scholarly journals Contribution of NRAMP1 gene expression and protein level in pulmonary and latent TB infection in Indonesia

2021 ◽  
Author(s):  
Handayani Irda ◽  
Djaharuddin Irawaty ◽  
Natzir Rosdiana ◽  
Arief Mansyur ◽  
Ahmad Ahyar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Level ◽  
Nramp1 Gene ◽  
Latent Tb ◽  
Latent Tb Infection

scholarly journals Comparing tuberculosis gene signatures in malnourished individuals using the TBSignatureProfiler

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
W. Evan Johnson ◽  
Aubrey Odom ◽  
Chelsie Cintron ◽  
Mutharaj Muthaiah ◽  
Selby Knudsen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Sequencing ◽  
Area Under The Curve ◽  
Severe Malnutrition ◽  
Gene Set ◽  
Gene Sets ◽  
Z Scores ◽  
Latent Tb ◽  
Latent Tb Infection ◽  
User Friendly

Abstract Background Gene expression signatures have been used as biomarkers of tuberculosis (TB) risk and outcomes. Platforms are needed to simplify access to these signatures and determine their validity in the setting of comorbidities. We developed a computational profiling platform of TB signature gene sets and characterized the diagnostic ability of existing signature gene sets to differentiate active TB from LTBI in the setting of malnutrition. Methods We curated 45 existing TB-related signature gene sets and developed our TBSignatureProfiler software toolkit that estimates gene set activity using multiple enrichment methods and allows visualization of single- and multi-pathway results. The TBSignatureProfiler software is available through Bioconductor and on GitHub. For evaluation in malnutrition, we used whole blood gene expression profiling from 23 severely malnourished Indian individuals with TB and 15 severely malnourished household contacts with latent TB infection (LTBI). Severe malnutrition was defined as body mass index (BMI) < 16 kg/m2 in adults and based on weight-for-height Z scores in children < 18 years. Gene expression was measured using RNA-sequencing. Results The comparison and visualization functions from the TBSignatureProfiler showed that TB gene sets performed well in malnourished individuals; 40 gene sets had statistically significant discriminative power for differentiating TB from LTBI, with area under the curve ranging from 0.662–0.989. Three gene sets were not significantly predictive. Conclusion Our TBSignatureProfiler is a highly effective and user-friendly platform for applying and comparing published TB signature gene sets. Using this platform, we found that existing gene sets for TB function effectively in the setting of malnutrition, although differences in gene set applicability exist. RNA-sequencing gene sets should consider comorbidities and potential effects on diagnostic performance.

scholarly journals Prevalence of latent tuberculosis infection and feasibility of TB preventive therapy among Thai prisoners: a cross-sectional study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sivaporn Gatechompol ◽  
Weerakit Harnpariphan ◽  
Ruamthip Supanan ◽  
Gompol Suwanpimolkul ◽  
Jiratchaya Sophonphan ◽  
...  
Keyword(s):  
Latent Tuberculosis ◽  
Cross Sectional Study ◽  
Preventive Therapy ◽  
Sectional Study ◽  
Cross Sectional ◽  
Ltbi Prevalence ◽  
History Of ◽  
Chest X Ray ◽  
Latent Tb ◽  
Latent Tb Infection

Abstract Background Prisons are considered as major reservoirs for tuberculosis. Preventive therapy for latent TB infection (LTBI) is an adjunctive strategy to control TB. However, LTBI data in Thai prisoners is limited. This study assessed the prevalence of LTBI and feasibility of isoniazid preventive therapy (IPT). Methods A cross-sectional study was conducted among prisoners in Klong Prem Central Prison, Bangkok. Participants were screened for active TB by questionnaire and chest X-ray. LTBI was evaluated by Tuberculin skin test (TST) and QuantiFERON-TB Gold Plus (QFTP) among subgroup. Participants with positive TST or QFTP were considered to have LTBI. Participants with LTBI were offered IPT. Results From August 2018–November 2019, 1002 participants were analyzed. All participants were male with a median age of 38 (IQR 32–50) years. LTBI identified by either TST/QFTP was present in 466 (46.5%) participants. TST was positive in 359 (36%) participants. In the subgroup of 294 participants who had both TST and QFTP results, 181/294 (61.6%) tested positive by QFTP. Agreement between TST and QFTP was 55.1% (Kappa = 0.17). The risk factors associated with LTBI were previous incarceration (aOR 1.53, 95%CI, 1.16–2.01, p = 0.002), history of prior active TB (aOR 3.02, 95%CI, 1.74–5.24, p < 0.001) and duration of incarceration ≥10 years (aOR 1.86, 95%CI, 1.24–2.79, p = 0.003). Majority of LTBI participants (82%) agreed to take IPT. Three hundred and 56 (93%) participants completed treatment whereas 27 (7%) participants discontinued IPT due to the side effects of INH. Conclusion This is the first study to evaluate the prevalence of LTBI and feasibility of IPT among Thai prisoners. LTBI prevalence in male prisoners in Thailand is high. LTBI screening and treatment should be implemented together with other preventive components.

scholarly journals Ex vivo mRNA expression of toll-like receptors during latent tuberculosis infection

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Birhan Alemnew ◽  
Soren T. Hoff ◽  
Tamrat Abebe ◽  
Markos Abebe ◽  
Abraham Aseffa ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Expression Patterns ◽  
Fold Change ◽  
Mrna Levels ◽  
Healthy Children ◽  
Toll Like Receptors ◽  
Relative Expression ◽  
Latently Infected ◽  
Latent Tb ◽  
Latent Tb Infection

Abstract Background Understanding immune mechanisms, particularly the role of innate immune markers during latent TB infection remains elusive. The main objective of this study was to evaluate mRNA gene expression patterns of toll-like receptors (TLRs) as correlates of immunity during latent TB infection and further infer their roles as potential diagnostic biomarkers. Methods Messenger RNA (mRNA) levels were analysed in a total of 64 samples collected from apparently healthy children and adolescents latently infected with tuberculosis (n = 32) or non-infected (n = 32). Relative expression in peripheral blood of selected genes encoding TLRs (TLR-1, TLR-2, TLR-4, TLR-6 and TLR-9) was determined with a quantitative real-time polymerase chain reaction (qRT-PCR) using specific primers and florescent labelled probes and a comparative threshold cycle method to define fold change. Data were analysed using Graph-Pad Prism 7.01 for Windows and a p-value less than 0.05 was considered statistically significant. Results An increased mean fold change in the relative expression of TLR-2 and TLR-6 mRNA was observed in LTBI groups relative to non-LTBI groups (p < 0.05), whereas a slight fold decrease was observed for TLR-1 gene. Conclusions An increased mRNA expression of TLR-2 and TLR-6 was observed in latently infected individuals relative to those non-infected, possibly indicating the roles these biomarkers play in sustenance of the steady state interaction between the dormant TB bacilli and host immunity.

scholarly journals Upregulation of PD-1 expression on circulating CD8+ but not CD4+ T cells is associated with tuberculosis infection in health care workers

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Cui-lin Shi ◽  
Jian-ping Zhang ◽  
Ping Xu ◽  
Jin Li ◽  
Jie Shen ◽  
...  
Keyword(s):  
Health Care ◽  
T Cells ◽  
T Cell ◽  
Health Care Workers ◽  
Cd4 T Cells ◽  
Receptor Expression ◽  
Effector Memory ◽  
Care Workers ◽  
Latent Tb ◽  
Latent Tb Infection

Abstract Background Health care workers (HCWs) are at risk for occupationally acquired Mycobacterium tuberculosis infection and tuberculosis (TB) disease due to repeated exposure to workplace tubercle bacilli. To determine whether continual mycobacterial stimulation correlates with increased expression of inhibitory T cell receptors, here we compared PD-1 receptor expression on surfaces of circulating T cells between naïve (uninfected) HCWs and HCWs with latent TB infection (LTBI). Result Data collected from 133 medical workers who met study selection criteria were included in the final analysis. QuantiFERON-TB Gold In-​Tube (QFT-GIT) testing yielded positive results for 32 HCWs, for an overall LTBI rate of 24.1%. Multivariate analysis identified HCW length of service > 15 years as an independent risk factor for a positive QFT-GIT result. In addition, comparisons of blood T cell subgroup profiles between QFT- and QFT+ groups indicated QFT+ subjects possessed greater proportions of mature (TM), transitional memory (TTM) and effector memory (TEM) CD4+ T cell subgroups and lower proportions of naïve T cells (TN). Moreover, the QFT+ group percentage of CD8+ T cells with detectable surface PD-1 was significantly higher than the corresponding percentage for the QFT- group. Meanwhile, no statistical intergroup difference was observed in percentages of CD4+ T cells with detectible surface PD-1. Conclusions Our data demonstrated that upregulated PD-1 expression on circulating CD8+, but not CD4+ T cells, was associated with latent TB infection of HCWs. As compared to other hospitals, occupational TB infection risk in our hospital was substantially mitigated by implementation of multitiered infection control measures.

scholarly journals Adhesion Behaviour of Primary Human Osteoblasts and Fibroblasts on Polyether Ether Ketone Compared with Titanium under In Vitro Lipopolysaccharide Incubation

Materials ◽  
2019 ◽  
Vol 12 (17) ◽  
pp. 2739 ◽  
Author(s):  
Korbinian Benz ◽  
Andreas Schöbel ◽  
Marisa Dietz ◽  
Peter Maurer ◽  
Jochen Jackowski
Keyword(s):  
Gene Expression ◽  
Protein Level ◽  
Binding Protein ◽  
Sem Images ◽  
Human Osteoblasts ◽  
Polyether Ether Ketone ◽  
Primary Human Osteoblasts ◽  
Titanium Surfaces ◽  
Ether Ketone

The aim of this in vitro pilot study was to analyse the adhesion behaviour of human osteoblasts and fibroblasts on polyether ether ketone (PEEK) when compared with titanium surfaces in an inflammatory environment under lipopolysaccharide (LPS) incubation. Scanning electron microscopy (SEM) images of primary human osteoblasts/fibroblasts on titanium/PEEK samples were created. The gene expression of the LPS-binding protein (LBP) and the LPS receptor (toll-like receptor 4; TLR4) was measured by real-time polymerase chain reaction (PCR). Immunocytochemistry was used to obtain evidence for the distribution of LBP/TLR4 at the protein level of the extra-cellular-matrix-binding protein vinculin and the actin cytoskeleton. SEM images revealed that the osteoblasts and fibroblasts on the PEEK surfaces had adhesion characteristics comparable to those of titanium. The osteoblasts contracted under LPS incubation and a significantly increased LBP gene expression were detected. This was discernible at the protein level on all the materials. Whereas no increase of TLR4 was detected with regard to mRNA concentrations, a considerable increase in the antibody reaction was detected on all the materials. As is the case with titanium, the colonisation of human osteoblasts and fibroblasts on PEEK samples is possible under pro-inflammatory environmental conditions and the cellular inflammation behaviour towards PEEK is lower than that of titanium.

scholarly journals 806. 2013–2015 Nationwide Tuberculosis Contact Investigation in Childcare Centers and Schools in Korea

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S289-S289
Author(s):  
Woosuck Suh ◽  
Jong-Hyun Kim ◽  
Ji Hyen Hwang ◽  
Sodam Lee ◽  
Kang-Hee Lee ◽  
...  
Keyword(s):  
School Setting ◽  
Age Groups ◽  
Disease Status ◽  
Childcare Centers ◽  
X Ray ◽  
Contact Investigation ◽  
Chest X Ray ◽  
Latent Tb ◽  
The Republic ◽  
Latent Tb Infection

Abstract Background The Republic of Korea has the highest incidence rate of tuberculosis (TB) among members of the OECD, reported as 78.8/100,000 population in 2016. In response, a state-run intensive contact investigation for TB is being conducted. More effective TB control requires an epidemiologic emphasis on the diagnosis and treatment of latent TB infections in children and adolescents, compared with other age groups. Here we present an analysis of data from the childcare center and school contact investigation by the Korea Centers for Disease Control and Prevention (CDC) in 2013–2015. Methods Data collected from index patients included age, sex, occupation, disease status, results of AFB smear/culture, and chest x-ray. Data collected from contacts included age, sex, results of serial tuberculin skin test (TST), and chest x-ray. Congregate settings included childcare centers, kindergartens, elementary and secondary schools, and age groups were stratified as follows: 0–4 years, 5–12 years, and 13–18 years. TSTs were considered positive if induration ≥10 mm on the first test (TST1) or demonstrated an increase ≥6 mm over the induration of TST1 on repeat testing after 8 weeks (TST2). Results Of the 197,801 subjects with data collected, 173,998 were eligible and included in our analysis. TST1 results were available for 159,346 (91.6%) and when results were positive, induration was 10–14 mm in 7.6% and ≥15 mm in 1.5%. TST2 results were available for 119,797 (82.7%) of the 144,904 with negative TST1, and conversion rate was 9.0%. Altogether considering TST1 and TST2, 17.3% contacts had latent TB infections. Positive rates of TST significantly decreased with age: 20.3% in 0–4 years, 18.8% in 5–12 years, 17.1% in 13–18 years. Conclusion In this 3-year school-setting contact investigation, 17.3% contacts were diagnosed with latent TB infection, as demonstrated by TST reactions. Positive rates of TST significantly but mildly decreased with age. Disclosures All authors: No reported disclosures.

scholarly journals Expected background rates of latent TB infection in London inner city schools: lessons from a TB contact investigation exercise in a secondary school

2018 ◽  
Vol 146 (16) ◽  
pp. 2102-2106 ◽  
Author(s):  
S. Anaraki ◽  
A.J. Bell ◽  
S. Perkins ◽  
S. Murphy ◽  
S. Dart ◽  
...  
Keyword(s):  
Contact Tracing ◽  
London Borough ◽  
Contact Group ◽  
Contact Investigation ◽  
High Prevalence ◽  
Cohort Study Design ◽  
Latent Tb ◽  
Group 2 ◽  
Latent Tb Infection ◽  
Group 1

AbstractFollowing an extensive contact tracing exercise at a school in a London borough with one of highest tuberculosis (TB) rates in England, we estimated the background prevalence of latent TB infection to be significantly less than the widely accepted 10%. We screened 271 pupils aged 14–15 years in two groups: 96 pupils in group 1 had significant exposure (>8 h/week in the same room) to a case of infectious TB and 175 in group 2 who had minimal exposure. In group 1, 26% were diagnosed with latent or active TB, compared to 6.3% in group 2. Risk factors for TB infection (e.g. previous exposure or link to high-prevalence communities) were analysed using a cohort study design. In the univariable analysis only being in contact group 1 was statistically significantly associated with being a case (OR 5.25, 95%, P < 0.001). In the multivariable model contact group 1 remained significantly associated with being a case (adjusted OR 4.40, P = 0.001). We concluded that the 6.3% yield of TB infection in contact group 2 is either similar to or higher than the background prevalence rate of latent TB infection (LTBI) in this high TB prevalence London borough. Other parts of England with lower TB prevalence are likely to have even lower LTBI rates.

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