “Biologic therapies and reactivation of LTBI”, Waikoloa Hawaii, 2012
Critical Path for TB Regimens, 2nd annual meeting, “Update on PNU-100480”, Arlington VA, 2011
ACTG Leadership Retreat, TB Transformative Science Group, “Update on PNU-100480 and the whole blood model”, Washington DC, 2011
STOP-TB Working Group on New Drugs, “Update on PNU-100480”, Lille France, 2011
II Encontro sobre Pesquisas em Tuberculose na Bahia, “Biomarkers for tuberculosis: Near-term and distant horizons” and "Biomarker acceleration of development of PNU-100480 for TB", Salvador Brazil, 2011
Gordon Research Conference on TB Drug Development, “PNU-100480: Strategies for new TB drugs”, Lucca (Barga) Italy, 2011
Informa Life Sciences, “Translational Research in Tuberculosis”, Berlin Germany, 2011
NIH Conference on TB Biomarkers, keynote address, Bethesda MD, 2011
World PK/PD Summit, “The Role of Biomarkers to Reduce Risks in Early Development: Lessons from Tuberculosis”, Boston MA, 2011
University of Cape Town, “TB risks of TNF blockade: Lessons for biologist and clinicians”, Cape Town South Africa, 2011
STOP TB/World Conference Lung Health, “PNU-100480 update”, Berlin Germany, 2010
New York Medical College, “Biomarkers for Tuberculosis”, Valhalla NY, 2010
Kilimanjaro Medical Research Center, "Biomarker acceleration of early TB drug development" and "Infectious Complications of TNF Blockade", Moshi Tanzania, 2010.
Netherlands Society for Microbiology Annual Meeting, “Infectious Complications of TNF blockade”, Arnhem Netherlands, 2010.
Joint GCC and WHO/TDR workshop on priority setting for TB/HIV research, “Optimising TB diagnostics in the era of HIV/AIDS”, Riyadh Saudi Arabia, 2010.
Genopole International Conference on Biomarkers, “Biomarkers for Tuberculosis”, Paris France, 2009.
Hungarian Academy of Science, “Infectious complications of TNF blockers”, Budapest Hungary, 2009.
TB Alliance, “Symposium: Recent Advances in TB Drug Development”, in IUATLD 40th Union Conference on Lung Health, Cancun Mexico, 2009.
Global Fund AIDS TB Malaria, Lancet TB Series Theme Review, Geneva Switzerland, 2009.
RESIST-TB, “Workshop on TB trials design”, Amsterdam Netherlands, 2009.
ICAAC, “Infectious complications of TNF blockade”, San Francisco CA, 2009.
FDA workshop, “Issues in the Design of Clinical Trials of Antimycobacterial Drugs for Treatment of Tuberculosis”, Silver Spring MD, 2009.
IAS International Meeting. “Anti-TNF treatment of IRIS/PR”, in INSHI program, Cape Town SA, 2009.
Danish Society of Infectious Medicine Annual Meeting, “Infectious Complications of Anti-cytokine Therapy, Hindsgavl Castle, Denmark, 2009.
Arizona Infectious Disease Society Annual Meeting, “Infectious Complications of TNF Blockade”, Sedona AZ, 2009.
Keystone Conference, Tuberculosis: Biology, Pathology and Therapy. “Targeted Immunotherapy for TB: Lessons from biologics”, in program of the Stop TB Working Group for New Drugs. Keystone CO, 2009.
Wyeth, "Infectious Complications of Anti-TNF Therapies", Bogota, Medellin, Cali, Barranquilla and Bucaramanga, Colombia 2008
IDSA Annual Meeting, “Infectious Complications of Anti-TNF Therapies”, Washington DC, 2008. .
1st International Conference on Drug Discovery and Development, “Assessing the infection risks of new anti-inflammatory therapies”, Dubai, 2008. Invited lecturer and session chair.
Wyeth International Summit, “Infectious Complications of TNF Blockade: Where do we stand now?”, Munich Germany, 2007.
Annual Meeting, Saskatoon Rheumatological Society, “Infectious Complications of TNF Blockade” Saskatchewan Canada, 2006.
IDSA Annual Meeting, “Infectious Risks of TNF blockade”, Toronto Canada, 2006.
Gene Therapy Press, “Immunotherapy of tuberculosis”, 9th International Conference on Drug and Gene-based Therapeutics, Crete Greece, 2006
Wyeth, "Infectious risks of TNF blockade", Vancouver, Ottawa, Toronto, Quebec City, and Montreal, Canada, 2006
Johns Hopkins University Division of Infectious Diseases, “Differential effects of TNF blockade on mycobacterial immunity”, Baltimore MD, 2006
Wyeth, “Differential effects of TNF blockade on mycobacterial immunity”, Philadelphia PA, 2006.
Amgen, “TNF and human tuberculosis”, Thousand Oaks CA, 2005.
Global Alliance for TB Drug Development, “Whole blood bactericidal activity to assess new drugs for tuberculosis”, London UK, 2005.
IUATLD International Annual Meeting, “Immunotherapy of tuberculosis”, Paris France, 2004.
World Conference on Dosing of Anti-infectives, “Tuberculosis therapy: PK/PD, resistance, and persistence”, Nuremburg, Germany, 2004.
Mount Sinai School of Medicine, “Granulomatous infections and TNF antagonists”, New York NY, 2004.
Cleveland Clinic Foundation, “Granulomatous infections and TNF antagonists”, Cleveland OH, 2004.
Amgen, "International Conference on TNF Antagonists’ Mechanisms ", Montreal Canada, 2003.
Amgen, "TNF inhibition and infection risk", Thousand Oaks CA, 2003.
University of North Carolina, "AIDS and Tuberculosis: Challenges and Promises", Chapel Hill NC, 2003.
ACTG National Meeting, "Immunity and relapse in tuberculosis", Arlington VA, 2003
Amgen, “TNF inhibitors mechanisms of action”, New York, 2003.
South Africa TB Clinical Trials Consortium, "Advanced Technology Laboratories for Tuberculosis", Cape Town SA, 2003
Texas A&M University, "Models to evaluate TB vaccines and therapeutics", College Station TX, 2002
Astra Zeneca, "Improving therapy for tuberculosis", Bangalore India, 2002
Sequella Foundation, "A model to evaluate TB therapy", Washington DC 2001
Global Alliance for TB Drug Development, "Surrogate markers for TB therapy", Paris France 2001
Gordon Conference on TB Drug Development, , "A whole blood bactericidal assay for TB pathogenesis and treatment", New London NH 2001
Russian Academy of Medicine Conference on Nosocomial Tuberculosis, "A whole blood bactericidal assay for TB pathogenesis and treatment", Moscow Russia 2001
Astra Zeneca, "Surrogate markers for tuberculosis", Bangalore India 2001
NY Medical College, Research Conference, "Predicting TB relapse", Valhalla NY 2000
Beth Israel Hospital, ID Grand Rounds, "Predicting TB relapse", New York NY 2000
ICAAC, "Microbiologic monitoring of tuberculosis for therapeutic endpoints", Toronto Canada 2000
Cleveland Clinic Foundation, "The biology of granuloma formation", Cleveland OH 2000
Emilio Ribas Hospital of Infectious Diseases, “TB relapse: Immunologic and microbiologic factors”, Sao Paulo Brazil 1999
NIAID Forum on Therapy of MDR TB, “A whole blood bactericidal assay for tuberculosis”, Bethesda MD 1999
Imperial College of Medicine, "Drug tolerance in M. tuberculosis", London UK 1999
Institute for Human Virology, "Immune Reconstitution in HIV Infection", Bethesda MD 1999
Korea-US Forum, Fogarty Institute NIH, "Drug tolerance in M. tuberculosis", Bethesda MD 1999
Int. Soc. Tropical Medicine, Annual Meeting,, "Cytokines in HIV/TB pathogenesis", San Juan PR 1998
IBC Conference on Tuberculosis, "Predicting the outcome of therapy for pulmonary tuberculosis", Washington DC 1998
US-Japan Cooperative Medical Science Program, Annual Meeting, "Predicting the outcome of therapy for pulmonary tuberculosis", Osaka Japan 1998
Korean National Tuberculosis Hospital, "Predicting the outcome of therapy for pulmonary tuberculosis", Masan Korea 1998
CWRU Dept Biology, “Cytokines in HIV TB copathogenesis”, Cleveland OH 1997
NMHCC Biotechnology Conference Division, "Tuberculosis: cytokines in HIV/TB pathogenesis", Washington DC 1997
International Union Against Tuberculosis, “Antigen detection for TB diagnosis: applicability to low income countries”, Paris France 1997
CWRU/Makerere University Research Collaboration, “Immune activation and survival in HIV+ tuberculosis: opportunities for intervention”, Kampala Uganda 1997
Cleveland Clinic Foundation, “Immunology of tuberculosis”, Cleveland OH 1997
Litigation Management, Inc., “Chronic fatigue syndrome - an Infectious Disease perspective”, Cleveland OH 1995
Infectious Disease Society of America, “AIDS and tuberculosis: Prospects for interventions from an immunologic perspective”, IDSA Annual Meeting, Orlando FL 1994
Boston University/ Boston City Hosp., “Monocyte activation, tuberculosis and HIV”, BCH Division of Infectious Diseases, Boston MA 1993
Makerere University, “HIV and tuberculosis”, Kampala Uganda 1993
University of Akron, “AIDS in Uganda”, Akron OH 1993
Fairview General Hospital, “Current issues in tuberculosis”, Cleveland OH 1992
American Society for Microbiology, “Detection of mycobacterial antigens using human monoclonal antibodies”, ASM Annual Meeting, Division U (mycobacteriology), New Orleans LA 1991
Ohio State University, “Current approaches to diagnosis and management of HIV infection”, Columbus OH 1987
TB RELAPSE RISK CALCULATOR
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The calculator to the right predicts TB relapse risk based on the proportion with positive cultures on solid medium after 2 months of treatment and the total duration of treatment. The risk of >10% relapses assumes a single phase 3 trial with 680 subjects per arm. The database now includes regimen-level outcome data from studies involving 11766 patients including the TBRU treatment shortening trial, 2 trials of a clofazimine-containing 12 month MDR-TB regimen conducted in Niger and Cameroon, as well as data from REMox, RIFAQUIN, and OFLOTUB. The overall correlation between observed and predicted relapse rates in the validation dataset is shown in the figure below. The predictions are all the more remarkable in that relapses in the fluoroquinolone trials were predicted without prior FQ data; those for the TBRU study, without prior host data: and those for the MDR-TB trials without prior data for clofazimine or MDR-TB.
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Please cite as follows:
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Wallis RS, Wang C, Meyer D, Thomas N. Month 2 culture status and treatment duration as predictors of tuberculosis relapse risk in a meta-regression model. PLoS One. 2013 Aug 5;8(8):e71116.
and
Wallis RS, Peppard T, Hermann D. Month 2 culture status and treatment duration as predictors of recurrence in pulmonary tuberculosis: model validation and update. PLoS One. 2015 Apr 29;10(4):e0125403.
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Whole blood bactericidal activitiy (WBA)
review chapter
Criteria for classifying radiographic extent
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