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  1. Article ; Online: Tuberculosis "Autoregression": A Historical Context.

    Wallis, Robert S

    The American journal of tropical medicine and hygiene

    2022  Volume 108, Issue 1, Page(s) 235–236

    MeSH term(s) Humans ; Tuberculosis
    Language English
    Publishing date 2022-12-12
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2942-7
    ISSN 1476-1645 ; 0002-9637
    ISSN (online) 1476-1645
    ISSN 0002-9637
    DOI 10.4269/ajtmh.22-0590
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  2. Article ; Online: Cardiac safety of extensively drug-resistant tuberculosis regimens including bedaquiline, delamanid and clofazimine.

    Wallis, Robert S

    The European respiratory journal

    2016  Volume 48, Issue 5, Page(s) 1526–1527

    Language English
    Publishing date 2016-11
    Publishing country England
    Document type Letter
    ZDB-ID 639359-7
    ISSN 1399-3003 ; 0903-1936
    ISSN (online) 1399-3003
    ISSN 0903-1936
    DOI 10.1183/13993003.01207-2016
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  3. Article: Mathematical Models of Tuberculosis Reactivation and Relapse.

    Wallis, Robert S

    Frontiers in microbiology

    2016  Volume 7, Page(s) 669

    Abstract: The natural history of human infection with Mycobacterium tuberculosis (Mtb) is highly variable, as is the response to treatment of active tuberculosis. There is presently no direct means to identify individuals in whom Mtb infection has been eradicated, ...

    Abstract The natural history of human infection with Mycobacterium tuberculosis (Mtb) is highly variable, as is the response to treatment of active tuberculosis. There is presently no direct means to identify individuals in whom Mtb infection has been eradicated, whether by a bactericidal immune response or sterilizing antimicrobial chemotherapy. Mathematical models can assist in such circumstances by measuring or predicting events that cannot be directly observed. The 3 models discussed in this review illustrate instances in which mathematical models were used to identify individuals with innate resistance to Mtb infection, determine the etiologic mechanism of tuberculosis in patients treated with tumor necrosis factor blockers, and predict the risk of relapse in persons undergoing tuberculosis treatment. These examples illustrate the power of various types of mathematic models to increase knowledge and thereby inform interventions in the present global tuberculosis epidemic.
    Language English
    Publishing date 2016-05-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2016.00669
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  4. Article ; Online: Sputum culture conversion as a tuberculosis biomarker: a glass half empty or half full?

    Wallis, Robert S

    The Lancet. Respiratory medicine

    2015  Volume 3, Issue 3, Page(s) 174–175

    MeSH term(s) Humans ; Sputum/microbiology ; Tuberculosis, Multidrug-Resistant/drug therapy ; Tuberculosis, Pulmonary/drug therapy
    Language English
    Publishing date 2015-03
    Publishing country England
    Document type Comment ; Journal Article
    ZDB-ID 2686754-0
    ISSN 2213-2619 ; 2213-2600
    ISSN (online) 2213-2619
    ISSN 2213-2600
    DOI 10.1016/S2213-2600(15)00058-2
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  5. Article ; Online: Sputum culture conversion in new TB regimens.

    Wallis, Robert S

    The Lancet. Respiratory medicine

    2015  Volume 3, Issue 6, Page(s) e18–9

    MeSH term(s) Adjuvants, Immunologic/therapeutic use ; Antitubercular Agents/therapeutic use ; Humans ; Tuberculosis, Multidrug-Resistant/drug therapy
    Chemical Substances Adjuvants, Immunologic ; Antitubercular Agents
    Language English
    Publishing date 2015-06
    Publishing country England
    Document type Comment ; Letter
    ZDB-ID 2686754-0
    ISSN 2213-2619 ; 2213-2600
    ISSN (online) 2213-2619
    ISSN 2213-2600
    DOI 10.1016/S2213-2600(15)00182-4
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  6. Article ; Online: Host-directed immunotherapy of viral and bacterial infections: past, present and future.

    Wallis, Robert S / O'Garra, Anne / Sher, Alan / Wack, Andreas

    Nature reviews. Immunology

    2022  Volume 23, Issue 2, Page(s) 121–133

    Abstract: The advent of COVID-19 and the persistent threat of infectious diseases such as tuberculosis, malaria, influenza and HIV/AIDS remind us of the marked impact that infections continue to have on public health. Some of the most effective protective measures ...

    Abstract The advent of COVID-19 and the persistent threat of infectious diseases such as tuberculosis, malaria, influenza and HIV/AIDS remind us of the marked impact that infections continue to have on public health. Some of the most effective protective measures are vaccines but these have been difficult to develop for some of these infectious diseases even after decades of research. The development of drugs and immunotherapies acting directly against the pathogen can be equally challenging, and such pathogen-directed therapeutics have the potential disadvantage of selecting for resistance. An alternative approach is provided by host-directed therapies, which interfere with host cellular processes required for pathogen survival or replication, or target the host immune response to infection (immunotherapies) to either augment immunity or ameliorate immunopathology. Here, we provide a historical perspective of host-directed immunotherapeutic interventions for viral and bacterial infections and then focus on SARS-CoV-2 and Mycobacterium tuberculosis, two major human pathogens of the current era, to indicate the key lessons learned and discuss candidate immunotherapeutic approaches, with a focus on drugs currently in clinical trials.
    MeSH term(s) Humans ; COVID-19/therapy ; SARS-CoV-2 ; Bacterial Infections/therapy ; Immunotherapy ; Communicable Diseases
    Language English
    Publishing date 2022-06-07
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Intramural
    ZDB-ID 2062776-2
    ISSN 1474-1741 ; 1474-1733
    ISSN (online) 1474-1741
    ISSN 1474-1733
    DOI 10.1038/s41577-022-00734-z
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  7. Article ; Online: Lack of a therapeutic role for interferon γ in patients with tuberculosis.

    Wallis, Robert S

    The Journal of infectious diseases

    2014  Volume 209, Issue 4, Page(s) 627–628

    MeSH term(s) Humans ; Interferon-gamma/physiology ; Macrophages/physiology ; Mycobacterium tuberculosis/physiology
    Chemical Substances Interferon-gamma (82115-62-6)
    Language English
    Publishing date 2014-02-15
    Publishing country United States
    Document type Comment ; Letter
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jit555
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    Zs.MO 445: Show issues

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  8. Article: Corticosteroid effects on sputum culture in pulmonary tuberculosis: a meta-regression analysis.

    Wallis, Robert S

    Open forum infectious diseases

    2014  Volume 1, Issue 1, Page(s) ofu020

    Abstract: Objectives: There is increasing interest in the potential role of adjunctive anti-inflammatory therapy to accelerate tuberculosis (TB) treatment. Sputum culture conversion is an important biomarker predictor of durable TB cure.: Methods: This study ... ...

    Abstract Objectives: There is increasing interest in the potential role of adjunctive anti-inflammatory therapy to accelerate tuberculosis (TB) treatment. Sputum culture conversion is an important biomarker predictor of durable TB cure.
    Methods: This study used meta-regression analysis to examine the relationship between corticosteroid dose and sputum culture conversion, using published data from controlled clinical trials including 1806 corticosteroid-treated TB patients.
    Results: Linear models with 2 or 3 variables, including corticosteroid dose and the proportion of culture positive control subjects, predicted therapeutic benefit of corticosteroids at 1 and 2 months. The 3-variable model predicted that 134 mg of prednisolone per day, given together with standard 4-drug TB chemotherapy, would reduce the proportion of positive culture at 2 months from 15% to 2%. The estimate accounts for a 50% reduction in steroid exposure due to rifampin. A proportion of 2% of subjects with positive cultures at 2 months has been proposed as a target for new 4-month TB regimens.
    Conclusions: These positive findings must be tempered by recognition that the metabolic and cardiovascular risks of corticosteroids administered at this dose for this duration are unlikely to be acceptable when examined from a patient-level benefit-risk perspective. In future research studies to shorten TB treatment, biologic anti-inflammatory therapies with similar therapeutic effects but superior safety profiles should be considered.
    Language English
    Publishing date 2014-06-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2757767-3
    ISSN 2328-8957
    ISSN 2328-8957
    DOI 10.1093/ofid/ofu020
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  9. Article ; Online: Repurposing N-acetylcysteine for management of non-acetaminophen induced acute liver failure: an evidence scan from a global health perspective.

    Jerome, Rebecca N / Zahn, Laura A / Abner, Jessica J / Joly, Meghan M / Shirey-Rice, Jana K / Wallis, Robert S / Bernard, Gordon R / Pulley, Jill M

    Translational gastroenterology and hepatology

    2024  Volume 9, Page(s) 2

    Abstract: Background: The World Health Organization (WHO)'s Essential Medicines List (EML) plays ...

    Abstract Background: The World Health Organization (WHO)'s Essential Medicines List (EML) plays an important role in advocating for access to key treatments for conditions affecting people in all geographic settings. We applied our established drug repurposing methods to one EML agent, N-acetylcysteine (NAC), to identify additional uses of relevance to the global health community beyond its existing EML indication (acetaminophen toxicity).
    Methods: We undertook a phenome-wide association study (PheWAS) of a variant in the glutathione synthetase (
    Results: PheWAS of
    Conclusions: This body of literature indicates efficacy and safety of NAC in non-acetaminophen induced ALF. Given the presence of NAC on the EML, this medication is likely to be available across a range of resource settings; promulgating its use in this novel subset of ALF can provide healthcare professionals and patients with a valuable and safe complement to supportive care for this disease.
    Language English
    Publishing date 2024-01-18
    Publishing country China
    Document type Journal Article
    ISSN 2415-1289
    ISSN (online) 2415-1289
    DOI 10.21037/tgh-23-40
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  10. Article ; Online: Sustainable tuberculosis drug development.

    Wallis, Robert S

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

    2013  Volume 56, Issue 1, Page(s) 106–113

    Abstract: Six new antituberculosis compounds in 4 classes are presently in clinical trials. Although these show substantial promise for drug-resistant (DR) tuberculosis, the presently planned studies of these compounds will not inform their optimal use, as each ... ...

    Abstract Six new antituberculosis compounds in 4 classes are presently in clinical trials. Although these show substantial promise for drug-resistant (DR) tuberculosis, the presently planned studies of these compounds will not inform their optimal use, as each will be tested singly vs placebo with existing drugs, rather than in new regimens. Each successive regulatory approval will increase the size, cost, and complexity of trials for those that follow, causing delays during which suboptimal use will occur and resistance will emerge. This paper proposes the development of a novel regimen with the potential for use in both drug-sensitive (DS) and DR tuberculosis. Adaptive licensing for DR tuberculosis based on 2-month sputum culture would shorten time to initial approval by several years. A global outcomes registry would confirm safety and effectiveness in both DS and DR tuberculosis, making possible the second transformation of tuberculosis treatment. We should do our utmost to see it succeed.
    MeSH term(s) Animals ; Antitubercular Agents/chemistry ; Antitubercular Agents/therapeutic use ; Biomarkers ; Clinical Trials as Topic/methods ; Drug Discovery/methods ; Global Health ; Humans ; Mice ; Randomized Controlled Trials as Topic ; Regression Analysis ; Sputum/microbiology ; Tuberculosis/drug therapy ; Tuberculosis, Multidrug-Resistant
    Chemical Substances Antitubercular Agents ; Biomarkers
    Language English
    Publishing date 2013-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1099781-7
    ISSN 1537-6591 ; 1058-4838
    ISSN (online) 1537-6591
    ISSN 1058-4838
    DOI 10.1093/cid/cis849
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