scholarly journals The Dynamic Change of Immune Checkpoints and CD14+ Monocytes in Latent Tuberculosis Infection

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1479
Author(s):  
Ping-Huai Wang ◽  
Ming-Fang Wu ◽  
Chi-Yu Hsu ◽  
Shu-Yung Lin ◽  
Ya-Nan Chang ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Latent Tuberculosis Infection ◽  
Dynamic Change ◽  
Latent Tuberculosis ◽  
Immune Defense ◽  
Tuberculosis Infection ◽  
Immune Checkpoints ◽  
Peripheral Blood Mononuclear ◽  
Ltbi Treatment ◽  
Ltbi Group

Controlling latent tuberculosis infection (LTBI) is important for preventing tuberculosis (TB). However, the immune regulation of LTBI remains uncertain. Immune checkpoints and CD14+ monocytes are pivotal for immune defense but have been scarcely studied in LTBI. We prospectively enrolled participants with LTBI and controls from January 2017 to December 2019. We measured their CD14+ monocytes and the expression of immune checkpoints, including programmed death-1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and T cell immunoglobulin mucin domain-containing-3 (TIM3) on T lymphocytes in peripheral blood mononuclear cells before and after LTBI treatment. A total of 87 subjects were enrolled, including 29 IGRA-negative healthy controls (HC), 58 in the LTBI group (19 without chronic kidney disease (non-CKD), and 39 with end-stage renal disease (ESRD)). All PD-1, CTLA-4, and TIM3 on lymphocytes and monocytes were higher in the LTBI group than that in the HC group. Total CD14+ monocytes were higher and PD-L2+CD14+ over monocytes were lower in patients with LTBI-non-CKD than that in the HC group. After LTBI treatment, CD14+ monocytes, TIM3+ on CD4+ and monocytes, and CTLA-4 on lymphocytes decreased significantly. Multivariable logistic regression indicated that CD14+ monocytes was an independent factor for LTBI-non-CKD from the HC group, whereas PD-L2+CD14+ monocytes and TIM3+ monocytes were significant for LTBI-ESRD from the HC group. In conclusion, LTBI status was associated with increasing CD14+ monocytes plus low PD-L2 expression. By contrast, increased expression of immune checkpoints over all immune cells might be due to Mycobacterium tuberculosis related immune exhaustion, which decreased after treatment.

Benefit of treatment of latent tuberculosis infection in individual patients

2015 ◽  
Vol 46 (5) ◽  
pp. 1397-1406 ◽  
Author(s):  
Claudia C. Dobler ◽  
Andrew Martin ◽  
Guy B. Marks
Keyword(s):  
Decision Aid ◽  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
Tuberculosis Infection ◽  
Quality Adjusted Life Years ◽  
Net Benefit ◽  
Ltbi Treatment ◽  
Life Years ◽  
Numbers Needed To Treat ◽  
Quality Adjusted Life

We aimed to develop a decision aid that estimates whether treatment of latent tuberculosis infection (LTBI) is likely to have a net gain in quality-adjusted life-years for an individual.A Markov model was developed which incorporated personalised estimates for risk of tuberculosis (TB) reactivation, TB death, quality-of-life impairments and treatment side-effects. The net effect of LTBI treatment was quantified in terms of quality-adjusted life-years gained or lost. Analyses were conducted for a representative set of hypothetical patients.LTBI treatment was estimated to be beneficial when the annual risk of TB reactivation exceeded 13/100 000 to 93/100 000 for females aged 10–75 years and 15/100 000 to 119/100 000 for males aged 10–75 years; the numbers needed to treat to avoid one case of TB were 93, 77, 85 and 72, respectively, at these threshold levels.LTBI treatment was estimated to confer a positive net benefit across a broad range of patients with characteristics typically seen in a low incidence setting for TB. Use of the decision aid has the potential to facilitate and increase confidence with LTBI treatment decisions by providing clinicians and patients with personalised estimates of likely net benefit.

scholarly journals Immigrant screening for latent tuberculosis infection: numbers needed to test and treat, a Norwegian population-based cohort study

BMJ Open ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. e023412 ◽  
Author(s):  
Brita Askeland Winje ◽  
Gry Marysol Grøneng ◽  
Richard Aubrey White ◽  
Peter Akre ◽  
Preben Aavitsland ◽  
...  
Keyword(s):  
Cohort Study ◽  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
Population Based ◽  
Tuberculosis Infection ◽  
Number Needed To Treat ◽  
Ltbi Treatment ◽  
Ltbi Screening ◽  
Number Needed To Screen ◽  
Source Countries

ObjectivesTo estimate the number needed to screen (NNS) and the number needed to treat (NNT) to prevent one tuberculosis (TB) case in the Norwegian immigrant latent tuberculosis infection (LTBI) screening programme and to explore the effect of delay of LTBI treatment initiation.DesignPopulation-based, prospective cohort study.ParticipantsImmigrants to Norway.OutcomeIncident TB.MethodsWe obtained aggregated data on immigration to Norway in 2008–2011 and used data from the Norwegian Surveillance System for Infectious Diseases to assess the number of TB cases arising in this cohort within 5 years after arrival. We calculated the average NNS and NNT for immigrants from the top 10 source countries for TB in Norway and by estimated TB incidence rates in source countries. We explored the sensitivity of these estimates with regard to test performance, treatment efficacy and treatment adherence using an extreme value approach, and assessed the effects of emigration, time to TB diagnosis (to define incident TB) and intervention timing.ResultsNNS and NNT were overall high, with substantial variation. NNT showed numerically stronger negative correlation with TB notification rate in Norway (−0.75 [95% CI −1.00 to −0.44]) than with the WHO incidence rate (IR) (−0.32 [95% CI −0.93 to 0.29]). NNT was affected substantially by emigration and the definition of incident TB. Estimates were lowest for Somali (NNS 99 [70–150], NNT 27 [19–41]) and highest for Thai immigrants (NNS 585 [413–887], NNT 111 [79–116]). Implementing LTBI treatment in immigrants sooner after arrival may improve the effectiveness of the programme.ConclusionUsing TB notifications in Norway, rather than IR in source countries, would improve targeting of immigrants for LTBI management. However, the overall high NNT is a concern and challenges the scale-up of preventive LTBI treatment for significant public health impact. Better data are urgently needed to monitor and evaluate NNS and NNT in countries implementing LTBI screening.

scholarly journals The Association Between Mycobacteria-Specific Antigen-Induced Cytokines and Host Response to Latent Tuberculosis Infection Treatment in a Chinese Population

2021 ◽  
Vol 12 ◽  
Author(s):  
Xuefang Cao ◽  
Henan Xin ◽  
Haoran Zhang ◽  
Jianmin Liu ◽  
Shouguo Pan ◽  
...  
Keyword(s):  
Treatment Effectiveness ◽  
Latent Tuberculosis Infection ◽  
Controlled Trial ◽  
Specific Antigen ◽  
Latent Tuberculosis ◽  
Preventive Treatment ◽  
Tuberculosis Infection ◽  
Host Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Ltbi Treatment

ObjectivesExploring biomarkers monitoring latent tuberculosis infection (LTBI) treatment effectiveness would benefit optimizing the therapeutic regimen. This study aims to identify potential mycobacteria-specific antigen-induced cytokines associated with host responses to preventive treatment.MethodsBased on a randomized controlled trial on LTBI treatment among individuals with chest radiography abnormalities suggestive of prior tuberculosis (TB), the dynamically changed cytokine levels in QuantiFERON-TB Gold In-Tube (QFT) supernatants were estimated during the treatment by bead-based multiplex assays and enzyme-linked immunosorbent assay.ResultsIn total, 63 treated participants and 32 untreated controls were included in the study. The levels of 13 background-corrected mycobacteria-specific antigen-stimulated cytokines [basic fibroblast growth factor (FGF), growth-regulated oncogene (GRO)-α, interleukin (IL)-1α, IL-1ra, IL-12 (p70), stem cell factor (SCF), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), IL-8, interferon (IFN)-α2, IL-5, IL-12 (p40), leukemia inhibitory factor (LIF), and IL-17A] were found to be statistically different between before and after treatment in treated participants, while no statistically differences were observed in untreated controls. Among these 13 cytokines, the level of IL-8 was significantly lower in the QFT reversed group than that in the non-reversed group (p = 0.028) among treated participants, while such a difference was not found for untreated controls (p = 0.292).ConclusionOur results suggested that the lower level of mycobacteria-specific antigen-induced IL-8 might be associated with the host’s positive response to LTBI treatment.

scholarly journals Interferon gamma release assay tests are associated with persistence and completion of latent tuberculosis infection treatment in the United States: Evidence from commercial insurance data

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243102
Author(s):  
Erica L. Stockbridge ◽  
Abiah D. Loethen ◽  
Esther Annan ◽  
Thaddeus L. Miller
Keyword(s):  
United States ◽  
Interferon Gamma ◽  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
Treatment Completion ◽  
The United States ◽  
Tuberculosis Infection ◽  
Healthcare Sector ◽  
Treatment Persistence ◽  
Ltbi Treatment

Background Risk-targeted testing and treatment of latent tuberculosis infection (LTBI) is a critical component of the United States’ (US) tuberculosis (TB) elimination strategy, but relatively low treatment completion rates remain a challenge. Both treatment persistence and completion may be facilitated by diagnosing LTBI using interferon gamma release assays (IGRA) rather than tuberculin skin tests (TST). Methods We used a national sample of administrative claims data to explore associations diagnostic test choice (TST, IGRA, TST with subsequent IGRA) and treatment persistence and completion in persons initiating a daily dose isoniazid LTBI treatment regimen in the US private healthcare sector between July 2011 and March 2014. Associations were analyzed with a generalized ordered logit model (completion) and a negative binomial regression model (persistence). Results Of 662 persons initiating treatment, 327 (49.4%) completed at least the 6-month regimen and 173 (26.1%) completed the 9-month regimen; 129 (19.5%) persisted in treatment one month or less. Six-month completion was least likely in persons receiving a TST (42.2%) relative to persons receiving an IGRA (55.0%) or TST then IGRA (67.2%; p = 0.001). Those receiving an IGRA or a TST followed by an IGRA had higher odds of completion compared to those receiving a TST (aOR = 1.59 and 2.50; p = 0.017 and 0.001, respectively). Receiving an IGRA or a TST and subsequent IGRA was associated with increased treatment persistence relative to TST (aIRR = 1.14 and 1.25; p = 0.027 and 0.009, respectively). Conclusions IGRA use is significantly associated with both higher levels of LTBI treatment completion and treatment persistence. These differences are apparent both when IGRAs alone were administered and when IGRAs were administered subsequent to a TST. Our results suggest that IGRAs contribute to more effective LTBI treatment and consequently individual and population protections against TB.

Comparative efficacy of rifapentine alone and in combination with isoniazid for latent tuberculosis infection: a translational pharmacokinetic-pharmacodynamic modelling study

2021 ◽  
Author(s):  
Kendra K. Radtke ◽  
Jacqueline P. Ernest ◽  
Nan Zhang ◽  
Nicole C. Ammerman ◽  
Eric Nuermberger ◽  
...  
Keyword(s):  
Clinical Efficacy ◽  
Latent Tuberculosis Infection ◽  
Bacterial Load ◽  
Latent Tuberculosis ◽  
Tuberculosis Infection ◽  
Mouse Lung ◽  
Ltbi Treatment ◽  
Pharmacodynamic Modelling ◽  
Exposure Response ◽  
Daily Dose

Background Rifapentine has facilitated treatment shortening of latent tuberculosis infection (LTBI) in combination with isoniazid once weekly for 3 months (3HP) or daily for 1 month (1HP). Objective We determine the optimal rifapentine dose for a 6-week monotherapy regimen (6wP) and predict clinical efficacy. Methods Rifapentine and isoniazid pharmacokinetics were simulated in mice and humans. Mouse lung colony-forming unit data were used to characterize exposure-response relationships of 1HP, 3HP, and 6wP and translated to predict clinical efficacy. Results A 600 mg daily dose for 6wP delivered greater cumulative rifapentine exposure than 1HP or 3HP. The maximum regimen effect (E max ) was 0.24 day −1 . The regimen potencies, measured as concentration at 50% of E max (EC 50 ), were estimated as 2.12 mg/L for 3HP, 3.72 mg/L for 1HP, and 4.71 mg/L for 6wP, suggesting that isoniazid contributes little to 1HP efficacy. Clinical translation predicted that 6wP reduces bacterial load at a faster rate than 3HP and a greater extent than 3HP and 1HP. Conclusions 6wP (600 mg daily) is predicted to result in equal or better efficacy than 1HP and 3HP for LTBI treatment without the potential added toxicity of isoniazid. Results from ongoing and future clinical studies will be required to support these findings.

scholarly journals The latent tuberculosis infection cascade of care in Iqaluit, Nunavut, 2012–2016

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Christopher Pease ◽  
Alice Zwerling ◽  
Ranjeeta Mallick ◽  
Mike Patterson ◽  
Patricia Demaio ◽  
...  
Keyword(s):  
Latent Tuberculosis Infection ◽  
Multivariable Analysis ◽  
Latent Tuberculosis ◽  
Arctic Region ◽  
Older Age ◽  
Tuberculosis Infection ◽  
Older Individuals ◽  
Ltbi Treatment ◽  
Employment Screening ◽  
Cascade Of Care

Abstract Background A remote arctic region of Canada predominantly populated by Inuit with the country’s highest incidence of tuberculosis. Methods The study was undertaken to describe the latent tuberculosis infection (LTBI) cascade of care and identify factors associated with non-initiation and non-completion of LTBI treatment. Data were extracted retrospectively from medical records for all patients with a tuberculin skin test (TST) implanted in Iqaluit, Nunavut between January 2012 and March 2016. Associations between demographic and clinical factors and both treatment non-initiation among and treatment non-completion were identified using log binomial regression models where convergence could be obtained and Poisson models with robust error variance where convergence was not obtained. Results Of 2303 patients tested, 439 (19.1%) were diagnosed with LTBI. Treatment was offered to 328 patients, was initiated by 246 (75.0% of those offered) and was completed by 186 (75.6% of initiators). In multivariable analysis, older age (adjust risk ratio [aRR] 1.17 per 5-year increase, 95%CI:1.09–1.26) and undergoing TST due to employment screening (aRR 1.63, 95%CI:1.00–2.65, compared to following tuberculosis exposure) were associated with increased non-initiation of treatment. Older age (aRR 1.13, 95%CI: 1.03–1.17, per 5-year increase) was associated with increased non-completion of treatment. Conclusions A similar rate of treatment initiation and higher rate of treatment completion were found compared to previous North American studies. Interventions targeting older individuals and those identified via employment screening may be considered to help to address the largest losses in the cascade of care.

scholarly journals Levels of Interferon-Gamma Increase after Treatment for Latent Tuberculosis Infection in a High-Transmission Setting

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Iukary Takenami ◽  
Brook Finkmoore ◽  
Almério Machado ◽  
Krisztina Emodi ◽  
Lee W. Riley ◽  
...  
Keyword(s):  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
Tuberculosis Infection ◽  
Ltbi Treatment ◽  
High Transmission ◽  
Transmission Setting ◽  
Before And After ◽  
Specific Antigens ◽  
Study Participants

Objectives. We investigated IFN-γlevels before and after a six month course of isoniazid among individuals with latent tuberculosis infection (LTBI) in a high-transmission setting.Design. A total of 26 household contacts of pulmonary tuberculosis patients who were positive for LTBI by tuberculin skin test completed six months of treatment and submitted a blood sample for a follow-up examination. The IFN-γresponse toMycobacterium tuberculosis-specific antigens was measured, and the results before and after the completion of LTBI treatment were compared.Results. Of the 26 study participants, 25 (96%) showed an IFN-γlevel higher than their baseline level before treatment (P≤0.001). Only one individual had a decreased IFN-γlevel after treatment but remained positive for LTBI.Conclusion. In a high-transmission setting, the IFN-γlevel has increased after LTBI treatment. Further studies must be undertaken to understand if this elevation is transient.

Evaluation of 3 Months of Once-Weekly Rifapentine and Isoniazid for Latent Tuberculosis Infection

2019 ◽  
Vol 54 (5) ◽  
pp. 457-463
Author(s):  
Ramara E. Walker ◽  
Stephanie Bass ◽  
Pavithra Srinivas ◽  
Cyndee Miranda ◽  
Lucileia Johnson ◽  
...  
Keyword(s):  
Latent Tuberculosis Infection ◽  
Cleveland Clinic ◽  
Latent Tuberculosis ◽  
Tuberculosis Infection ◽  
High Rate ◽  
Completion Rates ◽  
Directly Observed Therapy ◽  
Ltbi Treatment ◽  
Control And Prevention ◽  
Low Incidence

Background: Centers for Disease Control and Prevention recommends 3 months of once-weekly rifapentine/isoniazid (3HP) for latent tuberculosis infection (LTBI) treatment given by directly observed therapy (DOT) or self-administered therapy (SAT) in patients ≥2 years old. 3HP has been associated with increased incidence of hepatic, gastrointestinal, flu-like, and cutaneous adverse drug reactions (ADRs) compared with isoniazid monotherapy. Objective: This study evaluated 3HP completion rates and tolerability for LTBI treatment in a real-world setting. Methods: A single-center retrospective cohort with a nested case-control study, comparing patients experiencing ADRs with those who did not, evaluated patients ≥18 years old receiving 3HP by DOT or SAT for LTBI at Cleveland Clinic from October 2011 through July 2018. Information on baseline characteristics, 3HP administrations, and ADRs were collected. Results: Of 199 patients screened, 144 were included (111 DOT, 33 SAT). 3HP completion rates were high at 82.6% and similar between DOT and SAT groups. During treatment, 92/144 (63.9%) patients experienced any ADR. The most common ADR included flu-like symptoms (38.2%) and gastrointestinal (31.9%) and hepatic (2.1%) reactions. Despite high rate of overall ADRs, rates of significant ADRs (grade 2 or higher) were 4.2%. Overall, 9% of patients discontinued 3HP because of ADRs. After adjusting for other factors associated with ADRs at baseline, SAT was not associated with increased incidence of ADRs, but female sex was a significant predictor (odds ratio = 2.61 [95% CI, 1.23 to 5.56]). Conclusion and Relevance: This study observed high 3HP treatment completion rates, low incidence of significant ADRs, and low discontinuation rates resulting from ADRs.

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