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1.
Genes (Basel) ; 14(1)2023 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-36672948

RESUMO

BACKGROUND: Tuberculosis (TB) manifests itself primarily in the lungs as pulmonary disease (PTB) and sometimes disseminates to other organs to cause extra-pulmonary TB, such as lymph node TB (LNTB). This study aimed to investigate the role of host genetic polymorphism in immunity related genes to find a genetic basis for such differences. METHODS: Sixty-three, Single nucleotide polymorphisms (SNPs) in twenty-three, TB-immunity related genes including eleven innate immunity (SLCA11, VDR, TLR2, TLR4, TLR8, IRGM, P2RX7, LTA4H, SP110, DCSIGN and NOS2A) and twelve cytokine (TNFA, IFNG, IL2, Il12, IL18, IL1B, IL10, IL6, IL4, rs1794068, IL8 and TNFB) genes were investigated to find genetic associations in both PTB and LNTB as compared to healthy community controls. The serum cytokine levels were correlated for association with the genotypes. RESULTS: PTB and LNTB showed differential genetic associations. The genetic variants in the cytokine genes (IFNG, IL12, IL4, TNFB and IL1RA and TLR2, 4 associated with PTB susceptibility and cytokine levels but not LNTB (p < 0.05). Similarly, genetic variants in LTA4H, P2RX7, DCSIGN and SP110 showed susceptibility to LNTB and not PTB. Pathway analysis showed abundance of cytokine related variants for PTB and apoptosis related variants for LNTB. CONCLUSIONS: PTB and LNTB outcomes of TB infection have a genetic component and should be considered for any future functional studies or studies on susceptibility to pulmonary and extra-pulmonary TB.


Assuntos
Tuberculose dos Linfonodos , Tuberculose Pulmonar , Humanos , Predisposição Genética para Doença , Tuberculose Pulmonar/genética , Receptor 2 Toll-Like/genética , Interleucina-4/genética , Citocinas/genética , Polimorfismo de Nucleotídeo Único , Interleucina-12/genética , Pulmão
2.
Braz. j. biol ; 83: e244311, 2023. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1285616

RESUMO

Abstract Tuberculosis is a communicable disease with high morbidity and mortality rates in developing countries. The study's primary objective is to compare conventional methods such as acid-fast bacillus (AFB) culture and microscopy with rapid diagnostic methods. The secondary objective is to compare histopathological and microbiological findings in suspected patients with tubercular lymphadenitis. A total of 111 samples (August 2018 to September 2019) of lymph nodes were processed for AFB microscopy, AFB cultures, drug-susceptibility testing (DST), histopathology, and Xpert Mycobacterium Tuberculosis (MTB)/resistance to Rifampin (RIF) assays. Out of 111 lymph node samples, 6 (5.4%) were positive for AFB smear microscopy, 84 (75.6%) were positive for AFB culture, 80 (70.7%) were positive on Gene Xpert, and 102 (91.8%) were indicative of tuberculosis for histopathology studies. Mycobacteria growth indicator tube (MGIT) culture positivity was 84 (75.6%) higher than solid Lowenstein-Jensen (LJ) culture 74 (66.6%). Positive cultures underwent phenotypic DST. Two cases were Multidrug-resistant (MDR) on DST, while three cases were Rifampicin resistant on Gene Xpert. The sensitivity of Genexpert was (62%) against the conventional AFB culture method. The poor performance of conventional lymphadenitis diagnostic methods requires early and accurate diagnostic methodology. Xpert MTB/RIF test can help in the treatment of multidrug-resistant TB cases. Nonetheless, rapid and conventional methods should be used for complete isolation of Mycobacterium tuberculosis.


Resumo A tuberculose é uma doença transmissível com altas taxas de morbimortalidade nos países em desenvolvimento. O objetivo principal do estudo é comparar métodos convencionais, como cultura de bacilo álcool-ácido resistente (BAAR) e microscopia, com métodos de diagnóstico rápido. O objetivo secundário é comparar os achados histopatológicos e microbiológicos em pacientes com suspeita de linfadenite tubercular. Um total de 111 amostras (agosto de 2018 a setembro de 2019) de gânglios linfáticos foi processado ​​para microscopia de AFB, culturas de AFB, teste de susceptibilidade a drogas (DST), histopatologia e Xpert Mycobacterium tuberculosis (MTB)/ensaios de resistência à rifampicina (RIF). Das 111 amostras de linfonodos, 6 (5,4%) foram positivas para baciloscopia de AFB, 84 (75,6%) foram positivas para cultura de AFB, 80 (70,7%) foram positivas para o GeneXpert e 102 (91,8%) foram indicativas de tuberculose para estudos histopatológicos. A positividade da cultura do tubo indicador de crescimento de micobactérias (MGIT) foi 84 (75,6%), maior que a cultura sólida de Lowenstein-Jensen (LJ), 74 (66,6%). As culturas positivas foram submetidas a DST fenotípico. Dois casos eram multirresistentes (MDR) ao DST, enquanto três casos eram resistentes à rifampicina no GeneXpert. A sensibilidade do GeneXpert foi 62% contra o método convencional de cultura AFB. O fraco desempenho dos métodos convencionais de diagnóstico de linfadenite requer metodologia de diagnóstico precoce e precisa. O teste Xpert MTB/RIF pode ajudar no tratamento de casos de tuberculose multirresistente. No entanto, métodos rápidos e convencionais devem ser usados ​​para o isolamento completo do Mycobacterium tuberculosis.


Assuntos
Humanos , Tuberculose dos Linfonodos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos , Mycobacterium tuberculosis , Rifampina/uso terapêutico , Rifampina/farmacologia
3.
BMC Infect Dis ; 22(1): 899, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36457066

RESUMO

BACKGROUND: Active tuberculosis (ATB) originates from primary Mycobacterium tuberculosis (MTB) infection or reactivation of latent tuberculosis. Besides bacteriological examination, MTB-reactive immunocytes detection can be an alternative testing for discrimination of active tuberculosis. The purpose of this study is to investigate the accuracy of peripheral blood CD27-CD38+IFN-γ+CD4+T cells in ATB diagnosis. METHODS: This prospective diagnostic accuracy study was conducted at Shanghai Pulmonary Hospital between January 2019 and December 2021. Patients with ATB, non-tuberculosis mycobacterium infection (NTM), latent tuberculosis infection (LTBI), other respiratory diseases (OD), and healthy individuals (HC) were enrolled. The accuracy of CD27-CD38+IFN-γ+CD4+/CD4+ and other phenotypic markers for ATB diagnosis was assessed. RESULTS: A total of 376 patients (237 ATB, 38 LTBI, 8 NTM, 50 OD, and 43 HC) were enrolled. The ratios of CD4+IFN-γ+CD27- and CD4+IFN-γ+CD27-CD38+ profiles in CD4+IFN-γ+ cells and the ratios of CD4+IFN-γ+CD38+, CD4+IFN-γ+CD27-, and CD4+IFN-γ+CD38+CD27- profiles in CD4+ cells in the ATB group were significantly higher than in the other groups. The area under the curve (AUC) of CD27-CD38+IFN-γ+CD4+/CD4+ for the diagnosis of ATB was the highest, with a value of 0.890. With the optimal cutoff value of 1.34 × 10-4, the sensitivity and specificity of CD27-CD38+IFN-γ+CD4+/CD4+ for ATB diagnosis was 0.869 and 0.849, respectively. CONCLUSION: CD27-CD38+IFN-γ+CD4+/CD4+ might be a potential biomarker for active tuberculosis diagnosis.


Assuntos
Tuberculose Latente , Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Humanos , Estudos Prospectivos , China , Interferon gama , Micobactérias não Tuberculosas , Linfócitos T CD4-Positivos
4.
Indian J Tuberc ; 69(4): 389-403, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36460368

RESUMO

Tuberculosis, caused by Mycobacterium tuberculosis, is a disease long dealt with, but still remains the second leading cause of death world-wide. The current anti-tubercular chemotherapy primarily targets the microbial pathogenesis, which however, is failing due to the development of drug resistance. Moreover, with fewer new drugs reaching the market, there is a need to focus on alternate treatment approaches that could be used as stand-alone or adjunct therapy and the existing drugs, referred to as Track II chemotherapy. This article is an attempt to review the changing global patterns of tuberculosis and its treatment. Further, newer drug delivery approaches like multi-particulate drug carriers which increase the therapeutic efficacy and bring down the systemic toxicity associated with drugs have also been discussed. There is also a need to use interventions which can be used as Track II therapy. Host-directed therapeutics (HDT) is an emerging area concept in which host cell functions and hence the response to pathogens can be modulated, which can help manage TB. HDT decreases damage induced due to inflammation and necrosis in the lungs and other parts of the body due to the disease. Various immuno-modulatory pathways have been discussed in this review which could be explored further to treat TB. An in-depth understanding of multi-particulate drug carriers and HDT could help in dealing with tuberculosis; however, there is still a long way to go.


Assuntos
Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Humanos , Terapia Combinada , Portadores de Fármacos , Poeira
5.
Indian J Tuberc ; 69(4): 482-495, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36460380

RESUMO

BACKGROUND: Tuberculosis (TB) is a global infectious disease, but there is no ideal vaccine against TB except the Bacille Calmette-Guérin (BCG) vaccine. METHODS: Herein, 25 candidate peptides were predicted from four antigens of Mycobacterium tuberculosis based on their high-affinity binding capacity for the human leukocyte antigen (HLA) DRB1∗0101. Three T-helper 1 (Th1) immunodominant peptides (Ag85B12-26, CFP2112-26, and PPE18149-163) were identified by ELISPOT assays in the humanized C57BL/6 mice. They resulted in a novel Th1 peptide-based vaccine ACP named by the first letter of the three peptides. In addition, the protective efficacy was evaluated in humanized or wild-type C57BL/6 mice and the humoral and cellular immune responses were confirmed in vitro. RESULTS: Compared with the PBS group, the ACP vaccinated mice showed slight decreases in colony-forming units (CFUs) and pathological lesions. However, when using it as a booster, the ACP vaccine did not significantly enhance the protective efficacy of BCG in humanized or wild-type mice. Interestingly, we found that ACP vaccination significantly increased the number of interferon-γ positive (IFN-γ+) T lymphocytes and the levels of IFN-γ cytokines as well as antibodies. Furthermore, the IL-2 level was significantly higher in humanized mice prime-boosted with BCG and ACP. CONCLUSIONS: Our results suggested that ACP vaccination could stimulate higher levels of cytokines and antibodies but failed to improve the protective efficacy of BCG in mice, indicating that the secretion level of IFN-γ may not be positively correlated with the protection efficiency of the vaccine. These findings provided important information on the feasibility of a peptide vaccine as a booster for enhancing the protective efficacy of BCG.


Assuntos
Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Humanos , Camundongos , Animais , Camundongos Endogâmicos C57BL , Vacina BCG , Vacinas de Subunidades , Interferon gama , Citocinas
6.
Indian J Tuberc ; 69(4): 503-522, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36460382

RESUMO

BACKGROUND: Multi-drug resistance tuberculosis is chronic and highly affected to mankind. Millions of people are affected by tuberculosis and lost their lives every year. Mycobacterium tuberculosis is resistant to the most commonly used anti-TB drugs, hence new drugs need to be developed in a short time. In this direction, many chemical compounds including benzimidazole derivatives have been identified as potent anti-tb agents. METHOD: Various benzimidazole derivatives were subjected to in-silico computational screening to identify the potent anti-tubercular analogues. The ADME pharmacokinetics evaluation was performed to identify the drug-like molecules. Molecular docking investigation of selected compounds was performed against Mycobacterium Tuberculosis Enoyl Reductase (Inha) with PDB ID: 2B37, 1QG6, 4TZK, and 4TZK. The common pharmacophore hypothesis was generated using the molecular docking post-processing module. RESULT: The result of ADME pharmacokinetics of some compounds is very close to the drug-like properties and can be developed as good inhibitors. Molecular docking study suggests that the proposed benzimidazole and 4H-pyran derivative have better binding affinity than standard and triclosan derivatives. Results from the pharmacophore hypothesis development study also support and suggest our prediction regarding the minimum pharmacophore features required in ligands to behave as a Mycobacterium Tuberculosis inhibitor. CONCLUSION: Coumarin, phenylurea clubbed benzimidazole moiety and pyrano[2,3-c]pyrazole derivatives have shown greater selectivity and potency towards Mycobacterium Tuberculosis. By employing a combination of ADME, docking, and pharmacophore study calculations, novel potent hits to inhibit enoyl-acp reductase were identified with the points for consideration for designing of enoyl-acp reductase inhibitor.


Assuntos
Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Humanos , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Simulação de Acoplamento Molecular , Benzimidazóis , Oxirredutases
7.
Indian J Tuberc ; 69(4): 530-534, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36460384

RESUMO

BACKGROUND: Globally, EPTB accounts for 15% of the notified incident TB cases. Laboratory confirmation of EPTB is challenging and majority of the cases remain undetected for a longer time. A major breakthrough in the diagnosis of EPTB was the introduction of nucleic acid amplification tests (NAAT). One such test-the Xpert MTB/RIF assay also known as Cartridge based nucleic acid amplification test (CBNAAT) was endorsed by the Scientific and Technical Advisory Board of the WHO for the diagnosis of Tuberculosis. The present study was conduct to evaluate the outcome of various extrapulmonary samples tested in the year 2019 at different standalone NAAT laboratories in Delhi. MATERIALS AND METHODS: A total of 20,238 samples consisting mainly of Pus (21.77%), Cerebrospinal fluid (CSF) (14.96%), Biopsies (13.87%), Pleural fluid (10.49%), Lymph node aspirations (FNAC aspirates) (6.75%), synovial fluid (0.54%) and gastric aspirates (26.4%) tested at 22 standalone NAAT laboratories were included in this study. RESULTS: Mycobacterium tuberculosis was detected in 3496 samples and resistance to rifampicin was detected in 329 of the samples. The overall yield of all the specimens combined was 17.2%. Highest yield was seen in Lymph nodes aspirates (FNAC) (36.0%), followed by pus (35.4%), tissues (15.7%), synovial fluid (13.5%), Endometrial tissues (10.7%), Pleural fluid (9.5%), Gastric aspirates (9.4%) and CSF (6.5%). The lowest yield was seen in Cavitary fluids (6.2%). CONCLUSION: The results of this study highlight the usefulness of Xpert MTB/RIF assay in the diagnosis of EPTB. In particular, this assay proved to be of great utility while testing pus samples, tissue samples and lymph node FNACs.


Assuntos
Rifampina , Tuberculose dos Linfonodos , Humanos , Rifampina/uso terapêutico , Laboratórios , Índia/epidemiologia , Supuração
8.
Indian J Tuberc ; 69(4): 565-570, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36460390

RESUMO

INTRODUCTION: Mediastinal granulomatous lymphadenopathies, such as tuberculous lymphadenitis, sarcoidosis, are frequently encountered by respiratory physicians, and their diagnosis is based on histological and microbiological tests. Endobronchial ultrasound-guided Trans bronchial needle aspiration (EBUS-TBNA) is widely used to perform mediastinal lymph node sampling. However, very limited data is available on the yield of polymerase chain reaction for Mycobacterium tuberculosis (TB-PCR) using EBUS-TBNA samples in patients with mediastinal granulomatous lymphadenopathy. MATERIALS AND METHODS: A retrospective study using a prospectively collected database was performed from January 1, 2018 to December 31, 2018, to evaluate the efficacy of the TB-PCR test using EBUS-TBNA samples in patients with benign mediastinal lymphadenopathy which included both granulomatous lymphadenopathy and reactive lymphadenopathy. The cohort with reactive lymphadenopathy acted as the control group of the study population. The patients with mediastinal lymphadenopathy who were awaiting EBUS-TBNA either for diagnostic evaluation of primary disease or for staging of a known malignancy were included in the study. The patients were then followed up for 1 year post procedure with clinical and radiological evaluation. RESULTS: Of the 310 patients with mediastinal lymphadenopathy who underwent EBUS-TBNA, 190 cases had a benign pathology with granulomatous lymphadenopathy in 120 and reactive lymphadenopathy in 70 patients. The sensitivity, specificity, the positive predictive value and the negative predictive value of TB-PCR was at 90%, 97.14%, 98.18%, and 85% respectively. The accuracy of TB-PCR is 92.63%. CONCLUSION: TB-PCR using EBUS-TBNA samples is an effective tool for diagnosing mediastinal granulomatous lymphadenopathy. This technique can prevent further invasive interventions like mediastinoscopy in patients whose histological and microbiological tests are non-diagnostic. It should always be performed when tuberculosis is in the differential diagnosis of a patient with mediastinal lymphadenopathy.


Assuntos
Linfadenopatia , Tuberculose dos Linfonodos , Humanos , Estudos Retrospectivos , Linfadenopatia/diagnóstico , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Reação em Cadeia da Polimerase , Tuberculose dos Linfonodos/diagnóstico
9.
Indian J Tuberc ; 69(4): 647-654, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36460403

RESUMO

BACKGROUND/OBJECTIVES: Mycobacterium tuberculosis, the causative agent of tuberculosis has developed resistance to most of the available antimicrobials. Therefore research on the detection of new antimicrobials against Mycobacterium tuberculosis is needed urgently. Essential oils extracted from plants have been shown to have anti-Mycobacterium tuberculosis effect in in-vitro experiments. Essential oil contains many chemicals and any one or more than one chemical may have the anti-Mycobacterium tuberculosis effect. Eugenol is one such chemical in the essential oil and the anti-Mycobacterium tuberculosis effect of eugenol is investigated. METHODS: The anti-Mycobacterium tuberculosis effect of eugenol was evaluated against H37Rv and twelve clinical isolates of Mycobacterium tuberculosis in the BD BACTEC MGIT instrument using different volumes of eugenol. RESULTS: H37Rv and all the twelve clinical isolates of Mycobacterium tuberculosis were inhibited by eugenol. The minimal inhibitory concentration of H37Rv was 2.5 µl (2.67 mg) and those of the clinical isolates of Mycobacterium tuberculosis ranged from to 2.5 µl (2.67 mg) to 10 µl (10.68 mg). CONCLUSION: Eugenol has anti-Mycobacterium tuberculosis effect in the in-vitro BD BACTEC MGIT method.


Assuntos
Mycobacterium tuberculosis , Óleos Voláteis , Tuberculose dos Linfonodos , Humanos , Eugenol/farmacologia , Óleos Voláteis/farmacologia , Testes de Sensibilidade Microbiana
10.
Indian J Tuberc ; 69(4): 695-698, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36460410

RESUMO

INTRODUCTION: Kikuchi-Fujimoto disease is a benign and self-limiting systemic disorder of unknown aetiology characterised by fever, superficial lymphadenopathy and leukopenia. In highly endemic & low-resource country like India, it is frequently misdiagnosed as tuberculosis. CASE REPORT: Both the cases were diagnosed as necrotizing lymphadenitis by fine-needle aspiration cytology. Tuberculin skin prick test (TST) was positive for one case and negative for the other case. Cartridge based nucleic acid amplification test (CBNAAT) from lymph node aspirate was negative for mycobacterium tuberculosis in both the cases, later on histopathology of lymph node showed diagnosis of Kikuchi-Fujimoto disease. CONCLUSION: Kikuchi Fujimoto is a self-limiting disease systemic disease of unknown aetiology. A definite diagnosis can be established by incisional/excisional biopsy of the lymph node. When dealing with cases of tubercular lymphadenitis, Kikuchi-Fujimoto disease should be kept as differential diagnosis.


Assuntos
Linfadenite Histiocítica Necrosante , Linfadenite , Tuberculose dos Linfonodos , Humanos , Linfadenite Histiocítica Necrosante/diagnóstico , Teste Tuberculínico , Tuberculose dos Linfonodos/diagnóstico , Biópsia por Agulha Fina
11.
PLoS One ; 17(12): e0278295, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36454773

RESUMO

Mycobacterium tuberculosis (M.tb) causes tuberculosis (TB) and remains one of the leading causes of mortality due to an infectious pathogen. Host immune responses have been implicated in driving the progression from infection to severe lung disease. We analyzed longitudinal RNA sequencing (RNAseq) data from the whole blood of 74 TB progressors whose samples were grouped into four six-month intervals preceding diagnosis (the GC6-74 study). We additionally analyzed RNAseq data from an independent cohort of 90 TB patients with positron emission tomography-computed tomography (PET-CT) scan results which were used to categorize them into groups with high and low levels of lung damage (the Catalysis TB Biomarker study). These groups were compared to non-TB controls to obtain a complete whole blood transcriptional profile for individuals spanning from early stages of M.tb infection to TB diagnosis. The results revealed a steady increase in the number of genes that were differentially expressed in progressors at time points closer to diagnosis with 278 genes at 13-18 months, 742 at 7-12 months and 5,131 detected 1-6 months before diagnosis and 9,205 detected in TB patients. A total of 2,144 differentially expressed genes were detected when comparing TB patients with high and low levels of lung damage. There was a large overlap in the genes upregulated in progressors 1-6 months before diagnosis (86%) with those in TB patients. A comprehensive pathway analysis revealed a potent activation of neutrophil and platelet mediated defenses including neutrophil and platelet degranulation, and NET formation at both time points. These pathways were also enriched in TB patients with high levels of lung damage compared to those with low. These findings suggest that neutrophils and platelets play a critical role in TB pathogenesis, and provide details of the timing of specific effector mechanisms that may contribute to TB lung pathology.


Assuntos
Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Humanos , Neutrófilos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Ativação de Neutrófilo , Mycobacterium tuberculosis/genética
12.
Int J Mycobacteriol ; 11(4): 448-453, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36510933

RESUMO

Most patients with early recurrent tuberculous lymphadenitis (RTL) can be overlooked due to the paucibacillary character of Mycobacterium tuberculosis complex (MTBC) causing difficulty in the differential diagnosis. Here, we present three cases with early RTL that occurred after completing pulmonary tuberculosis (TB) therapy with a cure, and that improved by early diagnosis and therapy. A 30-year-old migrant male, HIV-negative patient, who had used immunosuppressive drugs for Crohn's disease presented to the TB outpatient clinic with a new anterior cervical lymph node enlargement. Two months ago, his therapy for pulmonary TB and intra-abdominal tuberculous lymphadenitis (TL) was completed. Real-time polymerase chain reaction (RT-PCR) of purulent fine-needle aspiration (FNA) specimen from the anterior cervical lymphadenopathy (LAP) was detected positive for MTBC. Isoniazid (H) resistance was determined via the Seegene system. The 6 cm anterior cervical LAP regressed to a 1.6 cm LAP at the 4th month of initial therapy with first-line antitubercular drugs. A 25-year-old female, the HIV-negative patient, was admitted to the TB outpatient clinic with a bulge on the submandibular area 3 months after the cessation of pulmonary multidrug-resistance TB therapy lasting 2 years. She had an index case but no comorbidity. The cytomorphology of FNA biopsy from the submandibular LAP reported granuloma with necrosis. RT-PCR of the purulent FNA specimen was positive for MTBC. H and rifampicin (R) resistances were found via the Seegene system. The right submandibular 2.9 cm LAP improved to a 1.7 cm LAP 6 months after the initiation of second-line antitubercular therapy. A 19-year-old male, the HIV-negative patient, presented to the TB outpatient clinic with a new bulge on the left supraclavicular area 9 months after cessation of pulmonary TB. He had no comorbidity and index case. RT-PCR of the purulent FNA specimen was positive for MTBC. H and R sensitivities were determined via the Seegene system. After the initial therapy with first-line antitubercular drugs for 2 months, the 1.5 cm left supraclavicular LAP improved to a 1.2 cm LAP.


Assuntos
Infecções por HIV , Linfadenopatia , Mycobacterium tuberculosis , Mycobacterium , Tuberculose dos Linfonodos , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose Pulmonar , Feminino , Humanos , Masculino , Adulto , Adulto Jovem , Tuberculose dos Linfonodos/diagnóstico , Tuberculose dos Linfonodos/tratamento farmacológico , Tuberculose dos Linfonodos/patologia , Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Linfadenopatia/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Mycobacterium tuberculosis/genética
13.
Front Cell Infect Microbiol ; 12: 1009901, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389170

RESUMO

Despite more than a decade of active study, tuberculosis (TB) remains a serious health concern across the world, and it is still the biggest cause of mortality in the human population. Pathogenic bacteria recognize host-induced responses and adapt to those hostile circumstances. This high level of adaptability necessitates a strong regulation of bacterial metabolic characteristics. Furthermore, the immune reponse of the host virulence factors such as host invasion, colonization, and survival must be properly coordinated by the pathogen. This can only be accomplished by close synchronization of gene expression. Understanding the molecular characteristics of mycobacterial pathogenesis in order to discover therapies that prevent or resolve illness relies on the bacterial capacity to adjust its metabolism and replication in response to various environmental cues as necessary. An extensive literature details the transcriptional alterations of host in response to in vitro environmental stressors, macrophage infection, and human illness. Various studies have recently revealed the finding of several microRNAs (miRNAs) that are believed to play an important role in the regulatory networks responsible for adaptability and virulence in Mycobacterium tuberculosis. We highlighted the growing data on the existence and quantity of several forms of miRNAs in the pathogenesis of M. tuberculosis, considered their possible relevance to disease etiology, and discussed how the miRNA-based signaling pathways regulate bacterial virulence factors.


Assuntos
MicroRNAs , Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de Sinais , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
14.
Front Cell Infect Microbiol ; 12: 1014897, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439208

RESUMO

Rv0790c is predicted to be a conserved hypothetical protein encoded by Mycobacterium tuberculosis (Mtb). However, its function in Mtb infection remains largely unknown. In this study, we found that Rv0790c promoted bacillary survival of M. smegmatis (Ms), both in vitro and in vivo. The bacillary burden of Ms exogenously expressing Rv0790c increased, whereas in Rv0790c-knockouts the bacillary burden decreased in infected macrophages. Multiple cellular processes were analyzed to explore the underlying mechanisms. We found that neither inflammatory regulation nor apoptotic induction were responsible for the promotion of bacillary survival mediated by Rv0790c. Interestingly, we found that Rv0790c facilitates mycobacterial survival through cellular autophagy at its early stage. Immunoprecipitation assay of autophagy initiation-related proteins indicated that Rv0790c interacted with mTOR and enhanced its activity, as evidenced by the increased phosphorylation level of mTOR downstream substrates, ULK-1, at Ser757 and P70S6K, at Thr389. Our study uncovers a novel autophagy suppressor encoded by mycobacterial Rv0790c, which inhibits the early stage of cellular autophagy induction upon Mtb infection and takes an important role in maintaining intracellular mycobacterial survival. It may aid in understanding the mechanism of Mtb evasion of host cellular degradation, as well as hold the potential to develop new targets for the prevention and treatment of tuberculosis.


Assuntos
Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Humanos , Mycobacterium tuberculosis/metabolismo , Autofagia/fisiologia , Macrófagos/microbiologia , Serina-Treonina Quinases TOR/metabolismo
15.
Tuberculosis (Edinb) ; 137: 102273, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36403561

RESUMO

Tuberculosis phenotypic detection assays are commonly used in low-resource countries. Therefore, reliable detection methods are crucial for early diagnosis and treatment. The microscopic observation drug susceptibility (MODS) assay is a culture-based test to detect Mycobacterium tuberculosis and characterize drug resistance in 7-10 days directly from sputum. The use of MODS is limited by the availability of supplies necessary for preparing the enriched culture. In this study, we evaluated three dry culture media that are easier to produce and cheaper than the standard one used in MODS [1]: an unsterilized powder-based mixed (Boldú et al., 2007) [2], a sterile-lyophilized medium, and (Sengstake et al., 2017) [3] an irradiated powder-based mixed. Mycobacterial growth and drug susceptibility were evaluated for rifampin, isoniazid, and pyrazinamide (PZA). The alternative cultures were evaluated using 282 sputum samples with positive acid-fast smears. No significant differences were observed in the positivity test rates. The positivity time showed high correlations (Rho) of 0.925, 0.889, and 0.866 between each of the three alternative media and the standard. Susceptibility testing for MDR and PZA showed an excellent concordance of 1 compared to the reference test. These results demonstrate that dry culture media are appropriate and advantageous for use in MODS in low-resource settings.


Assuntos
Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Pós/farmacologia , Pós/uso terapêutico , Análise Custo-Benefício , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Testes de Sensibilidade Microbiana , Sensibilidade e Especificidade , Tuberculose dos Linfonodos/tratamento farmacológico , Meios de Cultura
16.
Front Immunol ; 13: 1038960, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405761

RESUMO

Tuberculosis (TB) presents a serious health problem with approximately a quarter of the world's population infected with Mycobacterium tuberculosis (M. tuberculosis) in an asymptomatic latent state of which 5-10% develops active TB at some point in their lives. The antimicrobial protein cathelicidin has broad antimicrobial activity towards viruses and bacteria including M. tuberculosis. Vitamin D increases the expression of cathelicidin in many cell types including macrophages, and it has been suggested that the vitamin D-mediated antimicrobial activity against M. tuberculosis is dependent on the induction of cathelicidin. However, unraveling the immunoregulatory effects of vitamin D in humans is hampered by the lack of suitable experimental models. We have previously described a family in which members suffer from hereditary vitamin D-resistant rickets (HVDRR). The family carry a mutation in the DNA-binding domain of the vitamin D receptor (VDR). This mutation leads to a non-functional VDR, meaning that vitamin D cannot exert its effect in family members homozygous for the mutation. Studies of HVDRR patients open unique possibilities to gain insight in the immunoregulatory roles of vitamin D in humans. Here we describe the impaired ability of macrophages to produce cathelicidin in a HVDRR patient, who in her adolescence suffered from extrapulmonary TB. The present case is a rare experiment of nature, which illustrates the importance of vitamin D in the pathophysiology of combating M. tuberculosis.


Assuntos
Raquitismo Hipofosfatêmico Familiar , Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Humanos , Adolescente , Feminino , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Mycobacterium tuberculosis/metabolismo , Macrófagos/metabolismo , Vitamina D/farmacologia , Vitamina D/metabolismo , Vitaminas/metabolismo , Raquitismo Hipofosfatêmico Familiar/metabolismo , Catelicidinas
17.
BMC Infect Dis ; 22(1): 864, 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36401164

RESUMO

BACKGROUND: Mycobacterium tuberculosis (Mtb) has been found to persist within cavities in patients who have completed their anti-tuberculosis therapy. The clinical implications of Mtb persistence after therapy include recurrence of disease and destructive changes within the lungs. Data on residual changes in patients who completed anti-tuberculosis therapy are scarce. This case highlights the radiological and pathological changes that persist after anti-tuberculosis therapy completion and the importance of achieving sterilization of cavities in order to prevent these changes. CASE PRESENTATION: This is a case report of a 33 year old female with drug-sensitive pulmonary tuberculosis who despite successfully completing standard 6-month treatment had persistent changes in her lungs on radiological imaging. The patient underwent multiple adjunctive surgeries to resect cavitary lesions, which were culture positive for Mtb. After surgical treatment, the patient's chest radiographies improved, symptoms subsided, and she was given a definition of cure. CONCLUSIONS: Medical therapy alone, in the presence of severe cavitary lung lesions may not be able to achieve sterilizing cure in all cases. Cavities can not only cause reactivation but also drive inflammatory changes and subsequent lung damage leading to airflow obstruction, bronchiectasis, and fibrosis. Surgical removal of these foci of bacilli can be an effective adjunctive treatment necessary for a sterilizing cure and improved long term lung health.


Assuntos
Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Tuberculose Pulmonar , Humanos , Feminino , Adulto , Tuberculose Pulmonar/diagnóstico , Pulmão/diagnóstico por imagem , Pulmão/patologia , Tuberculose dos Linfonodos/tratamento farmacológico , Antituberculosos/uso terapêutico , Antituberculosos/farmacologia
18.
PLoS One ; 17(11): e0277536, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36417400

RESUMO

BACKGROUND: Consistently deciding its current extent and chance elements of tuberculosis (TB) in all levels of clinical settings contributes to the anticipation and control exertion of the disease. In Ethiopia, updated information is still needed at every healthcare level and in different risk groups to monitor the national program's performance, which aims to attain the 2035 goal. Hence, this study aimed to generate additional evidence data on the magnitude of Mycobacterium tuberculosis using the Gene Xpert assay among TB-suspected patients at Mizan-Tepi university teaching hospital, southwest Ethiopia. METHODS: A cross-sectional descriptive study was conducted from June to September 30, 2021. The required socio-demographic and other risk factor data were collected from a total of 422 suspected TB patients using a structured questionnaire. Approximately 392 pulmonary and 30 extra-pulmonary samples were collected and examined using the Gene Xpert-MTB/RIF assay. The statistical package for social sciences (SPSS) version 25 software was used to analyze the data. RESULTS: In this study, Mycobacterium tuberculosis was detected in 12.5% (49/392) of pulmonary samples and 13.3% (4/30) of extra-pulmonary samples, giving an overall TB positivity of 12.6% (53/422). Rifampicin-resistant M. tuberculosis was detected in 3/53 (5.7%). Male sex (AOR: 2.54; 95% CI: 1.210, 5.354), previous contact (AOR: 4.25; 95% CI: 1.790, 10.092), smoking cigarette (AOR: 4.708; 95% CI: 1.004, 22.081), being HIV-positive (AOR: 4.27; 95% CI: 1.606, 11.344), and malnutrition (AOR: 3.55; 95% CI: 1.175, 10.747) were all significantly associated with M. tuberculosis detection using the GeneXpert MTB/RIF assay. CONCLUSION: The overall frequency of M. tuberculosis in this study was still significant in different risk groups, despite the proposed strategies, which aimed to reduce TB prevalence to as low as 10 per 100,000 populations by 2035. Early case detection with better diagnostic tools and public health measures are important prevention and control strategies to meet the proposed target and reduce the burden of TB in the country.


Assuntos
Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Masculino , Mycobacterium tuberculosis/genética , Estudos Transversais , Universidades , Rifampina/uso terapêutico , Etiópia/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Hospitais de Ensino
20.
Tuberculosis (Edinb) ; 137: 102272, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36375278

RESUMO

The increase of global cases of drug resistant (DR) Mycobacterium tuberculosis (M.tb) is a serious problem for the tuberculosis research community and the goals to END TB by 2030. Due to the need for advancing and screening next generation therapeutics and vaccines, we aimed to design preclinical DR models of Beijing lineage M.tb HN878 strain in different mouse backgrounds. We found escalating sensitivities of morbidity due to low dose aerosol challenge (50-100 bacilli) in CB6F1, C57BL/6 and SWR mice, respectively. We also observed that pulmonary bacterial burden at morbidity endpoints correlated inversely with survival over time between mouse strains. Interestingly, with in vitro passaging and in the process of selecting individual DR mutant colonies, we observed a significant decrease in in vivo HN878 strain virulence, which correlated with the acquisition of a large genetic duplication. We confirmed that low passage infection stocks with no or low prevalence of the duplication, including stocks directly acquired from the BEI resources biorepository, retained virulence, measured by morbidity over time. These data help confirm previous reports and emphasize the importance of monitoring virulence and stock fidelity.


Assuntos
Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Tuberculose Resistente a Múltiplos Medicamentos , Camundongos , Animais , Virulência/genética , Camundongos Endogâmicos C57BL
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