The immune response to tuberculosis infection in the setting ofHelicobacter pyloriand helminth infections

SUMMARYWe screened 176 healthy, adult (aged 18–55 years) US refugees from tuberculosis (TB)-endemic countries to evaluate whether cytokine responses to latent TB infection (LTBI) are modified in the setting of concurrentH. pyloriand helminth infection. As measured by the Quantiferon-TB GOLD interferon-γ release assay, a total 38 (22%) subjects had LTBI, of which 28 (74%) also wereH. pyloriseropositive and/or helminth infected. Relative to ten subjects with LTBI only, 16 subjects with concurrentH. pyloriinfection had significantly elevated levels of IFN-γ, and nine subjects with bothH. pyloriand helminth infection had significantly elevated levels of IFN-γ, IL-2, IL-13, and IL-5.H. pyloriis associated with enhanced IFN-γ responses to TB, even in the setting of concurrent helminth infection. Efficacy of TB vaccines may vary with the co-existence of these three infections in the developing world.

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

Journal of Clinical Microbiology ◽

10.1128/jcm.01360-17 ◽

2017 ◽

Vol 56 (2) ◽

Cited By ~ 3

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.

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Development of an interferon-γ release assay (IGRA) for detection of Brucella abortus and clinical diagnosis of brucellosis

The Journal of Infection in Developing Countries ◽

10.3855/jidc.9265 ◽

2017 ◽

Vol 11 (11) ◽

pp. 847-853 ◽

Cited By ~ 1

Author(s):

Yu Feng ◽

Liangquan Zhu ◽

Xiaowei Peng ◽

Hui Jiang ◽

Ge Zhang ◽

...

Keyword(s):

Clinical Diagnosis ◽

Great Risk ◽

Brucella Abortus ◽

Interferon Γ ◽

Clinical Samples ◽

Somatic Antigen ◽

Release Assay ◽

Ifn Γ ◽

Negative Controls ◽

Somatic Antigens

Introduction: Brucellosis, caused by Brucella abortus (B. abortus), is an important zoonosis posing a great risk to both livestock and humans. Currently, most assays for clinical diagnosis of brucellosis have been developed based on serological principles; however, these assays have a number of limitations and disadvantages. Methodology: To address this concern, the aim of this study was to develop a gamma interferon (IFN-γ) release assay (IGRA) for the diagnosis of brucellosis. Towards this end, the stimulating effect induced by different somatic antigens of B. abortus on the secretion of IFN-γ was evaluated. Results: The best antigen candidate, B. abortus strain 2308, able to induce high levels of IFN-γ expression in peripheral blood (PB) cells from cattle, was used for the development of the IGRA. The optimal concentration for stimulation was determined as 1.0×107 CFU/mL. This study demonstrated that IFN-γ was detectable on day 5 post infection (p.i.) and peaked on day 14 p.i.. Finally, the IGRA developed was used for detection of B. abortus in clinical samples, and a higher level of IFN-γ was detected in Brucella-infected samples compared to vaccination samples and negative controls. Conclusions: The optimal somatic antigen for B. abortus was identified and used to establish a robust IGRA. The IGRA developed is suitable for clinical diagnosis of brucellosis, especially in the early stages of infection.

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

10.21203/rs.3.rs-96905/v1 ◽

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.

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High tuberculosis incidence among people living with diabetes in Indonesia

Transactions of the Royal Society of Tropical Medicine and Hygiene ◽

10.1093/trstmh/trz100 ◽

2019 ◽

Cited By ~ 1

Author(s):

Susan M McAllister ◽

Raspati C Koesoemadinata ◽

Prayudi Santoso ◽

Nanny N M Soetedjo ◽

Abdul Kamil ◽

...

Keyword(s):

Incidence Rate ◽

Preventive Therapy ◽

Incidence Rates ◽

Urban Setting ◽

Sputum Smear ◽

Interferon Gamma Release Assay ◽

Release Assay ◽

Chest X Ray ◽

Latent Tb ◽

Latent Tb Infection

Abstract Background Data regarding the incidence of tuberculosis (TB) among people living with diabetes (PLWD) in TB-endemic settings are scarce. We examined TB incidence among PLWD in Indonesia who had previously been screened for latent TB infection (LTBI) and TB disease. Methods PLWD (≥18 y of age) in an urban setting were examined a mean 3.4 y after they had been screened for active TB and LTBI. Data on subsequent TB diagnosis were collected by interview and with chest X-ray, sputum smear and Mycobacterium tuberculosis culture. TB incidence rates were stratified for baseline LTBI status, as determined by the QuantiFERON interferon-gamma release assay (IGRA). Results Of 590 PLWD, 101 had died and 163 could not be contacted or refused. Among the 326 who were re-examined, 6 (1.8%; 95% confidence interval [CI] 0.7 to 4.0) reported being diagnosed already and a further 5 were diagnosed with active TB (1.5%; 95% CI 0.50 to 3.5). The TB incidence rate was 9.85 (95% CI 4.03 to 15.68) per 1000 person-years. TB incidence was higher among PLWD with baseline LTBI (17.13; 95% CI 5.25 to 29.00/1000 person-years) compared with those without LTBI (4.79; 95% CI −0.63 to 10.21), with an incidence rate ratio of 3.57 (95% CI 0.86 to 20.92; p=0.054). Conclusions PLWD with LTBI in Indonesia and similar settings are likely to benefit from TB preventive therapy.

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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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Rate of Latent Tuberculosis Infection Detected by Occupational Health Screening of Nurses New to a London Teaching Hospital

Infection Control and Hospital Epidemiology ◽

10.1086/597546 ◽

2009 ◽

Vol 30 (6) ◽

pp. 581-584 ◽

Cited By ~ 13

Author(s):

Priya Khanna ◽

Vladyslav Nikolayevskyy ◽

Fiona Warburton ◽

Elek Dobson ◽

Francis Drobniewski

Keyword(s):

Tuberculin Skin Test ◽

Skin Test ◽

Latent Tuberculosis Infection ◽

Latent Tuberculosis ◽

Interferon Γ ◽

Tuberculosis Infection ◽

Release Assay ◽

Ifn Γ ◽

Positive Results ◽

Tuberculosis Prevalence

The prevalence of latent tuberculosis infection in a cohort of nurses new to a London hospital was 7.6% (13 of 171), using an interferon-γ(IFN-γ) release assay, and 16.2% (24 of 148), using the tuberculin skin test. On multivariate analysis, birth in a country with tuberculosis prevalence of more than 40 cases per 100,000 population was associated with positive results of both the IFN-γ release assay and the tuberculin skin test.

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Tuberculosis care among refugees arriving in Europe: a ERS/WHO Europe Region survey of current practices

European Respiratory Journal ◽

10.1183/13993003.00840-2016 ◽

2016 ◽

Vol 48 (3) ◽

pp. 808-817 ◽

Cited By ~ 55

Author(s):

Masoud Dara ◽

Ivan Solovic ◽

Giovanni Sotgiu ◽

Lia D'Ambrosio ◽

Rosella Centis ◽

...

Keyword(s):

Management Practices ◽

Interferon Γ ◽

Control Measures ◽

European Countries ◽

Ltbi Treatment ◽

Ltbi Screening ◽

Infection Control Measures ◽

Latent Tb ◽

Latent Tb Infection ◽

Tuberculosis Care

No evidence exists on tuberculosis (TB) and latent TB infection (LTBI) management policies among refugees in European countries.A questionnaire investigating screening and management practices among refugees was sent to 38 national TB programme representatives of low and intermediate TB incidence European countries/territories of the WHO European Region.Out of 36 responding countries, 31 (86.1%) reported screening for active TB, 19 for LTBI, and eight (22.2%) reporting outcomes of LTBI treatment. Screening for TB is based on algorithms including different combinations of symptom-based questionnaires, bacteriology and chest radiography and LTBI screening on different combinations of tuberculin skin test and interferon-γ release assays. In 22 (61.1%) countries, TB and LTBI screening are performed in refugee centres. In 22 (61.1%) countries, TB services are organised in collaboration with the private sector. 27 (75%) countries answered that screening for TB is performed as per national and international guidelines, while 19 (52.7%) gave the same answer with regards to LTBI screening. Infection control measures are inadequate in several of the countries surveyed.There is need for improved coordination of TB screening in Europe to implement the End TB Strategy and achieve TB elimination.

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Modulation of Innate Cytokine Responses by Products of Helicobacter pylori

Infection and Immunity ◽

10.1128/iai.68.11.6265-6272.2000 ◽

2000 ◽

Vol 68 (11) ◽

pp. 6265-6272 ◽

Cited By ~ 59

Author(s):

Frank Meyer ◽

Keith T. Wilson ◽

Stephen P. James

Keyword(s):

Immune Response ◽

Helicobacter Pylori ◽

Lymphocyte Proliferation ◽

Mononuclear Cells ◽

Cytokine Production ◽

Peripheral Blood Mononuclear ◽

Cytokine Responses ◽

Ifn Γ ◽

H Pylori ◽

Th1 Polarization

ABSTRACT The gastric inflammatory and immune response in Helicobacter pylori infection may be due to the effect of different H. pylori products on innate immune mechanisms. The aim of this study was to determine whether bacterial components could modulate cytokine production in vitro and thus contribute to Th1 polarization of the gastric immune response observed in vivo. The effect of H. pylori recombinant urease, bacterial lysate, intact bacteria, and bacterial DNA on proliferation and cytokine production by peripheral blood mononuclear cells (PBMCs) from H. pylori-negative donors was examined as a model for innate cytokine responses. Each of the different H. pylori preparations induced gamma interferon (IFN-γ) and interleukin-12p40 (IL-12p40), but not IL-2 or IL-5, production, and all but H. pylori DNA stimulated release of IL-10. Addition of anti-IL-12 antibody to cultures partially inhibited IFN-γ production. In addition, each bacterial product inhibited mitogen-stimulated IL-2 production by PBMCs and Jurkat T cells. The inhibitory effect of bacterial products on IL-2 production correlated with inhibition of mitogen-stimulated lymphocyte proliferation, although urease inhibited IL-2 production without inhibiting proliferation, suggesting that inhibition of IL-2 production alone is not sufficient to inhibit lymphocyte proliferation. The results of these studies demonstrate that Th1 polarization of the gastric immune response may be due in part to the direct effects of multiple different H. pylori components that enhance IFN-γ and IL-12 production while inhibiting both IL-2 production and cell proliferation that may be necessary for Th2 responses.

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