Robert S Wallis, MD, FIDSA, FRCPE

  • INFECTIOUS DISEASES
  • TUBERCULOSIS DRUG DEVELOPMENT
  • HOST-DIRECTED THERAPIES
  • BIOMARKERS
     
 

BACKGROUND

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 Case Western Reserve University and Rutgers-New Jersey Medical School, where I previously held full time positions. 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. I have particular expertise in the use of innovative models (biological and mathematical) to assess the efficacy of new anti-infective treatments, and to assess the infection risks posed by novel immunosuppressive treatments. I was the first to differentiate soluble TNF receptor from anti-TNF antibodies with regard to granulomatous infection risks. A biomarker I developed, measuring viability of intracellular M tuberculosis in whole blood culture, has been used extensively in TB drug and vaccine development. 

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 worked closely with PPD’s business development group to review RFPs for global trials of anti-infectives, vaccines, and biologic therapies, and to prepare scientifically sound proposals for these trials. 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. 

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 current projects include studies of host-directed TB therapy funded by the Gates foundation, the German Ministry of Education and Research (BMBF), US NIH, and the European Commission (Horizon 2020). 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).

PUBLICATIONS

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

TB-SEQUEL: Incidence, pathogenesis, and risk factors of long-term medical and social sequelae of pulmonary tuberculosis.

           BMC Pulm Med 2019

A patient level pooled analysis of treatment shortening regimens for drug-susceptible pulmonary tuberculosis.

           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-TBIJTLD 2016

High dose rifampin, moxifloxacin, and SQ109: The PANACEA MAMS TB trialLancet ID 2016

Cardiac safety of XDR-TB regimens including bedaquiline, delamanid, and clofazimineERJ 2016

Vitamin D as adjunctive host-directed therapy in TB: A systematic reviewOpen Forum Infect Dis 2016

Safety and immunogenicity of rBCG AERAS-422 in healthy adultseBioMedicine 2016

Activity of nitazoxanide and tizoxanide againt Mtb in vitro and whole blood cultureTuberc 2016

Tuberculosis - Advances in drugs, regimens, HDT and biomarkersLancet Infect Dis 2016

Mathematical models of tuberculosis relapse and reactivationFrontiers Microbiol 2016

Toward host-directed therapies for tuberculosisNature Rev Drug Discov 2015 (preprint: here)

Sputum culture conversion in new TB regimensLancet Respir Med 2015

Early biomarkers and regulatory innovation in MDR-TBClin 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 tuberculosisNature Rev Immunol 2015

Sputum culture conversion as a tuberculosis biomarker: A glass half empty or half full? 

          Lancet Respir Med 2015 

Corticosteroid effects on sputum culture in pulmonary tuberculosisOpen Forum Infect Dis 2014

Mycobactericidal activity of sutezolid (PNU-100480) in sputum (EBA) and blood (WBA) of TB patients.

          PLoS ONE 2014

Population PK/PD analysis of the bactericidal activity of sutezolid (PNU-100480) and its major metabolite

          (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 challengesLancet Infect Dis 2013

Early bactericidal activity of new drug regimens for tuberculosisLancet 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 DevelopmentClin 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 vitroJ Antimicrob Chemother 2012
Biologics and infections: lessons from tumor necrosis factor blocking agentsInfect 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 practiceLancet 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 adalimumabClin Infect Dis 2010

Biomarkers of disease activity, cure, and relapse in tuberculosis. Clin Chest Med 2009

Advances in immunotherapy for tuberculosis treatmentClin Chest Med 2009

Infectious complications of tumor necrosis factor blockadeCurr 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 diagnosisCurr Opin Pulm Med 2009

Adalimumab treatment of life-threatening tuberculosisClin Infect Dis 2009

Strain specificity of antimycobacterial immunity in whole blood culture after TB cure. Tuberculosis 2009

Biomarkers for tuberculosis disease activity, cure, and relapseLancet Infect Dis 2009

Mycobacterial disease attributable to tumor necrosis factor-alpha blockersClin Infect Dis 2008

Tumour necrosis factor antagonists: structure, function, and tuberculosis risksLancet Infect Dis 2008

Therapeutic use of infliximab in TB to control severe paradoxical reaction of the brain and lymph nodes.

          Clin Infect Dis 2008

Mathematical modeling of the cause of TB during TNF blockadeArthritis Rheum 2008

Acquired rifamycin resistance: pharmacology and biologyExpert Rev Anti Infect Ther 2008

Bactericidal activity of OPC-67683 against drug-tolerant Mycobacterium tuberculosisJAC 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 effectJ Infect Dis 2007

Corticosteroids and HIV infection: a review of experienceCurr Opin HIV AIDS 2007

Surrogate markers to assess new therapies for drug-resistant TBExpert 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 immunityJ Infect Dis 2006

Glutathione and growth inhibition of M tuberculosis in healthy and HIV infected subjectsAIDS Res Ther 2006

Clinical, microbiological, and immunological characteristics in HIV-infected subjects at risk for DMAC disease.

          AIDS Res Hum Retroviruses 2005

Anti-tuberculosis treatment and infliximabRespir Med 2005

Reconsidering adjuvant immunotherapy for tuberculosisClin Infect Dis 2005

Reactivation of latent granulomatous infections by infliximabClin 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

Survival and replication of clinical M tuberculosis isolates in the context of human innate immunity.

          Infect Immun 2005

Sutton's lawInt J Tuberc Lung Dis 2005

Immunoadjuvant prednisolone therapy for HIV-TB: a phase 2 clinical trial in UgandaJ Infect Dis 2005

Mechanisms of action of TNF antagonist and granulomatous infectionsJ Rheumatol 2004

Granulomatous infections due to tumor necrosis factor blockade  &  CorrectionClin Infect Dis 2004

Lack of activity of orally administered clofazimine against intracellular Mycobacterium tuberculosis in

          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 sterilizationAm J Respir Crit Care Med 2004

A study of the immunology, virology, and safety of prednisone in HIV-1-infected subjects with CD4 cell

          counts of 200 to 700 mm-3. J Acquir Immune Defic Syndr 2003

Whole blood bactericidal activity during treatment of pulmonary tuberculosisJ Infect Dis 2003

Bactericidal activity in whole blood as a potential surrogate marker of immunity after vaccination against

          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 tuberculosisJ 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 tuberculosisAm 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 tuberculosisAntimicrob Agents Chemother 1999

Instability of tuberculin and Candida skin test reactivity in HIV-infected Ugandans. AJRCCM 1998

Pentoxifylline in HIV-TB: safety at 4 yearsJ Infect Dis 1998

Induction of the antigen 85 complex of Mycobacterium tuberculosis in sputum: a determinant of outcome

          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

High incidence of Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus in tumor lesions and

          blood mononuclear cells from patients with Kaposi's sarcoma in Uganda. J Infect Dis 1997

Tuberculosis vaccines: how close to human testingTuber 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 tuberculosisTuber 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 tuberculosisInfect Agents Dis 1996

Mapping of T cell epitopes of the 30-kDa alpha antigen of Mycobacterium bovis strain bacillus Calmette-

          Guérin in purified protein derivative (PPD)-positive individuals. J Immunol 1995

Cytokines and tuberculosisJ Leukoc Biol 1994
Screening of a cosmid library of BCG in M smegmatis for novel T-cell stimulatory antigens.  

          Res Microbiol 1993

Identification by two-dimensional gel electrophoresis of a 58-kilodalton tumor necrosis factor-inducing

          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 endocarditisMedicine (Baltimore) 1992

PROBIT: a computer program analysisJ 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-1J Lab Clin Med 1991

T cell activation by mycobacterial antigens in inflammatory synovitisCell Immunol 1991

Human immune response to Mycobacterium tuberculosis antigensInfect 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 cellsJ Clin Invest 1990

More on zidovudine and HIV-related thrombocytopeniaN Engl J Med 1989

Identification of antigens of M tuberculosis using human monoclonal antibodiesJ Clin Invest 1989

Dyscoordinate expression of TNF-a by human blood monocytes and alveolar macrophagesARRD 1989

Immunologic aspects of mycobacterial infectionsRev 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 pleurisySemin Respir Infect 1988

Tumor necrosis factor is the major monocyte product that increases complement receptor expression on

          mature human neutrophils. Blood 1988

Deleterious effect of UV-B radiation on accessory function of human blood adherent mononuclear cells. 

          Clin Exp Immunol 1987

Testing for AIDS: more problems with predictive valuesJAMA 1986

Direct stimulation of monocyte release of IL 1 by mycobacterial protein antigensJ Immunol 1986
Increased IL-1 production and monocyte suppressor cell activity associated with human TB
ARRD 1986

BOOK CHAPTERS

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.

INVITED LECTURES

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
 

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. 

Please cite as follows:

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.

 

Whole blood bactericidal activitiy (WBA)
       review chapter 

WBA protocol

TB HDT study protocol

Criteria for classifying radiographic extent
       of disease in TB

WBA AND OTHER RESEARCH RESOURCES
 
CONTACT ME

© 2018 By Robert Wallis