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1.
Int J Infect Dis ; 91: 177-181, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31877486

RESUMO

OBJECTIVES: High accuracy diagnostic screening tests for tuberculosis (TB) are required to improve the diagnosis of both active TB and latent Mycobacterium tuberculosis (MTB) infection (LTBI). The novel IGRA LIOFeron®TB/LTBI assay was tested and its accuracy was compared to the QuantiFERON®-TB Gold Plus assay. METHODS: A total of 389 subjects were enrolled in two cohorts and classified as healthy, active TB or LTBI persons. The blood of all the patients was tested with LIOFeron®TB/LTBI assay, containing MTB alanine dehydrogenase, able to differentiate active TB from LTBI diagnosis. The results obtained with both IGRAs, performed on the same 250 samples, were finally compared. RESULTS: The two assays demonstrated an excellent concordance of their results with patients' diagnosis of MTB infection. ROC analysis for QuantiFERON®-TB Gold Plus showed sensitivity and specificity respectively of 98% and 97% in diagnosing active TB patients and 85% and 94% in diagnosing LTBI subjects. LIOFeron®TB/LTBI assay showed sensitivity and specificity respectively of 90% and 98% in diagnosing active TB patients and 94% and 97% in diagnosing LTBI subjects. CONCLUSIONS: The two IGRAs displayed the same high accuracy in diagnosing MTB infection/TB disease, and LIOFeron®TB/LTBI assay demonstrated higher sensitivity than QuantiFERON®-TB Gold Plus test in LTBI detection.


Assuntos
Testes Diagnósticos de Rotina/métodos , Tuberculose Latente/diagnóstico , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Tuberculose Latente/imunologia , Tuberculose Latente/microbiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Mycobacterium tuberculosis/fisiologia , Curva ROC , Sensibilidade e Especificidade , Linfócitos T/imunologia
3.
BMC Immunol ; 20(1): 35, 2019 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-31601184

RESUMO

BACKGROUND: HIV-infected individuals with latent TB infection are at increased risk of developing active TB. HAART greatly reduces the incidence rate of TB in HIV-infected patients and reconstitutes Mycobacterium tuberculosis (M. tuberculosis)-specific immune response in the first 12 months of therapy. The durability of the anti-mycobacterial immune restoration after a year of HAART however remains less investigated. METHOD: A cross-sectional study was conducted to evaluate M. tuberculosis-specific functional immune responses in HIV/latent TB co-infected patients who were on HAART for at least 1.5 up to 9 years as compared to HAART-naïve patients. Three-hundred sixteen HIV-infected patients without active TB were screened by tuberculin skin testing for M. tuberculosis infection and peripheral blood mononuclear cells (PBMCs) were isolated from 61 HIV/latent TB co-infected patients (30 HAART-naïve and 31 HAART-treated). IFN-γ and IL-2 ELISPOT as well as CFSE cell proliferation assays were performed after stimulation with M. tuberculosis antigens PPD and ESAT-6. RESULT: The median frequency of PPD and ESAT-6 specific IFN-γ secreting cells was significantly higher in the HAART-treated patients as compared to HAART-naïve patients, p = 0.0021 and p = 0.0081 respectively. However, there was no significant difference in the median frequency of IL-2 secreting cells responding to PPD (p = 0.5981) and ESAT-6 (p = 0.3943) antigens between HAART-naïve and-treated groups. Both IFN-γ and IL-2 responses were independent of CD4+ T cell count regardless of the HAART status. Notably, the frequency of PPD and ESAT-6 specific IL-2 secreting cells was positively associated with CD4+ T cell proliferation while inversely correlated with duration of HAART, raising the possibility that M. tuberculosis-specific IL-2 response that promote the antigen-specific CD4+ T cell proliferation diminish with time on antiretroviral therapy in HIV/latent TB co-infected patients. CONCLUSION: This study shows an increased M. tuberculosis-specific IFN-γ, but not IL-2, response in HIV/latent TB co-infected patients with long-term HAART, consistent with only partial immune restoration. Future studies should, therefore, be done to prospectively define the rate and extent to which functional immune responses to M. tuberculosis are restored after long-term HAART.


Assuntos
Antígenos de Bactérias/imunologia , Coinfecção , Infecções por HIV/imunologia , Infecções por HIV/metabolismo , Interferon gama/metabolismo , Interleucina-2/metabolismo , Tuberculose Latente/imunologia , Tuberculose Latente/metabolismo , Adulto , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Estudos Transversais , Citocinas/metabolismo , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Tuberculose Latente/microbiologia , Masculino
4.
PLoS Pathog ; 15(9): e1008050, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31557262

RESUMO

Crimean-Congo hemorrhagic fever (CCHF) is the most medically important tick-borne viral disease of humans and tuberculosis is the leading cause of death worldwide by a bacterial pathogen. These two diseases overlap geographically, however, concurrent infection of CCHF virus (CCHFV) with mycobacterial infection has not been assessed nor has the ability of virus to persist and cause long-term sequela in a primate model. In this study, we compared the disease progression of two diverse strains of CCHFV in the recently described cynomolgus macaque model. All animals demonstrated signs of clinical illness, viremia, significant changes in clinical chemistry and hematology values, and serum cytokine profiles consistent with CCHF in humans. The European and Asian CCHFV strains caused very similar disease profiles in monkeys, which demonstrates that medical countermeasures can be evaluated in this animal model against multiple CCHFV strains. We identified evidence of CCHFV persistence in the testes of three male monkeys that survived infection. Furthermore, the histopathology unexpectedly revealed that six additional animals had evidence of a latent mycobacterial infection with granulomatous lesions. Interestingly, CCHFV persisted within the granulomas of two animals. This study is the first to demonstrate the persistence of CCHFV in the testes and within the granulomas of non-human primates with concurrent latent tuberculosis. Our results have important public health implications in overlapping endemic regions for these emerging pathogens.


Assuntos
Febre Hemorrágica da Crimeia/complicações , Tuberculose Latente/complicações , Testículo/patologia , Animais , Anticorpos Antivirais/sangue , Doenças Transmissíveis Emergentes/complicações , Doenças Transmissíveis Emergentes/patologia , Doenças Transmissíveis Emergentes/virologia , Citocinas/sangue , Modelos Animais de Doenças , Progressão da Doença , Granuloma/microbiologia , Granuloma/patologia , Granuloma/virologia , Vírus da Febre Hemorrágica da Crimeia-Congo/genética , Vírus da Febre Hemorrágica da Crimeia-Congo/imunologia , Vírus da Febre Hemorrágica da Crimeia-Congo/patogenicidade , Febre Hemorrágica da Crimeia/patologia , Febre Hemorrágica da Crimeia/virologia , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Tuberculose Latente/microbiologia , Tuberculose Latente/patologia , Macaca fascicularis , Masculino , Testículo/microbiologia , Testículo/virologia
5.
Indian J Med Res ; 149(4): 517-527, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31411176

RESUMO

Background & objectives: To support recent political commitments to end tuberculosis (TB) in the World Health Organization South-East Asian Region (SEAR), there is a need to understand by what measures, and with what investment, these goals could be reached. These questions were addressed by using mathematical models of TB transmission by doing the analysis on a country-by-country basis in SEAR. Methods: A dynamical model of TB transmission was developed, in consultation with each of the 11 countries in the SEAR. Three intervention scenarios were examined: (i) strengthening basic TB services (including private sector engagement), (ii) accelerating TB case-finding and notification, and (iii) deployment of a prognostic biomarker test by 2025, to guide mass preventive therapy of latent TB infection. Each scenario was built on the preceding ones, in successive combination. Results: Comprehensive improvements in basic TB services by 2020, in combination with accelerated case-finding to increase TB detection by at least two-fold by 2020, could lead to a reduction in TB incidence rates in SEAR by 67.3 per cent [95% credible intervals (CrI) 65.3-69.8] and TB deaths by 80.9 per cent (95% CrI 77.9-84.7) in 2035, relative to 2015. These interventions alone would require an additional investment of at least US$ 25 billion. However, their combined effect is insufficient to reach the end TB targets of 80 per cent by 2030 and 90 per cent by 2035. Model projections show how additionally, deployment of a biomarker test by 2025 could end TB in the region by 2035. Targeting specific risk groups, such as slum dwellers, could mitigate the coverage needed in the general population, to end TB in the Region. Interpretation & conclusions: While the scale-up of currently available strategies may play an important role in averting TB cases and deaths in the Region, there will ultimately be a need for novel, mass preventive measures, to meet the end TB goals. Achieving these impacts will require a substantial escalation in funding for TB control in the Region.


Assuntos
Tuberculose Latente/epidemiologia , Modelos Teóricos , Tuberculose/epidemiologia , Humanos , Índia/epidemiologia , Tuberculose Latente/microbiologia , Tuberculose Latente/prevenção & controle , Tuberculose/microbiologia , Tuberculose/prevenção & controle , Organização Mundial da Saúde
6.
Tuberculosis (Edinb) ; 117: 7-17, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31378272

RESUMO

The currently available methods are unable to directly detect dormant forms of Mycobacterium tuberculosis (Mtb) in vivo. The persistence of Mtb in the host body is detectable only in an indirect manner via the immunological response to Mtb-specific antigens. It is commonly recognized that the pathogen prevalently exists in the human body in a latent stage. Additional research efforts focusing on the Mtb dormancy are needed for development of sterilizing drugs, which are necessary to control LTBI and stop TB epidemic. To this end, the in vitro models of Mtb dormancy may be useful. This review briefly describes the phenomenon of Mtb dormancy and its role in the context of tuberculosis as a persistent bacterial infection; then the article characterizes in details the in vitro methods used for modeling the Mtb dormancy in bacterial cultures.


Assuntos
Tuberculose Latente/microbiologia , Modelos Biológicos , Mycobacterium tuberculosis/isolamento & purificação , Antibióticos Antituberculose/farmacologia , Fenômenos Fisiológicos Bacterianos , Proliferação de Células/genética , Proliferação de Células/fisiologia , Tolerância a Medicamentos , Regulação da Expressão Gênica/fisiologia , Humanos , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/fisiologia
7.
Nat Commun ; 10(1): 3035, 2019 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-31292443

RESUMO

Mycobacterium tuberculosis readily adapts to survive a wide range of assaults by modifying its physiology and establishing a latent tuberculosis (TB) infection. Here we report a sophisticated mode of regulation by a tRNA-cleaving toxin that enlists highly selective ribosome stalling to recalibrate the transcriptome and remodel the proteome. This toxin, MazF-mt9, exclusively inactivates one isoacceptor tRNA, tRNALys43-UUU, through cleavage at a single site within its anticodon (UU↓U). Because wobble rules preclude compensation for loss of tRNALys43-UUU by the second M. tuberculosis lysine tRNA, tRNALys19-CUU, ribosome stalling occurs at in-frame cognate AAA Lys codons. Consequently, the transcripts harboring these stalled ribosomes are selectively cleaved by specific RNases, leading to their preferential deletion. This surgically altered transcriptome generates concomitant changes to the proteome, skewing synthesis of newly synthesized proteins away from those rich in AAA Lys codons toward those harboring few or no AAA codons. This toxin-mediated proteome reprogramming may work in tandem with other pathways to facilitate M. tuberculosis stress survival.


Assuntos
Proteínas de Bactérias/metabolismo , Endorribonucleases/metabolismo , Mycobacterium tuberculosis/fisiologia , Proteoma/genética , Ribossomos/metabolismo , Sistemas Toxina-Antitoxina/fisiologia , Toxinas Bacterianas/metabolismo , Tuberculose Latente/microbiologia , Mycobacterium tuberculosis/patogenicidade , Proteoma/metabolismo , RNA Bacteriano/metabolismo , RNA de Transferência/metabolismo , Transcriptoma/genética
8.
Clin Lab ; 65(7)2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31307161

RESUMO

BACKGROUND: It is important to distinguish those with active Mycobacterium tuberculosis infection (ATB) from latent tuberculosis infection (LTBI) for monitoring and treating the disease. Monocytes play an important role and may undergo morphological changes against active TB infection. The aim of this study is to investigate the clinical usefulness of the monocyte morphometric parameters and monocyte chemoattractant protein-1 (MCP-1) to distinguish active tuberculosis (ATB) from latent tuberculosis infection (LTBI) and healthy controls (HC). METHODS: Peripheral blood was collected from 97 ATB patients, 113 LTBI patients, and 101 healthy controls. The monocyte morphometric parameters were obtained using a UniCel Coulter DxH800 system. MCP-1 level was determined by enzyme-linked immunosorbent assay method. Cutoff values were established based on receiver operator characteristic (ROC) curve analysis. RESULTS: Mean monocyte volume with its standard deviation, mean monocyte conductivity, and MCP-1 were significantly increased in ATB compared with LTBI and HC. ROC curve analyses showed that simultaneous measurements of mean monocyte volume with its standard deviation, mean monocyte conductivity and MCP-1 achieved good sensitivity and specificity (93.8% and 93.1%), which may be clinically useful. CONCLUSIONS: The findings using monocyte morphometric parameters and MCP-1 to distinguish ATB from LTBI with high sensitivity and specificity may be a potential parameter for clinical.


Assuntos
Quimiocina CCL2/sangue , Tuberculose Latente/diagnóstico , Monócitos/metabolismo , Adulto , Idoso , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Tuberculose Latente/sangue , Tuberculose Latente/microbiologia , Masculino , Pessoa de Meia-Idade , Monócitos/citologia , Mycobacterium tuberculosis/fisiologia , Curva ROC , Estudos Retrospectivos , Tuberculose/sangue , Tuberculose/diagnóstico , Tuberculose/microbiologia
9.
PLoS One ; 14(7): e0218800, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31361755

RESUMO

BACKGROUND: Tuberculosis (TB) and HIV co-infection challenges treatment and worsens the outcome of TB treatment. This study aimed to assess the outcome of TB treatment and factors facilitating treatment success among people living with HIV/AIDS in Fako Division of the South West Region of Cameroon. METHODS: A hospital-based retrospective cohort study was conducted by manually reviewing medical records of HIV/TB co-infected patients from January 2010 to September 2017. A structured data collection form was used to review the medical records of HIV patients co-infected with TB aged 10 years and older. Patients with incomplete files were dropped from the study. Treatment success was defined as the sum of patients who were declared cured and those who had completed treatment, as per the World Health Organization's recommendations. Data were analyzed using Statistical Package for Social Sciences version 21. Bivariate and multivariate logistic regression model was carried out to identify factors facilitating successful TB treatment outcome. Significance was obtained through adjusted odds ratio with its 95% confidence interval and a p<0.05. RESULTS: A total of 2,986 files were reviewed but 2,928 (98.1%) were retained. Out of the 2,928 medical files of adult TB patients reviewed, 1,041 (35.6%, [95% CI 33.8%-37.3%]) were HIV/TB co-infected. The 1,041 co-infected patients had a mean age of 37.07 (SD of10.02) years and 56.3% were females. The treatment outcome of TB patients were 795(76.4%) cured, 23(2.2%) treatment completed, 99(9.5%) were lost to follow-up, 16 (1.5%) failed, 72(6.9%) died and 36(3.5%) transferred out. A successful treatment outcome was achieved in 818(78.6%,[95% CI: 76.0%-81.0%]) patients. Being a female [COR 1.61, 95% CI: 1.19-2.17, p = 0.002], receiving TB treatment in 2014 [COR 2.00, 95% CI: 1.11-3.60, p = 0.021] and 2015 [COR 2.50, 95% CI: 1.39-4.50, p = 0.002], having relapsed TB infection [COR 0.46, 95% CI: 0.23-0.93, p = 0.031], receiving ART [COR 1.95, 95% CI: 1.28-2.97, p = 0.002] and Cotrimoxazole [COR 2.03, 95% CI: 1.12-3.66, p = 0.019] were factors significantly associated with successful treatment. After adjusting for confounders, successful treatment outcome were associated with being a female [AOR 1.6; 95% CI: 1.21-2.22, p = 0.001], diagnosis of TB in 2014 [AOR 1.90; 95% CI: 1.04-3.45, p = 0.036] and 2015 [AOR 2.43; 95% CI: 1.33-4.43, p = 0.004]. CONCLUSION: There is a high TB treatment success rate among HIV/TB co-infected patients in our setting, although below the target set by the WHO. Specific interventions aimed at enhancing patient outcomes are recommended.


Assuntos
Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Tuberculose Latente/tratamento farmacológico , Tuberculose/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida/epidemiologia , Síndrome de Imunodeficiência Adquirida/microbiologia , Síndrome de Imunodeficiência Adquirida/virologia , Adulto , Idoso , Antituberculosos/uso terapêutico , Camarões/epidemiologia , Coinfecção , Gerenciamento Clínico , Feminino , HIV/patogenicidade , Infecções por HIV/epidemiologia , Infecções por HIV/microbiologia , Infecções por HIV/virologia , Humanos , Tuberculose Latente/epidemiologia , Tuberculose Latente/microbiologia , Tuberculose Latente/virologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/patogenicidade , Fatores de Risco , Falha de Tratamento , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Tuberculose/epidemiologia , Tuberculose/microbiologia , Tuberculose/virologia
10.
World J Gastroenterol ; 25(26): 3291-3298, 2019 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-31341356

RESUMO

Solid organ transplantation (SOT) is the best treatment option for end-stage organ disease. Newer immunosuppressive agents have reduced the incidence of graft rejection but have increased the risk of infection, particularly due to the reactivation of latent infections due to opportunistic agents such as Mycobacterium tuberculosis. Active tuberculosis (TB) after SOT is a significant cause of morbidity and mortality. Most cases of posttransplant TB are secondary to reactivation of latent tuberculosis infection (LTBI) due to the effects of long-term immunosuppressive therapy. Risk minimization strategies have been developed to diagnose LTBI and initiate treatment prior to transplantation. Isoniazid with vitamin B6 supplementation is the treatment of choice. However, liver transplantation (LT) candidates and recipients have an increased risk of isoniazid-induced liver toxicity, leading to lower treatment completion rates than in other SOT populations. Fluoroquinolones (FQs) exhibit good in vitro antimycobacterial activity and a lower risk of drug-induced liver injury than isoniazid. In the present review, we highlight the disease burden posed by posttransplant TB and summarize the emerging clinical evidence supporting the use of FQs for the treatment of LTBI in LT recipients and candidates.


Assuntos
Antituberculosos/administração & dosagem , Fluoroquinolonas/administração & dosagem , Tuberculose Latente/tratamento farmacológico , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Aloenxertos , Antituberculosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Terminal/cirurgia , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/efeitos adversos , Incidência , Isoniazida/efeitos adversos , Tuberculose Latente/imunologia , Tuberculose Latente/microbiologia , Fígado , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/isolamento & purificação , Complicações Pós-Operatórias/imunologia , Complicações Pós-Operatórias/microbiologia , Fatores de Risco , Resultado do Tratamento
11.
Mol Immunol ; 112: 103-114, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31082644

RESUMO

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (M.tb). New cases are now mainly caused by the progression of latent tuberculosis infection (LTBI). Thus, methods to diagnose and treat LTBI are urgently needed to prevent the development of active TB in infected individuals and the subsequent spread of the disease. In this study, a systems biology approach was utilized to obtain numerous microarray data sets for mRNAs and microRNAs (miRNAs) expressed in the peripheral blood mononuclear cells (PBMCs) of TB patients and individuals with LTBI. Within these data sets, we identified the differentially expressed mRNAs and miRNAs and further investigated which differentially expressed genes and miRNAs were uniquely expressed during LTBI. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was employed to analyze the functional annotations and pathway classifications of the identified genes. To further understand the unique miRNA-gene regulatory network of LTBI, we constructed a protein-protein interaction (PPI) network for the targeted genes. The PPI network included 39 genes that were differentially and uniquely expressed in PBMCs of individuals with LTBI, and KEGG pathway enrichment analysis showed that these genes were predominantly involved in the PI3K-Akt signaling pathway, which plays an important role in chronic inflammation. DIANA TOOLs-mirPath analysis revealed that the identified miRNAs in the miRNA-gene regulatory network for LTBI were mainly associated with the Hippo signaling pathway, which functions in the development of inflammation. Quantitative real-time PCR verified the up expression of hsa-miR-212-3p and its predicted target gene -MAPK1 which had low expression and was a major component of the PPI network, and MAPK1 expression was correlated with the clinicopathological characteristics of LTBI by receiver operating characteristic (ROC) curve analysis. Therefore, MAPK1 has potential to be a new investigable marker during LTBI, which merits our further study and solution. The unique aberrant miRNA-gene regulatory network and the related PPI network identified in this study provide insight into the molecular mechanisms of the immune response to LTBI, and thus, may aid in the development of a novel treatment strategy.


Assuntos
Redes Reguladoras de Genes/genética , Tuberculose Latente/genética , MicroRNAs/genética , Biomarcadores/metabolismo , Células Cultivadas , Perfilação da Expressão Gênica/métodos , Humanos , Inflamação/genética , Inflamação/microbiologia , Proteínas de Ligação a TGF-beta Latente/genética , Tuberculose Latente/microbiologia , Leucócitos Mononucleares/microbiologia , Proteína Quinase 1 Ativada por Mitógeno/genética , Mycobacterium tuberculosis/patogenicidade , RNA Mensageiro/genética , Transdução de Sinais/genética , Transcriptoma/genética
12.
Tuberculosis (Edinb) ; 116S: S11-S18, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31072689

RESUMO

TB is a catastrophic infectious disease, affecting roughly one third of the world's population. Mucosal-associated invariant T (MAIT) cells are innate-like T cells that recognize vitamin B metabolites produced by bacteria, possess effector memory phenotype, and express tissue-homing markers driving migration to sites of infection. Previous research in both Mtb and HIV infections has shown that MAIT cells are depleted in the human periphery, possibly migrating to the tissue sites of infection. We investigated this hypothesis using rhesus macaques (RMs) with active TB, latent TB (LTBI), and SIV-coinfection to explore the effects of different disease states on the MAIT cell populations in vivo. Early in infection, we observed that MAIT cells increased in the blood and bronchoalveolar lavage fluid (BAL) of all infected RMs, irrespective of clinical outcome. However, the frequency of MAIT cells rapidly normalized such that they had returned to baseline levels prior to endpoint. Furthermore, following infection, the chemokines expressed on MAIT cells reflected a strong shift towards a Th1 phenotype from a shared Th1/Th17 phenotype. In conclusion, MAIT cells with enhanced Th1 functions migrating to the site of Mtb-infection. The anti-mycobacterial effector functions of MAIT cells, particularly during the early stages of Mtb infection, had been of interest in promoting protective long-term TB immunity. Our research shows, however, that they have relatively short-acting responses in the host.


Assuntos
Movimento Celular , Proliferação de Células , Imunidade nas Mucosas , Tuberculose Latente/microbiologia , Pulmão/microbiologia , Ativação Linfocitária , Células T Invariáveis Associadas à Mucosa/microbiologia , Mycobacterium tuberculosis/patogenicidade , Tuberculose Pulmonar/microbiologia , Animais , Coinfecção , Modelos Animais de Doenças , Interações Hospedeiro-Patógeno , Tuberculose Latente/imunologia , Pulmão/imunologia , Macaca mulatta , Células T Invariáveis Associadas à Mucosa/imunologia , Células T Invariáveis Associadas à Mucosa/virologia , Mycobacterium tuberculosis/imunologia , Fenótipo , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus 40 dos Símios/imunologia , Vírus 40 dos Símios/patogenicidade , Células Th1/imunologia , Células Th1/microbiologia , Células Th2/imunologia , Células Th2/microbiologia , Fatores de Tempo , Tuberculose Pulmonar/imunologia
13.
Eur Respir Rev ; 28(152)2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31142548

RESUMO

AIMS: What is the evidence base for the effectiveness of interventions to reduce tuberculosis (TB) incidence in countries which have low TB incidence? METHODS: We conducted a systematic review of interventions for TB control and prevention relevant to low TB incidence settings (<10 cases per 100 000 population). Our analysis was stratified according to "direct" or "indirect" effects on TB incidence. Review quality was assessed using AMSTAR2 criteria. We summarised the strength of review level evidence for interventions as "sufficient", "tentative", "insufficient" or "no" using a framework based on the consistency of evidence within and between reviews. RESULTS: We found sufficient review level evidence for direct effects on TB incidence/case prevention of vaccination and treatment of latent TB infection. We also found sufficient evidence of beneficial indirect effects attributable to drug susceptibility testing and adverse indirect effects (measured as sub-optimal treatment outcomes) in relation to use of standardised first-line drug regimens for isoniazid-resistant TB and intermittent dosing regimens. We found insufficient review level evidence for direct or indirect effects of interventions in other areas, including screening, adherence, multidrug-resistant TB, and healthcare-associated infection. DISCUSSION: Our review has shown a need for stronger evidence to support expert opinion and country experience when formulating TB control policy.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose Latente/tratamento farmacológico , Comportamento de Redução do Risco , Vacinas contra a Tuberculose/uso terapêutico , Tuberculose/prevenção & controle , Medicina Baseada em Evidências , Humanos , Incidência , Tuberculose Latente/epidemiologia , Tuberculose Latente/microbiologia , Tuberculose Latente/transmissão , Programas de Rastreamento , Aceitação pelo Paciente de Cuidados de Saúde , Valor Preditivo dos Testes , Fatores de Risco , Resultado do Tratamento , Tuberculose/epidemiologia , Tuberculose/microbiologia , Tuberculose/transmissão
14.
Zhonghua Jie He He Hu Xi Za Zhi ; 42(4): 262-267, 2019 Apr 12.
Artigo em Chinês | MEDLINE | ID: mdl-30955283

RESUMO

Objective: The aim of this study was to determine the performance of the ratio of tuberculosis-specific antigen (TBAg) to phytohemagglutinin (PHA) (TBAg/PHA ratio) in T-SPOT assay in the diagnosis of active tuberculosis (ATB). Methods: Between January 2014 and January 2017, 378 Mycobacterium tuberculosis (MTB) culture positive patients (268 cases of pulmonary tuberculosis, 110 extra-pulmonary tuberculosis) and 824 healthy individuals were recruited from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. T-SPOT assay was performed and TBAg/PHA ratio was calculated in all the participants. To validate the study, another group of 223 MTB culture positive TB patients with positive T-SPOT results were recruited from Guangzhou Chest Hospital between January 2017 and December 2017. This was a retrospective case-control study and differences between groups were analyzed using the Mann-Whitney U-test. Results: Of the 378 culture positive ATB patients, 344 patients had positive T-SPOT results. Of the 824 healthy individuals, 204 individuals had positive T-SPOT results. Using healthy individuals as the control group, the sensitivity and specificity of T-SPOT assay in the diagnosis of ATB were 91.0% (344/378) and 75.2% (620/824). Directly using T-SPOT results had a limited accuracy in distinguishing ATB from latent tuberculosis infection (LTBI). The area under the receiver operating characteristic (ROC) curve was between 0.7 and 0.8. However, a further calculation of the TBAg/PHA ratio showed a better performance than TBAg in distinguishing these two conditions, and the area under the ROC curve was 0.881 (95% CI: 0.853-0.909). If using the threshold value of 0.234, the sensitivity and specificity of the TBAg/PHA ratio in distinguishing ATB from LTBI were 69.5% (239/344) and 94.12% (192/204). The validation data showed that the performance of the TBAg/PHA ratio in distinguishing ATB from LTBI was also satisfactory, and the area under the ROC curve was 0.901 (95% CI: 0.872-0.931). Furthermore, the TBAg/PHA ratio had an important role in the diagnosis of extra-pulmonary tuberculosis. If using the threshold value of 0.234, the sensitivity and specificity of the TBAg/PHA ratio in the diagnosis of extra-pulmonary tuberculosis were 79.2% (76/96) and 94.1% (192/204). The area under the ROC curve was 0.932 (95% CI: 0.897-0.967). Conclusions: The TBAg/PHA ratio in T-SPOT assay was better than directly using T-SPOT results in distinguishing ATB from LTBI. This ratio also showed a potential use in the diagnosis of extra-pulmonary tuberculosis.


Assuntos
Antígenos de Bactérias/análise , Tuberculose Latente/diagnóstico , Mycobacterium tuberculosis/isolamento & purificação , Mycobacterium/imunologia , Fito-Hemaglutininas/análise , Tuberculose/diagnóstico , Estudos de Casos e Controles , Feminino , Humanos , Interferon gama , Tuberculose Latente/microbiologia , Masculino , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Tuberculose/microbiologia
15.
Emerg Infect Dis ; 25(4): 661-671, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30882302

RESUMO

Prospective migrants to countries where the incidence of tuberculosis (TB) is low (low-incidence countries) receive TB screening; however, screening for latent TB infection (LTBI) before immigration is rare. We evaluated the cost-effectiveness of mandated and sponsored preimmigration LTBI screening for migrants to low-incidence countries. We used discrete event simulation to model preimmigration LTBI screening coupled with postarrival follow-up and treatment for those who test positive. Preimmigration interferon-gamma release assay screening and postarrival rifampin treatment was preferred in deterministic analysis. We calculated cost per quality-adjusted life-year gained for migrants from countries with different TB incidences. Our analysis provides evidence of the cost-effectiveness of preimmigration LTBI screening for migrants to low-incidence countries. Coupled with research on sustainability, acceptability, and program implementation, these results can inform policy decisions.


Assuntos
Emigração e Imigração , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Programas de Rastreamento , Análise Custo-Benefício , Humanos , Incidência , Testes de Liberação de Interferon-gama , Tuberculose Latente/microbiologia , Programas de Rastreamento/economia , Programas de Rastreamento/métodos , Anos de Vida Ajustados por Qualidade de Vida , Sensibilidade e Especificidade , Migrantes , Teste Tuberculínico
16.
Int J Infect Dis ; 80S: S58-S61, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30822547

RESUMO

Latent tuberculosis infection (LTBI) is established in over 90% of persons infected with Mycobacterium tuberculosis (Mtb), from whom new active TB cases will arise. Understanding the spatio-temporal dynamics of host immune responses in LTBI granulomas is essential to designing effective post-exposure therapies that inhibit progression to TB. Information arising from cancer studies and other modalities - where local chronic inflammation leads to immunopathology - can help provide insights into the biological pathways at play in LTBI granulomas. Translational studies using patient material as well as LTBI+ donor-derived tissue samples are instrumental in understanding the various components of granuloma dynamics, immunological landscapes therein and how this could help to identify therapeutic targets. Deep sequencing technologies may aid to decipher the genetic changes in lung granuloma and blood samples from LTBI+ individuals associated with progression to active TB disease. This may lead to advancement of development of targeted Host-Directed Therapies (HDTs) and their evaluation as adjunct TB therapies for improving treatment outcomes for LTBI and pulmonary TB.


Assuntos
Granuloma/microbiologia , Tuberculose Latente/microbiologia , Tuberculose Latente/patologia , Mycobacterium tuberculosis , Tuberculose Pulmonar/microbiologia , Granuloma/patologia , Humanos , Tuberculose Pulmonar/patologia
17.
J Infect Chemother ; 25(7): 537-542, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30905632

RESUMO

Renal transplant recipients are at increased risk of reactivating latent tuberculosis infection (LTBI) and developing active tuberculosis. QuantiFERON®-TB Gold Plus (QFT-Plus) has two TB-specific antigens tubes (TB1 and TB2). TB1 elicits CD4 T-cell response, and TB2 elicits both CD4 and CD8 T-cells responses, with expected increased sensitivity. The aim of this study was to estimate the prevalence of LTBI in renal transplant recipients in Japan. We conducted a cross-sectional study by using two interferon-γ release assays (IGRAs), QFT-Plus and T-SPOT®.TB (TSPOT). One hundred thirty-five recipients were prospectively enrolled. The median age was 49 years (range: 20 to 79). The positivity rates of QFT-Plus and TSPOT were 5.9% (95%CI 3.0-11.3) and 3.7% (95%CI 1.6-8.4), respectively, with no significant difference. The concordance rate was 95.5% (κ coefficient, 0.76). Age of 60 years and higher was related to the higher positivity rate in both QFT-Plus and TSPOT. The positivity rates of TB1 and TB2 were 5.1% (95%CI 2.5-10.2) and 5.9% (95%CI 3.0-11.2), respectively, with no significant difference. The concordance rate was 99.3% (κ coefficient, 0.93). TB2 did not show a higher positivity rate compared with TB1. The estimated prevalence of LTBI by using the both IGRAs was 3.7-5.9% in renal transplant recipients. These results were equivalent to the IGRAs positivity rate in the general Japanese population, even under the condition of immunosuppressive therapy. In consideration of the higher risk of developing active TB from LTBI, we can use both IGRAs as acceptable tools for LTBI diagnosis in renal transplant recipients.


Assuntos
Testes de Liberação de Interferon-gama/estatística & dados numéricos , Transplante de Rim/efeitos adversos , Tuberculose Latente/epidemiologia , Transplantados/estatística & dados numéricos , Adulto , Idoso , Antígenos de Bactérias/imunologia , Estudos Transversais , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Japão/epidemiologia , Tuberculose Latente/diagnóstico , Tuberculose Latente/microbiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/isolamento & purificação , Prevalência , Adulto Jovem
18.
Microbiol Immunol ; 63(3-4): 130-138, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30851131

RESUMO

One-third of the world's humans has latent tuberculosis infection (LTBI), representing a large pool of potentially active TB. Recent LTBI carries a higher risk of disease progression than remote LTBI. Recent studies suggest important roles of antibodies in TB pathology, prompting us to investigate serum antibody profiles in a cohort with LTBI. In this single-center prospective observational study, we analyzed IgG-antibody concentrations against five major Mycobacterium tuberculosis (Mtb) antigens (including 6 kDa early secretory antigenic target (ESAT6), CFP10, and antigen 85A, which are expressed mainly in the growth phase; and mycobacterial DNA-binding protein 1 (MDP1) and alpha-crystallin like protein (Acr), which are expressed in the dormant phases) in individuals with recent (n=13) or remote (n=12) LTBI, no Mtb infection (n=19), or active TB (n=15). Antibody titers against ESAT6 and MDP1 were significantly higher in individuals with recent LTBI than in those with no Mtb infection or remote LTBI. All pairwise antibody titers against these five major antigens were significantly correlated throughout the stages of Mtb infection. Five individuals with recent LTBI had significantly higher antibody titers against ESAT6 (P = 0.03), Ag85A (P = 0.048), Acr (P = 0.057), and MDP1 (P = 0.0001) than in individuals with remote LTBI; they were also outside the normal range (+2 SDs). One of these individuals was diagnosed with active pulmonary TB at 18-month follow-up examination. These findings indicated that concentrations of antibodies against both multiplying and dormant Mtb are higher in recent LTBI and that individuals with markedly higher antibody titers may be appropriate candidates for prophylactic therapy.


Assuntos
Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/imunologia , Tuberculose Latente/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/diagnóstico , Aciltransferases/imunologia , Adulto , Anticorpos Antibacterianos/imunologia , Proteínas de Bactérias/imunologia , Proteínas de Ligação a DNA/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Tuberculose Latente/microbiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tuberculose Pulmonar/microbiologia , alfa-Cristalinas/imunologia
19.
Int J Tuberc Lung Dis ; 23(2): 212-218, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30808454

RESUMO

BACKGROUND: Latent tuberculous infection (LTBI) can function as a 'reservoir' for Mycobacterium tuberculosis. Given that T-regulatory cell (Treg) numbers are augmented in LTBI, it is likely that Toll-like receptors (TLRs) may have a role in Treg function. Elucidation of the immune mechanisms associated with tuberculosis (TB) development may help to control M. tuberculosis spread.OBJECTIVE: To investigate the role of TLR2, TLR4 and TLR9 in hindered in vitro microbicidal activity and increase Treg number during LTBI. DESIGN: Whole blood cell cultures from individuals with LTBI and healthy controls (HCs) infected with live M. tuberculosis H37Rv strain were used to investigate the effect of TLR2, TLR4 and TLR9 on Treg number, microbicidal activity, and interferon-gamma and interleukin (IL)10 production. RESULTS: LTBI subjects were characterised by increased Treg number and impaired microbicidal activity when compared with HCs. Specific blockade of TLR4 and TLR9 led to a significant reduction in Treg number, a decrease in IL-10 production and substantial upregulation of microbicidal activity. CONCLUSION: M. tuberculosis infection may activate TLR4 and TLR9 pathways to suppress M. tuberculosis-specific immune responses. Here, we show that activation of TLR4 and TLR9 hinder microbicidal activity during LTBI.


Assuntos
Tuberculose Latente/imunologia , Mycobacterium tuberculosis/imunologia , Receptor 4 Toll-Like/imunologia , Receptor Toll-Like 9/imunologia , Adulto , Feminino , Humanos , Técnicas In Vitro , Interferon gama/imunologia , Interleucina-10/imunologia , Tuberculose Latente/microbiologia , Masculino , Pessoa de Meia-Idade , Linfócitos T Reguladores/imunologia , Receptor 2 Toll-Like/imunologia , Adulto Jovem
20.
Eur J Clin Invest ; 49(5): e13068, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30620398

RESUMO

BACKGROUND: The dysbiosis of gut microbiome and interaction with host immunity after Mycobacterium tuberculosis (MTB) infection are under investigation. We had found fatigue symptom concurrent with dysbiosis by decreasing the ratio of Firmicutes to Bacteroidetes (F/B ratio) in active tuberculosis (TB). The study aims to assess the inflammatory biomarkers and their interaction with gut microbiome in active TB and latent TB infection before starting anti-TB regimens. MATERIALS AND METHOD: Interleukin-1 beta (IL-1B), IL-4, IL-6, IL-10, CD3+, CD4+, CD8+ T cells and interferon-gamma (IFN-γ) releasing assay (IGRA) were measured in 25 active TB patients, 32 LTBI subjects and 23 healthy controls (HC). Gut microbiome profiles were obtained using 16S rRNA MiSeq sequencing method. RESULTS: The leucocytosis (7032 ± 387 cell/cum, P < 0.05), increase in IL-6 (229.7 ± 104 µg/dL, P < 0.05), and decrease in IL-4 (0.27 µg/dL ± 0.1, P < 0.05) were presented in active TB. The proportion of polymorphic neutrophil (PMN) in peripheral blood was positively related to the relative abundance of Bacteroidetes in LTBI and active TB (R2  = 0.23, P < 0.05). The F/B ratio was positively related to the detectable IL-1B in TB (R2  = 0.97, P < 0.01) and to the IL-4 in LTBI (R2  = 0.27, P < 0.05). In LTBI, the relative abundances of Coriobacteriaceae were positively related to the secretion of IFN-gamma against MTB-antigens more likely associated with of CD4+ T cell (R2  = 0.42, P < 0.05). CONCLUSION: In active TB, dysbiosis with higher relative abundances of Bacteroidetes in stool and low F/B ratio was related to systemic proinflammation. In LTBI, dose-response relationship between peripheral PMN and relative abundances of Bacteroidetes was remained but not leads to systemic inflammation.


Assuntos
Microbioma Gastrointestinal/fisiologia , Inflamação/microbiologia , Tuberculose Latente/microbiologia , Tuberculose Pulmonar/microbiologia , Actinobacteria/imunologia , Actinobacteria/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteroidaceae/imunologia , Bacteroidaceae/fisiologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/microbiologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/microbiologia , Estudos de Casos e Controles , Citocinas/metabolismo , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/imunologia , Humanos , Inflamação/imunologia , Tuberculose Latente/imunologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tuberculose Pulmonar/imunologia , Adulto Jovem
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