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Altered serum microRNAs as biomarkers for the early diagnosis of pulmonary tuberculosis infection  [cached]
Qi Yuhua,Cui Lunbiao,Ge Yiyue,Shi Zhiyang
BMC Infectious Diseases , 2012, DOI: 10.1186/1471-2334-12-384
Abstract: Background Pulmonary tuberculosis (TB) is a highly lethal infectious disease and early diagnosis of TB is critical for the control of disease progression. The objective of this study was to profile a panel of serum microRNAs (miRNAs) as potential biomarkers for the early diagnosis of pulmonary TB infection. Methods Using TaqMan Low-Density Array (TLDA) analysis followed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) validation, expression levels of miRNAs in serum samples from 30 patients with active tuberculosis and 60 patients with Bordetella pertussis (BP), varicella-zoster virus (VZV) and enterovirus (EV) were analyzed. Results The Low-Density Array data showed that 97 miRNAs were differentially expressed in pulmonary TB patient sera compared with healthy controls (90 up-regulated and 7 down-regulated). Following qRT-PCR confirmation and receiver operational curve (ROC) analysis, three miRNAs (miR-361-5p, miR-889 and miR-576-3p) were shown to distinguish TB infected patients from healthy controls and other microbial infections with moderate sensitivity and specificity (area under curve (AUC) value range, 0.711-0.848). Multiple logistic regression analysis of a combination of these three miRNAs showed an enhanced ability to discriminate between these two groups with an AUC value of 0.863. Conclusions Our study suggests that altered levels of serum miRNAs have great potential to serve as non-invasive biomarkers for early detection of pulmonary TB infection.
Screening and Identification of Six Serum microRNAs as Novel Potential Combination Biomarkers for Pulmonary Tuberculosis Diagnosis  [PDF]
Xing Zhang, Jing Guo, Shufeng Fan, Yanyuan Li, Liliang Wei, Xiuyun Yang, Tingting Jiang, Zhongliang Chen, Chong Wang, Jiyan Liu, Zepeng Ping, Dandan Xu, Jiaxiong Wang, Zhongjie Li, Yunqing Qiu, Ji-Cheng Li
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0081076
Abstract: Background It is very difficult to prevent pulmonary tuberculosis (TB) due to the lack of specific and diagnostic markers, which could lead to a high incidence of pulmonary TB. We screened the differentially expressed serum microRNAs (miRNAs) as potential biomarkers for the diagnosis of pulmonary TB. Methods In this study, serum miRNAs were screened using the Solexa sequencing method as the potential biomarkers for the diagnosis of pulmonary TB. The stem-loop quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assay was used to verify differentially expressed serum miRNAs. The receiver operating characteristic (ROC) curve and logistic regression model were used to analyze the sensitivity and specificity of the single miRNA and a combination of miRNAs for diagnosis, respectively. Using the predicted target genes, we constructed the regulatory networks of miRNAs and genes that were related to pulmonary TB. Results The Solexa sequencing data showed that 91 serum miRNAs were differentially expressed in pulmonary TB patients, compared to healthy controls. Following qRT-PCR confirmation, six serum miRNAs (hsa-miR-378, hsa-miR-483-5p, hsa-miR-22, hsa-miR-29c, hsa-miR-101 and hsa-miR-320b) showed significant difference among pulmonary TB patients, healthy controls (P<0.001) and differential diagnosis groups (including patients with pneumonia, lung cancer and chronic obstructive pulmonary disease) (P<0.05). The logistic regression analysis of a combination of six serum miRNAs revealed that the sensitivity and the specificity of TB diagnosis were 95.0% and 91.8% respectively. The miRNAs-gene regulatory networks revealed that several miRNAs may regulate some target genes involved in immune pathways and participate in the pathogenesis of pulmonary TB. Conclusion Our study suggests that a combination of six serum miRNAs have great potential to serve as non-invasive biomarkers of pulmonary TB.
Differential Expression of Host Biomarkers in Saliva and Serum Samples from Individuals with Suspected Pulmonary Tuberculosis  [PDF]
Khutso G. Phalane,Magdalena Kriel,Andre G. Loxton,Angela Menezes,Kim Stanley,Gian D. van der Spuy,Gerhard Walzl,Novel N. Chegou
Mediators of Inflammation , 2013, DOI: 10.1155/2013/981984
Abstract: The diagnosis of tuberculosis remains challenging in individuals with difficulty in providing good quality sputum samples such as children. Host biosignatures of inflammatory markers may be valuable in such cases, especially if they are based on more easily obtainable samples such as saliva. To explore the potential of saliva as an alternative sample in tuberculosis diagnostic/biomarker investigations, we evaluated the levels of 33 host markers in saliva samples from individuals presenting with pulmonary tuberculosis symptoms and compared them to those obtained in serum. Of the 38 individuals included in the study, tuberculosis disease was confirmed in 11 (28.9%) by sputum culture. In both the tuberculosis cases and noncases, the levels of most markers were above the minimum detectable limit in both sample types, but there was no consistent pattern regarding the ratio of markers in serum/saliva. Fractalkine, IL-17, IL-6, IL-9, MIP-1β, CRP, VEGF, and IL-5 levels in saliva and IL-6, IL-2, SAP, and SAA levels in serum were significantly higher in tuberculosis patients ( ). These preliminary data indicate that there are significant differences in the levels of host markers expressed in saliva in comparison to those expressed in serum and that inflammatory markers in both sample types are potential diagnostic candidates for tuberculosis disease. 1. Introduction Tuberculosis (TB) remains a global health problem. An estimated 8.7 million new cases and 1.4 million deaths resulted from the disease in 2011 [1]. A delay or failure in the diagnosis of the disease results in treatment delay with consequent increased opportunity for transmission, with potentially ten people infected annually per untreated case [2]. The low sensitivity of smear microscopy, the most commonly used TB diagnostic test in resource-constrained settings, is well-publicized [3, 4]. Mycobacterium tuberculosis (M.tb) culture facilities are not widely available in resource-limited settings and culture results may take up to 42 days to become available [5]. The development of the Xpert MTB/RIF test (Cepheid Inc., CA, USA) has been the most important advance in the field as the test yields results within 2 hours coupled with the detection of rifampicin resistance [6]. The test has a pooled sensitivity of 67–98% and specificity of about 98% in adults [7]. However, limitations, including high costs and the requirement for a stable electricity supply and short shelf life of consumables [8], hamper the massive roll-out of the test in resource-constrained and often high-burden settings. Furthermore,
Significance of serum neopterin level in diagnosis of active pulmonary tuberculosis
Xue-ping SHI,Qimanguli Wushouer,Quan WANG,Li JIE
Medical Journal of Chinese People's Liberation Army , 2011,
Abstract: Objective To investigate the sensitivity and specificity of serum neopterin(Np) level in diagnosis of active pulmonary tuberculosis.Methods Patients with pulmonary tuberculosis,admitted to Xinjiang Chest Hospital from Apr.2009 to May 2010,were consecutively enrolled in present study.Serum neopterin level was determined with enzyme linked immunosorbent assay(ELISA) in the next morning of admission.VCG purified protein derivative test(PPD) was concurrently performed.Results Fifty-eight cases with active(group A) and 18 with stable(group S) pulmonary tuberculosis were recruited,and 32 healthy volunteers served as control(group C).The mean Np level was significantly higher in group A(54.14±19.85 nmol/L) than in group S(29.51±8.23 nmol/L) and group C(20.67±9.68 nmol/L,P < 0.01).No statistical difference was found between group S and group C(P > 0.05).Among patients with active pulmonary tuberculosis,the mean Np level increased significantly in cases with the fibro-cavitative pulmonary tuberculosis(77.43±22.13),compared with those cases with invasive(46.07±13.04) and hematogenous disseminated pulmonary tuberculosis(48.48±8.34 nmol/L,P < 0.01),while no statistical difference existed between the latter two.The receiver operating characteristic(ROC) curve showed that the area under curve(AUC) was 0.951 in the cutoff value of 36.73 nmol/L,and the sensitivity and specificity were 86% and 92% for predicting active pulmonary tuberculosis,and it was significantly higher than PPD test(P < 0.01),in which the sensitivity was 52% and specificity was 78%.Conclusions Np level may serve as one of the important adjunctive parameters for early diagnosis of active pulmonary tuberculosis due to its high sensitivity and specificity.
Identification of Serum microRNA Biomarkers for Tuberculosis Using RNA-seq  [PDF]
Hongtai Zhang, Zhaogang Sun, Wenjing Wei, Zhonghui Liu, Joy Fleming, Shuai Zhang, Nan Lin, Ming Wang, Maoshan Chen, Yuhui Xu, Jie Zhou, Chuanyou Li, Lijun Bi, Guangming Zhou
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0088909
Abstract: Tuberculosis (TB) remains a significant human health issue. More effective biomarkers for use in tuberculosis prevention, diagnosis, and treatment, including markers that can discriminate between healthy individuals and those with latent infection, are urgently needed. To identify a set of such markers, we used Solexa sequencing to examine microRNA expression in the serum of patients with active disease, healthy individuals with latent TB, and those with or without prior BCG inoculation. We identified 24 microRNAs that are up-regulated (2.85–1285.93 fold) and 6 microRNAs that are down-regulated (0.003–0.11 fold) (P<0.05) in patients with active TB relative to the three groups of healthy controls. In addition, 75 microRNAs were up-regulated (2.05–2454.58 fold) and 11 were down-regulated (0.001–0.42 fold) (P<0.05) in latent-TB infected individuals relative to BCG- inoculated individuals. Of interest, 134 microRNAs were differentially-expressed in BCG-inoculated relative to un-inoculated individuals (18 up-regulated 2.9–499.29 fold, 116 down-regulated 0.0002–0.5 fold), providing insights into the effects of BCG inoculation at the microRNA level. Target prediction of differentially-expressed microRNAs by microRNA-Gene Network analysis and analysis of pathways affected suggest that regulation of the host immune system by microRNAs is likely to be one of the main factors in the pathogenesis of tuberculosis. qRT-PCR validation indicated that hsa-miR-196b and hsa-miR-376c have potential as markers for active TB disease. The microRNA differential-expression profiles generated in this study provide a good foundation for the development of markers for TB diagnosis, and for investigations on the role of microRNAs in BCG-inoculated and latent-infected individuals.
Serum Lipase in Pulmonary Tuberculosis Patients in Kinshasa—A Hospital Based Study  [PDF]
M. K. Mbelu, J. J. Malemba, B. Kabengele, J. M. Kayembe, D. N. Kayembe
Journal of Tuberculosis Research (JTR) , 2018, DOI: 10.4236/jtr.2018.62015
Abstract: Context: The increase of serum lipase is established for pancreatic and bile duct disorders. However, the production of this enzyme by other organs, including the lungs, leads to the question of its potential role in the diagnosis of other conditions including lung diseases. Objective: The aim of the present study was to describe the profile of serum lipase in patients who suffered from the pulmonary tuberculosis and to identify its determinants. Patients and methods: A cross-sectional study was performed from July to October 2013 in four hospitals of Kinshasa (The University Hospital of Kinshasa, Lisanga medical Center and 2 medical centers of Save Army). Patients who suffered from tuberculosis were included. The levels of serum lipase, triglyceridemia, cholesterolemia, c-reactive protein were noted, as so as the hemogram profile and the prescribed treatment (category and phase). Results: One hundred and twenty-eight patients suffering from pulmonary tuberculosis were included. Forty three women (33.6%) and 85 men (66.4%). The sex ratio M/F was 1:9. Hyperlipasemia was observed in 44.5% of patients. The average level of serum lipase was 36.6 ± 5.0 IU/L (normal value: ≤ 38 IU/L) in tuberculosis patients and 30 ± 2.3 IU/L in controls The lipid profile of the patients was normal. Conclusion: L Hyperlipasemia can be encountered, in varying proportions, during pulmonary tuberculosis. It would be an indication of inflammation of the pulmonary parenchyma.
SIGNIFICANCE OF ADENOSINE DEAMINASE SERUM CONCENTRATIONS IN THE DIAGNOSIS OF EXTRA-PULMONARY TUBERCULOSIS  [PDF]
Stevanovic G,,Pelemis M,,Pavlovic M,,Lavadinovic L
Journal of IMAB : Annual Proceeding (Scientific Papers) , 2011,
Abstract: Extra pulmonary tuberculosis (EPTB) is a growing problem worldwide. Due to the nature of the disease, the diversity of clinical pictures as well as its minor epidemiological importance, the diagnosis is difficult and often late.In addition to standard TB diagnostic techniques use of new biochemical (surrogate markers) are increased. With this work we wanted to examine the usefulness of serum adenosine deaminase levels as a diagnostic parameter for EPTB.The work included 116 patients with fever of unknown origin in which tuberculosis or infectious mononucleosis was not proven and 51 person who had proven EPTB. Correlated adenosine deaminase levels between these two groups we obtained significantly higher values in patients with EPTB. The calculated sensitivity was 0.56, specificity 0.89, positive predictive value 0.80 and negative predictive value 0.72. Certain reducing of the values observed during anti TB therapy. In previous studies the diagnostic importance of adenosine deaminase in the diagnosis of tuberculosis serosityes was demonstrated. The significance of serum levels in diagnosis is rarely evaluated during EPTB. Our findings are similar to the results of authors who have conducted such testing in the pediatric population.Increased concentrations of serum adenosine deaminase have shown the potential of usable screening test and can be used as an indicative EPTB parameter. To fully assess its diagnostic significance require future clinical research.
Role of Serum Procalcitonin Level in Differentiating between Pulmonary Tuberculosis and Community-Acquired Pneumonia  [PDF]
Mohammad Shameem, Mazhar Alam, Shagufta Moin, Rakesh Bhargava, Zuber Ahmad, Jamal Akhtar
International Journal of Clinical Medicine (IJCM) , 2014, DOI: 10.4236/ijcm.2014.515121
Abstract:

Pulmonary Tuberculosis (PTB) and Community-Acquired Pneumonia (CAP) are common causes of consolidation patch in chest radiograph. Sputum Z-N staining is positive in 30% to 60% cases only and sputum examination has poor yield in CAP. This study aimed to assess the value of serum Procalcitonin (PCT) levels in patients with Pulmonary Tuberculosis (PTB) and Community-Acquired Pneumonia (CAP). Patients with new opacity in chest radiograph were included in the study. Serum sample were taken at admission and stored. Patient’s diagnosis were confirmed and categorized into pulmonary TB group (32) and community-acquired pneumonia group (23). Their mean PCT level was compared with mean PCT level of 25 controls. Serum procalcitonin levels were found to be significantly elevated in patients of community-acquired pneumonia as compared to patients of pulmonary tuberculosis. In presence of consolidation in x-ray chest, increased level of serum procalcitonin might be used to differentiate pulmonary tuberculosis from community-acquired pneumonia. High level of serum procalcitonin was associated with high mortality rate in community-acquired pneumonia patients.

Effect of Antituberculosis Regimen Containing Ethambutol on Serum magnesium Level in Pulmonary Tuberculosis Patients
Mohammad Abbasi Nazari,Farzad Kobarfard,Payam Tabarsi,Maryam Azimi
Iranian Journal of Pharmaceutical Research , 2009,
Abstract: Magnesium is an essential metal that has important roles in physiological function of the body organs. Ethambutol is an oral antitubercular agent with chelating effects owing to its chemical structure. The aim of present study is to determine whether ethambutol usage can alter serum magnesium concentration in patients with pulmonary tuberculosis. Sixty patients with diagnosis of pulmonary tuberculosis were enrolled in the study. Blood samples were obtained before treatment from patients. Ten days after starting anti tuberculosis therapy, second blood samples were obtained. The amounts of serum magnesium were determined in all samples by spectrophotometric method. Statistical analysis showed that serum magnesium concentrations at baseline (0.61±0.08 mmol/l) and at day 10 (0.62±0.11 mmol/l) were not different. It is possible that ethambotol does not affect magnesium concentration in tuberculosis patients, however further studies about the other cationic trace elements are recommended.
Biomarkers of Oxidative Stress and Personalized Treatment of Pulmonary Tuberculosis: Emerging Role of Gamma-Glutamyltransferase  [PDF]
Etienne Mokondjimobe,Benjamin Longo-Mbenza,Jean Akiana,Ulrich Oswald Ndalla,Regis Dossou-Yovo,Joseph Mboussa,Henri-Joseph Parra
Advances in Pharmacological Sciences , 2012, DOI: 10.1155/2012/465634
Abstract: Background. The objectives were (i) to evaluate the impact of acute pulmonary tuberculosis (PTB) and anti-TB therapy on the relationship between AST, ALT, and GGT levels in absence of conditions related to hepatotoxicity; (ii) to evaluate the rate and the time of alterations of AST, ALT, and GGT. Design and Methods. A prospective followup of 40 adults (21 males; mean age of years) with active PTB on initial phase and continuation phase anti-TB. Results. Only 3% ( ) developed a transient and benign ADR at day 30 without interruption of anti-TB treatment. Within normal ranges, GGT decreased significantly from day 0 to day 60, while AST and ALT increased significantly and respectively. During day 0–day 60, there was a significant, negative, and independent association between GGT and AST. Conclusion. The initial two months led to significant improvement of oxidative stress. Values of oxidative markers in normal ranges might predict low rate of ADR. 1. Background The concept of biomarkers is very important in this paper. The role of biomarkers is now exponentially increasing in guiding decisions in drug development and personalized medicine. A biomarker is not predictive or casual to a disease, but it can predict patients’ response to compound by identifying certain patient groups that are more likely to response to the drug therapy or to avoid specific adverse events [1]. In patients with pulmonary tuberculosis (PTB), a significant improvement in oxidative stress and suppression of inflammatory response have been recently reported after the initial two-month therapy [2]. However, the literature showed that even after six months of successful chemotherapy, PTB is still associated with increased levels of circulating lipid peroxides and low plasma concentrations of antioxidants such as vitamin E [2, 3]. Before chemotherapy, Mycobacteria induce reactive oxygen species (ROS) production by activating both mononuclear and polymorphonuclear phagocytes. Tuberculosis is, therefore, characterized by poor antioxidants defence that exposes to oxidative host tissue damage [3, 4]. Yasuda et al. found that more than 50% of 113 PTB cases with normal liver function on admission showed abnormalities of transaminases that were aggravated up to 4th week after administration of drugs, and 80% up to the 8th week [5]. Almost 33% of the world population infected with Mycobacterium tuberculosis live in developing countries including Brazzaville, the Republic of Congo [6]. Anti-PTB drug-related adverse reactions [7] include benign or fatal hepatic transaminase elevation without any
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