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 Safety and medical cost effectiveness of preventive treatment of children with latent tuberculosis infection

2020 ◽  
Vol 98 (9) ◽  
pp. 25-31
Author(s):  
O. D. Baronova ◽  
V. A. Aksenova ◽  
N. I. Klevno ◽  
V. S. Odinets ◽  
O. V. Pilipenko
Keyword(s):  
Cost Effectiveness ◽  
Medical Cost ◽  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
Preventive Treatment ◽  
Tuberculosis Infection ◽  
Ltbi Treatment ◽  
Treatment Regimens ◽  
Prospective Group ◽  
Treatment Interruptions

The objective: to assess the safety and medical cost effectiveness of different LTBI treatment regimens in children and adolescents.Subjects and methods. 205 children in the age from 6 to 17 years old with latent tuberculosis infection were included in the study: The main (prospective) group included 31 children who were treated with isoniazid and rifapentine (HRpt). The comparison (retrospective) group included 174 pediatric patients: 128 patients received the regimen consisting of isoniazid and pyrazinamide (HZ), 14 patients received isoniazid and rifampicin (HR), and 32 patients received isoniazid and ethambutol (HE).Results. When using the HRpt regimen, the treatment was well tolerated; adverse events (eosinophilia) were documented in 6.5% of children. The medications were taken once a week and it allowed reducing the frequency of treatment interruptions for non-medical reasons. The overall cost per patient was lower with the HRpt regimen than with the other three LTBI treatment regimens. 

scholarly journals MicroRNA-889 Inhibits Autophagy To Maintain Mycobacterial Survival in Patients with Latent Tuberculosis Infection by Targeting TWEAK

mBio ◽  
2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Der-Yuan Chen ◽  
Yi-Ming Chen ◽  
Chin-Fu Lin ◽  
Che-Min Lo ◽  
Hung-Jen Liu ◽  
...  
Keyword(s):  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
Granuloma Formation ◽  
Tuberculosis Infection ◽  
Renal Diseases ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antibody Treatment ◽  
Content Type ◽  
Tnf Α

ABSTRACT Autophagy plays an important role in protecting the host against pathogens. Mycobacterium tuberculosis can suppress autophagy and then remain dormant and survive within the host for an extended period, which is responsible for latent tuberculosis infection (LTBI). Here, we explored the role of microRNAs (miRNAs) in LTBI. The miRNA profiles were explored using the next-generation sequencing approach, followed by quantitative reverse transcription-PCR validation. The biological function of candidate miRNA was evaluated using immunoblotting, immunofluorescence techniques, and enzyme-linked immunosorbent assay in an in vitro human TB granuloma model. An increased miR-889 expression was observed in patients with LTBI compared with that in patients without infection. The reporter assay identified tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) as the target of miR-889. Mycobacterial infection induced TWEAK upregulation in the early phase. TWEAK induced autophagy and promoted mycobacterial autophagosome maturation through activation of AMP-activated protein kinase (AMPK). Upon entry to LTBI status, elevated miR-889 levels were associated with TNF alpha (TNF-α) and granuloma formation/maintenance. MiR-889 inhibited autophagy via posttranscriptional suppression of TWEAK expression to maintain mycobacterial survival in granulomas. Adalimumab (anti-TNF-α monoclonal antibody) treatment reduced levels of both TNF-α and miR-889 and caused granuloma destruction and LTBI reactivation. The circulating miR-889 and TWEAK levels were correlated with LTBI and subsequently associated with anti-TNF-α-related LTBI reactivation in patients. We propose that miR-889 and TWEAK can act as targets that can be manipulated for antimycobacterial therapeutic purposes and act as candidate biomarkers for LTBI and LTBI reactivation, respectively. IMPORTANCE TB remains a leading cause of morbidity and mortality worldwide. Approximately one-quarter of the world’s population has latent TB infection. TWEAK is a multiple-function cytokine and may be used as a target for the treatment of rheumatic diseases, cardiovascular diseases, and renal diseases. Here, we demonstrated a novel relationship between TWEAK and activation of the autophagic machinery which promotes antimycobacterial immunity. Additionally, TB infection is highly dynamic and determined by the interaction between the host and mycobacterium. We demonstrated a mechanism of fine-tuned balance between the mycobacterium and host for granuloma formation and/or maintenance in LTBI status. Once patients entered LTBI status, the upregulation of miR-889 was associated with TNF-α levels and granuloma formation to maintain mycobacterial survival. Adalimumab (a TNF-α inhibitor) reduced both TNF-α and miR-889 levels and caused LTBI reactivation and, thus, TWEAK enhancement. MiR-889 and TWEAK may become potential diagnostic biomarkers or therapeutic targets for LTBI and LTBI reactivation, respectively.

scholarly journals Increasing Latino Adolescents’ Adherence to Treatment for Latent Tuberculosis Infection: A Controlled Trial

2003 ◽  
Vol 93 (11) ◽  
pp. 1871-1877 ◽  
Author(s):  
Melbourne F. Hovell ◽  
Carol L. Sipan ◽  
Elaine J. Blumberg ◽  
C. Richard Hofstetter ◽  
Donald Slymen ◽  
...  
Keyword(s):  
Latent Tuberculosis Infection ◽  
Controlled Trial ◽  
Latent Tuberculosis ◽  
Tuberculosis Infection ◽  
Latino Adolescents ◽  
Adherence To Treatment

scholarly journals Randomized Controlled Trial of Interventions to Improve Follow-up for Latent Tuberculosis Infection After Release From Jail

2002 ◽  
Vol 162 (9) ◽  
pp. 1044 ◽  
Author(s):  
Mary Castle White ◽  
Jacqueline P. Tulsky ◽  
Joe Goldenson ◽  
Carmen J. Portillo ◽  
Masae Kawamura ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Latent Tuberculosis Infection ◽  
Controlled Trial ◽  
Latent Tuberculosis ◽  
Tuberculosis Infection ◽  
Randomized Controlled

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 VITAMIN D AND LATENT TUBERCULOSIS INFECTION IN SCHOOLCHILDREN

2019 ◽  
Vol 22 (6) ◽  
pp. 344-348
Author(s):  
A. D. Petrushina ◽  
Daria M. Slashcheva ◽  
N. S. Brynza ◽  
N. D. Pirogova ◽  
S. V. Sosnovskaya ◽  
...  
Keyword(s):  
Vitamin D ◽  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
Preventive Treatment ◽  
Tuberculosis Infection ◽  
World Health ◽  
Skin Tests ◽  
Initial Examination ◽  
Treatment And Prevention ◽  
Vitamin D Levels

The World Health Organization has adopted the global TB strategy for the period of 2016-2035. To achieve its targets, it is necessary to propose and introduce new approaches for the prevention and treatment of latent tuberculosis infection (LTBI) in children and adolescents, as a potential source of active tuberculosis development. In this regard, the use of vitamin D (cholecalciferol) may become promising in combating tuberculosis, since most researchers suppose an adequate level of cholecalciferol to have a positive preventive and therapeutic effect in children with active and latent tuberculosis. So far the use of vitamin D may be appropriate, especially in children not adequately provided with vitamin D. The paper presents the results of the vitamin D levels study before and after prescribing cholecalciferol, as well as the dynamics of the tuberculin skin tests in school-age LTBI children receiving preventive treatment with anti-TB drugs. At the initial examination, a normal level of 25-hydroxycholecalciferol (25(OH)D) was not detected in any child. After 3 months of administration of vitamin D in therapeutic doses, a normal concentration of 25(OH)D was observed in 52% of the children examined repeatedly. Analysis of the tuberculin skin test dynamics showed 47.6% of children to have a negative/doubtful test result after 3 months of treatment with anti-TB drugs and vitamin D. In 9.5% of patients, the size of the papule did not change during treatment. It is important to note that in these children, the 25(OH)D level also did not increase. А vitamin D intake at a therapeutic dosage did not cause hypercalcemia or hypercalciuria in any child. LTBI children are inadequately provided with cholecalciferol. There fore it is necessary to determine the level of vitamin D in the blood, then to prescribe the vitamin D, regardless of the time of year, along with standard therapy for a more effective outcome of LTBI treatment and prevention of active forms of tuberculosis in the future.

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.

scholarly journals Prevention of Tuberculosis Reactivation

2021 ◽  
Vol 1 (8) ◽  
Author(s):  
Kendra Brett ◽  
Melissa Severn
Keyword(s):  
Latent Infection ◽  
Treatment Effectiveness ◽  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
Ltbi Treatment ◽  
Reactivation Treatment ◽  
Increased Risk ◽  
Quality Guideline ◽  
Tuberculosis Reactivation ◽  
Tuberculosis Disease

It is not known if screening for latent tuberculosis infection (LTBI) is useful for reducing the risk of tuberculosis reactivation among people at risk (no evidence was found). In people with LTBI, providing treatment for the latent infection may be helpful for preventing the development of active tuberculosis disease. (In addition, LTBI treatments do not appear to increase the risk for hepatotoxicity.) Treatment effectiveness may depend on the specific LTBI treatment regimen used. For people at an increased risk for tuberculosis ― including those from areas with high rates of tuberculosis ― guidelines recommend screening and treatment for LTBI, as this may help prevent TB reactivation. Treatment is recommended for those who are 65 years old or younger and with a positive LTBI result (recommendation from 1 high-quality guideline).

Vitamin D deficiency in children with latent tuberculosis infection

2020 ◽  
Vol 98 (6) ◽  
pp. 27-31
Author(s):  
D. M. Slаschevа ◽  
A. D. Petrushinа ◽  
N. S. Brynzа ◽  
А. P. Chernovа ◽  
N. D. Pirogovа ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Blood Level ◽  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
Preventive Treatment ◽  
Tuberculosis Infection ◽  
Ionized Calcium ◽  
Mantoux Test ◽  
Total Calcium

The objective: to assess the level of vitamin D and parameters of phosphorus-calcium metabolism in children with latent tuberculosis infection.Subjects and methods. 40 children from 3 to 17 years were enrolled in the study, they all had the abnormal reaction to Mantoux test with 2 TU but no clinical, radiological and bacteriological signs of active tuberculosis; 39 of them received preventive treatment for latent tuberculosis infection during the study. The following parameters were tested: blood level of 25-hydroxycholecalciferol (calcidiol, 25(OH)D) (the level of less than 10 ng/ml was considered as pronounce severe deficiency, the level of 11-20 ng/ml as moderate deficiency, 21-29 ng/ml – minor deficiency, above 30 ng/ml – an adequate level of vitamin D); total calcium, and ionized calcium.Results: 87.5% (14/16) of children from the group of 3-6 years old and 96% (23/24) of children from the group of 7-17 years old were found to have vitamin D deficiency; p > 0.05. The blood level of total calcium and ionized calcium in all children was within the age norm.

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