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  1. Article ; Online: Mucosal-associated invariant T cells in natural immunity and vaccination against infectious diseases in humans.

    Masina, Nomawethu / Bekiswa, Abulele / Shey, Muki

    Current opinion in immunology

    2021  Volume 71, Page(s) 1–5

    Abstract: Mucosal-associated invariant T (MAIT) cells are subsets of T cells abundant in human mucosal tissues and in blood. These cells are activated directly by cytokines or by vitamin B metabolites antigen presentation. MAIT cells possess antimicrobial ... ...

    Abstract Mucosal-associated invariant T (MAIT) cells are subsets of T cells abundant in human mucosal tissues and in blood. These cells are activated directly by cytokines or by vitamin B metabolites antigen presentation. MAIT cells possess antimicrobial potential against viruses and bacteria through production of cytokines and cytotoxic molecules. MAIT cells generally reduce in numbers and function during viral and bacterial infections/diseases. Mice and humans lacking MAIT cells cannot effectively control bacterial infections. MAIT cells respond rapidly to infections and are rapidly recruited to the site of vaccination or infection including the lungs where they can be involved in controlling local inflammation. These characteristics of MAIT cells offer them a unique potential to be explored as potential targets for vaccines.
    MeSH term(s) Animals ; Bacterial Infections/immunology ; Humans ; Inflammation/immunology ; Mucosal-Associated Invariant T Cells/immunology ; Vaccination ; Vaccines/immunology
    Chemical Substances Vaccines
    Language English
    Publishing date 2021-03-24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1035767-1
    ISSN 1879-0372 ; 0952-7915
    ISSN (online) 1879-0372
    ISSN 0952-7915
    DOI 10.1016/j.coi.2021.03.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Mycobacterial-specific secretion of cytokines and chemokines in healthcare workers with apparent resistance to infection with

    Shey, Muki Shehu / Balfour, Avuyonke / Masina, Nomawethu / Bekiswa, Abulele / Schutz, Charlotte / Goliath, Rene / Dielle, Rachel / Katoto, Patrick Dmc / Wilkinson, Katalin Andrea / Lewinsohn, David / Lewinsohn, Deborah Anne / Meintjes, Graeme

    Frontiers in immunology

    2023  Volume 14, Page(s) 1176615

    Abstract: Background: Currently, diagnosis of latent TB infection (LTBI) is based on the secretion of IFN-γ in response to : Methods: We enrolled HIV-uninfected healthcare workers who had worked in high TB-exposure environments for 5 years or longer. We ... ...

    Abstract Background: Currently, diagnosis of latent TB infection (LTBI) is based on the secretion of IFN-γ in response to
    Methods: We enrolled HIV-uninfected healthcare workers who had worked in high TB-exposure environments for 5 years or longer. We screened them for LTBI using the tuberculin skin test and the QuantiFERON-TB Gold Plus assay. We performed multiplex Luminex to measure concentrations of T cell-associated cytokines and chemokines as well as total antibodies in plasma collected from unstimulated fresh whole blood and supernatants from QuantiFERON-TB Gold Plus tubes following incubation of whole blood for 16-24 hours with ESAT6/CFP10 peptides.
    Results: Samples from 78 individuals were analyzed: 33 resisters (TST<10mm; IGRA<0.35 IU/mL), 33 with LTBI (TST≥10mm and IGRA≥0.35 IU/mL) and 12 discordant (TST=0mm; IGRA≥1.0 IU/mL). There were no differences in concentrations of cytokines and chemokines in plasma between the different groups. Resisters had significantly lower concentrations of IFN-γ, IL-2, TNF-α, MIP-1α, MIP-1β, ITAC, IL-13 and GM-CSF in supernatants compared with LTBI group. There were no significant differences in the concentrations in supernatants of IL-10, IL-1β, IL-17A, IL-21, IL-23, MIP-3α, IL-4, IL-5, IL-6, IL-7, IL-8, Fractalkine and IL-12p70 between the groups. We observed that resisters had similar concentrations of total antibodies (IgG1, IgG2, IgG3, IgG4, IgA, and IgM) in plasma and supernatants compared to the LTBI and discordant groups.
    Conclusion: Resistance to Mtb infection despite sustained exposure is associated with lower Mtb-specific secretion of Th1-associated cytokines and chemokines. However, resisters showed secreted concentrations after Mtb stimulation of total antibodies and cytokines/chemokines associated with innate and Th17 immune responses similar to those with Mtb infection. This suggests an ability to mount non-IFN-γ immune responses to Mtb in apparent resisters.
    MeSH term(s) Humans ; Mycobacterium tuberculosis ; Cytokines ; Tuberculosis ; Latent Tuberculosis ; Tuberculin Test ; Latent Infection
    Chemical Substances Cytokines
    Language English
    Publishing date 2023-05-18
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1176615
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Testing novel strategies for patients hospitalised with HIV-associated disseminated tuberculosis (NewStrat-TB): protocol for a randomised controlled trial.

    Namale, Phiona E / Boloko, Linda / Vermeulen, Marcia / Haigh, Kate A / Bagula, Fortuna / Maseko, Alexis / Sossen, Bianca / Lee-Jones, Scott / Msomi, Yoliswa / McIlleron, Helen / Mnguni, Ayanda Trevor / Crede, Thomas / Szymanski, Patryk / Naude, Jonathan / Ebrahim, Sakeena / Vallie, Yakoob / Moosa, Muhammed Shiraz / Bandeker, Ismail / Hoosain, Shakeel /
    Nicol, Mark P / Samodien, Nazlee / Centner, Chad / Dowling, Wentzel / Denti, Paolo / Gumedze, Freedom / Little, Francesca / Parker, Arifa / Price, Brendon / Schietekat, Denzil / Simmons, Bryony / Hill, Andrew / Wilkinson, Robert J / Oliphant, Ida / Hlungulu, Siphokazi / Apolisi, Ivy / Toleni, Monica / Asare, Zimkhitha / Mpalali, Mkanyiseli Kenneth / Boshoff, Erica / Prinsloo, Denise / Lakay, Francisco / Bekiswa, Abulele / Jackson, Amanda / Barnes, Ashleigh / Johnson, Ryan / Wasserman, Sean / Maartens, Gary / Barr, David / Schutz, Charlotte / Meintjes, Graeme

    Trials

    2024  Volume 25, Issue 1, Page(s) 311

    Abstract: Background: HIV-associated tuberculosis (TB) contributes disproportionately to global tuberculosis mortality. Patients hospitalised at the time of the diagnosis of HIV-associated disseminated TB are typically severely ill and have a high mortality risk ... ...

    Abstract Background: HIV-associated tuberculosis (TB) contributes disproportionately to global tuberculosis mortality. Patients hospitalised at the time of the diagnosis of HIV-associated disseminated TB are typically severely ill and have a high mortality risk despite initiation of tuberculosis treatment. The objective of the study is to assess the safety and efficacy of both intensified TB treatment (high dose rifampicin plus levofloxacin) and immunomodulation with corticosteroids as interventions to reduce early mortality in hospitalised patients with HIV-associated disseminated TB.
    Methods: This is a phase III randomised controlled superiority trial, evaluating two interventions in a 2 × 2 factorial design: (1) high dose rifampicin (35 mg/kg/day) plus levofloxacin added to standard TB treatment for the first 14 days versus standard tuberculosis treatment and (2) adjunctive corticosteroids (prednisone 1.5 mg/kg/day) versus identical placebo for the first 14 days of TB treatment. The study population is HIV-positive patients diagnosed with disseminated TB (defined as being positive by at least one of the following assays: urine Alere LAM, urine Xpert MTB/RIF Ultra or blood Xpert MTB/RIF Ultra) during a hospital admission. The primary endpoint is all-cause mortality at 12 weeks comparing, first, patients receiving intensified TB treatment to standard of care and, second, patients receiving corticosteroids to those receiving placebo. Analysis of the primary endpoint will be by intention to treat. Secondary endpoints include all-cause mortality at 2 and 24 weeks. Safety and tolerability endpoints include hepatoxicity evaluations and corticosteroid-related adverse events.
    Discussion: Disseminated TB is characterised by a high mycobacterial load and patients are often critically ill at presentation, with features of sepsis, which carries a high mortality risk. Interventions that reduce this high mycobacterial load or modulate associated immune activation could potentially reduce mortality. If found to be safe and effective, the interventions being evaluated in this trial could be easily implemented in clinical practice.
    Trial registration: ClinicalTrials.gov NCT04951986. Registered on 7 July 2021 https://clinicaltrials.gov/study/NCT04951986.
    MeSH term(s) Humans ; Rifampin/therapeutic use ; Rifampin/administration & dosage ; HIV Infections/complications ; HIV Infections/drug therapy ; Hospitalization ; Tuberculosis/drug therapy ; Tuberculosis/diagnosis ; Tuberculosis/mortality ; Levofloxacin/therapeutic use ; Treatment Outcome ; Clinical Trials, Phase III as Topic ; Antitubercular Agents/therapeutic use ; Antitubercular Agents/adverse effects ; Equivalence Trials as Topic ; Drug Therapy, Combination ; Prednisone/therapeutic use ; Prednisone/administration & dosage ; Prednisone/adverse effects ; AIDS-Related Opportunistic Infections/drug therapy ; AIDS-Related Opportunistic Infections/mortality ; AIDS-Related Opportunistic Infections/microbiology ; AIDS-Related Opportunistic Infections/diagnosis ; Time Factors
    Chemical Substances Rifampin (VJT6J7R4TR) ; Levofloxacin (6GNT3Y5LMF) ; Antitubercular Agents ; Prednisone (VB0R961HZT)
    Language English
    Publishing date 2024-05-08
    Publishing country England
    Document type Journal Article ; Clinical Trial Protocol
    ZDB-ID 2040523-6
    ISSN 1745-6215 ; 1468-6694 ; 1745-6215
    ISSN (online) 1745-6215
    ISSN 1468-6694 ; 1745-6215
    DOI 10.1186/s13063-024-08119-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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