Screening for tuberculosis infections (TBI) using the tuberculin skin test or interferon-gamma release assays (IGRA) is crucial in controlling the global TB burden. This study evaluates the performance of a new IGRA for the detection of T-cell responses against Mycobacterium tuberculosis. Blood samples from 34 adults with tuberculosis disease (TB) and from 30 children with TB, TBI or without TB were analyzed using the prototype Quan-T-Cell TB (EUROIMMUN). The pediatric samples were additionally measured using the established QuantiFERON-TB Gold Plus assay (Qiagen). Clinical performance and inter-assay concordance were analyzed. The prototype Quan-T-Cell TB yielded positivity rates of 88.2% and 100% in adults with TB and children with TBI, respectively, at a specificity of 93.8%. Comparison between the two IGRAs showed positive, negative and overall agreement rates of 100%, 93.8% and 96.3%, respectively, with a kappa score of 0.924 indicating almost perfect agreement. Our study shows promising results of the new prototype Quan-T-Cell TB, as reflected by high concordance with the final diagnosis in adults and children and performance comparable to that of the QuantiFERON IGRA. In individual cases, the data suggest that the prototype Quan-T-Cell TB may be even more consistent with TBI-related clinical findings. Unlike the QuantiFERON assay, the Quan-T-Cell TB has a predefined borderline range, which is advantageous as it may help to differentiate non-specific variation near the cut-off, and fewer sample tubes are required per analysis. The new Quan-T-Cell TB may therefore be a good alternative to the established QuantiFERON IGRA for TBI screening. Further assay optimization is underway, including evaluation studies based on larger patient and control cohorts.

• Klíčová slova
• Mycobacterium tuberculosis, IFN-γ, IGRA, Interferon-gamma release assay, T-cell response, Tuberculosis disease, Tuberculosis infection,
• MeSH
• dítě MeSH
• dospělí MeSH
• interferon gama MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• Mycobacterium tuberculosis * imunologie   MeSH
• předškolní dítě MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• T-lymfocyty * imunologie   MeSH
• test pomocí interferonu gama * metody   MeSH
• tuberkulóza * diagnóza   imunologie   mikrobiologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• Názvy látek
• interferon gama MeSH

INTRODUCTION: HIV replication leads to a change in lymphocyte phenotypes that impairs immune protection against opportunistic infections. We examined current HIV replication as an independent risk factor for tuberculosis (TB). METHODS: We included people living with HIV from 25 European cohorts 1983-2015. Individuals <16 years or with previous TB were excluded. Person-time was calculated from enrolment (baseline) to the date of TB diagnosis or last follow-up information. We used adjusted Poisson regression and general additive regression models. RESULTS: We included 272,548 people with a median follow-up of 5.9 years (interquartile range [IQR] 2.3-10.9). At baseline, the median CD4 cell count was 355 cells/μL (IQR 193-540) and the median HIV-RNA level 22,000 copies/mL (IQR 1,300-103,000). During 1,923,441 person-years of follow-up, 5,956 (2.2%) people developed TB. Overall, TB incidence was 3.1 per 1,000 person-years (95% confidence interval [CI] 3.02-3.18) and was four times higher in patients with HIV-RNA levels of 10,000 compared with levels <400 copies/mL in any CD4 stratum. CD4 and HIV-RNA time-updated analyses showed that the association between HIV-RNA and TB incidence was independent of CD4. The TB incidence rate ratio for people born in TB-endemic countries compared with those born in Europe was 1.8 (95% CI 1.5-2.2). CONCLUSIONS: Our results indicate that ongoing HIV replication (suboptimal HIV control) is an important risk factor for TB, independent of CD4 count. Those at highest risk of TB are people from TB-endemic countries. Close monitoring and TB preventive therapy for people with suboptimal HIV control is important.

• MeSH
• dospělí MeSH
• HIV infekce * epidemiologie   imunologie   komplikace   MeSH
• incidence MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• počet CD4 lymfocytů MeSH
• replikace viru MeSH
• rizikové faktory MeSH
• RNA virová MeSH
• tuberkulóza * epidemiologie   imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH
• Názvy látek
• RNA virová MeSH

Mycobacterium tuberculosis (Mtb) remains a major threat worldwide, although only a fraction of infected individuals develops tuberculosis (TB). TB susceptibility is shaped by multiple genetic factors, and we performed comparative immunological analysis of two mouse strains to uncover relevant mechanisms underlying susceptibility and resistance. C57BL/6 mice are relatively TB-resistant, whereas I/St mice are prone to develop severe TB, partly due to the MHC-II allelic variant that shapes suboptimal CD4+ T cell receptor repertoire. We investigated the repertoires of lung-infiltrating helper T cells and B cells at the progressed stage in both strains. We found that lung CD4+ T cell repertoires of infected C57BL/6 but not I/St mice contained convergent TCR clusters with functionally confirmed Mtb specificity. Transcriptomic analysis revealed a more prominent Th1 signature in C57BL/6, and expression of pro-inflammatory IL-16 in I/St lung-infiltrating helper T cells. The two strains also showed distinct Th2 signatures. Furthermore, the humoral response of I/St mice was delayed, less focused, and dominated by IgG/IgM isotypes, whereas C57BL/6 mice generated more Mtb antigen-focused IgA response. We conclude that the inability of I/St mice to produce a timely and efficient anti-Mtb adaptive immune responses arises from a suboptimal helper T cell landscape that also impacts the humoral response, leading to diffuse inflammation and severe disease.

• Klíčová slova
• B cells, CD4 + T cells, TB-susceptible mouse strain, TCR repertoire, immunoglobulins, transcriptomic signatures, tuberculosis,
• MeSH
• adaptivní imunita * genetika   MeSH
• B-lymfocyty imunologie   MeSH
• genetická predispozice k nemoci * MeSH
• modely nemocí na zvířatech MeSH
• Mycobacterium tuberculosis * imunologie   MeSH
• myši inbrední C57BL * MeSH
• myši MeSH
• plíce imunologie   patologie   MeSH
• receptory antigenů T-buněk genetika   imunologie   MeSH
• tuberkulóza * imunologie   genetika   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• receptory antigenů T-buněk MeSH

Mycobacterium tuberculosis is the main etiological agent of tuberculosis. The Bacillus Calmette-Guérin (BCG) microbes that are primarily used as a vaccine against tuberculosis also constitute the dominant infection model for studying the interaction of mycobacteria with the host cell types. The majority of interaction experiments have been conducted using macrophages and monocytes as prototype phagocyte cell types. Here, we report that M. bovis BCG infects mouse primary B cells as well as human B cell line. The complement receptors, along with B cell receptors, are engaged in the process of bacterial entry into the host B cells. Once inside the B cells, the intracellular trafficking of BCG follows the complete endocytic pathway of the ingested particles, which is in contrast to the events taking place during ingestion of BCG by macrophages. In vivo infection of mice with M. bovis BCG activated peritoneal as well as splenic B cells to produce proinflammatory cytokines. This paper further supports the evidence that B cells are involved in a host's early interactions with intracellular bacterial pathogens and participate in the induction of innate defense responses.

• Klíčová slova
• Activating markers, B cells, Cytokines, M. bovis BCG, Receptors,
• MeSH
• B-lymfocyty * imunologie   mikrobiologie   MeSH
• BCG vakcína MeSH
• cytokiny metabolismus   MeSH
• lidé MeSH
• Mycobacterium bovis imunologie   MeSH
• myši MeSH
• primární buněčná kultura MeSH
• přirozená imunita MeSH
• tuberkulóza imunologie   mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• BCG vakcína MeSH
• cytokiny MeSH

Mycobacterium avium subsp. avium (MAA) and Mycobacterium avium subsp. hominissuis (MAH) are the most common mycobacterial species isolated from granulomatous lesions in swine in countries with controlled bovine tuberculosis. This study is focused on the immunological aspect of MAA and MAH infection in pigs. We detected induction of humoral and cell-mediated immunity in experimentally infected pigs. Specific antibodies were analyzed in serum by ELISA and the IFN-γ release assay was used for evaluation of cell-mediated immunity. While MAA induced a significant increase of both types of immune responses, MAH-infected pigs had an unvarying level of specific antibodies and showed low cell-mediated immunity with high individual variability. The subsequent in vitro experiment confirmed the lower immunogenicity of the MAH strain in comparison to MAA. MAH-infected porcine monocyte-derived macrophages showed a weaker induction of pro-inflammatory mediators in comparison to MAA, which included mRNA for IL-1β, TNF-α, IL-23p19, IL-18 and chemokines CCL-3, CCL-5, CXCL-8 and CXCL-10. Additionally, qualitative proteomic analysis revealed 28 proteins exclusively in MAA and 7 proteins unique to MAH. In conclusion, closely related M. avium subspecies MAA and MAH showed different capacities to stimulate the porcine immune system. From a diagnostic point of view, the IFN-γ release assay showed higher sensitivity than the detection of specific antibodies by ELISA and seems to be an effective tool for discrimination of MAA-infected pigs. In the case of MAH infection, the IFN-γ release assay could fail because of the low immunogenic capacity of the MAH strain.

• MeSH
• buněčná imunita MeSH
• interleukin-18 genetika   imunologie   metabolismus   MeSH
• interleukin-23 - podjednotka p19 genetika   imunologie   MeSH
• makrofágy imunologie   MeSH
• mediátory zánětu imunologie   MeSH
• Mycobacterium avium klasifikace   izolace a purifikace   fyziologie   MeSH
• nemoci prasat genetika   imunologie   mikrobiologie   MeSH
• prasata MeSH
• TNF-alfa genetika   imunologie   MeSH
• tuberkulóza imunologie   veterinární   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• interleukin-18 MeSH
• interleukin-23 - podjednotka p19 MeSH
• mediátory zánětu MeSH
• TNF-alfa MeSH

The zoonotic characteristic of Mycobacterium avium subsp. avium (MAA) represents a veterinary and economic problem in infected pigs. In this study, we analysed cell-mediated immunity six months after experimental infection by measuring interferon-γ (IFN-γ) production and by performing lymphocyte transformation tests after in vitro re-stimulation with the MAA-derived antigen. At the same time, IFN-γ-producing cells were characterised by flow cytometry. In MAA-infected animals, the production of IFN-γ increased in response to the MAA antigen in the blood, spleen and mesenteric lymph nodes. Similarly, a positive antigen-driven response was detected by the proliferation assay. In contrast, IFN-γ production and proliferation was undetectable after stimulation with the MAA antigen in uninfected control animals. These results indicate that both methods can be used for the identification of individual MAA-infected pigs. Using flow cytometry, we found that double-positive CD4(+)CD8(+) lymphocytes were the major T lymphocyte subset producing IFN-γ after in vitro re-stimulation.

• MeSH
• aktivace lymfocytů imunologie   MeSH
• buněčná imunita imunologie   MeSH
• interferon gama fyziologie   MeSH
• Mycobacterium avium imunologie   MeSH
• nemoci prasat imunologie   mikrobiologie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí veterinární   MeSH
• prasata imunologie   MeSH
• průtoková cytometrie veterinární   MeSH
• T-lymfocyty - podskupiny imunologie   MeSH
• tuberkulóza imunologie   mikrobiologie   veterinární   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• interferon gama MeSH

BACKGROUND: Tuberculin skin test was evaluated in patients with bacteriologically verified tuberculosis notified in the Czech Republic during 2003 and 2004. METHODS AND RESULTS: Out of 1172 patients with bacteriologically verified tuberculosis altogether 28.8% were tuberculin-negative. The average value of tuberculin reaction in this cohort was 11.6 mm. Among 30-year-old patients with bacteriologically verified tuberculosis the number of tuberculin-negative individuals was statistically lower (14 %) in comparison with 70-year-old and older patients, where the prevalence of tuberculin-negative individuals was 42 %. Higher rate of tuberculin-negative individuals with bacteriologically verified tuberculosis was found among patients who were diagnosed with liver disease (42 % of tuberculin-negative) or malignant tumor (47 % of tuberculin-negative). Presented results show that in circumstances of the Czech Republic the tuberculin skin test can be used to follow up the spreading of tuberculosis infection in younger age groups without accompanying serious disease only. CONCLUSIONS: The improvement of the diagnostics of latent tuberculosis infection can bring the routine introduction of new tests, e.g. Quantiferon-TB Gold or other methods.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• Mycobacterium tuberculosis izolace a purifikace   MeSH
• senioři MeSH
• tuberkulinový test * MeSH
• tuberkulóza komplikace   diagnóza   imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

• MeSH
• alveolární makrofágy imunologie   mikrobiologie   fyziologie   MeSH
• apoptóza MeSH
• fyziologická adaptace MeSH
• lidé MeSH
• Mycobacterium tuberculosis genetika   imunologie   patogenita   fyziologie   MeSH
• počet mikrobiálních kolonií MeSH
• přenašečství MeSH
• regulace genové exprese u bakterií MeSH
• tuberkulóza imunologie   mikrobiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• úvodníky MeSH

We assessed the direct and indirect economic costs and benefits of the current policy of revaccinating tuberculin-negative schoolchildren in the Czech Republic. The analysis is conducted from the perspective of the payer for health care. In considering whether revaccination should be discontinued, we consistently made assumptions which tend to favor revaccination. The direct costs of revaccination are estimated at Czech Koruna (KCR) 15.0 million (US$0.46 million) annually. The direct benefits are the treatment costs saved for future cases averted by revaccination. These range from KCR 0.5 million (US$0.015 million, ambulatory care, excluding transmission benefits) to KCR 13.7 million (US$0.4 million, hospitalization, including transmission benefits). Costs exceed benefits even if children are revaccinated without prior tuberculin testing. The major indirect cost is the loss of work output attributable to tuberculosis morbidity. Counting the averted loss in output as a benefit does not change the results qualitatively, although there is a 50% chance that the benefits will be greater than costs if treatment continues to be hospital-based. Thus, the costs of revaccination in the Czech Republic are found to exceed benefits over most, plausible variations in parameter values. The cost-benefit ratio is especially large if patients are given ambulatory treatment, as recommended by the World Health Organization.

• MeSH
• ambulantní péče ekonomika   MeSH
• analýza nákladů a výnosů MeSH
• BCG vakcína ekonomika   imunologie   MeSH
• časové faktory MeSH
• dítě MeSH
• hospitalizace ekonomika   MeSH
• incidence MeSH
• kohortové studie MeSH
• lidé MeSH
• multivariační analýza MeSH
• naděje dožití MeSH
• náklady na zdravotní péči MeSH
• očkovací schéma MeSH
• osobní újma zaviněná nemocí MeSH
• Světová zdravotnická organizace MeSH
• tuberkulinový test ekonomika   MeSH
• tuberkulóza ekonomika   epidemiologie   imunologie   prevence a kontrola   MeSH
• vakcinace ekonomika   MeSH
• výsledek terapie MeSH
• zdravotní pojištění ekonomika   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• BCG vakcína MeSH

The routine diagnosis of tuberculosis and other mycobacterial diseases based on organism identification was completed during a period of one year in 730 patients, with serological IgG, IgM and IgA determination of antibodies against antigen 60 from M. bovis , strain BCG. The analysis was performed on 10 groups of patients consisting of 1) inflammatory diseases of the respiratory tract, 2) pericarditis, myocarditis, lymphadenitis and CNS diseases, 3) chronic non-inflammatory diseases of kidneys, liver and pancreas, 4) non-inflammatory diseases of the heart, sarcoidosis and pneumoconiosis, 5) tumor, 6) healthy people with TB contact, 7) inactive TB, 8) culture-positive pulmonary and extra-pulmonary TB, 9) culture-negative TB and extra-pulmonary TB, and 10) potentially pathogenic mycobacteria. The specificity of the test (100% negative cases in Group 6, composed of healthy people) is estimated at about 90%, in accordance with determinations made in other laboratories. In non-tuberculous patients, the specificity varied according to the analysed groups. Group 1 was largely unspecific for IgM (76% positives) but the specificity was acceptable for IgG (6.2% positives ) and IgA (7.4% positives). Group 2 was similar to Group 1. Group 3 was associated with positive IgA titers. Group 4 was only exceptiony seropositive and Group 5 was positive mainly for IgA (11. 4%) associated with lower respiratory tract ailments. This unspecific seropositivity was attributed to inapparent infections by PPM whose colonisation was favored by the particular disease of the patients. The sensitivity of serological measurements applied to the diagnosis of TB patients and PPM patients was similar, regardless if the disease was pulmonary or non-pulmonary, regardless if cultures were positive or not and, in our hands, was low (positivity for IgA about 30 %, for IgM about 10% and for IgG about 30%). This poor sensitivity observed with people presenting for treatment is attributed to an immune depression occuring mainly in elderly patients. The remarkable sensitivity of the serological instrument applied to culture-negative pulmonary and non-pulmonary TB cases as well as PPM cases makes the test a good adjuvant in cases of suspicion of TB. The assessment of the serological status of people under chemotherapy is worth the analysis, a high IgG level being associated with immunocompetence while the absence of IgG antibodies and/or the presence of IgA antibodies denotes an immunologically misdirected response potentially opening the way to chronic infections.

• MeSH
• biologické markery MeSH
• diferenciální diagnóza MeSH
• ELISA metody   MeSH
• imunoglobulin A krev   MeSH
• imunoglobulin G krev   MeSH
• imunoglobulin M krev   MeSH
• lidé MeSH
• mykobakteriózy diagnóza   imunologie   terapie   MeSH
• plicní tuberkulóza diagnóza   imunologie   terapie   MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• reagenční diagnostické soupravy MeSH
• reprodukovatelnost výsledků MeSH
• senzitivita a specificita MeSH
• sérologické testy metody   MeSH
• tuberkulóza diagnóza   imunologie   terapie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• imunoglobulin A MeSH
• imunoglobulin G MeSH
• imunoglobulin M MeSH
• reagenční diagnostické soupravy MeSH