scholarly journals Identification of Immunological Biomarkers Which May Differentiate Latent Tuberculosis from Exposure to Environmental Nontuberculous Mycobacteria in Children

2013 ◽  
Vol 21 (2) ◽  
pp. 133-142 ◽  
Author(s):  
Yun-Gyoung Hur ◽  
Amelia C. Crampin ◽  
Christina Chisambo ◽  
James Kanyika ◽  
Rein Houben ◽  
...  
Keyword(s):  
Nontuberculous Mycobacteria ◽  
Latent Tuberculosis ◽  
Control Group ◽  
Content Type ◽  
Interleukin 5 ◽  
Bcg Vaccination ◽  
Early Secretory Antigenic Target ◽  
Latent Tb ◽  
Ifn Γ ◽  
Latent Tb Infection

ABSTRACTA positive gamma interferon (IFN-γ) response toMycobacterium tuberculosisearly secretory antigenic target-6 (ESAT-6)/culture filtrate protein-10 (CFP-10) has been taken to indicate latent tuberculosis (TB) infection, but it may also be due to exposure to environmental nontuberculous mycobacteria in which ESAT-6 homologues are present. We assessed the immune responses toM. tuberculosisESAT-6 and cross-reactive responses to ESAT-6 homologues ofMycobacterium aviumandMycobacterium kansasii. Archived culture supernatant samples from children at 3 years post-BCG vaccination were tested for cytokine/chemokine responses toM. tuberculosisantigens. Furthermore, the IFN-γ responses toM. tuberculosisantigens were followed up for 40 children at 8 years post-BCG vaccination, and 15 TB patients were recruited as a control group for theM. tuberculosisESAT-6 response in Malawi. IFN-γ enzyme-linked immunosorbent assays (ELISAs) on supernatants from diluted whole-blood assays, IFN-γ enzyme-linked immunosorbent spot (ELISpot) assays, QuantiFERON TB Gold-In Tube tests, and multiplex bead assays were performed. More than 45% of the responders toM. tuberculosisESAT-6 showed IFN-γ responses toM. aviumandM. kansasiiESAT-6. In response toM. tuberculosisESAT-6/CFP-10, interleukin 5 (IL-5), IL-9, IL-13, and IL-17 differentiated the stronger IFN-γ responders toM. tuberculosisESAT-6 from those who preferentially responded toM. kansasiiandM. aviumESAT-6. A cytokine/chemokine signature of IL-5, IL-9, IL-13, and IL-17 was identified as a putative immunological biosignature to differentiate latent TB infection from exposure toM. aviumandM. kansasiiin Malawian children, indicating that this signature might be particularly informative in areas where both TB and exposure to environmental nontuberculous mycobacteria are endemic.

scholarly journals Effect of isoniazid on antigen-specific interferon-γ secretion in latent tuberculosis

2014 ◽  
Vol 45 (2) ◽  
pp. 473-482 ◽  
Author(s):  
Martha Torres ◽  
Lourdes García-García ◽  
Pablo Cruz-Hervert ◽  
Heinner Guio ◽  
Claudia Carranza ◽  
...  
Keyword(s):  
Latent Tuberculosis ◽  
Peptide Pool ◽  
Interferon Γ ◽  
Treatment Regimes ◽  
Latent Tb ◽  
Ifn Γ ◽  
New Treatment ◽  
Latent Tb Infection ◽  
Culture Filtrate Protein

Treatment of persons with latent tuberculosis (TB) infection at greatest risk of reactivation is an important component of TB control and elimination strategies. Biomarkers evaluating the effectiveness of treatment of latent TB infection have not yet been identified. This information would enhance control efforts and assist the evaluation of new treatment regimes.We designed a two-group, two-arm, randomised clinical study of tuberculin skin test-positive participants: 26 with documented contact with TB patients and 34 with non-documented contact. Participants in each group were randomly assigned to the immediate- or deferred-isoniazid treatment arms. Assays ofin vitrointerferon (IFN)-γ secretion in response to recombinant Rv1737 and overlapping synthetic peptide pools from various groups of immunodominant proteins were performed.During isoniazid therapy, a significant increase from baseline in the proportion of IFN-γ responders to the 10-kDa culture filtrate protein, Rv2031, Rv0849, Rv1986, Rv2659c, Rv2693c and the recombinant Rv1737 protein was observed (p⩽0.05). The peptide pool of Rv0849 and Rv1737 recombinant proteins induced the highest percentage of IFN-γ responders after isoniazid therapy.Thein vitroIFN-γ responses to these proteins might represent useful markers to evaluate changes associated with treatment of latent TB infection.

scholarly journals Interferon Gamma Release Assay After BCG Vaccination Among Newborns and Family Members Living in an Overcrowded Area in Jakarta, Indonesia

2020 ◽  
Author(s):  
Francisca Srioetami Tanoerahar ◽  
Indri Rooslamiati ◽  
Natalie Kipuw ◽  
Hadiyanto ◽  
Soegianto Ali ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
Family Members ◽  
Latent Tuberculosis ◽  
Interferon Gamma Release Assay ◽  
Pulmonary Tb ◽  
Bcg Vaccination ◽  
Release Assay ◽  
Latent Tb ◽  
Poor Area ◽  
Latent Tb Infection

Abstract IntroductionActive tuberculosis (TB) patient is a potential source of Mycobacterium tuberculosis transmission in an overcrowded and poor area. Family members living in the same house may have been infected or latent tuberculosis infection (LTBI) may develop. The aim of the study was to explore LTBI among newborns and their family members living in an overcrowded area in Jakarta, Indonesia. MethodsA prospective analytical study was conducted among newborns from October 2016 to March 2017. Interferon gamma release assay (IGRA) was examined before BCG vaccination and after 12 weeks. In parallel, TB active case finding was performed among family members of the newborns.ResultsOf 135 newborns, only 117 (86.7%) came for BCG vaccination. Of 346 family members screened, 8 (2.3%) were detected as untreated active pulmonary TB, confirmed by positive sputum and/or MTB culture. Family members living in the same house with active TB individuals (p=0.011, OR 2.69) as well as being males (p = 0.025; OR 1.68) had a significant higher risk of having a positive IGRA. ConclusionsUntreated pulmonary TB infection in overcrowded areas infects the surrounding neighbors, resulting in latent TB infection. An active program for detecting pulmonary TB cases and preventive measures need to be taken seriously to contain the potential spreading of the infection.

The Diagnostic Value of Blood and Urine IP-10 Test in Children Having Active Tuberculosis or Latent Tuberculosis Infection

2021 ◽  
Author(s):  
Salim Can ◽  
Ayse Sahin ◽  
Nazan Dalgic ◽  
Deniz Aygün
Keyword(s):  
Pediatric Patients ◽  
Latent Tuberculosis ◽  
Diagnostic Value ◽  
Active Tuberculosis ◽  
Control Group ◽  
Healthy Children ◽  
Combined Use ◽  
Latent Tb ◽  
Inducible Protein ◽  
Latent Tb Infection

Abstract Objective This study aimed to investigate interferon-gamma-inducible protein-10 (IP-10) values in serum and urine in pediatric patients in the diagnosis of active tuberculosis (TB) or latent TB infection (LTBI). It also aimed to investigate whether it can be used as a biomarker to distinguish between active TB and LTBI. Methods Our study comprised active TB (25 patients), LTBI (25 patients), and the “infected” group (50 patients) formed by combining the two groups. As the control group, 37 healthy children were included in the study. TB skin test, plasma IP-10, and urine IP-10 measurements were performed in all patients included in the study. An additional QuantiFERON-TB Gold In-Tube (QFT-GIT) test was performed on patients evaluated as active TB or LTBI. Results Plasma IP-10 levels of the patients in the active TB, LTBI, and the “infected” groups were significantly higher than the control group (p = 0.022, p = 0.028, and p = 0.007, respectively). Urine IP-10 was successful in distinguishing the active TB and “infected” groups from the control group (p = 0.007 and p = 0.047, respectively). Also, in the combined use of the tests, when QFT-GIT and urine IP-10 were positive together, active TB and LTBI could be distinguished (p = 0.044). Urine IP-10 levels were found to be significantly higher in those with pulmonary TB than those with extrapulmonary TB (p = 0.012). Conclusion Our findings suggest that IP-10 can be used as a useful biomarker in the diagnosis of active TB in children.

scholarly journals Quantitative Analysis of Gamma Interferon Release Assay Response in Children with Latent and Active Tuberculosis

2017 ◽  
Vol 56 (2) ◽  
Author(s):  
Giulia Lombardi ◽  
Roberta Petrucci ◽  
Ilaria Corsini ◽  
Maria Letizia Bacchi Reggiani ◽  
Francesca Visciotti ◽  
...  
Keyword(s):  
Immune Response ◽  
Pediatric Population ◽  
Active Tuberculosis ◽  
University Hospital ◽  
Content Type ◽  
Release Assay ◽  
Latent Tb ◽  
Specific Antigens ◽  
Ifn Γ ◽  
Latent Tb Infection

ABSTRACT The use of interferon gamma (IFN-γ) release assays (IGRAs) for the diagnosis of tuberculosis (TB) infection in children is still under debate because of concerns about the immature immune response in children. The aim of this study was to investigate quantitative values of the QuantiFERON-TB Gold In-Tube (QFT-IT) test, a commercially available IGRA, in a large cohort of children screened for TB infection. A retrospective analysis was conducted on samples from 517 children aged 0 to 14 years old at the Pediatric Unit of S. Orsola-Malpighi University Hospital of Bologna (Italy); quantitative responses to QFT-IT stimuli were analyzed according to diagnosis and age. Elevated IFN-γ values in the QFT-IT nil (background) tube were statistically associated with diagnosis of active TB. Quantitative IFN-γ response to Mycobacterium tuberculosis-specific antigens (TB Ag) was not significantly different in children with active TB compared to those with latent TB infection (LTBI), even though the median values were higher in the first group. When children were grouped by age, those less than 5 years old produced significantly higher levels of IFN-γ in response to TB Ag if they had active TB (median 10 IU/ml) than those with LTBI (median 1.96 IU/ml). IFN-γ response to mitogen increased with age. The overall rate of indeterminate results was low (3.9%), and no indeterminate QFT-IT values were observed in active or latent TB patients. In conclusion, quantitative QFT-IT values could provide further information to clinicians to manage TB in children, and these observations could be transferred to the new version of the test, QuantiFERON-TB Gold Plus, which to date lacks data from the pediatric population.

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 Cytokine Biosignature of Active and Latent Mycobacterium Tuberculosis Infection in Children

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 517
Author(s):  
Magdalena Druszczynska ◽  
Michal Seweryn ◽  
Sebastian Wawrocki ◽  
Magdalena Kowalewska-Pietrzak ◽  
Anna Pankowska ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Inflammatory Mediators ◽  
Latent Tuberculosis ◽  
Serum Levels ◽  
Diagnostic Tools ◽  
Mycobacterium Tuberculosis Infection ◽  
Only Children ◽  
Latent Tb ◽  
Ifn Γ ◽  
Multiplex Bead

None of the currently used diagnostic tools are efficient enough in diagnosing Mycobacterium tuberculosis (M.tb) infection in children. The study was aimed to identify cytokine biosignatures characterizing active and latent tuberculosis (TB) in children. Using a multiplex bead-based technology, we analyzed the levels of 53 Th17-related cytokines and inflammatory mediators in sera from 216 BCG-vaccinated children diagnosed with active TB (TB) or latent TB (LTBI) as well as uninfected controls (HC). Children with active TB, compared to HC children, showed reduced serum levels of IL-17A, MMP-2, OPN, PTX-3, and markedly elevated concentrations of APRIL/TNFSF13. IL-21, sCD40L, MMP-2, and IL-8 were significantly differentially expressed in the comparisons between groups: (1) HC versus TB and LTBI (jointly), and (2) TB versus LTBI. The panel consisting of APRIL/TNFSF13, sCD30/TNFRSF8, IFN-α2, IFN-γ, IL-2, sIL-6Rα, IL-8, IL-11, IL-29/IFN-λ1, LIGHT/TNFSF14, MMP-1, MMP-2, MMP-3, osteocalcin, osteopontin, TSLP, and TWEAK/TNFSF12 possessed a discriminatory potential for the differentiation between TB and LTBI children. Serum-based host biosignatures carry the potential to aid the diagnosis of childhood M.tb infections. The proposed panels of markers allow distinguishing not only children infected with M.tb from uninfected individuals but also children with active TB from those with latent TB.

scholarly journals Latent Tuberculosis Infection

2018 ◽  
Vol 4 (1) ◽  
pp. 21 ◽  
Author(s):  
Jean-Pierre Zellweger ◽  
Keyword(s):  
Latent Tuberculosis ◽  
Public Health Problem ◽  
World Health Organisation ◽  
Pulmonary Involvement ◽  
World Health ◽  
Global Public Health ◽  
Expert Interview ◽  
Immunodeficiency Virus ◽  
Latent Tb ◽  
Latent Tb Infection

Tuberculosis (TB) is a major global public health problem and is the leading cause of death linked to a single pathogen, ranking above human immunodeficiency virus (HIV).1 Clinically, TB has been categorised as active disease (patients who are generally symptomatic and may be infectious if pulmonary involvement is present) and latent infection (asymptomatic and not infectious, but at variable risk for progression to active TB disease). It is increasingly being recognised that latent TB infection (LTBI) reflects diverse responses to infection with Mycobacterium tuberculosis and may lead to heterogeneous clinical outcomes. In an expert interview, Jean-Pierre Zellweger discusses the latest World Health Organisation (WHO) guidelines on the management of LTBI.

scholarly journals Interleukin-18, Functional IL-18 Receptor and IL-18 Binding Protein Expression in Active and Latent Tuberculosis

Pathogens ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 451
Author(s):  
Sebastian Wawrocki ◽  
Grzegorz Kielnierowski ◽  
Wieslawa Rudnicka ◽  
Michal Seweryn ◽  
Magdalena Druszczynska
Keyword(s):  
Mrna Expression ◽  
Binding Protein ◽  
Latent Tuberculosis ◽  
Buffy Coat ◽  
Active Tuberculosis ◽  
Control Group ◽  
Relative Expression ◽  
Ifn Γ ◽  
Blood Fraction ◽  
And Control

A thorough understanding of the processes modulating the innate and acquired immune response to Mycobacterium tuberculosis (M.tb) infection in the context of gene expression is still a scientific and diagnostic problem. The study was aimed to assess IL-18, IL-18 binding protein (IL-18BP), IL-18R, IFN-γ, and IL-37 mRNA expression in patients with active tuberculosis (ATB) and healthy volunteers with latent M.tb-infection (LTB) or M.tb-uninfected healthy controls (Control). The relative mRNA expression was assessed in the buffy coat blood fraction using the qPCR method. In total, 97 BCG-vaccinated Polish adults were enrolled in the study. The relative expression of IL-18 and IL-18BP mRNA was significantly elevated in the ATB and LTB groups. In ATB, but not LTB individuals, the overexpression of IL-18 and IL-18BP, as well as a significant increase in IFN-γ mRNA expression, might be considered as a manifestation of active tuberculosis disease. No statistically significant differences were observed in the IL-37 mRNA expression among the studied groups. Particularly noteworthy is the outstanding reduction in the relative expression of IL-18R mRNA in the LTB group as compared to the ATB and Control group. Reduced expression of IL-18R in LTB group may, at least partially, prevent the development of a pathological inflammatory reaction and promote the maintenance of homeostatic conditions between host immunity and M.tb.

scholarly journals CD4+ T-cell–independent mechanisms suppress reactivation of latent tuberculosis in a macaque model of HIV coinfection

2016 ◽  
Vol 113 (38) ◽  
pp. E5636-E5644 ◽  
Author(s):  
Taylor W. Foreman ◽  
Smriti Mehra ◽  
Denae N. LoBato ◽  
Adel Malek ◽  
Xavier Alvarez ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Latent Tuberculosis ◽  
Natural Immunity ◽  
Macaque Model ◽  
Hiv Coinfection ◽  
Immunodeficiency Virus ◽  
Latent Tb ◽  
Latent Tb Infection

The synergy between Mycobacterium tuberculosis (Mtb) and HIV in coinfected patients has profoundly impacted global mortality because of tuberculosis (TB) and AIDS. HIV significantly increases rates of reactivation of latent TB infection (LTBI) to active disease, with the decline in CD4+ T cells believed to be the major causality. In this study, nonhuman primates were coinfected with Mtb and simian immunodeficiency virus (SIV), recapitulating human coinfection. A majority of animals exhibited rapid reactivation of Mtb replication, progressing to disseminated TB and increased SIV-associated pathology. Although a severe loss of pulmonary CD4+ T cells was observed in all coinfected macaques, a subpopulation of the animals was still able to prevent reactivation and maintain LTBI. Investigation of pulmonary immune responses and pathology in this cohort demonstrated that increased CD8+ memory T-cell proliferation, higher granzyme B production, and expanded B-cell follicles correlated with protection from reactivation. Our findings reveal mechanisms that control SIV- and TB-associated pathology. These CD4-independent protective immune responses warrant further studies in HIV coinfected humans able to control their TB infection. Moreover, these findings will provide insight into natural immunity to Mtb and will guide development of novel vaccine strategies and immunotherapies.

Sign in / Sign up

Export Citation Format

Share Document