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Diagnosis of latent tuberculosis infection among immunodeficient individuals: Review of concordance between interferon-γ release assays and the tuberculin skin test

Abstract: Mycobacterium tuberculosis remains as a major threat to global health. Nearly a third of the world's population is estimated to have latent M. tuberculosis infection, and this is considered to be a major reservoir of potential active disease. Immunocompromised individuals, such as those with chronic renal failure requiring haemodialysis, solid organ transplant recipients, and individuals infected with the human immunodeficiency virus (HIV) have an increased likelihood of progression from latent infection to active disease, due to impaired cell-mediated immunity. Owing to the absence of a systematic review evaluating concordance between interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST) in the diagnosis of latent tuberculosis infection (LTBI) among immunodeficient individuals, this literature review aims to evaluate the reported agreement between IGRAs and TST in the diagnosis of LTBI. It will also assess the utility of IGRAs among individuals with weak immune systems as well as determine the degree of concordance among three diagnostic tests (TST, QuantiFERON, and TSPOT-TB) for LTBI.

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Novel T-cell assays for the discrimination of active and latent tuberculosis infection: the diagnostic value of PPE family

Abstract:Objective: The diagnosis of active and latent tuberculosis remains a challenge. Although a new approach based on detecting Mycobacterium tuberculosis-specific T-cells has been introduced, it cannot distinguish between latent infection and active disease. The aim of this study was to evaluate the diagnostic potential of interleukin-2 (IL-2) as biomarker after specific antigen stimulation with PE35 and PPE68 for the discrimination of active and latent tuberculosis infection (LTBI). Method: The production of IL-2 was measured in the antigen-stimulated whole-blood supernatants following stimulation with recombinant PE35 and PPE68. Results: The discrimination performance (assessed by the area under ROC curve) for IL-2 following stimulation with recombinant PE35 and PPE68 between LTBI and patients with active TB were 0.837 [95 % confidence interval (CI) 0.72–0.97] for LTBI diagnosis and 0.75 (95 % CI 0.63–0.89) for active TB diagnosis, respectively. Applying the 6.4 pg/mL cut-off for IL-2 induced by PE35 in the present study population resulted in sensitivity of 78 %, specificity of 83 %, PPV of 83 % and NPV of 78 % for the discrimination of active TB and LTBI. In addition, a sensitivity of 81 %, specificity of 71 %, PPV of 68 and 83 % of NPV was reported based on the 4.4 pg/mL cut-off for IL-2 induced by PPE68. Conclusion: This study confirms IL-2 induced by PE35 and PPE68 as a sensitive and specific biomarker and highlights IL-2 as new promising adjunct markers for discriminating of LTBI and active TB disease. © 2015, Springer International Publishing Switzerland.

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Association of serum TNF-α, IL-8 and free light chain with HLA-DR B alleles expression in pulmonary and extra-pulmonary sarcoidosis

Abstract:Background: Sarcoidosis is a systemic disease of unknown etiology characterized histologically by the observation of non-caseating granulomas and several immunological abnormalities. Sarcoidosis is a multi-organ disorder which involves formation of granulomas in many tissues including the lungs (pulmonary) and others such as skin, bone, heart (extra pulmonary). Associations between human leukocyte antigens (HLA), the encoded cell surface receptor (HLA-DR) and sarcoidosis have been reported in several studies. Several HLA-DR alleles have been described as potential risk factors for sarcoidosis in distinct ethnic groups however evidence for a relationship between HLA-DR alleles and pulmonary and extra-pulmonary sarcoidosis (EPS) is still scarce. Although the etiology of the disease remains unclear, infectious and environmental factors have been postulated. Inflammatory cytokines and chemokines may play important roles in the pathogenesis of sarcoidosis and serum free light chain (FLC) numbers have been implicated in several immunologic disorders. Purpose of the study: The aim of the present study was to investigate HLA associations with serum cytokines and FLC in Iranian patients with pulmonary (n = 86) and EPS (n = 46). Results: We found that among the 16 HLA DRB alleles only∗7 and∗12 were different in sarcoidosis patients. The levels of TNF-α and IL-8 in pulmonary sarcoidosis patients were higher than in EPS (P < 0.05) whereas the levels of FLC subunits in EPS were higher than in pulmonary sarcoidosis. Conclusion: This data may suggests a link between HLA-DRB∗12 and sarcoidosis in Iranian population. © 2015 Mortaz et al.; licensee BioMed Central.

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Radiologic manifestations of pulmonary tuberculosis in patients of intensive care units

Abstract:Background: Tuberculosis (TB) is a serpent disease with various pulmonary manifestations, and timely diagnosis of the disease is paramount, since delayed treatment is associated with severe morbidity, particularly in intensive care units (ICU). Therefore, it is imperative that intensivists understand the typical distribution, patterns, and imaging manifestations of TB. Aim: To describe different manifestations of pulmonary TB in patients in the ICU. Methods: In a retrospective study, all patients with a clinical and a laboratory-confirmed diagnosis of TB who were admitted to the ICU were entered in the study. All patients had a confirmatory laboratory diagnosis of TB including positive smears. The patterns of parenchymal lesions, involved segments and presence of cavity, bronchiectasis and bronchogenic spread of the lesions with computed tomography (CT) and chest/X-ray (CXR) were recorded and analyzed. Results: Data of 146 patients with TB were entered in the study. The most common finding in CT was acute respiratory distress syndrome (ARDS)-like radiologic manifestations (17.1%), followed by parenchymal nodular infiltration (13.6%) and cavitation (10.9%), consolidation (10.2%), interstitial involvement (9.5%), calcified parenchymal mass (8.3%), ground-glass opacities (7.5%), and pleural effusion or thickening (6.9%). Radiologic evidence of lymphadenopathy was seen in up to 43% of adults. Miliary TB was observed in 2.3% of patients, mostly in those older than 60. years of age. ARDS-like (64.5%) manifestations on CT and miliary TB (85.5%) had the highest mortality rates among other pulmonary manifestations. Conclusion: ARDS, interstitial involvement, and Parenchymal nodular infiltration are the most common manifestations of pulmonary TB. Various features of TB in ICU patients could be misleading for intensivists. © 2015 Asian African Society for Mycobacteriology.

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Pulmonary paecilomyces in a diabetic patient

Abstract:Paecilomyces species are among the most frequent saprophytes. Two species namely Paecilomyces lilacinus and Paecilomyces variotii are the most frequently isolated species from humans. Fungemia, endocarditis peritonitis, osteomyelitis and rarely pneumonia have been reported. We report a 74-year old diabetic woman with Paecilomyces variotii pneumonia. Paecilomyces variotii is a rare cause of pneumonia and in our knowledge, our case is the first case of pleural effusion due to this fungus. © 2015 NRITLD.

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A review of teicoplanin used in the prevention and treatment of serious infections caused by gram-positive bacteria and compared its effects with some other antibiotics

Abstract:Teicoplanin is an antibiotic used in the prevention and treatment of serious infections caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis. It is a semi-synthetic glycopeptide antibiotic with a spectrum of activities similar to vancomycin. Its mechanism of action is inhibition of bacterial cell wall synthesis teicoplanin is marketed by Sanofi Aventis Coperation under the brand name of Targocid. It has been shown that oral administration of teicoplanin is effective in the treatment of Pseudomembranous colitis and Clostridium difficile-associated diarrhoea, with comparable efficacy to vancomycin. The effectiveness of this antibiotic is associated with its carbon chain length. It's tried in this review article to introduce teicoplanin synthases, structure and its structure effect on treatment and also introduce the advantages of teicoplanin in bacterial infection treatment and compared its effects with some other antibiotics like vancomycin and linezolid. Based on the above data, it can be concluded that teicoplanin usage, specially intervenes injection of it, is a successful antibiotic treatment against bacterial infections caused by Gram-positive bacteria, particularly methicillin-resistant Staphylococcus aurous (MRSA). The teicoplanin effect is directly related to the length of its carbon chain. It was shown that treatment with combination of teicoplanin and vancomycin or teicoplanin and linezolid have more influence over the treatment process. The most important advantage of teicoplanin usage in treatments is its lower side effects on patients than other antibiotics.

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Flow cytometry applications in the study of immunological lung disorders

Abstract:The use of flow cytometry in the clinical laboratory has grown substantially in the past decade. Flow cytometric analysis provides a rapid qualitative and quantitative description of multiple characteristics of individual cells. For example, it is possible to detect the cell size and granularity, aspects of DNA and RNA content and the presence of cell surface and nuclear markers which are used to characterize the phenotype of single cells. Flow cytometry has been used for the immunophenotyping of a variety of specimens including whole blood, bone marrow, serous cavity fluids, (cerebrospinal fluid) CSF, urine and all types of body fluids. The technique has also been applied to human bronchoalveolar lavage (BAL) fluid, peritoneal fluids and blood. In this review, we describe the current status of the application of flow cytometry as a diagnostic tool in various lung diseases. We focus on the analysis of BAL cell composition in chronic obstructive lung disease (COPD), asthma, lung cancer, sarcoidosis, tuberculosis and idiopathic eosinophilic pneumonia (IEP). Copyright © Winter 2015.

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Discriminating between latent and active tuberculosis: The role of interleukin-2 as biomarker

We read with interest the paper by Mihret et al. who evaluated a number of cytokines or chemokines for the discrimination between active disease and non-active tuberculosis infection.1 In the last years, the potential role of distinct T-cell subsets as biomarkers of active tuberculosis (TB) and/or latent tuberculosis infection (LTBI) has been studied.2 Since the diagnosis of LTBI remains challenging without a gold standard reference,3 a rapid and specific diagnosis tool is essential for discrimination of active TB from LTBI. Cytokines play a critical role during primary and latent infection. Interleukin-2 (IL-2) is a well-known pro-inflammatory cytokine that promotes proliferation and differentiation of antigen-specific memory T-cells.4

We evaluated the potential role of IL-2 in whole blood stimulated with Mycobacterium tuberculosis-specific antigens in the QuantiFERON-TB Gold In Tube (QFT-G-IT) for the discrimination of active and latent tuberculosis. In this study, patients were recruited from the infectious diseases ward at the Masih Daneshvari Hospital, National Research Institute of Tuberculosis and Lung Diseases (NRITD), affiliated to Shahid Beheshti University of Medical Sciences, Tehran, Iran. Individuals were classified as having active TB when the diagnosis was confirmed by positive M. tuberculosis culture from sputum specimens and positive response to QFT-G-IT test. LTBI was defined as a positive response to QFT-G-IT in the absence of symptomatic, microbiological, or radiological evidence of active tuberculosis. Healthy controls were BCG vaccinated individuals with no known exposure to M. tuberculosis and a negative response to the QFT-G-IT. We do not include in the study individuals who had positive human immunodeficiency virus screening result. The study received approval from the Ethical Committee of Tehran University of medical sciences.

In this study, thirty patients with active TB and 30 cases with LTBI had positive QFT-G-IT test and all of the controls (N = 30) had negative QFT-G-IT result. After 72-h of stimulation by antigens from the QFT-G-IT assay, IL-2 secretion was quantitated in supernatants by using ELISA (Mabtech AB, Sweden). All the plasma specimens were tested in duplicate and expressed in pg/ml. The differences in levels of IL-2 among groups were analyzed using non-parametric analysis of variance with the Kruskall–Wallis test. As shown in Fig. 1, LTBI group induced significantly greater production of IL-2 than patients with active TB infection (P value = 0.019, Kruskal–Wallis test). The discrimination performance (assessed by the area under ROC curve) between LTBI and patients with active TB was 0.816 (95%CI: 0.72–0.97) (Fig. 2). Cut-offs were estimated at various sensitivities and specificities and at the maximum Youden's index (YI), i.e. sensitivity specificity–1. Maximum discrimination was reached at a cut-off of 13.9 pg/mL for IL-2 following stimulation with 82% sensitivity, 86% specificity, 85% PPV and 83% NPV.

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Association between occupational accidents and sleep apnea in hospital staff

Abstract:Background: Obstructive sleep apnea syndrome (OSAS) is a common disorder in which instability of the upper airways leads to a reduction or cessation of airflow during sleep. Sleep disorders such as OSAS increase the risk of occupational accidents and impaired work performance. Sleep deprivation during shift increases the risk of occupational accidents among health care employees. The purpose of this study was to determine the association between occupational injuries in hospital staff and the risk of sleep apnea. Materials and Methods: This cross-sectional study was conducted on hospital staff of Masih Daneshvari Hospital in 2012. In this study, the hospital staff's (715) response to the Berlin questionnaire plus additional information including a history of an occupational accident, night shifts, less than four hours of night sleep, history of smoking, chronic disease and quality of sleep were assessed. Information obtained was analyzed using SPSS 15. Results: In general, 27.6% reported a history of occupational accidents. The incidence of occupational accidents in the high-risk group for sleep apnea was significantly higher than the low-risk group (OR=2.736, CI=1.522-4.917, P=0.001). The results of logistic regression analysis also showed a statistically significant association between occupational accidents and risk of sleep apnea (OR = 2.247, CI = 1.194-4.231, P= 0.012). Conclusion: This study showed that the incidence of occupational accidents in the hospital employees is strongly related to the probability of OSA. Therefore, special attention should be directed to respiratory sleep disorders in order to reduce occupational injuries at hospitals. © 2015 NRITLD, National Research Institute of Tuberculosis and Lung Disease, Iran.

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Health care associated middle east respiratory syndrome (MERS): A case from Iran

Abstract:Middle East respiratory syndrome coronavirus (MERS-CoV) Infection, has caused recurrent outbreaks worldwide. It is associated with severe morbidity and mortality, and is not treatable with the currently available antiviral therapies. We present a case of a 43 year-old male healthcare provider, who admitted with productive cough, dyspnea, myalgia, pleuritic chest pain and fever. Computed tomography (CT) showed bilateral ground glass opacities and consolidation. Sputum polymerase chain reaction (PCR) for MERS-coronavirus was positive. © 2015 NRITLD.

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Acremonium pneumonia: Case report and literature review

Abstract:Acremonium spp. cause human superficial infections including mycetoma, onychomycosis and keratitis. There are a few reports of systemic involvement in immunocompromised patients. However, isolated pulmonary infection in otherwise healthy hosts has never been reported in the literature. Herein, we report a 59 year-old diabetic man with non-resolving pneumonia due to Acremonium spp. and provide a consensus review of the published clinical cases of systemic and respiratory tract infections. © 2015 NRITLD.

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Severity of anxiety disorders in patients with chronic obstructive pulmonary disease

Abstract:Objective: Patients with chronic physical diseases sometimes show increased loss of function; such patients need more care. Anxiety is a well-known symptom that is prevalent among chronic obstructive pulmonary disease patients that can prolong and increase the risk of hospitalization. The purpose of this study was to evaluate the severity of anxiety in the mentioned patients and to examine the presence of symptoms and appropriate treatment strategies to understand the role of psychological functions in physical patients. Methods: This was a cross sectional study conducted in Masih Daneshvari Hospital. One hundred forty- three patients entered into the project by accessible method and signed the informed consent; they filled demographic information and Hamilton anxiety and depression questionnaires. Data were analyzed by SPSS-16. Results: Of the participants, 68% were above 60 years of age; 78% were male; 89% were married; and 38% were self-employed. Also, among the participants, 51% were illiterate; 72% had history of smoking; 46% had history of substance abuse; and 49% had moderate to severe anxiety disorder. Moreover, of the patients with severe anxiety, 41.3% had severe muscle spasms; and severe sleeplessness was found in 38.5% of those with severe anxiety disorder. Severe anxiety related symptoms were found in 20.3% of the patients with severe anxiety disorder. Depressed mood was found in 27.3% of the patients with severe anxiety disorder. Severe physical and muscular signs were found in 35.7% of those with severe anxiety disorder. Conclusion: According to our findings, many chronic diseases such as chronic obstructive pulmonary disease may contain anxiety and depression which result in vulnerability. Therefore, evaluation of anxiety in such patients is of importance for alleviating the disease.

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The comparison of extemporaneous preparations of omeprazole, pantoprazole oral suspension and intravenous pantoprazole on the gastric pH of critically ill-patients

Abstract:Background: Stress-related mucosal disease occurs in many critically ill-patients within 24 h of admission. Proton pump inhibitor therapy has been documented to produce more potent inhibition of gastric acid secretion than histamine 2 receptor antagonists. This study aimed to compare extemporaneous preparations of omeprazole, pantoprazole oral suspension and intravenous (IV) pantoprazole on the gastric pH in intensive care unit patients. Materials and Methods: This was a randomized single-blind-study. Patients of ≥ 16 years of age with a nasogastric tube, who required mechanical ventilation for ≥ 48 h, were eligible for inclusion. The excluded patients were those with active gastrointestinal bleeding, known allergy to omeprazole and pantoprazole and those intolerant to the nasogastric tube. Fifty-six patients were randomized to treatment with omeprazole suspension 2 mg/ml (40 mg every day), pantoprazole suspension 2 mg/ml (40 mg every day) and IV pantoprazole (40 mg every day) for up to 14 days. Gastric aspirates were sampled before and 1-2.5 h after the drug administration for the pH measurement using an external pH meter. Data were analyzed using SPSS (version 21.0). Results: In this study, 56 critically ill-patients (39 male, 17 female, mean age: 61.5 ± 15.65 years) were followed for the control of the gastric pH. On each of the 14 trial days the mean of the gastric pH alteration was significantly higher in omeprazole and pantoprazole suspension-treated patients than in IV pantoprazole-treated patients (P < 0.001). Conclusion: Omeprazole and pantoprazole oral suspension are more effective than IV pantoprazole in increasing the gastric pH.

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Multidrug-resistant and extensively drug-resistant tuberculosis

Abstract:Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) are increasing globally. Treatment options for these patients are very limited. Although treatment of these patients with standardized regimen is associated with high mortality and morbidity, rational usage of new drugs might be promising. In this study we will review epidemiology of XDR-TB and TDR-TB in Iran and the world. © 2015, Pediatric Infections Research Center.

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Interaction of Pattern Recognition Receptors with Mycobacterium Tuberculosis

Abstract:Tuberculosis (TB) is considered a major worldwide health problem with 10 million new cases diagnosed each year. Our understanding of TB immunology has become greater and more refined since the identification of Mycobacterium tuberculosis (MTB) as an etiologic agent and the recognition of new signaling pathways modulating infection. Understanding the mechanisms through which the cells of the immune system recognize MTB can be an important step in designing novel therapeutic approaches, as well as improving the limited success of current vaccination strategies. A great challenge in chronic disease is to understand the complexities, mechanisms, and consequences of host interactions with pathogens. Innate immune responses along with the involvement of distinct inflammatory mediators and cells play an important role in the host defense against the MTB. Several classes of pattern recognition receptors (PRRs) are involved in the recognition of MTB including Toll-Like Receptors (TLRs), C-type lectin receptors (CLRs) and Nod-like receptors (NLRs) linked to inflammasome activation. Among the TLR family, TLR1, TLR2, TLR4, and TLR9 and their down-stream signaling proteins play critical roles in the initiation of the immune response in the pathogenesis of TB. The inflammasome pathway is associated with the coordinated release of cytokines such as IL-1β and IL-18 which also play a role in the pathogenesis of TB. Understanding the cross-talk between these signaling pathways will impact on the design of novel therapeutic strategies and in the development of vaccines and immunotherapy regimes. Abnormalities in PRR signaling pathways regulated by TB will affect disease pathogenesis and need to be elucidated. In this review we provide an update on PRR signaling during M. tuberculosis infection and indicate how greater knowledge of these pathways may lead to new therapeutic opportunities. © 2014, The Author(s).

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Disseminated Kaposi's sarcoma with the involvement of penis in the setting of Hiv infection

Abstract:Kaposi's sarcoma (KS) is a malignant proliferation of the endothelial cells. It typically presents with several vascular nodules on the skin and other organs. The penile localization of KS, particularly on the shaft area, is exceptional. We report an HIV-positive 34-year-old man who had multiple purplish-black plaques on his extremities and several small violaceous macules on the glans and shaft of the penis. Kaposi's sarcoma was diagnosed by histopathology. © 2015 Indian Journal of Dermatology.

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sychological symptoms before and after a 14-day initial inpatient treatment in tuberculosis patients compared with their primary caregivers and healthy controls

Abstract:Background: Tuberculosis (TB) is one of the most challenging public health burdens in the world. Recent research demonstrated high prevalence of mental disorders in TB patients and their caregivers. The purpose of this study was to assess mental health of TB patients and their caregivers in Iran before and after a two-week inpatient treatment and to determine the prevalence of psychological problems in these groups. Materials and Methods: A standardized questionnaire (SCL-90) was used to assess psychological symptoms in 146 hospitalized TB patients and their caregivers (n=89). Furthermore, the scores of both target groups were compared with those of a group of healthy individuals (n=85). Results: The mean scores before the start of the initial treatment of the patients were significantly lower for paranoid ideation (P=0.038) and hostility (P= 0.046), and the scores of depression (P=0.046) and somatization (P=0.001) were significantly higher than those of the healthy individuals. The patients scored significantly higher than the caregivers on depression (0.047) and somatization (P< 0.001), whereas the caregivers scored higher than the healthy individuals on paranoid ideation (P= 0.044) and hostility (P= 0.034). Multiple linear regression showed that age, educational level and marital status were factors affecting the mental health of TB patients and their caregivers. The variance in psychological symptoms of the patients was between 10% (paranoid ideation) and 27% (hostility) of the variance in the symptoms of their caregivers. Conclusion: Tuberculosis control and treatment programs should not only address issues like continued respiratory symptoms, but should also focus on mental health in TB patients and their caregivers. © 2015 NRITLD, National Research Institute of Tuberculosis and Lung Disease, Iran.

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