The Global Prevalence of Latent Tuberculosis: A Systematic Review and Meta-Analysis

Cohen, Adam; Mathiasen, Victor Dahl; Schӧn, Thomas; Wejse, Christian

doi:10.2139/ssrn.3289796

Cited by 4 publications

(3 citation statements)

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“…Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB) infection, remains a lethal infectious disease that needs to be paid more attention globally (1)(2)(3). It was reported that there were still an estimated 10 million cases and nearly 1.4 million deaths of the disease in 2019 (4).…”

Section: Introductionmentioning

confidence: 99%

Activation Phenotype of Mycobacterium tuberculosis-Specific CD4+ T Cells Promoting the Discrimination Between Active Tuberculosis and Latent Tuberculosis Infection

Luo

Xue

et al. 2021

Front. Immunol.

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BackgroundRapid and effective discrimination between active tuberculosis (ATB) and latent tuberculosis infection (LTBI) remains a challenge. There is an urgent need for developing practical and affordable approaches targeting this issue.MethodsParticipants with ATB and LTBI were recruited at Tongji Hospital (Qiaokou cohort) and Sino-French New City Hospital (Caidian cohort) based on positive T-SPOT results from June 2020 to January 2021. The expression of activation markers including HLA-DR, CD38, CD69, and CD25 was examined on Mycobacterium tuberculosis (MTB)-specific CD4+ T cells defined by IFN-γ, TNF-α, and IL-2 expression upon MTB antigen stimulation.ResultsA total of 90 (40 ATB and 50 LTBI) and another 64 (29 ATB and 35 LTBI) subjects were recruited from the Qiaokou cohort and Caidian cohort, respectively. The expression patterns of Th1 cytokines including IFN-γ, TNF-α, and IL-2 upon MTB antigen stimulation could not differentiate ATB patients from LTBI individuals well. However, both HLA-DR and CD38 on MTB-specific cells showed discriminatory value in distinguishing between ATB patients and LTBI individuals. As for developing a single candidate biomarker, HLA-DR had the advantage over CD38. Moreover, HLA-DR on TNF-α+ or IL-2+ cells had superiority over that on IFN-γ+ cells in differentiating ATB patients from LTBI individuals. Besides, HLA-DR on MTB-specific cells defined by multiple cytokine co-expression had a higher ability to discriminate patients with ATB from LTBI individuals than that of MTB-specific cells defined by one kind of cytokine expression. Specially, HLA-DR on TNF-α+IL-2+ cells produced an AUC of 0.901 (95% CI, 0.833–0.969), with a sensitivity of 93.75% (95% CI, 79.85–98.27%) and specificity of 72.97% (95% CI, 57.02–84.60%) as a threshold of 44% was used. Furthermore, the performance of HLA-DR on TNF-α+IL-2+ cells for differential diagnosis was obtained with validation cohort data: 90.91% (95% CI, 72.19–97.47%) sensitivity and 68.97% (95% CI, 50.77–82.73%) specificity.ConclusionsWe demonstrated that HLA-DR on MTB-specific cells was a potentially useful biomarker for accurate discrimination between ATB and LTBI.

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Section: Introductionmentioning

confidence: 99%

Activation Phenotype of Mycobacterium tuberculosis-Specific CD4+ T Cells Promoting the Discrimination Between Active Tuberculosis and Latent Tuberculosis Infection

Luo

Xue

et al. 2021

Front. Immunol.

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“…The conditional WHO recommendation does not require IGRA testing due to cost and feasibility considerations, since prevalence of IGRA-positivity among close contacts is high (World Health Organizataion [WHO], 2018b). For example, although overall Mtb infection prevalence in the South-East Asia region is estimated at 28% (Cohen et al, 2019), as determined by TST, a study of adult household contacts in India reported 78% prevalence (Dolla et al, 2019). A case could be made for post-exposure vaccination to prevent TB disease among household contacts, but several considerations temper enthusiasm for this approach.…”

Section: Household and Close Contactsmentioning

confidence: 99%

Clinical Development of New TB Vaccines: Recent Advances and Next Steps

2020

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Mycobacterium tuberculosis (Mtb) kills more people worldwide than any single infectious pathogen, yet the only vaccine licensed against tuberculosis, Bacille Calmette Guerin (BCG) is approaching its centenary. Two recent advances in clinical tuberculosis vaccine development have invigorated the field. BCG revaccination of interferon-gamma release assay (IGRA) negative adolescents provided 45% protection against sustained Mtb infection defined by IGRA conversion; and the protein-subunit vaccine M72/AS01 E provided 50% protection against progression from Mtb infection to tuberculosis disease in IGRA-positive adults. These findings provide encouraging evidence for pre-exposure and post-exposure approaches to vaccination against tuberculosis, both of which may be necessary to rapidly interrupt the cycle of Mtb transmission and sustain long-term impact on global tuberculosis control. New trials are needed to demonstrate efficacy of M72/AS01 E with greater precision, in a wider age range, in diverse epidemic settings, and in populations that include Mtb-uninfected and HIV-infected persons. Modeling the impact of mass campaigns with M72/AS01 E and other fast-follower vaccine candidates will be crucial to make the use case and demonstrate public health value for TB endemic countries. The size and scope of the next generation of efficacy trials, and the need to expand and accelerate the existing clinical development pipeline, will require public and private consortium funding and concerted political will.

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“…Mycobacterium tuberculosis (M.tb) is a deadly pathogen, which infects a large cluster of the population globally and is the cause of the maximum number of deaths due to a single infectious agent (1). The World Health Organization (WHO) has reported that around 10 million people across the globe suffer from active TB infection; with the mortality rate of around 1.3 million (2).…”

Section: Introductionmentioning

confidence: 99%

Repurposing Immunomodulatory Drugs to Combat Tuberculosis

2021

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Tuberculosis (TB) is an infectious disease caused by an obligate intracellular pathogen, Mycobacterium tuberculosis (M.tb) and is responsible for the maximum number of deaths due to a single infectious agent. Current therapy for TB, Directly Observed Treatment Short-course (DOTS) comprises multiple antibiotics administered in combination for 6 months, which eliminates the bacteria and prevents the emergence of drug-resistance in patients if followed as prescribed. However, due to various limitations viz., severe toxicity, low efficacy and long duration; patients struggle to comply with the prescribed therapy, which leads to the development of drug resistance (DR). The emergence of resistance to various front-line anti-TB drugs urgently require the introduction of new TB drugs, to cure DR patients and to shorten the treatment course for both drug-susceptible and resistant populations of bacteria. However, the development of a novel drug regimen involving 2-3 new and effective drugs will require approximately 20-30 years and huge expenditure, as seen during the discovery of bedaquiline and delamanid. These limitations make the field of drug-repurposing indispensable and repurposing of pre-existing drugs licensed for other diseases has tremendous scope in anti-DR-TB therapy. These repurposed drugs target multiple pathways, thus reducing the risk of development of drug resistance. In this review, we have discussed some of the repurposed drugs that have shown very promising results against TB. The list includes sulfonamides, sulfanilamide, sulfadiazine, clofazimine, linezolid, amoxicillin/clavulanic acid, carbapenems, metformin, verapamil, fluoroquinolones, statins and NSAIDs and their mechanism of action with special emphasis on their immunomodulatory effects on the host to attain both host-directed and pathogen-targeted therapy. We have also focused on the studies involving the synergistic effect of these drugs with existing TB drugs in order to translate their potential as adjunct therapies against TB.

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The Global Prevalence of Latent Tuberculosis: A Systematic Review and Meta-Analysis

Cited by 4 publications

References 0 publications

Activation Phenotype of Mycobacterium tuberculosis-Specific CD4+ T Cells Promoting the Discrimination Between Active Tuberculosis and Latent Tuberculosis Infection

Activation Phenotype of Mycobacterium tuberculosis-Specific CD4+ T Cells Promoting the Discrimination Between Active Tuberculosis and Latent Tuberculosis Infection

Clinical Development of New TB Vaccines: Recent Advances and Next Steps

Repurposing Immunomodulatory Drugs to Combat Tuberculosis

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