Cavitary tuberculosis: the gateway of disease transmission.
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ABSTRACT:
SUBMITTER: Urbanowski ME
PROVIDER: S-EPMC7357333 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Cavitary pulmonary tuberculosis (TB) is associated with poor outcomes, treatment recurrence, higher transmission rates, and the development of drug resistance. However, reports on its clinical characteristics, associated factors, and treatment outcomes are lacking. Hence, this study sought to evaluate the clinical factors associated with cavitary pulmonary TB and its treatment outcomes. We retrospectively evaluated 410 patients with drug-susceptible pulmonary TB in a university hospital in Korea between 2014 and 2019. To evaluate the factors associated with cavitary TB, multivariable logistic regression was performed with adjustments for potential confounders. We also compared the treatment outcomes between patients with cavitary TB and those without cavitary TB. Of the 410 patients, 244 (59.5%) had non-cavitary TB and 166 (40.5%) had cavitary TB. Multivariable logistic analysis with forward selection method showed that body mass index (BMI) (adjusted OR = 0.88, 95% CI: 0.81-0.97), previous history of TB (adjusted OR = 3.45, 95% CI: 1.24-9.59), ex- or current smoker (adjusted OR = 1.77, 95% CI: 1.01-3.13), diabetes mellitus (adjusted OR = 2.72, 95% CI: 1.36-5.44), and positive results on the initial sputum acid-fast bacilli (AFB) smear (adjusted OR = 2.24, 95% CI: 1.26-3.98) were significantly associated with cavitary TB. Although treatment duration was significantly longer in patients with cavitary TB than in those with non-cavitary TB (248 (102-370 days) vs. 202 (98-336 days), p < 0.001), the recurrence rate after successful treatment was significantly higher in the patients with cavitary TB than in those with non-cavitary TB (0.4% vs. 3.0% p = 0.042). In conclusion, ex- or current smoker, lower BMI, previous history of TB, diabetes mellitus, and positivity of the initial AFB smear were associated with cavitary TB. The patients with cavitary TB had more AFB culture-positive results at 2 months, longer treatment duration, and higher recurrence rates than those with non-cavitary TB.
| S-EPMC8622689 | biostudies-literature
Project description:The molecular determinants of the immune response to Mycobacterium tuberculosis HN878 infection in a rabbit model of pulmonary cavitary tuberculosis were studied. Aerosol infection of rabbits resulted in a highly differentially expressed global transcriptome in the lungs at 2 weeks, which dropped at 4 weeks and then gradually increased. While IFN? was progressively upregulated throughout the infection, several other genes in the IFN? network were not. T-cell activation network genes were gradually upregulated and maximally induced at 12 weeks. Similarly, the IL4 and B-cell activation networks were progressively upregulated, many reaching high levels between 12 and 16 weeks. Delayed peak expression of genes associated with macrophage activation and Th1 type immunity was noted. Although spleen CD4(+) and CD8(+) T cells showed maximal tuberculosis antigen-specific activation by 8 weeks, macrophage activation in lungs, lymph nodes and spleen did not peak until 12 weeks. In the lungs, infecting bacilli grew exponentially up to 4 weeks, followed by a steady-state high bacillary load to 12 weeks that moderately increased during cavitation at 16 weeks. Thus, the outcome of HN878 infection of rabbits was determined early during infection by a suboptimal activation of innate immunity and delayed T-cell activation.
| S-EPMC3352086 | biostudies-literature
Project description:Every year, tuberculosis kills nearly 1.8 million people through out the world. Though outcome of M. tuberculosis infection into active disease is determined by the host and bacterial factors, a strong host immune response controls the growth of the bacilli effectively. However, in a host with suboptimal immune response, the bacilli grows and mounts active disease. Activation of immune response following M. tuberculosis infection affects the expression of many host genes that are involved in the production of immune system molecules such as cytokines, chemokines, surface receptors and transcriptional regulators that manifest in the change of subsequent cellular events, including activation, maturation, chemotaxis and proliferation of effector cells. However, the specific nature of the host-pathogen interactions and the outcome of Mtb infection are not fully understood. In this study, we have analysed the systematic changes in the global host gene expression profile in the lungs of Mtb infected rabbits at various stages of infection. Mtb infected rabbit lung tissues were isolated at T=0,2, 4 and 16 weeks post-infection. Lung bacterial load, histologic changes and host and bacterial gene expression were determined for each timepoint and compared . Our data suggests a strong correlation between the significant changes in the global transcriptome of infected rabbits and the progression of Mtb infection into a chronic, cavitary TB disease. The microarray experiments involves comparison of: 1) Changes in rabbit gene expression between Mtb-HN878 infected and uninfected animals at 2,4 and 16 weeks post infection.
2011-12-07 | GSE33094 | GEO
Project description:BACKGROUND:Previous studies have shown that Mycobacterium tuberculosis (MTB) Uganda family, a sub-lineage of the MTB Lineage 4, is the main cause of tuberculosis (TB) in Uganda. Using a well characterized patient population, this study sought to determine whether there are clinical and patient characteristics associated with the success of the MTB Uganda family in Kampala. METHODS:A total of 1,746 MTB clinical isolates collected from 1992-2009 in a household contact study were genotyped. Genotyping was performed using Single Nucleotide Polymorphic (SNP) markers specific for the MTB Uganda family, other Lineage 4 strains, and Lineage 3, respectively. Out of 1,746 isolates, 1,213 were from patients with detailed clinical data. These data were used to seek associations between MTB lineage/sub-lineage and patient phenotypes. RESULTS:Three MTB lineages were found to dominate the MTB population in Kampala during the last two decades. Overall, MTB Uganda accounted for 63% (1,092/1,746) of all cases, followed by other Lineage 4 strains accounting for 22% (394/1,746), and Lineage 3 for 11% (187/1,746) of cases, respectively. Seventy-three (4 %) strains remained unclassified. Our longitudinal data showed that MTB Uganda family occurred at the highest frequency during the whole study period, followed by other Lineage 4 strains and Lineage 3. To explore whether the long-term success of MTB Uganda family was due to increased virulence, we used cavitary disease as a proxy, as this form of TB is the most transmissible. Multivariate analysis revealed that even though cavitary disease was associated with known risk factors such as smoking (adjusted odds ratio (aOR) 4.8, 95% confidence interval (CI) 3.33-6.84) and low income (aOR 2.1, 95% CI 1.47-3.01), no association was found between MTB lineage and cavitary TB. CONCLUSION:The MTB Uganda family has been dominating in Kampala for the last 18 years, but this long-term success is not due to increased virulence as defined by cavitary disease.
| S-EPMC3853102 | biostudies-literature
Project description:Matrix metalloproteinases (MMPs) degrade extracellular matrix and are implicated in tuberculosis pathogenesis and cavitation. In particular, MMP-7 is induced by hypoxia and highly expressed around pulmonary cavities of Mycobacterium tuberculosis-infected C3HeB/FeJ mice. In this study, we evaluated whether administration of cipemastat, an orally available potent inhibitor of MMP-7, could reduce pulmonary cavitation in M. tuberculosis-infected C3HeB/FeJ mice. We demonstrate that, compared with untreated controls, cipemastat treatment paradoxically increases the frequency of cavitation (32% vs 7%; P = .029), immunopathology, and mortality. Further studies are needed to understand the role of MMP inhibitors as adjunctive treatments for pulmonary tuberculosis.
| S-EPMC6601699 | biostudies-literature
Project description:BackgroundThe World Health Organization guidelines for management drug resistant tuberculosis include surgery as an additional method in selected cases. Pneumonectomies have higher risk of morbidity such as bronchial fistulas which may be prevented by bronchial stump covering. We compare two methods of bronchial stump reinforcement.Methods and materialsA retrospective single center follow-up study was done in 52 patients who underwent pneumonectomy for drug resistant pulmonary tuberculosis. Between 2000 and 2017 we performed pneumonectomies with pericardial fat reinforcement of bronchial stump in group 1 (n = 42), and between 2017 and 2021 in group 2 with pedicled muscle flap reinforcement group 2 (n = 10).ResultsBronchial fistulas occurred in 17/42 (41%) of patients group 1 and there was no fistula in group 2, and this was statistically different (Fisher's test p = 0.02). Post-operative complications were seen in 24/42 (57%) of the patients in Group 1, and 4/10 (40%) patients in Group 2 (Fischer's test p = 0.53). In group 1 positive bacteriology decreased from 74% to 24% just after surgery, and in group 2 it decreased from 90% to 10%, but this was not statistically different (Fisher's test p = 0.63). In group 1 no-one died the first month, but 8/42 (19%) died within a year; in group 2 one died within a month, and only this death (10%) within a year. This difference in case fatality was not statistically significant.ConclusionsThe use of pedicle muscle flap for bronchial stump coverage during the pneumonectomies for destructive drug resistant tuberculosis can prevent severe postoperative fistulas and improve postoperative life.
| S-EPMC10097893 | biostudies-literature
Project description:To present a computer-aided detection tool for identifying, quantifying, and evaluating tuberculosis (TB) cavities in the infected lungs from computed tomography (CT) scans.The authors' proposed method is based on a novel shape-based automated detection algorithm on CT scans followed by a fuzzy connectedness (FC) delineation procedure. In order to assess interaction between cavities and airways, the authors first roughly identified air-filled structures (airway, cavities, esophagus, etc.) by thresholding over Hounsfield unit of CT image. Then, airway and cavity structure detection was conducted within the support vector machine classification algorithm. Once airway and cavities were detected automatically, the authors extracted airway tree using a hybrid multiscale approach based on novel affinity relations within the FC framework and segmented cavities using intensity-based FC algorithm. At final step, the authors refined airway structures within the local regions of FC with finer control. Cavity segmentation results were compared to the reference truths provided by expert radiologists and cavity formation was tracked longitudinally from serial CT scans through shape and volume information automatically determined through the authors' proposed system. Morphological evolution of the cavitary TB were analyzed accordingly with this process. Finally, the authors computed the minimum distance between cavity surface and nearby airway structures by using the linear time distance transform algorithm to explore potential role of airways in cavity formation and morphological evolution.The proposed methodology was qualitatively and quantitatively evaluated on pulmonary CT images of rabbits experimentally infected with TB, and multiple markers such as cavity volume, cavity surface area, minimum distance from cavity surface to the nearest bronchial-tree, and longitudinal change of these markers (namely, morphological evolution of cavities) were determined precisely. While accuracy of the authors' cavity detection algorithm was 94.61%, airway detection part of the proposed methodology showed even higher performance by 99.8%. Dice similarity coefficients for cavitary segmentation experiments were found to be approximately 99.0% with respect to the reference truths provided by two expert radiologists (blinded to their evaluations). Moreover, the authors noted that volume derived from the authors' segmentation method was highly correlated with those provided by the expert radiologists (R(2) = 0.99757 and R(2) = 0.99496, p < 0.001, with respect to the observer 1 and observer 2) with an interobserver agreement of 98%. The authors quantitatively confirmed that cavity formation was positioned by the nearby bronchial-tree after exploring the respective spatial positions based on the minimum distance measurement. In terms of efficiency, the core algorithms take less than 2 min on a linux machine with 3.47 GHz CPU and 24 GB memory.The authors presented a fully automatic method for cavitary TB detection, quantification, and evaluation. The performance of every step of the algorithm was qualitatively and quantitatively assessed. With the proposed method, airways and cavities were automatically detected and subsequently delineated in high accuracy with heightened efficiency. Furthermore, not only morphological information of cavities were obtained through the authors' proposed framework, but their spatial relation to airways, and longitudinal analysis was also provided to get further insight on cavity formation in tuberculosis disease. To the authors' best of knowledge, this is the first study in computerized analysis of cavitary tuberculosis from CT scans.
| S-EPMC3815073 | biostudies-other
Project description:Th1 cells play an essential role in immune protection against tuberculosis. Th17 cells might be involved with immune pathology in active human tuberculosis (TB). The balance between Th1 and Th17 cells in patients with cavitary tuberculosis needs to be clarified which might help understanding the immunological basis of pathologic pathogenesis in TB.Initially treated pulmonary TB (PTB) patients with or without cavities were recruited before chemotherapy. We isolated peripheral blood mononuclear cells, stimulated with phytohemagglutinin (PHA), PPD, or ESAT-6 antigens, and assayed supernatant IFN-? and IL-17 by ELISA after 24 or 72 hours incubation, respectively. Cells were also stained with antibodies to CD3, CD4, CD8, IFN-? or IL-17 and the proportion of stained cells was measured by flow cytometry.We found wide variation of IFN-? response in active PTB patients, but less subject-to-subject variation of IL-17 was observed as we previously reported. There were no significant differences in IFN-? and IL-17 between cavitary and non-cavitary PTB; however, we found decreased IFN-? secretion in severe cavitary PTB compared to mild lesion non-cavitary PTB (p < 0.05). We also found a decrease in the proportion of CD3+CD4+ T cells in the blood of severe cavitary PTB patients (p < 0.05).IL-17 seemed to have no association with the formation of cavities in active PTB from the study of PBMC. Impaired IFN-? without IL-17 enhancement occurs in peripheral blood during severe cavitary PTB. Our results demonstrate that M. tuberculosis antigen-specific Th1 response is decreased when PTB lesions develop to severe cavities.
| S-EPMC4446217 | biostudies-literature
Project description:Every year, tuberculosis kills nearly 1.8 million people through out the world. Though outcome of M. tuberculosis infection into active disease is determined by the host and bacterial factors, a strong host immune response controls the growth of the bacilli effectively. However, in a host with suboptimal immune response, the bacilli grows and mounts active disease. Activation of immune response following M. tuberculosis infection affects the expression of many host genes that are involved in the production of immune system molecules such as cytokines, chemokines, surface receptors and transcriptional regulators that manifest in the change of subsequent cellular events, including activation, maturation, chemotaxis and proliferation of effector cells. However, the specific nature of the host-pathogen interactions and the outcome of Mtb infection are not fully understood. In this study, we have analysed the systematic changes in the global host gene expression profile in the lungs of Mtb infected rabbits at various stages of infection. Mtb infected rabbit lung tissues were isolated at T=0,2, 4 and 16 weeks post-infection. Lung bacterial load, histologic changes and host and bacterial gene expression were determined for each timepoint and compared . Our data suggests a strong correlation between the significant changes in the global transcriptome of infected rabbits and the progression of Mtb infection into a chronic, cavitary TB disease. The microarray experiments involves comparison of: 1) Changes in rabbit gene expression between Mtb-HN878 infected and uninfected animals at 2,4 and 16 weeks post infection. New Zealand White rabbits were infected with Mtb HN878 at 3.2log10 (on day 0). Lung tissue from Mtb-infected rabbits were isolated at Day0, 2, 4 and 16 weeks post infection and used for total RNA extraction.
2011-12-07 | E-GEOD-33094 | biostudies-arrayexpress
Project description:Tuberculosis (TB) remains as a leading infectious disease worldwide. Our previous study showed interferon (IFN)-γ and CD3 T cell impairment in patients with severe cavitary pulmonary TB (PTB). However, the cause of the change in immune responses during the progression of TB is still poorly understood. In this study, eight newly diagnosed patients with severe cavitary and mild lesion non-cavity PTB were recruited, and three healthy volunteers were recruited as the control. RNA extracted from blood was tested by whole genome oligo microarrays. A PCR array was used to further test the same samples. Two additional groups of patients were recruited according to the same criteria with healthy control(HC) recruited as well and subjected to peripheral blood mononuclear cell isolation (PBMC)and analysis of TCF-7, β-catenin, cyclin D2, IFN-γ, and tumor necrosis factor (TNF)-α expression in CD14- cells (lymphocytes) and CD14+ cells by quantitative PCR. The changes of expression of β-catenin, CD69+ and IFN-γ by CD3+, CD14- and CD14+ cells in vitro with stimulation of LiCl were tested by flow cytometry. Whole genome oligo microarrays showed a significant decrease in expression of the Wnt signaling pathway in severe PTB patients. Further analysis of the Wnt pathway by PCR array indicated that TCF-7, β-catenin, and cyclin D2 expression was significantly reduced in severe PTB patients compared with mild PTB patients. In the additionally recruited patients, TCF-7, β-catenin, and cyclin D2 were expressed in both CD14+ and CD14- cells, while β-catenin was decreased significantly in CD14- cells compared with CD14+ cells in severe PTB patients, and IFN-γ and TNF-α expression in CD14- cells was also reduced significantly in severe PTB patients. β-catenin can directly trigger T cell activation and IFN-γsecretion in PBMCs stimulated for 24 hours. These findings indicate that Wnt pathway and its key genes, such as β-catenin, were impaired in blood cells of patients with severe PTB. Therefore, Wnt/β-catenin pathway is closely associated with T cell proliferation and TB lesion deterioration.
| S-EPMC5363794 | biostudies-literature