Prospective evaluation of latent tuberculosis with interferon-γ release assays in drug and alcohol abusers

SUMMARYIn vitro tests have been developed for the diagnosis of tuberculosis (TB) infection. The objective was to analyse latent TB infection in drug and alcohol abusers through two interferon-γ techniques. One hundred and thirty-nine patients were admitted between February 2006 and May 2007. Mean age was 39·8 years [31% HIV positive]. The enzyme immunoassay (EIA) and enzyme-linked immunospot (ELISPOT) interferon-γ assays were positive in 34% of patients with an agreement of 83% (κ=0·63). Tuberculin skin test (TST) was positive in 29% of patients and the agreement of TST with EIA and ELISPOT interferon-γ assays was 85% (κ=0·62) and 83% (κ=0·57), respectively. Almost 50% of patients with history of TB had a positive in vitro test. In conclusion, we observed a high prevalence of latent TB and good agreement between the new in vitro tests that otherwise may continue to be positive long after developing TB disease.

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

European Respiratory Journal ◽

10.1183/09031936.00123314 ◽

2014 ◽

Vol 45 (2) ◽

pp. 473-482 ◽

Cited By ~ 7

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.

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

BMC Public Health ◽

10.1186/s12889-021-11271-0 ◽

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.

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Recent Progress in Diagnosis Methods for Latent Tuberculosis Infection and Its Clinical Applications

Infection International ◽

10.1515/ii-2017-0110 ◽

2015 ◽

Vol 4 (3) ◽

pp. 69-74

Author(s):

Ling Zhou

Keyword(s):

Mycobacterium Tuberculosis ◽

Recent Progress ◽

Latent Tuberculosis Infection ◽

Latent Tuberculosis ◽

Interferon Γ ◽

Clinical Applications ◽

Active Tuberculosis ◽

Advantages And Disadvantages ◽

Latent Tb ◽

Latent Tb Infection

AbstractMost people with latentMycobacterium tuberculosisinfection can partly develop active tuberculosis (TB). Therefore, diagnosis of this condition bears significance in early TB prevention. To date, the main methods for diagnosis of latent TB infection (LTBI) include tuberculin skin test and interferon γ release test. These two methods feature their own advantages and disadvantages. Although new diagnostic markers continually emerge, no uniform diagnostic criteria are available for TB detection. This study summarizes several methods for diagnosis of LTBI and new related markers and their application value in clinical practice.

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Comparison of Screening Procedures for Mycobacterium tuberculosis Infection Among Patients with Inflammatory Diseases

The Journal of Rheumatology ◽

10.3899/jrheum.081292 ◽

2009 ◽

Vol 36 (9) ◽

pp. 1876-1884 ◽

Cited By ~ 38

Author(s):

BOLETTE SOBORG ◽

MORTEN RUHWALD ◽

MERETE LUND HETLAND ◽

SØREN JACOBSEN ◽

AASE BENGAARD ANDERSEN ◽

...

Keyword(s):

Risk Factors ◽

Mycobacterium Tuberculosis ◽

Inflammatory Diseases ◽

Interferon Γ ◽

Mycobacterium Tuberculosis Infection ◽

Tb Treatment ◽

Latent Tb ◽

Latent Tb Infection ◽

High Degree

Objective.To test if Mycobacterium tuberculosis screening results differ among patients with inflammatory disease depending on whether the QuantiFeron TB-Gold test (QFT) or tuberculin skin test (TST) is used; and to evaluate if a possible difference is influenced by the presence of risk factors or immunosuppression.Methods.The interferon-γ response to in vitro stimulation of M. tuberculosis-specific antigens was measured with QFT and results were compared with TST. Associations to bacillus Calmette-Guerin (BCG) vaccination, risk factors, and immunosuppression were analyzed for both tests.Results.QFT and TST results were available for 294/302 and 241/302 patients, respectively; 234 had results from both tests. Twenty-one (7%) tested positive with QFT and 45 (19%) with TST. A positive QFT was associated with risk factors for M. tuberculosis infection: i.e., birth or upbringing in a TB-endemic area [risk ratio (RR) = 7.8, 95% CI 1.5–18.2, p < 0.001], previous TB treatment (RR 4.7, 95% CI 1.6–13.5, p = 0.005), and any latent TB infection risk factor (RR 4.7, 95% CI 2.1–11.0, p = 0.0002). Treatment with corticosteroids increased the risk for an inconclusive QFT result (RR 4.2, 95% CI 1.6–10.7, p = 0.04) and decreased the risk for a positive TST result (RR 0.4, 95% CI 0.1–1.0, p = 0.04). Agreement between the tests was low (kappa 0.2, 95% CI 0.02–0.3, p = 0.002).Conclusion.The study documented a high degree of discordant positive QFT and TST results. A positive QFT was more closely associated with risk factors for M. tuberculosis infection than the TST. The use of corticosteroids affected test outcome by increasing the risk for an inconclusive QFT result and decreasing the risk for a positive TST result.

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

Epidemiology and Infection ◽

10.1017/s0950268818002327 ◽

2018 ◽

Vol 146 (16) ◽

pp. 2102-2106 ◽

Cited By ~ 1

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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Latent Tuberculosis Infection

European Respiratory & Pulmonary Diseases ◽

10.17925/erpd.2018.4.1.21 ◽

2018 ◽

Vol 4 (1) ◽

pp. 21 ◽

Cited By ~ 2

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.

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In vitro Mycobacterial Growth Inhibition in South Korean Adults With Latent TB Infection

Frontiers in Immunology ◽

10.3389/fimmu.2019.00896 ◽

2019 ◽

Vol 10 ◽

Author(s):

Hyejon Lee ◽

Jungho Kim ◽

Young Ae Kang ◽

Deok Ryun Kim ◽

Bora Sim ◽

...

Keyword(s):

Growth Inhibition ◽

South Korean ◽

Korean Adults ◽

Latent Tb ◽

Latent Tb Infection ◽

Mycobacterial Growth

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Gluthathione S-transferase-resuscitation-promoting factor B recombinant protein of Mycobacterium tuberculosis induces the production of interferon-γ and interleukin-12 in mice splenocytes

Medical Journal of Indonesia ◽

10.13181/mji.v28i3.2444 ◽

2019 ◽

Vol 28 (3) ◽

pp. 234-40

Author(s):

Andriansjah Rukmana ◽

Burhanuddin Rasyid ◽

Fitriyah Sjatha

Keyword(s):

Mycobacterium Tuberculosis ◽

Recombinant Protein ◽

Polyacrylamide Gel Electrophoresis ◽

Sodium Dodecyl ◽

Interferon Γ ◽

Interleukin 12 ◽

Potential Candidate ◽

Factor B ◽

Latent Tb

BACKGROUND As the only TB vaccine available, Bacillus Calmette-Guérin shows variable efficacy in adults and does not provide protection against the resuscitation of latent TB infections. Resuscitation-promoting factor B (RpfB) is a protein produced by Mycobacterium tuberculosis during the resuscitation phase and is promising as a novel TB vaccine. This study was aimed to analyze the immunogenicity of the gluthathione S-transferase (GST)-RpfB recombinant protein on mice splenocytes in vitro. METHODS After induction with isopropyl β-D-1-thiogalactopyranoside, the protein was extracted by sonication followed by solubilization in 8 M urea buffer. Protein was then re-natured and purified with a GST chromatography column. The isolated protein was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot using anti-GST antibodies, and its concentration was determined using the Bradford method. Each group of splenocytes was treated with 25 μg/ ml of the recombinant protein (GST-RpfB), GST, and phytohemagglutinin. Antigen induction was repeated twice at 24 and 72 hours. The supernatant was collected at 96 hours and interferon gamma (IFNγ), interleukin (IL-12, IL-4, and IL-10) levels were measured with enzyme-linked immunosorbent assays. RESULTS GST-RpfB recombinant proteins were expressed in the form of inclusion bodies with a molecular weight of approximately 66 kDa. Based on the independent t-test, GST-RpfB stimulated IFNγ and IL-12 production but not IL-4 and IL-10. CONCLUSIONS The GST-RpfB protein has been immunogenically proven and is a potential candidate as a novel subunit TB vaccine.

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BCG Vaccine Protection against TB Infection among Children Older than 5 Years in Close Contact with an Infectious Adult TB Case

Journal of Clinical Medicine ◽

10.3390/jcm9103224 ◽

2020 ◽

Vol 9 (10) ◽

pp. 3224

Author(s):

Angeliki Syggelou ◽

Nikolaos Spyridis ◽

Kyriaki Benetatou ◽

Eleni Kourkouni ◽

Georgia Kourlaba ◽

...

Keyword(s):

Index Case ◽

Close Contact ◽

Cross Sectional Study ◽

Protective Role ◽

Bcg Vaccine ◽

Cross Sectional ◽

History Of ◽

Latent Tb ◽

Latent Tb Infection ◽

History Of Migration

The Bacille Calmette–Guérin (BCG) vaccine has been shown to provide considerable protection against miliary or meningeal tuberculosis (TB), but whether it prevents other forms of disease remains controversial. Recent evidence has shown that the BCG vaccine also provides protection against latent TB infection (LTBI). The aim of the current study was to examine whether BCG has a protective role against LTBI among children in close contact with an adult index case in a low TB endemicity setting with the use of the QuantiFERON-TB Gold In-Tube test (QFT-GIT). A cross-sectional study was conducted over a 10-year period among children referred to our outpatient TB clinic with a history of close contact with an adult with pulmonary TB. All subjects had a QFT-GIT performed. In total, 207 children > 5 to 16 years of age with known recent exposure were enrolled. BCG-vaccinated subjects had a 59% lower risk of presenting with LTBI after close contact with an adult index case compared with unvaccinated subjects (OR = 0.41, 95% CI: 0.23–0.73, p = 0.002). After adjustment for possible confounders, the protective effect of prior BCG immunization was estimated at 68% (OR = 0.32, 95% CI: 0.15–0.66, p = 0.002). Other risk factors for LTBI included a history of migration (OR = 2.27, 95% CI: 1.13–4.53, p = 0.021) and transmission of infection to other exposed child contacts (OR = 4.62, 95% CI: 2.27–9.39, p = 0.001). We were able to determine a strong protective role of BCG vaccination among children older than 5 years, immunized at school entry, who had close contact with an adult infectious TB case.

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First evaluation of QuantiFERON-TB Gold Plus performance in contact screening

European Respiratory Journal ◽

10.1183/13993003.00510-2016 ◽

2016 ◽

Vol 48 (5) ◽

pp. 1411-1419 ◽

Cited By ~ 68

Author(s):

Lucia Barcellini ◽

Emanuele Borroni ◽

James Brown ◽

Enrico Brunetti ◽

Daniela Campisi ◽

...

Keyword(s):

Index Case ◽

Interferon Γ ◽

Recent Infection ◽

Latently Infected ◽

Release Assay ◽

New Type ◽

Latent Tb ◽

The Difference ◽

Latent Tb Infection ◽

Surrogate Measures

Identifying latently infected individuals is crucial for the elimination of tuberculosis (TB). We evaluated for the first time the performance of a new type of interferon-γ release assay, QuantiFERON-TB Plus (QFT-Plus), which includes an additional antigen tube (TB2), stimulating both CD4+ and CD8+ T-cells in contacts of TB patients.Contacts were screened for latent TB infection by tuberculin skin test, QFT-Plus and QuantiFERON-TB Gold in Tube (QFT-GIT).In 119 TB contacts, the overall agreement between QFT-Plus and QFT-GIT was high, with a Cohen's κ of 0.8. Discordant results were found in 12 subjects with negative QFT-GIT and positive QFT-Plus results. In analyses of markers of TB exposure and test results, the average time spent with the index case was the strongest risk factor for positivity in each of these tests. The difference in interferon-γ production between the two antigen tubes (TB2−TB1) was used as an estimate of CD8+ stimulation provided by the TB2. TB2−TB1 values >0.6 IU·mL−1 were significantly associated with proximity to the index case and European origin.QFT-Plus has a stronger association with surrogate measures of TB exposure than QFT-GIT in adults screened for latent TB infection. Interferon-γ response in the new antigen tube used an indirect estimate of specific CD8+ response correlates with increased Mycobacterium tuberculosis exposure, suggesting a possible role in identifying individuals with recent infection.

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