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Sample records for progressive pulmonary tuberculosis

  1. Pulmonary Paragonimiasis Mimicking Tuberculosis.

    PubMed

    Prasad, Kj; Basu, Arup; Khana, Shilpi; Wattal, Chand

    2015-08-01

    Paragonimiasis is a disease which is frequently misdiagnosed as pulmonary tuberculosis. In the areas where people eat crab/crayfish this disease should be considered in the differential diagnosis to avoid antituberculosis treatment for a non-tubercular condition. We are reporting a case of pulmonary paragonimiasis who had been treated for tuberculosis. PMID:27604443

  2. Crescentic Glomerulonephritis Associated with Pulmonary Tuberculosis

    PubMed Central

    Vanikar, A.V.; Patel, R.D.; Suthar, K. S.; Trivedi, H. L.

    2016-01-01

    Tuberculosis of kidney and urinary tract is caused by members of the Mycobacterium tuberculosis complex. Kidney is usually infected by haematogenous spread of bacilli from focus of infection in the lungs. Glomerular involvement in tuberculosis presenting as a rapidly progressive glomerulonephritis is a rare entity. We report a rare case of crescentic glomerulonephritis associated with pulmonary tuberculosis in a 26-year-old man. Patient was treated with corticosteroids, haemodialysis, intravenous immunoglobulin and four cycles of plasmapheresis. He did not respond to 4-drug anti-tuberculosis treatment for renal pathology and was switched over to maintenance haemodialysis. However, he responded to pulmonary TB. PMID:26894074

  3. Respiratory infections: pulmonary tuberculosis.

    PubMed

    Choby, Beth A; Hunter, Paul

    2015-02-01

    Family physicians can prevent mortality and disability due to pulmonary tuberculosis (TB) by identifying high-risk patients. Recognition of symptoms (eg, cough for 3 weeks or longer) helps prevent overlooked diagnoses because results of tuberculin skin tests and interferon-gamma release assays are negative in up to 25% and 21%, respectively, of severe acute cases. The typical x-ray findings of cavities, infiltrates, and lymphadenopathy are minimal among immunosuppressed patients. Cases of active TB must be reported to local or state health departments within 24 hours of diagnosis. Sputum acid-fast bacillus tests provide results within hours and help quantify bacterial load but are not highly sensitive, and infection with nontuberculous mycobacteria can cause positive test results. Sputum cultures are adequately sensitive, identify mycobacterial species, and provide organisms for antibiotic susceptibility testing but require weeks for results. Molecular detection of Mycobacterium tuberculosis and of antibiotic-resistant mutations can expedite diagnosis and management of drug-resistant TB. Management of active TB should include directly observed therapy. Standard 6-month therapy with rifampin, isoniazid, pyrazinamide, and ethambutol resolves infection in nearly all immunocompetent adults with pansensitive TB. Multidrug-resistant TB requires second-line antibiotics (eg, fluoroquinolones, linezolid) in individualized regimens lasting 2 years. Management of latent TB infection prevents progression to active TB disease, particularly if management is completed within 2 years of infection. PMID:25685923

  4. Diagnostics for pulmonary tuberculosis

    PubMed Central

    Cudahy, Patrick

    2016-01-01

    Tuberculosis (TB) remains a leading cause of human suffering and mortality despite decades of effective treatment being available. Accurate and timely diagnosis remains an unmet goal. The HIV epidemic has also led to new challenges in the diagnosis of TB. Several new developments in TB diagnostics have the potential to positively influence the global campaign against TB. We aim to review the performance of both established as well as new diagnostics for pulmonary TB in adults, and discuss the ongoing challenges. PMID:27005271

  5. Diagnostics for pulmonary tuberculosis.

    PubMed

    Cudahy, Patrick; Shenoi, Sheela V

    2016-04-01

    Tuberculosis (TB) remains a leading cause of human suffering and mortality despite decades of effective treatment being available. Accurate and timely diagnosis remains an unmet goal. The HIV epidemic has also led to new challenges in the diagnosis of TB. Several new developments in TB diagnostics have the potential to positively influence the global campaign against TB. We aim to review the performance of both established as well as new diagnostics for pulmonary TB in adults, and discuss the ongoing challenges. PMID:27005271

  6. Protective Effect of a Lipid-Based Preparation from Mycobacterium smegmatis in a Murine Model of Progressive Pulmonary Tuberculosis

    PubMed Central

    García, Maria de los Angeles; Lanio, Maria E.; Tirado, Yanely; Alvarez, Nadine; Puig, Alina; Aguilar, Alicia; Canet, Liem; Mata Espinoza, Dulce; Barrios Payán, Jorge; Sarmiento, María Elena; Hernández-Pando, Rogelio; Norazmi, Mohd-Nor; Acosta, Armando

    2014-01-01

    A more effective vaccine against tuberculosis (TB) is urgently needed. Based on its high genetic homology with Mycobacterium tuberculosis (Mtb), the nonpathogenic mycobacteria, Mycobacterium smegmatis (Ms), could be an attractive source of potential antigens to be included in such a vaccine. We evaluated the capability of lipid-based preparations obtained from Ms to provide a protective response in Balb/c mice after challenge with Mtb H37Rv strain. The intratracheal model of progressive pulmonary TB was used to assess the level of protection in terms of bacterial load as well as the pathological changes in the lungs of immunized Balb/c mice following challenge with Mtb. Mice immunized with the lipid-based preparation from Ms either adjuvanted with Alum (LMs-AL) or nonadjuvanted (LMs) showed significant reductions in bacterial load (P < 0.01) compared to the negative control group (animals immunized with phosphate buffered saline (PBS)). Both lipid formulations showed the same level of protection as Bacille Calmette and Guerin (BCG). Regarding the pathologic changes in the lungs, mice immunized with both lipid formulations showed less pneumonic area when compared with the PBS group (P < 0.01) and showed similar results compared with the BCG group. These findings suggest the potential of LMs as a promising vaccine candidate against TB. PMID:25548767

  7. Maxillary sinusitis with pulmonary tuberculosis

    PubMed Central

    Upadhyay, Rashmi; Prakash, Ved; Singh, Abhishek Bahadur; Saheer, S

    2014-01-01

    Tubercular infection of the nasal cavity is an infrequently encountered condition. More so, after the discovery of relevant antibiotics, nasal sinus tuberculosis is not commonly seen. Few cases have reported tuberculosis of the paranasal sinuses, nasopharynx and larynx. With the increasing incidence of HIV, these rare forms of infection have started re-emerging. We present a case of a middle aged man presenting with nasal cavity lesion along with pulmonary tuberculosis, which came to light only after the diagnosis of maxillary sinus tuberculosis. PMID:25085948

  8. Pulmonary Tuberculosis and Lepromatous Leprosy Coinfection

    PubMed Central

    Sendrasoa, F. A.; Ranaivo, I. M.; Raharolahy, O.; Andrianarison, M.; Ramarozatovo, L. S.; Rapelanoro Rabenja, F.

    2015-01-01

    Simultaneous occurrence of leprosy and pulmonary tuberculosis is reported infrequently in the modern era. We report a case of pulmonary tuberculosis diagnosed in patient being treated with glucocorticoids for complications of leprosy (type II reaction). Physicians should recognize that the leprosy patients treated with glucocorticoid may develop tuberculosis. PMID:26504603

  9. Trends and predictors of changes in pulmonary function after treatment for pulmonary tuberculosis

    PubMed Central

    Chung, Kuei-Pin; Chen, Jung-Yueh; Lee, Chih-Hsin; Wu, Huey-Dong; Wang, Jann-Yuan; Lee, Li-Na; Yu, Chong-Jen; Yang, Pan-Chyr

    2011-01-01

    OBJECTIVES: The present study aimed to investigate the trends in changes in pulmonary function and the risk factors for pulmonary function deterioration in patients with pulmonary tuberculosis after completing treatment. INTRODUCTION: Patients usually have pulmonary function abnormalities after completing treatment for pulmonary tuberculosis. The time course for changes in pulmonary function and the risk factors for deterioration have not been well studied. METHODS: A total of 115 patients with 162 pulmonary function results were analyzed. We retrieved demographic and clinical data, radiographic scores, bacteriological data, and pulmonary function data. A generalized additive model with a locally weighted scatterplot smoothing technique was used to evaluate the trends in changes in pulmonary function. A generalized estimating equation model was used to determine the risk factors associated with deterioration of pulmonary function. RESULTS: The median interval between the end of anti-tuberculosis treatment and the pulmonary function test was 16 months (range: 0 to 112 months). The nadir of pulmonary function occurred approximately 18 months after the completion of the treatment. The risk factors associated with pulmonary function deterioration included smear-positive disease, extensive pulmonary involvement prior to anti-tuberculosis treatment, prolonged anti-tuberculosis treatment, and reduced radiographic improvement after treatment. CONCLUSIONS: After the completion of anti-tuberculosis TB treatment, several risk factors predicted pulmonary function deterioration. For patients with significant respiratory symptoms and multiple risk factors, the pulmonary function test should be followed up to monitor the progression of functional impairment, especially within the first 18 months after the completion of anti-tuberculosis treatment. PMID:21655745

  10. Virulence and Immune Response Induced by Mycobacterium avium Complex Strains in a Model of Progressive Pulmonary Tuberculosis and Subcutaneous Infection in BALB/c Mice

    PubMed Central

    González-Pérez, Mónica; Mariño-Ramírez, Leonardo; Parra-López, Carlos Alberto; Murcia, Martha Isabel; Marquina, Brenda; Mata-Espinoza, Dulce; Rodriguez-Míguez, Yadira; Baay-Guzman, Guillermina J.; Huerta-Yepez, Sara

    2013-01-01

    The genus Mycobacterium comprises more than 150 species, including important pathogens for humans which cause major public health problems. The vast majority of efforts to understand the genus have been addressed in studies with Mycobacterium tuberculosis. The biological differentiation between M. tuberculosis and nontuberculous mycobacteria (NTM) is important because there are distinctions in the sources of infection, treatments, and the course of disease. Likewise, the importance of studying NTM is not only due to its clinical significance but also due to the mechanisms by which some species are pathogenic while others are not. Mycobacterium avium complex (MAC) is the most important group of NTM opportunistic pathogens, since it is the second largest medical complex in the genus after the M. tuberculosis complex. Here, we evaluated the virulence and immune response of M. avium subsp. avium and Mycobacterium colombiense, using experimental models of progressive pulmonary tuberculosis and subcutaneous infection in BALB/c mice. Mice infected intratracheally with a high dose of MAC strains showed high expression of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase with rapid bacillus elimination and numerous granulomas, but without lung consolidation during late infection in coexistence with high expression of anti-inflammatory cytokines. In contrast, subcutaneous infection showed high production of the proinflammatory cytokines TNF-α and gamma interferon with relatively low production of anti-inflammatory cytokines such as interleukin-10 (IL-10) or IL-4, which efficiently eliminate the bacilli but maintain extensive inflammation and fibrosis. Thus, MAC infection evokes different immune and inflammatory responses depending on the MAC species and affected tissue. PMID:23959717

  11. Public Transportation and Pulmonary Tuberculosis, Lima, Peru

    PubMed Central

    Sánchez-Pérez, Héctor J.; Sánchez, Inma; Bedoya, Alfredo; Martín, Miguel

    2007-01-01

    The association between public transportation for commuting and pulmonary tuberculosis (TB) was analyzed in workers in Lima, Peru. Traveling in minibuses was a risk factor for pulmonary TB. Preventive measures need to be taken by health services to prevent spread of this disease. PMID:18257992

  12. Animal models of cavitation in pulmonary tuberculosis.

    PubMed

    Helke, Kris L; Mankowski, Joseph L; Manabe, Yukari C

    2006-09-01

    Transmission of tuberculosis occurs with the highest frequency from patients with extensive, cavitary, pulmonary disease and positive sputum smear microscopy. In animal models of tuberculosis, the development of caseous necrosis is an important prerequisite for the formation of cavities although the immunological triggers for liquefaction are unknown. We review the relative merits and the information gleaned from the available animal models of pulmonary cavitation. Understanding the host-pathogen interaction important to the formation of cavities may lead to new strategies to prevent cavitation and thereby, block transmission. PMID:16359922

  13. Utility of PCR in diagnosing pulmonary tuberculosis.

    PubMed Central

    Bennedsen, J; Thomsen, V O; Pfyffer, G E; Funke, G; Feldmann, K; Beneke, A; Jenkins, P A; Hegginbothom, M; Fahr, A; Hengstler, M; Cleator, G; Klapper, P; Wilkins, E G

    1996-01-01

    At present, the rapid diagnosis of pulmonary tuberculosis rests with microscopy. However, this technique is insensitive and many cases of pulmonary tuberculosis cannot be initially confirmed. Nucleic acid amplification techniques are extremely sensitive, but when they are applied to tuberculosis diagnosis, they have given variable results. Investigators at six centers in Europe compared a standardized PCR system (Amplicor; Roche) against conventional culture methods. Defined clinical information was collected. Discrepant samples were retested, and inhibition assays and backup amplification with a separate primer pair were performed. Mycobacterium tuberculosis complex organisms were recovered from 654 (9.1%) of 7,194 samples and 293 (7.8%) of 3,738 patients. Four hundred fifty-two of the M. tuberculosis isolates from 204 patients were smear positive and culture positive. Among the culture-positive specimens, PCR had a sensitivity of 91.4% for smear-positive specimens and 60.9% for smear-negative specimens, with a specificity of 96.1%. Analysis of 254 PCR-positive, culture-negative specimens with discrepant results revealed that 130 were from patients with recently diagnosed tuberculosis and 94 represented a presumed laboratory error. Similar analysis of 118 PCR-negative, culture-positive specimens demonstrated that 27 discrepancies were due to presumed uneven aliquot distribution and 11 were due to presumed laboratory error; PCR inhibitors were detected in 8 specimens. Amplicor enables laboratories with little previous experience with nucleic acid amplification to perform PCR. Disease in more than 60% of the patients with tuberculosis with smear-negative, culture-positive specimens can be diagnosed at the time of admission, and potentially all patients with smear-positive specimens can immediately be confirmed as being infected with M. tuberculosis, leading to improved clinical management. PMID:8735089

  14. Laryngeal Leishmaniasis with Extra-pulmonary Tuberculosis.

    PubMed

    Tayal, Swati; Khatiwada, Saurav; Sehrawat, Priyanka; Nischal, Neeraj; Jorwal, Pankaj; Soneja, Manish; Sharma, M C; Sharma, S K; Verma, Pankaj; Singh, Anup

    2015-09-01

    Clinical presentations of Leishmania infection include visceral (most common form), cutaneous, mucocutaneous, mucosal and post-kala-azar dermal leishmaniasis. Mucosal form of leishmaniasis mostly involves oral and nasal mucosa. Rarely, laryngeal and pharyngeal mucosa may also be involved. Its concomitant presence with tuberculosis (TB), a disease rampant in India, is uncommon. Here we are reporting a case of isolated laryngeal leishmaniasis associated with extra-pulmonary tuberculosis (EPTB), with approach to diagnosis and treatment in a tropical resource-limited setting. PMID:27608871

  15. Pulmonary tuberculosis: clinical features and patient management.

    PubMed

    Gough, Andrea; Kaufman, Gerri

    Pulmonary tuberculosis (TB) is a common infectious disease and a major cause of illness and death throughout the world, particularly in developing countries. This article explores the difference between latent TB infection and active TB disease, and discusses the pharmacological management of TB and issues around adherence to medication. Although TB is usually managed by specialist teams it is essential that all practitioners have an understanding of the signs and symptoms of the disease to ensure early referral and accurate diagnosis. PMID:21888103

  16. [Immune complex glomerulonephritis associated with pulmonary tuberculosis].

    PubMed

    Villar, I; Hernández, E; Cozzi, J; Paletta, C; Mathurín, S

    1994-01-01

    A 32 year old man was admitted for dyspnea, hemoptysis, macroscopic hematuria, hypertension (140/100), peripheral edema and hemodynamic decompensation. Lung Xrays revealed pulmonary edema and a cavity in the left apex. Laboratory determinations revealed an altered renal function with increased creatinine and urea levels and nephrotic syndrome. There was leucocyturia, hematuria and cylindruria. The sputum showed a large number of acid-fast bacilli. The patient began anti-tuberculosis treatment with three drugs (isoniacid, rifampicin, pirazinamide). On ultrasonography, both kidneys revealed ecogenic lesions with size, shape and cortico-medular relationship preserved. The patient persisted with altered renal function, steady levels of urea nitrogen, creatinine and potassium, preserved diuresis and hypertension. Bidimensional echocardiogram: LVDD 55 mm, hypoquinetic septum, pericardic effusion, thickened pericardium, pleural effusion, shortening fraction decreased. He received treatment for this congestive cardiac failure and hypertension with enalapril, nifedipine and fursemide. A percutaneous renal biopsy was performed with anatomopathologic diagnosis of diffuse encocapillar proliferative glomerulonephritis with crescents (15%) and total glomerular sclerosis (33%). Immunofluorescence: positive, immune-complexes with IgM and C3. The patient gradually recovered his normal renal function, improved his pleural effusions and normalized his cardiac function. He was discharged in good clinical condition on the 69th day of anti-tuberculosis treatment. An association between pulmonary tuberculosis and glomerulonephritis is discussed. It is proposed that renal lesions might be the consequence of the tuberculosis due to the sedimentation of circulating immune-complexes. PMID:7854090

  17. Pulmonary gas transfer 20 years after pneumonectomy for pulmonary tuberculosis.

    PubMed Central

    Gimeno, F; Kraan, J K; Orie, N G; Peset, R

    1977-01-01

    The changes in pulmonary function after pneumonectomy in 13 patients with pulmonary tuberculosis have been studied. The data at the time of two follow-up studies are compared with those obtained before the pneumonectomy. The first follow-up was carried out between 5 and 30 months postoperatively and the second between 20 and 24 years later. The results of this second follow-up show a relatively normal arterial oxygen saturation and gas transfer factor but an increased residual volume which cannot be explained by increasing age alone. PMID:841538

  18. [The satisfaction of personal needs in patients with pulmonary tuberculosis].

    PubMed

    Sukhova, E V

    2005-01-01

    The founder of humanistic psychology A. Maslow divided the needs of a personality into several levels--from the lowest to the highest ones. Higher-leveled needs rise when the lower-leveled needs are satisfied. A great deal of factors affect the origination and satisfaction of needs, but they are always interrelated with social values. The extent to which personality needs are satisfied in patients with pulmonary tuberculosis has not been studied. A special questionnaire has been drawn up to study the extent to which personality needs are met. Its suitability has been determined, by using a group of patients with bronchial asthma. The extent to which personality needs are satisfied in patients with pulmonary tuberculosis was studied in 178 patients with infiltrative pulmonary tuberculosis and 253 patients with fibrocavernous pulmonary tuberculosis. The results have shown that the extent to which personality needs are satisfied in patients with tuberculosis is lower than that in apparently healthy individuals of the same social status. In females with infiltrative pulmonary tuberculosis, the needs for safety are satisfied to a lesser extent. In those with fibrocavernous pulmonary tuberculosis, the extent to which the physiological, safety, and self-realization needs is decreased. In males with infiltrative pulmonary tuberculosis, the physiological, noetic, and self-realization needs are satisfied to a lesser extent. In those with fibrocavernous pulmonary tuberculosis, the extent to which the physiological, safety, group decision-making, noetic and self-realization needs is decreased. PMID:15801639

  19. Anemia in hospitalized patients with pulmonary tuberculosis*

    PubMed Central

    Oliveira, Marina Gribel; Delogo, Karina Neves; de Oliveira, Hedi Marinho de Melo Gomes; Ruffino-Netto, Antonio; Kritski, Afranio Lineu; Oliveira, Martha Maria

    2014-01-01

    OBJECTIVE: To describe the prevalence of anemia and of its types in hospitalized patients with pulmonary tuberculosis. METHODS: This was a descriptive, longitudinal study involving pulmonary tuberculosis inpatients at one of two tuberculosis referral hospitals in the city of Rio de Janeiro, Brazil. We evaluated body mass index (BMI), triceps skinfold thickness (TST), arm muscle area (AMA), ESR, mean corpuscular volume, and red blood cell distribution width (RDW), as well as the levels of C-reactive protein, hemoglobin, transferrin, and ferritin. RESULTS: We included 166 patients, 126 (75.9%) of whom were male. The mean age was 39.0 ± 10.7 years. Not all data were available for all patients: 18.7% were HIV positive; 64.7% were alcoholic; the prevalences of anemia of chronic disease and iron deficiency anemia were, respectively, 75.9% and 2.4%; and 68.7% had low body weight (mean BMI = 18.21 kg/m2). On the basis of TST and AMA, 126 (78.7%) of 160 patients and 138 (87.9%) of 157 patients, respectively, were considered malnourished. Anemia was found to be associated with the following: male gender (p = 0.03); low weight (p = 0.0004); low mean corpuscular volume (p = 0.03);high RDW (p = 0; 0003); high ferritin (p = 0.0005); and high ESR (p = 0.004). We also found significant differences between anemic and non-anemic patients in terms of BMI (p = 0.04), DCT (p = 0.003), and ESR (p < 0.001). CONCLUSIONS: In this sample, high proportions of pulmonary tuberculosis patients were classified as underweight and malnourished, and there was a high prevalence of anemia of chronic disease. In addition, anemia was associated with high ESR and malnutrition. PMID:25210963

  20. Making a timely diagnosis of pulmonary tuberculosis

    PubMed Central

    Long, Richard

    2015-01-01

    Making a timely diagnosis of adult-type pulmonary tuberculosis (TB) is critical to interrupting transmission and optimizing treatment outcomes. A hypothesis based on clinical experience is that a timely diagnosis may be made by addressing seven clinical rubrics: six related to history, one to the laboratory. Responses may be considered to be part of a clinical heuristic for making a timely diagnosis of pulmonary TB. The larger the number of affirmative responses, the more likely the diagnosis, although it is probable some questions carry more weight than others. The radiograph is key and may almost be considered to be confirmatory of the history. Collectively, the responses should prompt suspicion of pulmonary TB – submission of sputum for acid-fast bacilli smear and culture, and respiratory isolation. PMID:26469154

  1. Antimicrobial therapy of pulmonary tuberculosis*

    PubMed Central

    McDermott, Walsh

    1960-01-01

    The discovery, some nine years ago, of the highly specific antituberculous drug, isoniazid, marked an important advance in the antimicrobial therapy of tuberculosis, first practised successfully with streptomycin and p-aminosalicylic acid (PAS) in the late 'forties. Isoniazid is relatively non-toxic and, unlike streptomycin, can be administered orally, so that it is eminently suitable for use, either alone or in combination with PAS, in the domiciliary treatment of tuberculous patients. The wisdom of employing it on a large scale in home-treatment programmes, however, has been questioned on the ground that such wide-spread use might result in a spread of tubercle bacilli resistant to the drug. This controversial subject is discussed in some detail in this general review of the chemotherapy of tuberculosis. The author is convinced that, so far, the benefits of isoniazid therapy have outweighed the disadvantages and, though well aware of the possible consequences in terms of isoniazid-resistance, sees no reason at the present time for not making full use of this valuable weapon in the antituberculosis armamentarium. PMID:20604078

  2. [Pulmonary function in patients with disseminated pulmonary tuberculosis].

    PubMed

    Nefedov, V B; Shergina, E A; Popova, L A

    2007-01-01

    Vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/VC%, PEF, MEF25%, MEF50%, MEF75%, TLS, TGV, pulmonary residual volume (PRV), Raw, Rin, Rex, DLCO-SB, DLCO-SS, PaO2, and PaCO2 were determined in 29 patients with disseminated pulmonary tuberculosis. Pulmonary dysfunction was detected in 93.1% of the patients. Changes were found in lung volumes and capacities in 65.5%, impaired bronchial patency and pulmonary gas exchange dysfunction were in 79.3 and 37.9%, respectively. The changes in pulmonary volumes and capacities appeared as increased PRV, decreased VC, FVC, and TLS, decreased and increased TGV; impaired bronchial patency presented as decreased PEF, MEF25%, MEF50%, MEF75%, and FEV1/VC% and increased Raw, Rin, and Rex; pulmonary gas exchange dysfunction manifested itself as reduced DLCO-SS and PaO2 and decreased and increased PaCO2. The observed functional changes varied from slight to significant and pronounced with a preponderance of small disorders, a lower detection rate of significant disorders, and rare detection of very pronounced ones. PMID:18041129

  3. [Pulmonary function in patients with infiltrative pulmonary tuberculosis].

    PubMed

    Nefedov, V B; Popova, L A; Shergina, E A

    2007-01-01

    Vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/VC%, PEF, MEF25, MEF50, MEF75, TLC, TGV, pulmonary residual volume (PRV), R(aw), R(in),, R(ex), DLCO-SB, DLCO-SS, PaO2, and PaCO2 were determined in 103 patients with infiltrative pulmonary tuberculosis. Pulmonary dysfunction was detected in 83.5% of the patients. Changes were found in lung volumes and capacities in 63.1%, impaired bronchial patency and pulmonary gas exchange dysfunction were in 60.2 and 41.7%, respectively. The changes in pulmonary volumes and capacities appeared as increased PRV, decreased VC and FVC, and decreased and increased TGV and TLC; impaired bronchial patency presented as decreased PEF, MEF25, MEF50, MEF75, FEV1/VC% and increased R(aw) R(in), and R(ex); pulmonary gas exchange dysfunction manifested itself as reduced DLCO-SB, DLCO-SS, and PaO2 and decreased and increased PaCO2. The magnitude of the observed functional changes was generally slight. Significant disorders were observed rarely and very pronounced ones were exceptional. PMID:17915466

  4. Acute Myeloid Leukemia Presenting with Pulmonary Tuberculosis

    PubMed Central

    Thomas, Merlin; AlGherbawe, Mushtak

    2014-01-01

    We report the case of a 58-year-old immunocompetent man presenting with fever, cough, anorexia, weight loss, and cervical lymphadenopathy. Blood investigations revealed severe neutropenia with monocytosis. Chest imaging showed bilateral reticular infiltrates with mediastinal widening. Bronchoalveolar lavage culture and molecular test were positive for Mycobacterium tuberculosis and treatment with isoniazid, rifampicin, pyrazinamide, and ethambutol was started. Although pulmonary tuberculosis could explain this clinical presentation we suspected associated blood dyscrasias in view of significant monocytosis and mild splenomegaly. Bone marrow aspiration revealed acute myeloid leukemia. Thereafter the patient received induction chemotherapy and continued antituberculous treatment. After first induction of chemotherapy patient was in remission and successfully completed 6 months antituberculosis therapy without any complications. To our knowledge there has been no such case reported from the State of Qatar to date. PMID:24987539

  5. A Multi-Antigenic Adenoviral-Vectored Vaccine Improves BCG-Induced Protection of Goats against Pulmonary Tuberculosis Infection and Prevents Disease Progression

    PubMed Central

    Pérez de Val, Bernat; Vidal, Enric; Villarreal-Ramos, Bernardo; Gilbert, Sarah C.; Andaluz, Anna; Moll, Xavier; Martín, Maite; Nofrarías, Miquel; McShane, Helen; Vordermeier, H. Martin; Domingo, Mariano

    2013-01-01

    The “One world, one health” initiative emphasizes the need for new strategies to control human and animal tuberculosis (TB) based on their shared interface. A good example would be the development of novel universal vaccines against Mycobacterium tuberculosis complex (MTBC) infection. This study uses the goat model, a natural TB host, to assess the protective effectiveness of a new vaccine candidate in combination with Bacillus Calmette-Guerin (BCG) vaccine. Thirty-three goat kids were divided in three groups: Group 1) vaccinated with BCG (week 0), Group 2) vaccinated with BCG and boosted 8 weeks later with a recombinant adenovirus expressing the MTBC antigens Ag85A, TB10.4, TB9.8 and Acr2 (AdTBF), and Group 3) unvaccinated controls. Later on, an endobronchial challenge with a low dose of M. caprae was performed (week 15). After necropsy (week 28), the pulmonary gross pathology was quantified using high resolution Computed Tomography. Small granulomatous pulmonary lesions (< 0.5 cm diameter) were also evaluated through a comprehensive qualitative histopathological analysis. M. caprae CFU were counted from pulmonary lymph nodes. The AdTBF improved the effects of BCG reducing gross lesion volume and bacterial load, as well as increasing weight gain. The number of Ag85A-specific gamma interferon-producing memory T-cells was identified as a predictor of vaccine efficacy. Specific cellular and humoral responses were measured throughout the 13-week post-challenge period, and correlated with the severity of lesions. Unvaccinated goats exhibited the typical pathological features of active TB in humans and domestic ruminants, while vaccinated goats showed only very small lesions. The data presented in this study indicate that multi-antigenic adenoviral vectored vaccines boosts protection conferred by vaccination with BCG. PMID:24278420

  6. [Update on the radiological study of pulmonary tuberculosis].

    PubMed

    Navarro Ballester, A; Marco Domenech, S F

    2015-01-01

    Tuberculosis has made a comeback in recent years. This upsurge has been attributed to factors such as increased immigration and the human immunodeficiency virus epidemic. Primary pulmonary tuberculosis manifests radiologically with parenchymal involvement, lymph node involvement, pleural effusion, and/or miliary disease. In post-primary tuberculosis, the earliest radiological sign is small nodules and branching centrilobular lesions that increase in size and coalesce to form ill-defined patchy consolidations; cavitations are very characteristic of active disease. The aim of this article is to describe the radiologic findings for pulmonary tuberculosis and its complications. PMID:26074301

  7. [Pulmonary function in patients with focal pulmonary tuberculosis].

    PubMed

    Nefedov, V B; Popova, L A; Shergina, E A

    2008-01-01

    Vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/VC%, PEF, MEF25, MEF50, MEF75, TLC, TGV, pulmonary residual volume (PRV), Raw, Rin, Rcx, DLCO-SB, DLCO-SS/VA, PaO2, and PaCO2 were determined in 40 patients with focal pulmonary tuberculosis. Changes were found in lung volumes and capacities in 75%, impaired bronchial patency and pulmonary gas exchange dysfunction were in 57.5 and 25%, respectively. The lung volume and capacity changes appeared mainly as increased TGV and PRV; impaired bronchial patency presented as decreased MEF50, MEF75, and FEV1/VC%; pulmonary gas exchange dysfunction manifested itself as reduced DLCO-SB, PaO2, and PaCO2. The magnitude of the observed functional changes was generally slight. TGV and PRL increased up to 148-187 and 142-223% of the normal values, respectively; MEF50, MEF75, FEV1/VC%, and DLCO decreased to 59-24, 58-26, 78-57, and 78-67% of the normal values and PaO2 and PaCO2 did to 79-69 and 34-30 cm Hg. PMID:18450075

  8. [Therapy and Rehabilitation of Patients with Pulmonary Tuberculosis and Different Treatment Adherence].

    PubMed

    Rubleva, N V; Kolomiets, V M; Kochetkova, E Ya

    2016-01-01

    The pulmonary tuberculosis process as dependent on the disease form and the therapy efficacy with the use of Cycloferon in the treatment scheme were investigated. The study had two stages. At the first stage the data concerning 358 patients with primary pulmonary tuberculosis and infiltration (93 patients) or degradation (89 patients) and 176 patients with pulmonary fibrocavernous tuberculosis were analysed. At the second stage the efficacy of the treatment schemes applied to the patients with pulmonary fibrocavernous tuberculosis was compared. The etiotropic therapy intensive phase was applied to all the patients. Moreover, 56 patients (group 1) under the therapy and rehabilitatinon were treated with Cycloferon in a dose of 0.25 administered intramuscularly twice a week (not less than 16 injections for the course), 60 patients (group 2) were treated with Omega 3, 30 patients (group 3) were given the standard complex (vitamins and tonics), 30 patients (group 4) were under the etiotropic therapy alone. The following additional factors promoting progression and aggravation of the tuberculosis process were confirmed: degradation at the time of the disease diagnosis, high resistance of the pathogen to antituberculosis drugs, low adherence to the treatment, social desadaptation and especially psychofunctional state of the patients. The use of Cycloferon in the schemes of the intensive phase treatment of the primary fibrocavernous tuberculosis resulted in reduction of the intoxication signs, bacteria isolation, positive dynamics of the cavity healing, lower lung infiltration and consequently high frequency of the treatment positive outcomes (94.1 ± 3.33%). PMID:27337863

  9. Diabetes mellitus with pulmonary tuberculosis--a double trouble.

    PubMed

    Kant, Surya; Lata, Hem; Natu, S M; Mishra, Arvind Kumar; Verma, N S

    2013-03-01

    Diabetic patients are often at a higher risk for developing several types of infections and infection does alter the handling of glucose by tissues. Pulmonary infections in diabetics are characterised by alteration in host defence, in entire body and in the lung locally as well as in the function of respiratory epithelium and ciliary motility. Association between diabetes mellitus and pulmonary tuberculosis is well established, while the prevalence of tuberculosis is increased 4-5 times more among diabetics. Impairment of host defence plays an important role for changing the clinical, radiological and bacteriological presentation in diabetic patients. It is also reported by the various studies that hyperglycaemia favours the growth of tuberculosis bacilli. So the severity of tuberculosis appears more cirtical with the degree of hyperglycaemia and host defence activity. This overlap between the diabetic and tuberculosis epidemics could adversely affect global tuberculosis control efforts. PMID:24592761

  10. Pathology and immune reactivity: understanding multidimensionality in pulmonary tuberculosis.

    PubMed

    Dorhoi, Anca; Kaufmann, Stefan H E

    2016-03-01

    Heightened morbidity and mortality in pulmonary tuberculosis (TB) are consequences of complex disease processes triggered by the causative agent, Mycobacterium tuberculosis (Mtb). Mtb modulates inflammation at distinct stages of its intracellular life. Recognition and phagocytosis, replication in phagosomes and cytosol escape induce tightly regulated release of cytokines [including interleukin (IL)-1, tumor necrosis factor (TNF), IL-10], chemokines, lipid mediators, and type I interferons (IFN-I). Mtb occupies various lung lesions at sites of pathology. Bacteria are barely detectable at foci of lipid pneumonia or in perivascular/bronchiolar cuffs. However, abundant organisms are evident in caseating granulomas and at the cavity wall. Such lesions follow polar trajectories towards fibrosis, encapsulation and mineralization or liquefaction, extensive matrix destruction, and tissue injury. The outcome is determined by immune factors acting in concert. Gradients of cytokines and chemokines (CCR2, CXCR2, CXCR3/CXCR5 agonists; TNF/IL-10, IL-1/IFN-I), expression of activation/death markers on immune cells (TNF receptor 1, PD-1, IL-27 receptor) or abundance of enzymes [arginase-1, matrix metalloprotease (MMP)-1, MMP-8, MMP-9] drive genesis and progression of lesions. Distinct lesions coexist such that inflammation in TB encompasses a spectrum of tissue changes. A better understanding of the multidimensionality of immunopathology in TB will inform novel therapies against this pulmonary disease. PMID:26438324

  11. Mycobacterium tuberculosis Zinc Metalloprotease-1 Elicits Tuberculosis-Specific Humoral Immune Response Independent of Mycobacterial Load in Pulmonary and Extra-Pulmonary Tuberculosis Patients

    PubMed Central

    Vemula, Mani H.; Ganji, Rakesh; Sivangala, Ramya; Jakkala, Kiran; Gaddam, Sumanlatha; Penmetsa, Sitaramaraju; Banerjee, Sharmistha

    2016-01-01

    Conventionally, facultative intracellular pathogen, Mycobacterium tuberculosis, the tuberculosis (TB) causing bacilli in human is cleared by cell-mediated immunity (CMI) with CD4+ T cells playing instrumental role in protective immunity, while antibody-mediated immunity (AMI) is considered non-protective. This longstanding convention has been challenged with recent evidences of increased susceptibility of hosts with compromised AMI and monoclonal antibodies conferring passive protection against TB and other intracellular pathogens. Therefore, novel approaches toward vaccine development include strategies aiming at induction of humoral response along with CMI. This necessitates the identification of mycobacterial proteins with properties of immunomodulation and strong immunogenicity. In this study, we determined the immunogenic potential of M. tuberculosis Zinc metalloprotease-1 (Zmp1), a secretory protein essential for intracellular survival and pathogenesis of M. tuberculosis. We observed that Zmp1 was secreted by in vitro grown M. tuberculosis under granuloma-like stress conditions (acidic, oxidative, iron deficiency, and nutrient deprivation) and generated Th2 cytokine microenvironment upon exogenous treatment of peripheral blood mononulear cells PBMCs with recombinant Zmp1 (rZmp1). This was supported by recording specific and robust humoral response in TB patients in a cohort of 295. The anti-Zmp1 titers were significantly higher in TB patients (n = 121) as against healthy control (n = 62), household contacts (n = 89) and non-specific infection controls (n = 23). A significant observation of the study is the presence of equally high titers of anti-Zmp1 antibodies in a range of patients with high bacilli load (sputum bacilli load of 300+ per mL) to paucibacillary smear-negative pulmonary tuberculosis (PTB) cases. This clearly indicated the potential of Zmp1 to evoke an effective humoral response independent of mycobacterial load. Such mycobacterial proteins can

  12. Mycobacterium tuberculosis Zinc Metalloprotease-1 Elicits Tuberculosis-Specific Humoral Immune Response Independent of Mycobacterial Load in Pulmonary and Extra-Pulmonary Tuberculosis Patients.

    PubMed

    Vemula, Mani H; Ganji, Rakesh; Sivangala, Ramya; Jakkala, Kiran; Gaddam, Sumanlatha; Penmetsa, Sitaramaraju; Banerjee, Sharmistha

    2016-01-01

    Conventionally, facultative intracellular pathogen, Mycobacterium tuberculosis, the tuberculosis (TB) causing bacilli in human is cleared by cell-mediated immunity (CMI) with CD4(+) T cells playing instrumental role in protective immunity, while antibody-mediated immunity (AMI) is considered non-protective. This longstanding convention has been challenged with recent evidences of increased susceptibility of hosts with compromised AMI and monoclonal antibodies conferring passive protection against TB and other intracellular pathogens. Therefore, novel approaches toward vaccine development include strategies aiming at induction of humoral response along with CMI. This necessitates the identification of mycobacterial proteins with properties of immunomodulation and strong immunogenicity. In this study, we determined the immunogenic potential of M. tuberculosis Zinc metalloprotease-1 (Zmp1), a secretory protein essential for intracellular survival and pathogenesis of M. tuberculosis. We observed that Zmp1 was secreted by in vitro grown M. tuberculosis under granuloma-like stress conditions (acidic, oxidative, iron deficiency, and nutrient deprivation) and generated Th2 cytokine microenvironment upon exogenous treatment of peripheral blood mononulear cells PBMCs with recombinant Zmp1 (rZmp1). This was supported by recording specific and robust humoral response in TB patients in a cohort of 295. The anti-Zmp1 titers were significantly higher in TB patients (n = 121) as against healthy control (n = 62), household contacts (n = 89) and non-specific infection controls (n = 23). A significant observation of the study is the presence of equally high titers of anti-Zmp1 antibodies in a range of patients with high bacilli load (sputum bacilli load of 300+ per mL) to paucibacillary smear-negative pulmonary tuberculosis (PTB) cases. This clearly indicated the potential of Zmp1 to evoke an effective humoral response independent of mycobacterial load. Such mycobacterial proteins

  13. Plasma metabolomics in human pulmonary tuberculosis disease: a pilot study.

    PubMed

    Frediani, Jennifer K; Jones, Dean P; Tukvadze, Nestan; Uppal, Karan; Sanikidze, Eka; Kipiani, Maia; Tran, ViLinh T; Hebbar, Gautam; Walker, Douglas I; Kempker, Russell R; Kurani, Shaheen S; Colas, Romain A; Dalli, Jesmond; Tangpricha, Vin; Serhan, Charles N; Blumberg, Henry M; Ziegler, Thomas R

    2014-01-01

    We aimed to characterize metabolites during tuberculosis (TB) disease and identify new pathophysiologic pathways involved in infection as well as biomarkers of TB onset, progression and resolution. Such data may inform development of new anti-tuberculosis drugs. Plasma samples from adults with newly diagnosed pulmonary TB disease and their matched, asymptomatic, sputum culture-negative household contacts were analyzed using liquid chromatography high-resolution mass spectrometry (LC-MS) to identify metabolites. Statistical and bioinformatics methods were used to select accurate mass/charge (m/z) ions that were significantly different between the two groups at a false discovery rate (FDR) of q<0.05. Two-way hierarchical cluster analysis (HCA) was used to identify clusters of ions contributing to separation of cases and controls, and metabolomics databases were used to match these ions to known metabolites. Identity of specific D-series resolvins, glutamate and Mycobacterium tuberculosis (Mtb)-derived trehalose-6-mycolate was confirmed using LC-MS/MS analysis. Over 23,000 metabolites were detected in untargeted metabolomic analysis and 61 metabolites were significantly different between the two groups. HCA revealed 8 metabolite clusters containing metabolites largely upregulated in patients with TB disease, including anti-TB drugs, glutamate, choline derivatives, Mycobacterium tuberculosis-derived cell wall glycolipids (trehalose-6-mycolate and phosphatidylinositol) and pro-resolving lipid mediators of inflammation, known to stimulate resolution, efferocytosis and microbial killing. The resolvins were confirmed to be RvD1, aspirin-triggered RvD1, and RvD2. This study shows that high-resolution metabolomic analysis can differentiate patients with active TB disease from their asymptomatic household contacts. Specific metabolites upregulated in the plasma of patients with active TB disease, including Mtb-derived glycolipids and resolvins, have potential as biomarkers

  14. Two Cases of Pulmonary Tuberculosis Caused by Mycobacterium tuberculosis subsp. canetti

    PubMed Central

    Morillon, Marc; Koeck, Jean-Louis; Varnerot, Anne; Briant, Jean-François; Nguyen, Gilbert; Verrot, Denis; Bonnet, Daniel; Vincent, Véronique

    2002-01-01

    We identified an unusual strain of mycobacteria from two patients with pulmonary tuberculosis by its smooth, glossy morphotype and, primarily, its genotypic characteristics. Spoligotyping and restriction fragment length polymorphism typing were carried out with the insertion sequence IS6110 patterns. All known cases of tuberculosis caused by Mycobacterium canetti have been contracted in the Horn of Africa. PMID:12453369

  15. Pulmonary disease due to Mycobacterium tuberculosis in a horse: zoonotic concerns and limitations of antemortem testing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A case of pulmonary tuberculosis caused by Mycobacterium tuberculosis was diagnosed in a horse. Clinical evaluation performed prior to euthanasia did not suggest tuberculosis, but postmortem examination provided pathological and bacteriological evidence of disease. In the lungs, multiple tuberculoid...

  16. Empyema necessitans: very late complication of pulmonary tuberculosis.

    PubMed

    Gomes, Manuel Mendes; Alves, Márcia; Correia, José Bernardes; Santos, Lèlita

    2013-01-01

    Empyema necessitans is a rare clinical finding nowadays. We report the case of a patient admitted in our ward for investigation of an unknown onset anterior chest wall mass, with no accompanying signs or symptoms. It is noteworthy that the patient had had pulmonary tuberculosis submitted to thoracoplasty more than 60 years before. Thoracic MRI showed a large heterogeneous mass, with a thick wall and internal septations located at the right anterior chest wall, as well as a heterogeneous content inside the right pleural cavity, with direct communication between both. An aspirative puncture of both masses was performed, with positive cultures for Mycobacterium tuberculosis, thus leading to the diagnosis of pleural tuberculosis with anterior chest wall empyema necessitans. A drain was inserted and antibiotics started. This case draws our attention to a very rare complication of pulmonary tuberculosis and its surgical treatment, though it aroused many decades after primary infection. PMID:24326441

  17. [Differential diagnosis of pulmonary tuberculosis and community-acquired pneumonia].

    PubMed

    Deĭkina, O N; Mishin, V Iu; Demikhova, O V

    2007-01-01

    The purpose of this investigation was to enhance the efficiency of differential diagnosis of pneumonia and pulmonary tuberculosis. A hundred and fifty-nine adult patients were examined. These included 78 patients with pulmonary tuberculosis and 81 with community-acquired p neumonia. The clinical features of infiltrative pulmonary tuberculosis (n = 48) and mild community-acquired pneumonia (n = 51) were compared. The course of caseous pneumonia (n = 30) was compared with that of moderate and severe community-acquired pneumonia (n = 30). Significant differences in the manifestations of the intoxication and bronchopulmonary syndrome were not found in patients with community-acquired pneumonia and infiltrative pulmonary tuberculosis. Physical studies showed that in patients with community-acquired pneumonia, moist rale (54.9%) and crepitation (11.8%) were prevalent, but in those with infiltrative tuberculosis rale was absent in 60.4% of cases and the pattern of respiration was unchanged in 79.2%. Chest X-ray studies indicated that in patients with community-acquired pneumonia, lower lobar inflammatory changes were predominant in 62.8% of cases whereas in those with infiltrative pulmonary tuberculosis the process was mainly bilateral (43.8%) with the presence of destructive changes (83.3%) and bronchogenic dissemination (66.7%). In patients with caseous pneumonia, the intoxication syndrome was more significant than in those with severe community-acquired pneumonia. Chest X-ray studies demonstrated that in patients with caseous pneumonia, specific changes were bilateral with the involvement of 2 lobes or more, with destruction and bronchogenic dissemination while in those with community-acquired pneumonia, the pulmonary processes were predominantly bilateral (76.6%) at the lower lobar site (36.7%). PMID:17338353

  18. Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers

    PubMed Central

    Bloom, Chloe I.; Graham, Christine M.; Berry, Matthew P. R.; Rozakeas, Fotini; Redford, Paul S.; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A.; Wilkinson, Robert J.; Kendrick, Yvonne; Devouassoux, Gilles; Ferry, Tristan; Miyara, Makoto; Bouvry, Diane; Dominique, Valeyre; Gorochov, Guy; Blankenship, Derek; Saadatian, Mitra; Vanhems, Phillip; Beynon, Huw; Vancheeswaran, Rama; Wickremasinghe, Melissa; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Ho, Ling-pei; Lipman, Marc; O’Garra, Anne

    2013-01-01

    Rationale New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. Objectives To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. Methods We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. Measurements and Main Results An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Conclusions Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the

  19. Pulmonary surfactant in innate immunity and the pathogenesis of tuberculosis.

    PubMed

    Ferguson, J S; Schlesinger, L S

    2000-01-01

    Components of the innate immune system serve to protect the host from invading pathogens prior to the generation of a directed immune response, and influence the manner in which the directed immune response develops. The pulmonary surfactant system consists of a complex array of proteins and lipids that reduce surface tension of the alveoli, and appears to play an essential role in innate immunity. Investigators have recently gained insight into the interactions between components of the surfactant system and the respiratory pathogen Mycobacterium tuberculosis. It is likely that pulmonary surfactant and other innate immune determinants play significant roles in the pathogenesis of tuberculosis. PMID:11052906

  20. Pulmonary Tuberculosis in Humanized Mice Infected with HIV-1.

    PubMed

    Nusbaum, Rebecca J; Calderon, Veronica E; Huante, Matthew B; Sutjita, Putri; Vijayakumar, Sudhamathi; Lancaster, Katrina L; Hunter, Robert L; Actor, Jeffrey K; Cirillo, Jeffrey D; Aronson, Judith; Gelman, Benjamin B; Lisinicchia, Joshua G; Valbuena, Gustavo; Endsley, Janice J

    2016-01-01

    Co-infection with HIV increases the morbidity and mortality associated with tuberculosis due to multiple factors including a poorly understood microbial synergy. We developed a novel small animal model of co-infection in the humanized mouse to investigate how HIV infection disrupts pulmonary containment of Mtb. Following dual infection, HIV-infected cells were localized to sites of Mtb-driven inflammation and mycobacterial replication in the lung. Consistent with disease in human subjects, we observed increased mycobacterial burden, loss of granuloma structure, and increased progression of TB disease, due to HIV co-infection. Importantly, we observed an HIV-dependent pro-inflammatory cytokine signature (IL-1β, IL-6, TNFα, and IL-8), neutrophil accumulation, and greater lung pathology in the Mtb-co-infected lung. These results suggest that in the early stages of acute co-infection in the humanized mouse, infection with HIV exacerbates the pro-inflammatory response to pulmonary Mtb, leading to poorly formed granulomas, more severe lung pathology, and increased mycobacterial burden and dissemination. PMID:26908312

  1. Pulmonary Tuberculosis in Humanized Mice Infected with HIV-1

    PubMed Central

    Nusbaum, Rebecca J.; Calderon, Veronica E.; Huante, Matthew B.; Sutjita, Putri; Vijayakumar, Sudhamathi; Lancaster, Katrina L.; Hunter, Robert L.; Actor, Jeffrey K.; Cirillo, Jeffrey D.; Aronson, Judith; Gelman, Benjamin B.; Lisinicchia, Joshua G.; Valbuena, Gustavo; Endsley, Janice J.

    2016-01-01

    Co-infection with HIV increases the morbidity and mortality associated with tuberculosis due to multiple factors including a poorly understood microbial synergy. We developed a novel small animal model of co-infection in the humanized mouse to investigate how HIV infection disrupts pulmonary containment of Mtb. Following dual infection, HIV-infected cells were localized to sites of Mtb-driven inflammation and mycobacterial replication in the lung. Consistent with disease in human subjects, we observed increased mycobacterial burden, loss of granuloma structure, and increased progression of TB disease, due to HIV co-infection. Importantly, we observed an HIV-dependent pro-inflammatory cytokine signature (IL-1β, IL-6, TNFα, and IL-8), neutrophil accumulation, and greater lung pathology in the Mtb-co-infected lung. These results suggest that in the early stages of acute co-infection in the humanized mouse, infection with HIV exacerbates the pro-inflammatory response to pulmonary Mtb, leading to poorly formed granulomas, more severe lung pathology, and increased mycobacterial burden and dissemination. PMID:26908312

  2. [Management of respiratory failure in patients with pulmonary tuberculosis].

    PubMed

    Machida, Kazuko

    2003-02-01

    The prognosis is very poor in patients with acute respiratory failure (ARF) due to active pulmonary tuberculosis, especially in those who necessitate mechanical ventilation. The underlining factors of ARF are low nutrition, old age and severity because of patient's delay and doctor's delay. So, management consists of two parts, one, early patient detection considering of tuberculosis and early treatment, the other, focused control to high risk groups. Patients with chronic respiratory failure due to pulmonary tuberculosis sequelae have long insidious period and mainly restrictive, sometimes mixed pulmonary dysfunction. Hypercapnea, pulmonary hypertension and respiratory disorder during sleep are seen in high percentage in them. In acute on chronic failure the principles of therapy are treatment of precipitating factors such as respiratory infection or congestive heart failure, controlled (low flow) oxygen therapy, bronchial hygiene and maintaining adequate pulmonary and circulatory condition. In chronic stage patient education is very important. Management of chronic stage is constructed of nutrition control, long-term oxygen therapy, pharmacological therapy, pulmonary rehabilitation including controlled breathing technique, physical chest therapy and exercise training. Noninvasive positive pressure ventilation is effective on improvement of prognosis in chronic respiratory failure, and on treatment in acute on chronic failure. PMID:12664448

  3. Pulmonary Angiography and Embolization for Severe Hemoptysis Due to Cavitary Pulmonary Tuberculosis

    SciTech Connect

    Sanyika, Charles; Corr, Peter; Royston, Duncan; Blyth, David F.

    1999-11-15

    Purpose: To identify the role of pulmonary angiography in the diagnosis and treatment of severe hemoptysis due to cavitary pulmonary tuberculosis. Methods: Selective pulmonary angiography was performed on eight patients with severe hemoptysis uncontrolled by previous bronchial and systemic arterial embolization. Results: Three (38%) patients had Rasmussen aneurysms, which were successfully embolized with steel coils. Five patients demonstrated pulmonary arterial hypoperfusion in the diseased lung. Conclusions: We recommend pulmonary angiography in cavitary tuberculous patients with severe hemoptysis who do not respond to systemic arterial embolization. Rasmussen aneurysms are effectively treated by steel coil occlusion.

  4. Passive administration of purified secretory IgA from human colostrum induces protection against Mycobacterium tuberculosis in a murine model of progressive pulmonary infection

    PubMed Central

    2013-01-01

    Background Immunoglobulin A is the most abundant isotype in secretions from mucosal surfaces of the gastrointestinal, respiratory and genitourinary tracts and in external secretions such as colostrum, breast milk, tears and saliva. The high concentration of human secretory IgA (hsIgA) in human colostrum strongly suggests that it should play an important role in the passive immune protection against gastrointestinal and respiratory infections. Materials and methods Human secretory IgA was purified from colostrum. The reactivity of hsIgA against mycobacterial antigens and its protective capacity against mycobacterial infection was evaluated. Results The passive administration of hsIgA reduces the pneumonic area before challenge with M. tuberculosis. The intratracheal administration of M. tuberculosis preincubated with hsIgA to mice greatly reduced the bacterial load in the lungs and diminished lung tissue injury. Conclusions HsIgA purified from colostrum protects against M. tuberculosis infection in an experimental mouse model. PMID:23458564

  5. Is tuberculosis a lymphatic disease with a pulmonary portal

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tuberculosis (TB) is commonly viewed as a pulmonary disease, in which infection, persistence, induction of pathology and bacterial expulsion all occur in the lungs. In this model, enlarged lymph nodes represent reactive adenitis and spread of organisms to extrapulmonary sites results in a non-transm...

  6. Tip of nose tuberculosis: A rare presentation of extra pulmonary tuberculosis.

    PubMed

    Bajaj, Darshan K; Verma, Ajay K; Jaiswal, Riddhi; Kant, Surya; Patel, Anand; Asnani, Mona

    2016-05-01

    Tuberculosis is notorious that it affects various sites of the human body and presents in different ways. One of the uncommon or rather rare presentation of extra pulmonary tuberculosis is nasal tuberculosis. The nose apart from its physiological functions also contributes to facial aesthetics and gives a defined appearance and its deformity imparts cosmetic disfigurement and unsightly appearance. Both primary and secondary forms of nasal tuberculosis are rare but should be considered in the differential diagnosis of ulcerative or crusting lesions of the nose. Here we report such a case of nasal tuberculosis, which presented as an ulcerative and crusting lesion over the tip of the nose in a female child. The patient was given antituberculous chemotherapy after establishing the diagnosis and responded well to treatment. PMID:27195200

  7. Tip of nose tuberculosis: A rare presentation of extra pulmonary tuberculosis

    PubMed Central

    Bajaj, Darshan K.; Verma, Ajay K.; Jaiswal, Riddhi; Kant, Surya; Patel, Anand; Asnani, Mona

    2016-01-01

    Summary Tuberculosis is notorious that it affects various sites of the human body and presents in different ways. One of the uncommon or rather rare presentation of extra pulmonary tuberculosis is nasal tuberculosis. The nose apart from its physiological functions also contributes to facial aesthetics and gives a defined appearance and its deformity imparts cosmetic disfigurement and unsightly appearance. Both primary and secondary forms of nasal tuberculosis are rare but should be considered in the differential diagnosis of ulcerative or crusting lesions of the nose. Here we report such a case of nasal tuberculosis, which presented as an ulcerative and crusting lesion over the tip of the nose in a female child. The patient was given antituberculous chemotherapy after establishing the diagnosis and responded well to treatment. PMID:27195200

  8. Opportunistic microorganisms in patients undergoing antibiotic therapy for pulmonary tuberculosis

    PubMed Central

    Querido, Silvia Maria Rodrigues; Back-Brito, Graziella Nuernberg; dos Santos, Silvana Soléo Ferreira; Leão, Mariella Vieira Pereira; Koga-Ito, Cristiane Yumi; Jorge, Antonio Olavo Cardoso

    2011-01-01

    Antimicrobial therapy may cause changes in the resident oral microbiota, with the increase of opportunistic pathogens. The aim of this study was to compare the prevalence of Candida, Staphylococcus, Pseudomonas and Enterobacteriaceae in the oral cavity of fifty patients undergoing antibiotic therapy for pulmonary tuberculosis and systemically healthy controls. Oral rinsing and subgingival samples were obtained, plated in Sabouraud dextrose agar with chloramphenicol, mannitol agar and MacConkey agar, and incubated for 48 h at 37°C. Candida spp. and coagulase-positive staphylococci were identified by phenotypic tests, C. dubliniensis, by multiplex PCR, and coagulase-negative staphylococci, Enterobacteriaceae and Pseudomonas spp., by the API systems. The number of Candida spp. was significantly higher in tuberculosis patients, and C. albicans was the most prevalent specie. No significant differences in the prevalence of other microorganisms were observed. In conclusion, the antimicrobial therapy for pulmonary tuberculosis induced significant increase only in the amounts of Candida spp. PMID:24031759

  9. Prevalence of nutritional deficiency in patients with pulmonary tuberculosis*

    PubMed Central

    Piva, Silvana Gomes Nunes; Costa, Maria da Conceição Nascimento; Barreto, Florisneide Rodrigues; Pereira, Susan Martins

    2013-01-01

    OBJECTIVE: To determine the prevalence of nutritional deficiency among patients with pulmonary tuberculosis. METHODS: This was a cross-sectional study using data obtained from the Brazilian Case Registry Database and from the medical records of patients diagnosed with pulmonary tuberculosis (15-59 years of age) residing in one of the municipalities that make up the 16th Regional Health District of the state of Bahia. We calculated the incidence, lethality, and mortality rates, as well as the prevalence of nutritional deficiency, as evaluated by body mass index. Demographic, social, clinical, and epidemiological data were collected. RESULTS: Of the 72 confirmed cases of tuberculosis, 59 (81.9%) were in males, and 21 (29.2%) of the patients were in the 40-49 year age bracket. The majority (85.3%) described themselves as Mulatto or Black; 55.2% reported using alcohol; and approximately 90% were treated as outpatients. In the district and age bracket studied, the incidence of pulmonary tuberculosis was 30.6/100,000 population. Among the 72 patients, data regarding nutritional status was available for 34. Of those, 50% and 25%, respectively, presented nutritional deficiency at the beginning and at the end of treatment. No statistically significant differences were found between normal-weight and malnourished patients regarding the characteristics studied. CONCLUSIONS: The prevalence of nutritional deficiency was high among our sample of patients with pulmonary tuberculosis. This underscores the importance of nutritional follow-up for the assessment of tuberculosis treatment in the decision-making process regarding therapeutic interventions. PMID:24068270

  10. Recent progress in the development and testing of vaccines against human tuberculosis.

    PubMed

    McMurray, David N

    2003-05-01

    The growing pandemic of human tuberculosis has not been affected significantly by the widespread use of the only currently available vaccine, bacille Calmette Guerin. Bacille Calmette Guerin protects uniformly against serious paediatric forms of tuberculosis and against adult pulmonary tuberculosis in some parts of the world, but there are clearly populations in high-burden countries which do not benefit from the current vaccination regimen. New tuberculosis vaccines will be essential for the ultimate control of this ancient disease. Research over the past 10 years has produced literally hundreds of new tuberculosis vaccine candidates representing all of the major vaccine design strategies; protein/peptide vaccines in adjuvants, DNA vaccines, naturally and rationally attenuated strains of mycobacteria, recombinant mycobacteria and other living vaccine vectors expressing genes coding for immunodominant mycobacterial antigens, and non-peptide vaccines. Many of these vaccines have been tested for immunogenicity and protective efficacy in mouse and guinea pig models of low-dose pulmonary tuberculosis. In addition, alternative routes of tuberculosis vaccine delivery (e.g. oral, respiratory, gene gun) and various combinations of priming or boosting an experimental vaccine with bacille Calmette Guerin have been examined in relevant animal models. One of the most promising of these vaccines is currently in Phase I trials in human subjects, and others are expected to follow in the near future. This review will summarise the most recent progress made toward the development and preclinical evaluation of novel vaccines for human tuberculosis. PMID:12782054

  11. 78 FR 66744 - Draft Guidance for Industry on Pulmonary Tuberculosis: Developing Drugs for Treatment; Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-06

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Pulmonary Tuberculosis... industry entitled ``Pulmonary Tuberculosis: Developing Drugs for Treatment.'' The purpose of the draft... tuberculosis. This guidance applies to the development of a single investigational drug as well as...

  12. Low level nitrogen laser therapy in pulmonary tuberculosis

    PubMed Central

    Bhatia, C.C.; Sharma, N.; Hemvani, N.; Chitnis, D.S.

    2015-01-01

    Background and aims: WHO estimated 9 million new Tuberculosis cases and 1.5 million TB deaths in 2013. Globally 480000 Multi drug resistant tuberculosis cases were noted and majority of them were in India, China and Russian federation. Multi drug resistant tuberculosis cases are difficult to treat and have high mortality. Presently, it was aimed to assess prevalence of drug resistance in M. tuberculosis isolates in Central India, to check the in-vitro effect of N2 Laser on M. tuberculosis and to study the therapeutic effect of intra cavitary N2 laser on pulmonary Tuberculosis cases not responding to chemotherapy. Materials and methods: Drug sensitivity testing was carried out on 567 isolates of M. tuberculosis by proportion method. To check the effect of N2 laser on M. tuberculosis, suspension spread on LJ plate and part of the plate exposed to N2 laser for 10 min and plate incubated for 4 weeks to see the effect. For exposure to lung cavity a needle was introduced into the lung through which fiber was passed to the cavity for N2 laser irradiation for 10 min. Results: Only 12.8% isolates of M. tuberculosis were sensitive to all anti-Tubercular drugs and 21.5% were found to be resistant to Rifampicin qualifying definition of Multi drug resistant tuberculosis. Bactericidal effect for N2 laser was seen in-vitro on exposure to N2 laser. Clinical improvement occurred in 90% of the 96 patients; 60% of the patients showed improvement on their X-rays and 75% turned out to be Acid fast bacilli smear negative in 4 to 15 days. Conclusions: Intra-cavitory N2 laser therapy was found to have remarkable success as an adjunct to chemotherapy. PMID:26557736

  13. Changes in Avidity and Level of Immunoglobulin G Antibodies to Mycobacterium tuberculosis in Sera of Patients Undergoing Treatment for Pulmonary Tuberculosis

    PubMed Central

    Pereira Arias-Bouda, Lenka M.; Kuijper, Sjoukje; Van Der Werf, Anouk; Nguyen, Lan N.; Jansen, Henk M.; Kolk, Arend H. J.

    2003-01-01

    Much is known about specific antibodies and their titers in patients with tuberculosis. However, little is known about the avidity of these antibodies or whether changes in avidity occur during the progression of the disease or during treatment. The aims of this study were to determine the avidity of antibodies to Mycobacterium tuberculosis in patients with pulmonary tuberculosis, to explore the value of avidity determination for the diagnosis of tuberculosis, and to study changes in levels of antibodies and their avidity during treatment. Antibody avidity was measured by an enzyme-linked immunosorbent assay with thiocyanate elution. Avidity indices and serum levels of immunoglobulin G to M. tuberculosis were determined for 22 patients with pulmonary tuberculosis before and during treatment and for 24 patients with other pulmonary diseases. Antibody levels and avidity were both significantly higher in untreated tuberculosis patients than in the controls. Avidity determination had more diagnostic potential than determination of the antibody levels. Tuberculosis patients with a long duration of symptoms had higher antibody avidity than those with a recent onset of symptoms, indicating affinity maturation of specific antibodies during active disease. In the early phase of treatment, a decrease in antibody avidity was observed for 73% of all tuberculosis patients, accompanied by an initial increase in antibody levels in 36% of these patients. These phenomena could be explained by an intense stimulation of the humoral response by antigens released from killed bacteria, reflecting early bactericidal activity of antituberculous drugs leading to the production of low-affinity antibodies against these released antigens. PMID:12853408

  14. Pulmonary tuberculosis and lung cancer: simultaneous and sequential occurrence*

    PubMed Central

    Silva, Denise Rossato; Valentini, Dirceu Felipe; Müller, Alice Mânica; de Almeida, Carlos Podalirio Borges; Dalcin, Paulo de Tarso Roth

    2013-01-01

    OBJECTIVE: Lung cancer (LC) is the leading cause of cancer-related death and represents a major public health problem worldwide. Another major cause of morbidity and mortality, especially in developing countries, is tuberculosis. The simultaneous or sequential occurrence of pulmonary tuberculosis and LC in the same patient has been reported in various case series and case-control studies. The objective of this study was to describe the characteristics of patients developing tuberculosis and LC, either simultaneously or sequentially. METHODS: This was a cross-sectional study based on the review of medical charts. RESULTS: The study involved 24 patients diagnosed with tuberculosis and LC between 2009 and 2012. The diagnoses of tuberculosis and LC occurred simultaneously in 10 patients, whereas tuberculosis was diagnosed prior to LC in 14. The median time between the two diagnoses was 5 years (interquartile range: 1-30 years). Fourteen patients (58.3%) were male, 20 (83.3%) were White, and 22 (91.7%) were smokers or former smokers. The most common histological type was adenocarcinoma, identified in 14 cases (58.3%), followed by epidermoid carcinoma, identified in 6 (25.0%). Seven patients (29.2%) presented with distant metastases at diagnosis; of those 7 patients, 5 (71%) were diagnosed with LC and tuberculosis simultaneously. CONCLUSIONS: In the present study, most of the patients with tuberculosis and LC were smokers or former smokers, and tuberculosis was diagnosed either before or simultaneously with LC. Non-small cell lung cancer, especially adenocarcinoma, was the most common histological type. PMID:24068271

  15. Hypercalcaemic crisis in an elderly patient with pulmonary tuberculosis

    PubMed Central

    Chan, Jason Yongsheng; Kanthaya, Mohanaruban

    2015-01-01

    Tuberculosis is an uncommon but recognized cause of hypercalcaemia, though calcium levels are seldom severely elevated and rarely result in symptoms. In the elderly patient however, several competing aetiologies may contribute to hypercalcaemia and the diagnostic evaluation may be confounded by polypharmacy as well as multiple co-existing medical conditions. We present here a case of an elderly man who presented with pulmonary tuberculosis and concomitant delirium secondary to hypercalcaemic crisis. Treatment with anti-tuberculous drugs, together with supportive care, eventually led to resolution of hypercalcaemia and restoration of mental function. PMID:26566450

  16. [Pulmonary tuberculosis complicated with tuberculosis of oral mucosa, mandible and cervical lymph nodes].

    PubMed

    Matsumoto, K; Ueda, S; Horie, T

    1995-04-01

    A case of pulmonary tuberculosis complicated with tuberculous of oral mucosa, mandible and cervical lymph nodes in 53-year-old man is reported. He was firstly treated for right side dental caries. He also received routinely an empiric antibiotic therapy, but discharge of pus continued. Then, pain of oral cavities spread to the right shoulder. The diagnosis of oral mucosa, osteomyelitis of mandible and lymph node tuberculosis was made by the histological examination of biopsy specimens and positive smear test for M. tuberculosis in granulation. The chest X-ray film showed multiple nodular shadows in bilateral lungs. The combination of INH, RFP and SM was applied initially and then SM was replaced by CS due to its side effect. Negative smear test for M. tuberculosis of oral mucosa was achieved five months after the initiation of treatment. PMID:7760539

  17. A Case of Good's Syndrome Presenting with Pulmonary Tuberculosis.

    PubMed

    Chaudhuri, Arunabha Datta; Tapadar, Sumit Roy; Dhua, Aparup; Dhara, Palash Nandan; Nandi, Saumen; Choudhury, Sabyasachi

    2015-01-01

    Adult onset immunodeficiency associated with thymoma is a rare condition. The combination of hypogammaglobulinemia, reduced number of peripheral B and CD4+ T cells, along with thymoma constitutes Good's syndrome (GS). This immunodeficiency condition is often complicated with opportunistic infection with organisms, like bacteria (Haemophilus influenzae, Streptococcus pneumonia etc), viruses (Cytomegalovirus, Herpes simplex etc), fungi and protozoa. We present an unusual case of Good's syndrome with pulmonary tuberculosis (PTB). A 40-year-old man presented with sputum-positive PTB and was started on anti-tuberculosis treatment. Subsequently, he developed symptoms and findings consistent with thymoma and other components of Good's syndrome. Although patients of Good's syndrome are susceptible to various opportunistic infections, infection with Mycobacterium tuberculosis is uncommon. Evidence of recurrent infections or some opportunistic infection in a thymoma patient should trigger a suspicion of Good's syndrome. PMID:27164735

  18. Agranulocytosis Induced by Ethambutol in a Patient with Pulmonary Tuberculosis

    PubMed Central

    Moon, Kyoung Min; Chung, So Hee; Kim, Ju Ri; Kim, Jin Young; Jung, Sun Young; Cho, Yongseon

    2015-01-01

    We report a case of agranulocytosis caused by ethambutol in a 79-year-old man with pulmonary tuberculosis. He was referred for fever and skin rash developed on 21th day after antituberculosis drugs (isoniazid, rifampicin, ethambutol, and pyrazinamide) intake. Complete blood count at the time of diagnosis of pulmonary tuberculosis was normal. On the seventh admission day, agranulocytosis was developed with absolute neutrophil count of 70/µL. We discontinued all antituberculosis drugs, and then treated with granulocyte colony-stimulating factor. Three days later, the number of white blood cell returned to normal. We administered isoniazid, pyrazinamide, and ethambutol in order with an interval. However, fever and skin rash developed again when adding ethambutol, so we discontinued ethambutol. After these symptoms disappeared, we added rifampicin and ethambutol in order with an interval. However after administering ethambutol, neutropenia developed, so we discontinued ethambutol again. He was cured with isoniazid, rifampicin, and pyrazinamide for 9 months. PMID:25861347

  19. Elevated ex vivo monocyte chemotactic protein-1 (CCL2) in pulmonary as compared with extra-pulmonary tuberculosis

    PubMed Central

    Hasan, Zahra; Zaidi, Irfan; Jamil, Bushra; Khan, M Aslam; Kanji, Akbar; Hussain, Rabia

    2005-01-01

    Background Tuberculosis causes 3 million deaths annually. The most common site of tuberculosis is pulmonary however; extra-pulmonary forms of the disease also remain prevalent. Restriction of Mycobacterium tuberculosis depends on effective recruitment and subsequent activation of T lymphocytes, mononuclear and polymorphonuclear cells to the site of infection. Tumor necrosis factor (TNF)-α is essential for granuloma formation and is a potent activator of monocyte chemotactic protein (MCP-1, CCL2). CCL2 is essential for recruitment of monocytes and T cells and has been shown to play a role in protection against tuberculosis. Interleukin -8 (CXCL8) is a potent activator of neutrophils. Increased levels of CCL2, CXCL8 and TNFα are reported in tuberculosis but their significance in different forms of tuberculosis is as yet unclear. We have used an ex vivo assay to investigate differences in immune parameters in patients with either pulmonary or extra-pulmonary tuberculosis. Methods Serum levels of CCL2, CXCL8 and TNFα were measured in patients with pulmonary tuberculosis (N = 12), extra-pulmonary tuberculosis (N = 8) and BCG-vaccinated healthy volunteers (N = 12). Whole blood cells were stimulated with non-pathogenic Mycobacterium bovis bacille-Calmette Guerin (BCG) vaccine strain or bacterial lipopolysaccharide (LPS) and cyto/chemokines were monitored in supernatants. Results Circulating serum levels of CXCL8 and TNFα were raised in all tuberculosis patients, while CCL2 levels were not. There was no difference in spontaneous cytokine secretion from whole blood cells between patients and controls. M. bovis BCG-induced ex vivo CCL2 secretion was significantly greater in pulmonary as compared with both extra-pulmonary tuberculosis patients and endemic controls. In response to LPS stimulation, patients with pulmonary tuberculosis showed increased CCL2 and TNFα responses as compared with the extra-pulmonary group. BCG-, and LPS-induced CXCL8 secretion was comparable

  20. Pulmonary Tuberculosis Diagnosis: Where We Are?

    PubMed Central

    Leylabadlo, Hamed Ebrahimzadeh; Yousefi, Mehdi; Aghazadeh, Mohammad; Asgharzadeh, Mohammad

    2016-01-01

    In recent years, in spite of medical advancement, tuberculosis (TB) remains a worldwide health problem. Although many laboratory methods have been developed to expedite the diagnosis of TB, delays in diagnosis remain a major problem in the clinical practice. Because of the slow growth rate of the causative agent Mycobacterium tuberculosis, isolation, identification, and drug susceptibility testing of this organism and other clinically important mycobacteria can take several weeks or longer. During the past several years, many methods have been developed for direct detection, species identification, and drug susceptibility testing of TB. A good understanding of the effectiveness and practical limitations of these methods is important to improve diagnosis. This review summarizes the currently-used advances in nonmolecular and molecular diagnostics. PMID:27433173

  1. Prevalence of Multidrug Resistant Pulmonary Tuberculosis in North Bihar

    PubMed Central

    Kumar, Rajesh; Singh, Surya Deo

    2015-01-01

    Introduction Multidrug resistant tuberculosis (MDR-TB) is caused by Infection with Mycobacterium tuberculosis which is resistant to both isoniazid (INH) and rifampicin (RIF), with or without any other anti tubercular drug. It is caused by resistant mutant strains due to inadequate treatment and poor compliance. Due to time taking conventional diagnostic methods, drug resistant strains continue to spread. Therefore rapid diagnosis and treatment of MDR-TB strains are prerequisites for the worldwide fight against TB. Objective To determine the prevalence of MDR TB in North Bihar by molecular diagnostic method and to facilitate early diagnosis and treatment. Also, to find out the number of those diagnosed cases who were successfully initiated the treatment in MDR TB Centre of DMCH. Materials and Methods This six month observational study was carried out in IRL Darbhanga, Damien TB research Centre of the Darbhanga Medical College and Hospital, Bihar, India. During the period of February-July 2014, 256 sputum samples were collected from suspected cases of multidrug resistant tuberculosis, from 6 districts of North Bihar around Darbhanga. These samples were subjected to routine microscopy and culture to detect Mycobacterium tuberculosis. Positive cases were subjected to drug sensitivity test by a molecular diagnostic method, Using Genotype MTBDR plus kit. Result Out of 256 sputum samples from suspected cases of MDR TB, 122 cases were microscopy positive for tuberculosis. Among these 122 cases, tuberculosis was confirmed by PCR in 114 cases. Finally with the help of Line Probe Assay (LPA), 39(15%) samples were found to have resistance to both INH and Rifampicin. Male female ratio was 4:1. Conclusion The Prevalence of Multi drug resistant pulmonary tuberculosis in North Bihar is 15%. It needs early diagnosis by molecular diagnostic method and prompt treatment to reduce the spread of MDR TB cases. PMID:26674711

  2. MicroRNA-365 in macrophages regulates Mycobacterium tuberculosis-induced active pulmonary tuberculosis via interleukin-6

    PubMed Central

    Song, Qingzhang; Li, Hui; Shao, Hua; Li, Chunling; Lu, Xiao

    2015-01-01

    The present study is to investigate the relationship between microRNA (miR)-365 expression and the levels of interleukin (IL)-6 mRNA and protein in patients with active tuberculosis. From June 2011 to June 2014, 48 patients with active pulmonary tuberculosis induced by Mycobacterium tuberculosis were included in the study. In addition, 23 healthy subjects were enrolled as control. Macrophages were collected by pulmonary alveolus lavage. In addition, serum and mononuclear cells were isolated from peripheral blood. The levels of miR-365 and IL-6 in macrophages, mononuclear cells and serum were determined using quantitative real-time polymerase chain reaction. The protein expression of IL-6 in macrophages and mononuclear cells was measured using Western blotting, while that in serum was detected by enzyme-linked immunoabsorbent assay. Expression of IL-6 mRNA and protein was significantly enhanced in patients with active pulmonary tuberculosis. Increase of IL-6 protein concentration in serum was probably due to the release of IL-6 protein from mononuclear cells in the blood. In addition, miR-365 levels were significantly lowered in patients with active pulmonary tuberculosis. Up-regulated IL-6 expression in macrophages, mononuclear cells and serum in patients with active pulmonary tuberculosis is related to the down-regulation of miR-365, suggesting that miR-365 may regulate the occurrence and immune responses of active pulmonary tuberculosis via IL-6. PMID:26629035

  3. MicroRNA-365 in macrophages regulates Mycobacterium tuberculosis-induced active pulmonary tuberculosis via interleukin-6.

    PubMed

    Song, Qingzhang; Li, Hui; Shao, Hua; Li, Chunling; Lu, Xiao

    2015-01-01

    The present study is to investigate the relationship between microRNA (miR)-365 expression and the levels of interleukin (IL)-6 mRNA and protein in patients with active tuberculosis. From June 2011 to June 2014, 48 patients with active pulmonary tuberculosis induced by Mycobacterium tuberculosis were included in the study. In addition, 23 healthy subjects were enrolled as control. Macrophages were collected by pulmonary alveolus lavage. In addition, serum and mononuclear cells were isolated from peripheral blood. The levels of miR-365 and IL-6 in macrophages, mononuclear cells and serum were determined using quantitative real-time polymerase chain reaction. The protein expression of IL-6 in macrophages and mononuclear cells was measured using Western blotting, while that in serum was detected by enzyme-linked immunoabsorbent assay. Expression of IL-6 mRNA and protein was significantly enhanced in patients with active pulmonary tuberculosis. Increase of IL-6 protein concentration in serum was probably due to the release of IL-6 protein from mononuclear cells in the blood. In addition, miR-365 levels were significantly lowered in patients with active pulmonary tuberculosis. Up-regulated IL-6 expression in macrophages, mononuclear cells and serum in patients with active pulmonary tuberculosis is related to the down-regulation of miR-365, suggesting that miR-365 may regulate the occurrence and immune responses of active pulmonary tuberculosis via IL-6. PMID:26629035

  4. The Prevalence of Latent Tuberculosis Infection and Smear Positive Pulmonary Tuberculosis in People with Household Close Contact with Tuberculosis in North of Iran

    PubMed Central

    Moosazadeh, Mahmood; Khanjani, Narges; Parsaee, Mohammadreza

    2015-01-01

    One of the recommended strategies for preventing tuberculosis is to screen high-risk populations with respect to Mycobacterium tuberculosis (TB) infection. The aim of the present study was to investigate latent infection and active tuberculosis in people with close household contact. It was a cross-sectional descriptive, analytical study with the sample size of 668 people from homes with one infected resident. In order to diagnose tuberculosis latent infection, the PPD test was done. To determine patients with smear-positive pulmonary tuberculosis, three sputum samples were taken from every patient and were examined using direct microscopy and culture. Data was analyzed by SPSS20 software. The prevalence of latent tuberculosis infection and smear-positive pulmonary tuberculosis were 42.8% and 0.9% respectively. The prevalence of latent tuberculosis infection and smear-positive pulmonary tuberculosis in people with close household contact were less than that of other studies. However, smear-positive pulmonary tuberculosis in people with close household contact was 199.5 times more than that of the general population. PMID:25821296

  5. Pulmonary tuberculosis in South African gold miners.

    PubMed

    Cowie, R L; Langton, M E; Becklake, M R

    1989-05-01

    In 1977, a comprehensive tuberculosis management program was introduced at a medical facility which then served approximately 65,000 black gold miners. The effectiveness of this program was evaluated from the relapse rate after treatment in 2,776 men. Post-treatment follow-up averaged 23.5 months. Limited information on potential determinants of relapse was available for all subjects and more detailed information for subsets. The drug regimen was the major determinant of relapse. Age was not a determinant of relapse nor was primary resistance of Mycobacterium tuberculosis to antituberculosis drugs, which was infrequent. The initial extent and severity of disease had a direct relation with the risk of relapse. The risk of relapse was greatest during the first 3 yr after treatment but persisted for the duration of the observation period. Neither continued exposure to mine dust nor the presence of pre-existing silicosis were shown to be determinants of relapse. A 4.5-month, four-drug weekday regimen was identified as being particularly effective in this working population and may be suitable for use in other working populations in the developing world. PMID:2712435

  6. Circulating Biomarkers of Pulmonary and Extrapulmonary Tuberculosis in Children

    PubMed Central

    Pavan Kumar, Nathella; Anuradha, R.; Andrade, Bruno B.; Suresh, N.; Ganesh, R.; Shankar, Janani; Kumaraswami, V.; Nutman, Thomas B.

    2013-01-01

    Tuberculosis (TB) in children is not only more likely to cause more severe disease than that seen in adults, it is also more likely to be extrapulmonary. Moreover, pediatric TB is very difficult to diagnose and suffers from a lack of understanding of host biomarkers for monitoring the progression of disease. Hence, we sought to identify the expression patterns of a variety of biomarkers in the plasma of children with pulmonary TB (PTB) and extrapulmonary TB (ETB), as well as in healthy control (HC) children. Thus, we examined a variety of circulating markers reflecting tissue inflammation, oxidative stress, innate immune activation, fibrosis, and the cytokine response. Children with active TB, compared to HC children, showed markedly elevated plasma levels of matrix metalloproteinases and their endogenous inhibitors. In addition, children with active TB had significantly elevated levels of C-reactive protein, α-2 macroglobulin, and haptoglobin, as well as hemoxygenase 1. Markers of innate immune activation (lipopolysaccharide [LPS] and lipopolysaccharide-binding protein [LBP]) were significantly lower in ETB than in PTB children. Although there were no significant differences between the two groups in their levels of cytokines (type 1 [gamma interferon (IFN-γ), tumor necrosis factor α (TNF-α), interleukin 2 (IL-2), and IL-12], type 2 [IL-4, IL-5, IL-13, and IL-33], and most type 17 [IL-17A, IL-22, IL-1β, and IL-6] and type 1 interferons [IFN-α and IFN-β]) or most of the cytokines associated with immune modulation (IL-10 and IL-20), pediatric TB was associated with elevated plasma transforming growth factor β (TGF-β), IL-21, and IL-23 levels. Thus, pediatric TB is characterized by elevated levels of a variety of biomarkers at homeostasis, suggesting that these responses may play a crucial role in disease pathogenesis. PMID:23486418

  7. Pulmonary Tuberculosis Caused by Mycobacterium bovis in China

    PubMed Central

    Jiang, Guanglu; Wang, Guirong; Chen, Suting; Yu, Xia; Wang, Xiaobo; Zhao, Liping; Ma, Yifeng; Dong, Lingling; Huang, Hairong

    2015-01-01

    The epidemiology of Mycobacterium bovis infection in humans in China is unknown. In this study, pulmonary tuberculosis caused by M. bovis in China was studied. A total of 4069 clinical strains isolated from sputa during the 2007–2009 nationwide surveillance of drug-resistant tuberculosis in China were analyzed. M. bovis was identified by para-nitrobenzoic acid and thiophen-2-carboxylic acid hydrazide growth tests, spoligotyping and multiplex PCR amplification. In addition, a total of 1828 clinical specimens were recruited from Beijing Chest Hospital (Beijing, China) for Löwenstein-Jensen (LJ) culture, both on standard LJ medium and LJ medium containing 4.5 mg/ml(W/V) sodium pyruvate, the latter being the preferred medium for M. bovis growth. The isolates which demonstrated more vigorous on pyruvate containing medium than on standard LJ medium were then identified by multiplex PCR amplification. Only 1 isolate from the nationwide surveillance was confirmed as M. bovis-BCG. The isolate belonged to a predominant spoligotype SB0120 (ST482). In addition, no M. bovis isolate was acquired by the continuous screening step in Beijing Chest Hospital. M. bovis has a negligible contribution to pulmonary tuberculosis in China, so neither laboratory identification nor clinical treatment of M. bovis infection need be considered in routine work. PMID:25736338

  8. Genetic Diversity and Dynamic Distribution of Mycobacterium tuberculosis Isolates Causing Pulmonary and Extrapulmonary Tuberculosis in Thailand

    PubMed Central

    Srilohasin, Prapaporn; Tokunaga, Katsushi; Nishida, Nao; Prammananan, Therdsak; Smittipat, Nat; Mahasirimongkol, Surakameth; Chaiyasirinroje, Boonchai; Yanai, Hideki; Palittapongarnpim, Prasit

    2014-01-01

    This study examined the genetic diversity and dynamicity of circulating Mycobacterium tuberculosis strains in Thailand using nearly neutral molecular markers. The single nucleotide polymorphism (SNP)-based genotypes of 1,414 culture-positive M. tuberculosis isolates from 1,282 pulmonary tuberculosis (PTB) and 132 extrapulmonary TB (EPTB) patients collected from 1995 to 2011 were characterized. Among the eight SNP cluster groups (SCG), SCG2 (44.1%), which included the Beijing (BJ) genotype, and SCG1 (39.4%), an East African Indian genotype, were dominant. Comparisons between the genotypes of M. tuberculosis isolates causing PTB and EPTB in HIV-negative cases revealed similar prevalence trends although genetic diversity was higher in the PTB patients. The identification of 10 reported sequence types (STs) and three novel STs was hypothesized to indicate preferential expansion of the SCG2 genotype, especially the modern BJ ST10 (15.6%) and ancestral BJ ST19 (13.1%). An association between SCG2 and SCG1 genotypes and particular patient age groups implies the existence of different genetic advantages among the bacterial populations. The results revealed that increasing numbers of young patients were infected with M. tuberculosis SCGs 2 and 5, which contrasts with the reduction of the SCG1 genotype. Our results indicate the selection and dissemination of potent M. tuberculosis genotypes in this population. The determination of heterogeneity and dynamic population changes of circulating M. tuberculosis strains in countries using the Mycobacterium bovis BCG (bacillus Calmette-Guérin) vaccine are beneficial for vaccine development and control strategies. PMID:25297330

  9. Heat shock proteins: possible biomarkers in pulmonary and extrapulmonary tuberculosis.

    PubMed

    Shekhawat, Seema D; Jain, Ruchika K; Gaherwar, Hari M; Purohit, Hemant J; Taori, Girdhar M; Daginawala, Hatim F; Kashyap, Rajpal S

    2014-02-01

    Tuberculosis (TB) and Tuberculous meningitis (TBM) caused by Mycobacterium tuberculosis (MTB) continue to be a major cause of morbidity and mortality. Therefore there is a need to explore potential biomarkers and heat shock proteins [Hsp(s)] could be one such candidate. We found that host (Hsp 25, Hsp 60, Hsp 70 and Hsp 90) and MTB Hsp(s) (Hsp 16, Hsp 65 and Hsp 71) to be an important feature of the immune response in human clinical samples of pulmonary and extrapulmonary TB patients and in MTB infected monocytes. Notably, the host (Hsp 25, Hsp 70 and Hsp 90) and MTB (Hsp 16, Hsp 65 and Hsp 71) Hsp(s) increases significantly in the clinical samples as well as in cell line model after TB infection. Collectively, results revealed that alteration in immune response leads to a change in the both host and MTB Hsp profile, highlighting them as possible biomarkers for the disease. PMID:24269695

  10. [Predictors of bacterial excretion in patients with infiltrative pulmonary tuberculosis].

    PubMed

    Volchegorskiĭ, I A; Novoselov, P N; Bolotov, A A

    2009-01-01

    An association of bacterial excretion with the magnitude of the X-ray and clinical symptoms of infiltrative pulmonary tuberculosis, with the intensity of concomitant anxiety-depression disorders and the results of complex laboratory peripheral blood tests was studied in 100 patients with this condition. The fact that M. tuberculosis was present in the sputum was shown to be linked to the significant increase in the size of tuberculous infiltrates, the extent of decay in the latter, their connection with the root of the lung, the spread of excretion foci, and the intensity of cough and bloody expectoration. The similar trend was demonstrated in the degree of situational anxiety, depressive indecision, and pessimism, as well as in the values of leukocytosis and erythrocyte sedimentation rate. The predictive informative value of a set of findings is illustrated by the discriminant function equation that allows the correct prediction of bacterial excretion in 76.8% of cases. PMID:20095373

  11. Treatment of Drug Susceptible Pulmonary Tuberculosis.

    PubMed

    Shin, Hong-Joon; Kwon, Yong-Soo

    2015-07-01

    Tuberculosis (TB) remains a major global health problem, and the incidence of TB cases has not significantly decreased over the past decade in Korea. The standard short course regimen is highly effective against TB, but requires multiple TB-specific drugs and a long treatment duration. Recent studies using late-generation fluoroquinolones and/or high-dose rifapentine-containing regimens to shorten the duration of TB treatment showed negative results. Extending the treatment duration may be considered in patients with cavitation on the initial chest radiograph and positivity in sputum culture at 2 months of treatment for preventing TB relapse. Current evidence does not support the use of fixed-dose combinations compared to separate drugs for the purpose of improving treatment outcomes. All patients receiving TB treatment should be monitored regularly for response to therapy, facilitation of treatment completion, and management of adverse drug reactions. Mild adverse effects can be managed with symptomatic therapy and changing the timing of the drug administration, but severe adverse effects require a discontinuation of the offending drugs. PMID:26175767

  12. Complete republication: Epidemiology of tuberculosis in the EU/EEA in 2010 – Monitoring the progress towards tuberculosis elimination

    PubMed Central

    Hollo, V.; Huitric, E.; Ködmön, C.

    2012-01-01

    The 2012 combined tuberculosis (TB) surveillance and monitoring report for the European Union and European Economic Area identifies a mean annual decline in TB notification rate by 4.4% from 2006 to 2010. Culture confirmation for new pulmonary cases and drug susceptibility testing have increased to 65.6% and 70.8%, but remain under their targets of 80% and 100%, respectively. Reporting of treatment outcome and coinfection with human immunodeficiency virus also remain suboptimal. Strengthened control practices are needed to allow progress towards TB elimination. PMID:24265912

  13. Inflammatory and immunogenetic markers in correlation with pulmonary tuberculosis*

    PubMed Central

    Muller, Beatriz Lima Alezio; Ramalho, Daniela Maria de Paula; dos Santos, Paula Fernanda Gonçalves; Mesquita, Eliene Denites Duarte; Kritski, Afranio Lineu; Oliveira, Martha Maria

    2013-01-01

    OBJECTIVE: To describe serum levels of the cytokines IL-10, TNF-α, and IFN-γ, as well as polymorphisms in the genes involved in their transcription, and their association with markers of the acute inflammatory response in patients with pulmonary tuberculosis. METHODS: This was a descriptive, longitudinal study involving 81 patients with pulmonary tuberculosis treated at two referral hospitals. We collected data on sociodemographic variables and evaluated bacteriological conversion at the eighth week of antituberculosis treatment, gene polymorphisms related to the cytokines studied, and serum levels of those cytokines, as well as those of C-reactive protein (CRP). We also determined the ESR and CD4+ counts. RESULTS: The median age of the patients was 43 years; 67 patients (82.7%) were male; and 8 patients (9.9%) were infected with HIV. The ESR was highest in the patients with high IFN-γ levels and low IL-10 levels. IFN-γ and TNF-α gene polymorphisms at positions +874 and −238, respectively, showed no correlations with the corresponding cytokine serum levels. Low IL-10 levels were associated with IL-10 gene polymorphisms at positions −592 and −819 (but not −1082). There was a negative association between bacteriological conversion at the eighth week of treatment and CRP levels. CONCLUSIONS: Our results suggest that genetic markers and markers of acute inflammatory response are useful in predicting the response to antituberculosis treatment. PMID:24473766

  14. Genetic Variants in MARCO Are Associated with the Susceptibility to Pulmonary Tuberculosis in Chinese Han Population

    PubMed Central

    Ma, Mai-Juan; Wang, Hai-Bing; Li, Hao; Yang, Jun-Hai; Yan, Yan; Xie, Lan-Pin; Qi, Ying-Cheng; Li, Jun-Lian; Chen, Mei-Juan; Liu, Wei; Cao, Wu-Chun

    2011-01-01

    Background Susceptibility to tuberculosis is not only determined by Mycobacterium tuberculosis infection, but also by the genetic component of the host. Macrophage receptor with a collagenous structure (MARCO) is essential components required for toll like receptor-signaling in macrophage response to Mycobacterium tuberculosis, which may contribute to tuberculosis risk. Principal Findings To specifically investigated whether single nucleotide polymorphisms (SNPs) in MARCO gene are associated with pulmonary tuberculosis in Chinese Han population. By selecting tagging SNPs in MARCO gene, 17 tag SNPs were identified and genotyped in 923 pulmonary tuberculosis patients and 1033 healthy control subjects using a hospital based case-control association study. Single-point and haplotype analysis revealed an association in intron and exon region of MARCO gene. One SNP (rs17009726) was associated with susceptibility to pulmonary tuberculosis, where the carriers of the G allele had a 1.65 fold (95% CI = 1.32–2.05, pcorrected = 9.27E–5) increased risk of pulmonary tuberculosis. Haplotype analysis revealed that haplotype GC containing G allele of 17009726 and haplotype TGCC (rs17795618T/A, rs1371562G/T, rs6761637T/C, rs2011839C/T) were also associated with susceptibility to pulmonary tuberculosis (pcorrected = 0.0001 and 0.029, respectively). Conclusions Our study suggested that genetic variants in MARCO gene were associated with pulmonary tuberculosis susceptibility in Chinese Han population, and the findings emphasize the importance of MARCO mediated immune responses in the pathogenesis of tuberculosis. PMID:21886847

  15. Acute Hypercalcaemia and Hypervitaminosis D in an Infant with Extra Pulmonary Tuberculosis.

    PubMed

    Dayal, Devi; Didel, Siya Ram; Agarwal, Sikha; Sachdeva, Naresh; Singh, Meenu

    2015-10-01

    In patients with tuberculosis, abnormal extrarenal production of 1,25-dihydroxyvitamin D3 by activated macrophages in granulomatous tissues may result in hypercalcaemia. More commonly reported in adults with active pulmonary tuberculosis, this complication may rarely occur in extrapulmonary tuberculosis, and children. The hypercalcaemia may be precipitated by usually recommended vitamin D and calcium supplementation in patients with tuberculosis. We report here an infant with tubercular meningitis who developed hypercalcaemia 12 days after starting routine vitamin D and calcium supplementation. This communication highlights the importance of close monitoring of calcium levels in patients with tuberculosis, especially if started on vitamin D and calcium replacement before anti-tubercular therapy. PMID:26557587

  16. Acute Hypercalcaemia and Hypervitaminosis D in an Infant with Extra Pulmonary Tuberculosis

    PubMed Central

    Didel, Siya Ram; Agarwal, Sikha; Sachdeva, Naresh; Singh, Meenu

    2015-01-01

    In patients with tuberculosis, abnormal extrarenal production of 1,25-dihydroxyvitamin D3 by activated macrophages in granulomatous tissues may result in hypercalcaemia. More commonly reported in adults with active pulmonary tuberculosis, this complication may rarely occur in extrapulmonary tuberculosis, and children. The hypercalcaemia may be precipitated by usually recommended vitamin D and calcium supplementation in patients with tuberculosis. We report here an infant with tubercular meningitis who developed hypercalcaemia 12 days after starting routine vitamin D and calcium supplementation. This communication highlights the importance of close monitoring of calcium levels in patients with tuberculosis, especially if started on vitamin D and calcium replacement before anti-tubercular therapy. PMID:26557587

  17. The Influence of Sex Steroid Hormones in the Immunopathology of Experimental Pulmonary Tuberculosis

    PubMed Central

    Bini, Estela Isabel; Mata Espinosa, Dulce; Marquina Castillo, Brenda; Barrios Payán, Jorge; Colucci, Darío; Cruz, Alejandro Francisco; Zatarain, Zyanya Lucía; Alfonseca, Edgar; Pardo, Marta Romano; Bottasso, Oscar; Pando, Rogelio Hernández

    2014-01-01

    The relation between men and women suffering pulmonary tuberculosis is 7/3 in favor to males. Sex hormones could be a significant factor for this difference, considering that testosterone impairs macrophage activation and pro-inflammatory cytokines production, while estrogens are proinflammatory mediator’s inducer. The aim of this work was to compare the evolution of tuberculosis in male and female mice using a model of progressive disease. BALB/c mice, male and female were randomized into two groups: castrated or sham-operated, and infected by the intratracheal route with a high dose of Mycobacterium tuberculosis strain H37Rv. Mice were euthanized at different time points and in their lungs were determined bacilli loads, inflammation, cytokines expression, survival and testosterone levels in serum. Non-castrated male mice showed significant higher mortality and bacilli burdens during late disease than female and castrated male animals. Compared to males, females and castrated males exhibited significant higher inflammation in all lung compartments, earlier formation of granulomas and pneumonia, while between castrated and non-castrated females there were not significant differences. Females and castrated males expressed significant higher TNF-α, IFN γ, IL12, iNOS and IL17 than non-castrated males during the first month of infection. Serum Testosterone of males showed higher concentration during late infection. Orchidectomy at day 60 post-infection produced a significant decrease of bacilli burdens in coexistence with higher expression of TNFα, IL-12 and IFNγ. Thus, male mice are more susceptible to tuberculosis than females and this was prevented by castration suggesting that testosterone could be a tuberculosis susceptibility factor. PMID:24722144

  18. Determinants of active pulmonary tuberculosis in Ambo Hospital, West Ethiopia

    PubMed Central

    Mengiste, Bezatu; Mesfin, Frehiwot; Godana, Wanzahun

    2015-01-01

    Objectives The aim of this study was to determine factors associated with active pulmonary tuberculosis seen in cases in Ambo Hospital, Ethiopia. Design A facility-based prospective case-control study. Setting Patients attending Ambo Hospital from 01 December 2011 to 29 March 2012. Participants The sample included 312 adult patients attending Ambo Hospital. The main outcome measure was presence of active pulmonary tuberculosis (TB). Explanatory measures Age, gender, occupation, educational status, marital status, place of residence, patient history of TB, family history of TB, human immunodeficiency virus (HIV) infection, smoking, alcohol intake, khat chewing, body mass index (BMI), employment, diabetes, history of asthma, previous history of worm infestation, history of hospitalisation, number of adults living in the household (HH), person per room, housing condition. Results A total of 312 study participants, including 104 active pulmonary tuberculosis (PTB) cases (cases) and 208 non-active PTB cases (controls), were recruited for the present study. Having one or more family member with a history of TB (OR = 4.4; 95% CI: 1.50–12.90), marital status (OR = 7.6; 95% CI: 2.2–12.6), male gender (OR = 3.2; 95% CI: 1.4–7), rural residence (OR = 3.3; P = 0.012), being a current or past smoker (OR = 2.8; 95% CI: 1.1–7.2), BMI < 18.5 (OR = 2.1; 95% CI: 1.03–4.2), HIV infection (OR = 8.8; 95% CI: 2.4–23.8) and a history of worm infestation (OR = 6.4; 95% CI: 2.6–15.4) remained significant independent host-related factors for active PTB. Conclusion Patients who came from a compound with more than two HHs were more likely to develop active PTB than those who came from a compound with only one HH. Those who lived in houses with no windows were more likely to develop active PTB than those who lived in houses with one or more windows, had a family history of TB, lived in rural areas. Sex of the patient was a predicting factor. Not being the owner of the house was

  19. [Lupus vulgaris as a complication of pulmonary tuberculosis--case report].

    PubMed

    Owczarek, Witold; Targowski, Tomasz; Kozera-Zywczyk, Anna; Paluchowska, Elwira; Patera, Janusz

    2009-10-01

    Tuberculosis is a contagious disease induced by Mycobacterium species, acid-fast bacilli. These are mostly human type--Mycobacterium tuberculosis, less often cattle type--mycobacterium bovis or other: mycobacterium avium, kansasii, marinom, scrofulaceum, heamophilium, gordonae. The infection can affect all organs, but pulmonary tuberculosis is the most common form. The importance of tuberculosis is definitely rising in the context of massive population migrations in regions affected by its higher incidence, increased HIV infections and AIDS development. Cutaneous tuberculosis is a particular tuberculosis form with differentiated clinical picture. Non-typicalness of skin changes and oligobacilleous course of extrapulmonary tuberculosis forms are repeatedly causing difficulties in adequate diagnosis and early treatment. In differential diagnostics of cutaneous tuberculosis one must take leishmaniasis, actinomycosis, leprosy, syphilis and deep mycosis (among others) into consideration. The study is presenting a case of lupus vulgaris as a complication of past pulmonary tuberculosis. In bacteriological diagnostics of skin changes bioptates, no tuberculosis mycobacteria were found. The disease was diagnosed based on specific granulation presence in histopathology test, tuberculin hypersensivity, bacilli DNA presence in polymerase chain reaction (PCR) test and skin changes regression after anti-mycobacterium treatment. According to authors of the study, the described case confirms the usefulness of PCR nucleonic acids amplification test in cutaneous tuberculosis diagnosis. PMID:19928663

  20. Altered serum microRNAs as biomarkers for the early diagnosis of pulmonary tuberculosis infection

    PubMed Central

    2012-01-01

    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. PMID:23272999

  1. Natural History of Tuberculosis: Duration and Fatality of Untreated Pulmonary Tuberculosis in HIV Negative Patients: A Systematic Review

    PubMed Central

    Tiemersma, Edine W.; van der Werf, Marieke J.; Borgdorff, Martien W.; Williams, Brian G.; Nagelkerke, Nico J. D.

    2011-01-01

    Background The prognosis, specifically the case fatality and duration, of untreated tuberculosis is important as many patients are not correctly diagnosed and therefore receive inadequate or no treatment. Furthermore, duration and case fatality of tuberculosis are key parameters in interpreting epidemiological data. Methodology and Principal Findings To estimate the duration and case fatality of untreated pulmonary tuberculosis in HIV negative patients we reviewed studies from the pre-chemotherapy era. Untreated smear-positive tuberculosis among HIV negative individuals has a 10-year case fatality variously reported between 53% and 86%, with a weighted mean of 70%. Ten-year case fatality of culture-positive smear-negative tuberculosis was nowhere reported directly but can be indirectly estimated to be approximately 20%. The duration of tuberculosis from onset to cure or death is approximately 3 years and appears to be similar for smear-positive and smear-negative tuberculosis. Conclusions Current models of untreated tuberculosis that assume a total duration of 2 years until self-cure or death underestimate the duration of disease by about one year, but their case fatality estimates of 70% for smear-positive and 20% for culture-positive smear-negative tuberculosis appear to be satisfactory. PMID:21483732

  2. [The interpretation of pulmonary tuberculosis in the 18th century].

    PubMed

    Bernier, Jacques

    2005-01-01

    Pulmonary tuberculosis took on alarming proportions in the 18th-century Europe. This study examines the ways learned medical practitioners presented the causes of the malady in Great Britain and France, by analyzing 12 medical treatises. Four etiological models appears to have dominated medical thinking in this context: theories that emphasize contagion; those which attribute the cause to physiological disorders; those which find the origin in hereditary predispositions; and those theories which observe a link with behaviour and lifestyles. The study also shows how one of these theories - the hereditary theory - eventually triumphed over the others and became the dominant for the better part of the 19th century, and will be examined within the context of the growth of liberal and individualist ideology. PMID:15977379

  3. 38 CFR 3.378 - Changes from activity in pulmonary tuberculosis pension cases.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Changes from activity in pulmonary tuberculosis pension cases. 3.378 Section 3.378 Pensions, Bonuses, and Veterans' Relief DEPARTMENT... tuberculosis pension cases. A permanent and total disability rating in effect during hospitalization will...

  4. 38 CFR 3.378 - Changes from activity in pulmonary tuberculosis pension cases.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Changes from activity in pulmonary tuberculosis pension cases. 3.378 Section 3.378 Pensions, Bonuses, and Veterans' Relief DEPARTMENT... tuberculosis pension cases. A permanent and total disability rating in effect during hospitalization will...

  5. 38 CFR 3.378 - Changes from activity in pulmonary tuberculosis pension cases.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Changes from activity in pulmonary tuberculosis pension cases. 3.378 Section 3.378 Pensions, Bonuses, and Veterans' Relief DEPARTMENT... tuberculosis pension cases. A permanent and total disability rating in effect during hospitalization will...

  6. 38 CFR 3.378 - Changes from activity in pulmonary tuberculosis pension cases.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Changes from activity in pulmonary tuberculosis pension cases. 3.378 Section 3.378 Pensions, Bonuses, and Veterans' Relief DEPARTMENT... tuberculosis pension cases. A permanent and total disability rating in effect during hospitalization will...

  7. 38 CFR 3.378 - Changes from activity in pulmonary tuberculosis pension cases.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Changes from activity in pulmonary tuberculosis pension cases. 3.378 Section 3.378 Pensions, Bonuses, and Veterans' Relief DEPARTMENT... tuberculosis pension cases. A permanent and total disability rating in effect during hospitalization will...

  8. Elucidating Novel Serum Biomarkers Associated with Pulmonary Tuberculosis Treatment

    PubMed Central

    De Groote, Mary A.; Nahid, Payam; Jarlsberg, Leah; Johnson, John L.; Weiner, Marc; Muzanyi, Grace; Janjic, Nebojsa; Sterling, David G.; Ochsner, Urs A.

    2013-01-01

    In an unbiased approach to biomarker discovery, we applied a highly multiplexed proteomic technology (SOMAscan, SomaLogic, Inc, Boulder, CO) to understand changes in proteins from paired serum samples at enrollment and after 8 weeks of TB treatment from 39 patients with pulmonary TB from Kampala, Uganda enrolled in the Center for Disease Control and Prevention’s Tuberculosis Trials Consortium (TBTC) Study 29. This work represents the first large-scale proteomic analysis employing modified DNA aptamers in a study of active tuberculosis (TB). We identified multiple proteins that exhibit significant expression differences during the intensive phase of TB therapy. There was enrichment for proteins in conserved networks of biological processes and function including antimicrobial defense, tissue healing and remodeling, acute phase response, pattern recognition, protease/anti-proteases, complement and coagulation cascade, apoptosis, immunity and inflammation pathways. Members of cytokine pathways such as interferon-gamma, while present, were not as highly represented as might have been predicted. The top proteins that changed between baseline and 8 weeks of therapy were TSP4, TIMP-2, SEPR, MRC-2, Antithrombin III, SAA, CRP, NPS-PLA2, LEAP-1, and LBP. The novel proteins elucidated in this work may provide new insights for understanding TB disease, its treatment and subsequent healing processes that occur in response to effective therapy. PMID:23637781

  9. Population Pharmacokinetics of Rifampicin in Chinese Patients With Pulmonary Tuberculosis.

    PubMed

    Jing, Ying; Zhu, Li Qin; Yang, Jian Wei; Huang, Shu Ping; Wang, Qian; Zhang, Jie

    2016-05-01

    Rifampicin (RIF) induces cytochrome P450, which in turn catalyzes drug metabolism; however, pharmacokinetic studies on this phenomenon in the Chinese population, especially in the context of disease, are limited. Therefore, we sought to establish population-based pharmacokinetic models of RIF in a Chinese population with pulmonary tuberculosis (TB). Clinical data were retrospectively collected from 54 patients with pulmonary TB and analyzed alongside RIF blood levels from 95 samples collected prior to RIF administration and between 2 and 12 hours after treatment. HPLC was used to measure serum RIF concentrations. A nonlinear mixed model used to characterize RIF pharmacokinetics and the data generated from the present study were validated using a bootstrap method. Covariates, including demographics, as well as hematological and biological indicators were analyzed. We observed a 1-compartment model with first-order absorption. Typical population values of apparent clearance (CL/F) and apparent volume of distribution (VD /F) were 4.02 L/h and 57.8 L, respectively. No covariate significantly changed the parameters of CL/F and VD . The present study may serve as a foundation for individualized therapy and offer a basis for pharmacokinetic-pharmacodynamic (PK-PD) analysis. PMID:26387492

  10. Detection of Mycobacterium tuberculosis complex by nested polymerase chain reaction in pulmonary and extrapulmonary specimens* ,**

    PubMed Central

    Furini, Adriana Antônia da Cruz; Pedro, Heloisa da Silveira Paro; Rodrigues, Jean Francisco; Montenegro, Lilian Maria Lapa; Machado, Ricardo Luiz Dantas; Franco, Célia; Schindler, Haiana Charifker; Batista, Ida Maria Foschiani Dias; Rossit, Andrea Regina Baptista

    2013-01-01

    OBJECTIVE: To compare the performance of nested polymerase chain reaction (NPCR) with that of cultures in the detection of the Mycobacterium tuberculosis complex in pulmonary and extrapulmonary specimens. METHODS: We analyzed 20 and 78 pulmonary and extrapulmonary specimens, respectively, of 67 hospitalized patients suspected of having tuberculosis. An automated microbial system was used for the identification of Mycobacterium spp. cultures, and M. tuberculosis IS6110 was used as the target sequence in the NPCR. The kappa statistic was used in order to assess the level of agreement among the results. RESULTS: Among the 67 patients, 6 and 5, respectively, were diagnosed with pulmonary and extrapulmonary tuberculosis, and the NPCR was positive in all of the cases. Among the 98 clinical specimens, smear microscopy, culture, and NPCR were positive in 6.00%, 8.16%, and 13.26%, respectively. Comparing the results of NPCR with those of cultures (the gold standard), we found that NPCR had a sensitivity and specificity of 100% and 83%, respectively, in pulmonary specimens, compared with 83% and 96%, respectively, in extrapulmonary specimens, with good concordance between the tests (kappa, 0.50 and 0.6867, respectively). CONCLUSIONS: Although NPCR proved to be a very useful tool for the detection of M. tuberculosis complex, clinical, epidemiological, and other laboratory data should also be considered in the diagnosis and treatment of pulmonary and extrapulmonary tuberculosis. PMID:24473765

  11. Monoarticular Poncet Disease after Pulmonary Tuberculosis: A Rare Case Report and Review of Literature

    PubMed Central

    Garg, Paritosh; Gupta, Nikhil; Arora, Mohit

    2016-01-01

    Introduction: Tuberculosis is a major health problem worldwide, more so in Asian countries and especially India. Being a communicable disease, it can affect the lives of many people. Tuberculosis has varied manifestations and can affect almost every part of the human body. Pulmonary tuberculosis is the most common form. Poncet disease (tuberculous rheumatism) is a polyarticular arthritis that occurs during acute tuberculosis infection in which no mycobacterial involvement can be found or no other known cause of polyarthritis is detected. Case presentation: We describe an atypical presentation of active pulmonary tuberculosis with monoarticular Poncet disease of the right knee in a 24-year-old woman. Discussion: The diagnosis of Poncet disease is mainly clinical with exclusion of other causes. It generally presents as an acute or subacute form; however, chronic forms have been described in the literature. PMID:27455057

  12. Drug-Resistant Tuberculosis: Challenges and Progress.

    PubMed

    Kurz, Sebastian G; Furin, Jennifer J; Bark, Charles M

    2016-06-01

    Antimicrobial resistance is a natural evolutionary process, which in the case of Mycobacterium tuberculosis is based on spontaneous chromosomal mutations, meaning that well-designed combination drug regimens provided under supervised therapy will prevent the emergence of drug-resistant strains. Unfortunately, limited resources, poverty, and neglect have led to the emergence of drug-resistant tuberculosis throughout the world. The international community has responded with financial and scientific support, leading to new rapid diagnostics, new drugs and regimens in advanced clinical development, and an increasingly sophisticated understanding of resistance mechanisms and their application to all aspects of TB control and treatment. PMID:27208770

  13. Haemoptysis in a female with diabetes mellitus: a unique presentation of chronic pulmonary aspergillosis, pulmonary tuberculosis, and Klebsiella peumoniae co-infection.

    PubMed

    Ekwueme, Chinonso; Otu, Akaninyene Asuquo; Chinenye, Sunny; Unachukwu, Chioma; Oputa, Reginald N; Korubo, Ibitrokoemi; Enang, Ofem E

    2016-04-01

    While chronic pulmonary aspergillosis (CPA), pulmonary tuberculosis (PTB), and Klebsiella pneumoniae pneumonia co-infection is rare, we present a 50-year-old woman with uncontrolled diabetes who presented with these three diseases. There is considerable overlap in symptoms of PTB and CPA. Treatment with antifungals, anti-tuberculosis therapy, and antibiotics is beneficial. PMID:27099746

  14. Pulmonary Disease due to Mycobacterium tuberculosis in a Horse: Zoonotic Concerns and Limitations of Antemortem Testing

    PubMed Central

    Lyashchenko, Konstantin P.; Greenwald, Rena; Esfandiari, Javan; Lecu, Alexis; Waters, W. Ray; Posthaus, Horst; Bodmer, Thomas; Janssens, Jean-Paul; Aloisio, Fabio; Graubner, Claudia; Grosclaude, Eléonore; Piersigilli, Alessandra; Schiller, Irene

    2012-01-01

    A case of pulmonary tuberculosis caused by Mycobacterium tuberculosis was diagnosed in a horse. Clinical evaluation performed prior to euthanasia did not suggest tuberculosis, but postmortem examination provided pathological and bacteriological evidence of mycobacteriosis. In the lungs, multiple tuberculoid granulomas communicating with the bronchiolar lumen, pleural effusion, and a granulomatous lymphadenitis involving mediastinal and tracheobronchial lymph nodes were found. Serologic response to M. tuberculosis antigens was detected in the infected horse, but not in the group of 42 potentially exposed animals (18 horses, 14 alpacas, 6 donkeys, and 4 dogs) which showed no signs of disease. Diagnosis of tuberculosis in live horses remains extremely difficult. Four of 20 animal handlers at the farm were positive for tuberculous infection upon follow-up testing by interferon-gamma release assay, indicating a possibility of interspecies transmission of M. tuberculosis. PMID:22567544

  15. Pulmonary Disease due to Mycobacterium tuberculosis in a Horse: Zoonotic Concerns and Limitations of Antemortem Testing.

    PubMed

    Lyashchenko, Konstantin P; Greenwald, Rena; Esfandiari, Javan; Lecu, Alexis; Waters, W Ray; Posthaus, Horst; Bodmer, Thomas; Janssens, Jean-Paul; Aloisio, Fabio; Graubner, Claudia; Grosclaude, Eléonore; Piersigilli, Alessandra; Schiller, Irene

    2012-01-01

    A case of pulmonary tuberculosis caused by Mycobacterium tuberculosis was diagnosed in a horse. Clinical evaluation performed prior to euthanasia did not suggest tuberculosis, but postmortem examination provided pathological and bacteriological evidence of mycobacteriosis. In the lungs, multiple tuberculoid granulomas communicating with the bronchiolar lumen, pleural effusion, and a granulomatous lymphadenitis involving mediastinal and tracheobronchial lymph nodes were found. Serologic response to M. tuberculosis antigens was detected in the infected horse, but not in the group of 42 potentially exposed animals (18 horses, 14 alpacas, 6 donkeys, and 4 dogs) which showed no signs of disease. Diagnosis of tuberculosis in live horses remains extremely difficult. Four of 20 animal handlers at the farm were positive for tuberculous infection upon follow-up testing by interferon-gamma release assay, indicating a possibility of interspecies transmission of M. tuberculosis. PMID:22567544

  16. Association of Serum Vitamin D Levels with Bacterial Load in Pulmonary Tuberculosis Patients

    PubMed Central

    Yuvaraj, B.; Kumar, S. Vinod; Kadhiravan, T.

    2016-01-01

    Background Vitamin D is known to have diverse effects on various systems in the body. There is evidence to suggest that a link exists between the serum vitamin D status and tuberculosis. The present study was designed to assess the alterations in serum 25-hydroxyvitamin D levels in newly diagnosed sputum acid fast bacilli (AFB) positive pulmonary tuberculosis patients and to study the association, if any, between serum vitamin D levels and different levels of sputum smear positivity. Methods Serum 25-hydroxyvitamin D levels were estimated in 65 sputum AFB positive pulmonary tuberculosis patients and 65 age and gender-matched healthy controls. Results The levels of serum 25 hydroxy-vitamin D in tuberculosis patients were not statistically different from the levels of serum 25 hydroxy-vitamin D in healthy controls. However, among patients with pulmonary tuberculosis, there was a significant negative correlation between the levels of serum 25 hydroxy-vitamin D and levels of sputum positivity. Conclusion Serum vitamin D levels negatively correlates with bacterial load in patients with active pulmonary tuberculosis. PMID:27433175

  17. Procollagen III N-terminal Propeptide and Desmosine are Released by Matrix Destruction in Pulmonary Tuberculosis

    PubMed Central

    Seddon, Jo; Kasprowicz, Victoria; Walker, Naomi F.; Yuen, Ho Ming; Sunpath, Henry; Tezera, Liku; Meintjes, Graeme; Wilkinson, Robert J.; Bishai, William R.; Friedland, Jon S.; Elkington, Paul T.

    2013-01-01

    Background. Tuberculosis is transmitted by patients with pulmonary disease. Matrix metalloproteinases (MMPs) drive lung destruction in tuberculosis but the resulting matrix degradation products (MDPs) have not been studied. We investigate the hypothesis that MMP activity generates matrix turnover products as correlates of lung pathology. Methods. Induced sputum and plasma were collected prospectively from human immunodeficiency virus (HIV) positive and negative patients with pulmonary tuberculosis and controls. Concentrations of MDPs and MMPs were analyzed by ELISA and Luminex array in 2 patient cohorts. Results. Procollagen III N-terminal propeptide (PIIINP) was 3.8-fold higher in induced sputum of HIV-uninfected tuberculosis patients compared to controls and desmosine, released during elastin degradation, was 2.4-fold higher. PIIINP was elevated in plasma of tuberculosis patients. Plasma PIIINP correlated with induced sputum MMP-1 concentrations and radiological scores, demonstrating that circulating MDPs reflect lung destruction. In a second patient cohort of mixed HIV seroprevalence, plasma PIIINP concentration was increased 3.0-fold above controls (P < .001). Plasma matrix metalloproteinase-8 concentrations were also higher in tuberculosis patients (P = .001). Receiver operating characteristic analysis utilizing these 2 variables demonstrated an area under the curve of 0.832 (P < .001). Conclusions. In pulmonary tuberculosis, MMP-driven immunopathology generates matrix degradation products. PMID:23922364

  18. Microbiome diversity in the sputum of patients with pulmonary tuberculosis.

    PubMed

    Krishna, P; Jain, A; Bisen, P S

    2016-07-01

    TB is a worldwide pandemic. India has the highest burden of TB, with WHO statistics for 2013 giving an estimated incidence figure of 2.1 million cases for India out of a global incidence of 9 million. Microbiota have been shown to be associated with many disease conditions; however, only few studies have been reported for microbiota associated with TB infection. For the first time, we characterized the composition of microbiota of TB patients of India, using high-throughput 16S rRNA gene sequencing and compared it with healthy controls. Phylum-level analysis showed that the relative abundance of Firmicutes and Actinobacteria was significantly higher in TB samples and Neisseria and Veillonella were two dominant genera after Streptococcus. In our study, significantly different core genera in TB and normal population were found as compared with the reported studies. Also, the presence of diverse opportunistic pathogenic microbiota in TB patients increases the complexity and diversity of sputum microbiota. Characterization of the sputum microbiome is likely to provide important pathogenic insights into pulmonary tuberculosis. PMID:27142586

  19. Drug Resistance among Pulmonary Tuberculosis Patients in Calabar, Nigeria

    PubMed Central

    Otu, Akaninyene; Umoh, Victor; Habib, Abdulrazak; Ameh, Soter; Lawson, Lovett

    2013-01-01

    Background. This study aimed to determine the pattern of drug susceptibility to first-line drugs among pulmonary TB patients in two hospitals in Calabar, Nigeria. Methods. This was a descriptive cross-sectional study carried out between February 2011 and April 2012. Sputum samples from consecutive TB patients in Calabar were subjected to culture on Lowenstein-Jensen (LJ) slopes followed by drug susceptibility testing (DST). The DST was performed on LJ medium by the proportion method. Results. Forty-two of the 100 Mycobacterium tuberculosis strains were found to be resistant to at least one drug. Resistance to only one drug (monoresistance) was found in 17 patients. No strains with monoresistance to rifampicin were found. Resistance to two drugs was found in 22 patients, while one patient was resistant to both three and four drugs. MDR TB was seen in 4% (4/100). The independent variables of HIV serology and sex were not significantly associated with resistance (P > 0.05). Conclusion. There was a high prevalence of anti-TB drug resistance in Calabar. PMID:24078872

  20. Specificity of antibodies to immunodominant mycobacterial antigens in pulmonary tuberculosis.

    PubMed Central

    Jackett, P S; Bothamley, G H; Batra, H V; Mistry, A; Young, D B; Ivanyi, J

    1988-01-01

    A serological survey was performed in groups of patients with active sputum smear-positive or smear-negative pulmonary tuberculosis, healthy household contacts, and controls. Sera were tested for titers of antibodies which bound to each of five purified mycobacterial antigens by enzyme immunoassay and for competition of binding to single epitopes, using six radiolabeled monoclonal antibodies directed toward corresponding molecules. The evaluation of diagnostic specificity was based on a positive score represented by titers above the cutoff point of 2 standard deviations above the mean titer of a control group. For smear-positive samples, the best sensitivity (83%) was achieved by exclusive use of the 38-kilodalton (kDa) antigen or its corresponding monoclonal antibodies. For smear-negative samples, levels of antibodies binding to the 19-kDa antigen showed a lower sensitivity of 62% compared with the control group or 38% compared with the contact group. Titers of antibody binding to the 14-kDa antigen were raised in Mycobacterium bovis BCG-vaccinated contacts, indicating that the greatest potential of this antigen may be in the detection of infection in a population for which tuberculin testing is unreliable. The results demonstrated the differing antibody responses to each of the tested antigens and distinct associations with the stage of infection or disease. PMID:2466869

  1. Imaging Features of Pulmonary CT in Type 2 Diabetic Patients with Multidrug-Resistant Tuberculosis

    PubMed Central

    Jiang, Hongbo; Ren, Yanwei; Lu, Xiwei

    2016-01-01

    Background Until now, radiographic manifestations of multidrug-resistant pulmonary tuberculosis (MDR- TB) in patients with diabetes mellitus (DM) have not been reported. We conducted a study to investigate the imaging features of pulmonary computed tomography (CT) for type 2 diabetic (T2DM) patients with MDR-TB. Methods The clinical data and pulmonary CT findings of 39 type 2 diabetic patients with MDR-TB, 46 type 2 diabetic patients with drug-susceptible tuberculosis (DS-TB), and 72 pure drug-susceptible TB cases (without T2DM and MDR) treated at Dalian Tuberculosis Hospital from 2012 to 2015 were collected, and the clinical features and imaging differences of the three groups were compared. Results The clinical characteristics of the three groups of patients were not significantly different except with respect to age and previous treatment history. However, on imaging, the patients with MDR-TB showed consolidation in and above the pulmonary segments was significantly more extensive than that seen in the DS-TB group with or without T2DM. Conclusion Consolidation in or above multiple pulmonary segments with multiple mouth-eaten cavities and bronchial damage on pulmonary CT images in type 2 diabetic patients with tuberculosis suggests the possibility of multi-drug resistance. PMID:27022735

  2. Multidrug-resistant pulmonary & extrapulmonary tuberculosis: A 13 years retrospective hospital-based analysis

    PubMed Central

    Raveendran, Reena; Oberoi, Jaswinder Kaur; Wattal, Chand

    2015-01-01

    Background & objectives: Multidrug-resistant tuberculosis (MDR-TB) is a public health problem of great significance in India. In the present study an attempt was made to analyse the progression of MDR-TB pattern during a course of 13 years (2000-2012) among the patient population at a tertiary care centre in New Delhi, India. Methods: Mycobacterial isolates obtained on Lowenstein-Jensen (L-J) medium/BacT/ALERT 3D were identified using AccuProbe molecular identification system, routine biochemical tests or GenoType Mycobacteria CM. Antimycobacterial susceptibility testing was performed using resistance ratio method on L-J medium (2000-2004) and one per cent proportion method on BacT/ALERT 3D system (2005-2012). Results: Of the total 14,849 samples subjected to mycobacterial culture, 6569 pulmonary and 8280 extrapulmonary, 2364 were detected positive for mycobacteria. The average percentage positivity rate was 15.9 per cent (18.9 and 13.6% in case of pulmonary and extrapulmonary samples, respectively). Our study revealed a significant increase (P<0.001) in multidrug resistance by 12 per cent (4.7% in 2000 to 19.8% in 2012). MDR-TB was more in case of pulmonary (28.2%) than extrapulmonary (11.6%) TB (P<0.001). Only 6.5 per cent (154) of mycobacterial isolates were non-tuberculous mycobacteria and rapid growers represented by Mycobacterium fortuitum and M. abscessus were the most commonly isolated species. Interpretation & conclusions: Increase in prevalence of MDR-TB by 12 per cent in the past 13 years is alarming. Policy modifications may have to be done to strengthen the existing TB control programmes to encourage contact tracing and culture and drug susceptibility testing for all smear positive pulmonary cases to ensure early and appropriate therapy. PMID:26658593

  3. The prevention and treatment of isoniazid toxicity in the therapy of pulmonary tuberculosis

    PubMed Central

    1963-01-01

    This paper from the Tuberculosis Chemotherapy Centre, Madras, presents the results of a study designed primarily (a) to assess the efficacy of two preparations—Tab. Aneurin. Co. (a vitamin B compound not containing pyridoxine) and glutamic acid—in preventing the development of peripheral neuropathy during high-dosage (12.5-15.2 mg/kg) isoniazid therapy for pulmonary tuberculosis, and (b) to compare the therapeutic efficacy, once isoniazid neuropathy has developed, of Tab. Aneurin. Co., administered at twice the prophylactic dosage, and a vitamin-B-complex preparation containing a small amount of pyridoxine (amounting to 6 mg daily). Tab. Aneurin. Co. was found to be ineffective in preventing peripheral neuropathy, which occurred in five of the 18 patients receiving this preparation, as compared with six of the 18 who received a placebo, calcium gluconate. Glutamic acid appeared to have some prophylactic effect, since only two of the 19 patients receiving it developed the neuropathy, but the difference between the frequency in the glutamic series and that in the placebo series did not attain statistical significance. As to the therapeutic efficacy of the two vitamin B preparations, Tab. Aneurin. Co., at twice the prophylactic dosage, did not prevent the progression of the neuropathy in five out of seven patients, whereas improvement occurred in eight of the nine patients who received the vitamin-B-complex preparation containing the small amount of pyridoxine. This study has confirmed that the frequency of peripheral neuropathy is significantly higher among slow than among rapid inactivators of isoniazid and has indicated that the therapeutic response of the tuberculosis is not materially affected by increasing the dosage of isoniazid from 7.8-9.6 mg/kg (the dosage used in a previous study) to 12.5-15.2 mg/kg. PMID:20604148

  4. Diagnosis and Treatment of Childhood Pulmonary Tuberculosis: A Cross-Sectional Study of Practices among Paediatricians in Private Sector, Mumbai

    PubMed Central

    Tauro, Carolyn Kavita; Gawde, Nilesh Chandrakant

    2015-01-01

    Majority of children with tuberculosis are treated in private sector in India with no available data on management practices. The study assessed diagnostic and treatment practices related to childhood pulmonary tuberculosis among paediatricians in Mumbai's private sector in comparison with International Standards for Tuberculosis Care (ISTC) 2009. In this cross-sectional study, 64 paediatricians from private sector filled self-administered questionnaires. Cough was reported as a symptom of childhood TB by 77.8% of respondents. 38.1% request sputum smear or culture for diagnosis and fewer (32.8%) use it for patients positive on chest radiographs and 32.8% induce sputum for those unable to produce it. Sputum negative TB suspect is always tested with X-ray or tuberculin skin test. 61.4% prescribe regimen as recommended in ISTC and all monitor progress to treatment clinically. Drug-resistance at beginning of treatment is suspected for child in contact with a drug-resistant patient (67.7%) and with prior history of antitubercular treatment (12.9%). About half of them (48%) request drug-resistance test for rifampicin in case of nonresponse after two to three months of therapy and regimen prescribed by 41.7% for multidrug-resistant TB was as per ISTC. The study highlights inappropriate diagnostic and treatment practices for managing childhood pulmonary TB among paediatricians in private sector. PMID:26379705

  5. The progress made in determining the Mycobacterium tuberculosis structural proteome

    PubMed Central

    Hecker, Michael

    2011-01-01

    Mycobacterium tuberculosis is a highly infectious pathogen that is still responsible for millions of deaths annually. Effectively treating this disease typically requires a course of antibiotics, most of which were developed decades ago. These drugs are, however, not effective against persistent tubercle bacilli and the emergence of drug-resistant stains threatens to make many of them obsolete. The identification of new drug targets, allowing the development of new potential drugs, is therefore imperative. Both proteomics and structural biology have important roles to play in this process, the former as a means of identifying promising drug targets and the latter allowing understanding of protein function and protein–drug interactions at atomic resolution. The determination of M. tuberculosis protein structures has been a goal of the scientific community for the last decade, who have aimed to supply a large amount of structural data that can be used in structure-based approaches for drug discovery and design. Only since the genome sequence of M. tuberculosis has been available has the determination of large numbers of tuberculosis protein structures been possible. Currently, the molecular structures of 8.5% of all the pathogen's protein-encoding ORFs have been determined. In this review, we look at the progress made in determining the M. tuberculosis structural proteome and the impact this has had on the development of potential new drugs, as well as the discovery of the function of crucial mycobaterial proteins. PMID:21674801

  6. [Real-time polymerase chain reaction in the diagnosis of pulmonary tuberculosis].

    PubMed

    Salina, T Iu; Morozova, T I

    2008-01-01

    To enhance the efficiency of diagnosis of oligo- and abacillar pulmonary tuberculosis and its differential diagnosis with other lung diseases, the authors studied the informative value of real-time polymerase chain reaction (PCR) used in 62 patients with different clinical forms of tuberculosis and 108 differentially diagnostic patients. Real-time PCR has been ascertained to be a significantly more sensitive and highly specific tool in tuberculosis diagnosis, which considerably improves the specific recognition of the etiology of a pathogenetic process in oligo- and abacillar patients. Particularly encouraging results have been obtained when examining differentially diagnostic patients with the rounded shadows being formed in the lung. PMID:18710048

  7. A Histomorphological Pattern Analysis of Pulmonary Tuberculosis in Lung Autopsy and Surgically Resected Specimens

    PubMed Central

    Lobo, Flora D.; Adiga, Deepa Sowkur Anandarama

    2016-01-01

    Background. Tuberculosis (TB) is a major cause of morbidity and mortality globally. Many cases are diagnosed on autopsy and a subset of patients may require surgical intervention either due to the complication or sequelae of TB. Materials and Methods. 40 cases of resected lung specimens following surgery or autopsy in which a diagnosis of pulmonary tuberculosis was made were included. Histopathological pattern analysis of pulmonary tuberculosis along with associated nonneoplastic changes and identification of Mycobacterium tuberculosis bacilli was done. Results. The mean age of diagnosis was 41 years with male predominance (92.5%). Tuberculosis was suspected in only 12.1% of cases before death. Seven cases were operated upon due to associated complications or suspicion of malignancy. Tubercular consolidation was the most frequent pattern followed by miliary tuberculosis. The presence of necrotizing granulomas was seen in 33 cases (82.5%). Acid fast bacilli were seen in 57.5% cases on Ziehl-Neelsen stain. Conclusion. Histopathology remains one of the most important methods for diagnosing tuberculosis, especially in TB prevalent areas. It should be considered in the differential diagnosis of all respiratory diseases because of its varied clinical presentations and manifestations. PMID:27088035

  8. Pregnancy and chronic progressive pulmonary disease.

    PubMed

    Wexler, Isaiah D; Johannesson, Marie; Edenborough, Frank P; Sufian, Beth S; Kerem, Eitan

    2007-02-15

    Progressive pulmonary disease may preclude the option of pregnancy for a number of women in their child-bearing years due to the severity of the disease. For a subset of women with chronic lung disease including cystic fibrosis, pregnancy is possible, but can have a devastating effect both on the prospective mother and fetus. The potential hazards of pregnancy in cystic fibrosis or other progressive pulmonary diseases may trigger a moral conflict between physician and patient. The female patient may argue that her autonomy cannot be circumscribed and that the physician is obliged to assist her reproductive efforts. The physician can counter that his/her participation in potentially harmful interventions is not consistent with professional norms requiring adherence to the principles of beneficence and nonmaleficence. Whenever possible, the ethical conflict between physician and patient should be resolved before initiation of pregnancy. We propose that this best be done through structured negotiations between physician and patient with the goal of constructing an ethical framework for reducing the moral tension between the two. Steps in the negotiating process include defining the therapeutic alliance, information exchange, dialog, and deliberation. As part of the information exchange, it is important to discuss alternatives to pregnancy such as adoption and surrogacy, especially when there are strong contraindications to pregnancy. If negotiations reach a satisfactory conclusion for both sides, there should be a well-delineated consensual agreement to commence the pregnancy with the full support of the medical team. PMID:17110647

  9. Association of Pulmonary Tuberculosis and Diabetes in Mexico: Analysis of the National Tuberculosis Registry 2000–2012

    PubMed Central

    Delgado-Sánchez, Guadalupe; García-García, Lourdes; Castellanos-Joya, Martín; Cruz-Hervert, Pablo; Ferreyra-Reyes, Leticia; Ferreira-Guerrero, Elizabeth; Hernández, Andrés; Ortega-Baeza, Victor Manuel; Montero-Campos, Rogelio; Sulca, José Antonio; Martínez-Olivares, Ma. de Lourdes; Mongua-Rodríguez, Norma; Baez-Saldaña, Renata; González-Roldán, Jesús Felipe; López-Gatell, Hugo; Ponce-de-León, Alfredo; Sifuentes-Osornio, José; Jiménez-Corona, María Eugenia

    2015-01-01

    Background Tuberculosis (TB) remains a public health problem in Mexico while the incidence of diabetes mellitus type 2 (DM) has increased rapidly in recent years. Objective To describe the trends of incidence rates of pulmonary TB associated with DM and not associated with DM and to compare the results of treatment outcomes in patients with and without DM. Materials and Methods We analysed the National Tuberculosis Registry from 2000 to 2012 including patients with pulmonary TB among individuals older than 20 years of age. The association between DM and treatment failure was analysed using logistic regression, accounting for clustering due to regional distribution. Results In Mexico from 2000 to 2012, the incidence rates of pulmonary TB associated to DM increased by 82.64%, (p <0.001) in contrast to rates of pulmonary TB rate without DM, which decreased by 26.77%, (p <0.001). Patients with a prior diagnosis of DM had a greater likelihood of failing treatment (adjusted odds ratio, 1.34 (1.11–1.61) p <0.002) compared with patients who did not have DM. There was statistical evidence of interaction between DM and sex. The odds of treatment failure were increased in both sexes. Conclusion Our data suggest that the growing DM epidemic has an impact on the rates of pulmonary TB. In addition, patients who suffer from both diseases have a greater probability of treatment failure. PMID:26075393

  10. Protocol for studying cough frequency in people with pulmonary tuberculosis

    PubMed Central

    Bravard, Marjory A; Tracey, Brian H; López, José W; Comina, German; Zimic, Mirko; Coronel, Jorge; O'Neill Lee, Gwenyth; Caviedes, Luz; Luis Cabrera, Jose; Salas, Antonio; Ticona, Eduardo; Kirwan, Daniela E; Friedland, Jon S; Evans, Carlton A; Moore, David A; Gilman, Robert H

    2016-01-01

    Introduction Cough is a key symptom of tuberculosis (TB) as well as the main cause of transmission. However, a recent literature review found that cough frequency (number of coughs per hour) in patients with TB has only been studied once, in 1969. The main aim of this study is to describe cough frequency patterns before and after the start of TB treatment and to determine baseline factors that affect cough frequency in these patients. Secondarily, we will evaluate the correlation between cough frequency and TB microbiological resolution. Methods This study will select participants with culture confirmed TB from 2 tertiary hospitals in Lima, Peru. We estimated that a sample size of 107 patients was sufficient to detect clinically significant changes in cough frequency. Participants will initially be evaluated through questionnaires, radiology, microscopic observation drug susceptibility broth TB-culture, auramine smear microscopy and cough recordings. This cohort will be followed for the initial 60 days of anti-TB treatment, and throughout the study several microbiological samples as well as 24 h recordings will be collected. We will describe the variability of cough episodes and determine its association with baseline laboratory parameters of pulmonary TB. In addition, we will analyse the reduction of cough frequency in predicting TB cure, adjusted for potential confounders. Ethics and dissemination Ethical approval has been obtained from the ethics committees at each participating hospital in Lima, Peru, Asociación Benéfica PRISMA in Lima, Peru, the Universidad Peruana Cayetano Heredia in Lima, Peru and Johns Hopkins University in Baltimore, USA. We aim to publish and disseminate our findings in peer-reviewed journals. We also expect to create and maintain an online repository for TB cough sounds as well as the statistical analysis employed. PMID:27105713

  11. Polymorphisms of SP110 Are Associated with both Pulmonary and Extra-Pulmonary Tuberculosis among the Vietnamese

    PubMed Central

    Fox, Gregory J.; Sy, Dinh Ngoc; Nhung, Nguyen Viet; Yu, Bing; Ellis, Magda K.; Van Hung, Nguyen; Cuong, Nguyen Kim; Thi Lien, Luu; Marks, Guy B.; Saunders, Bernadette M.; Britton, Warwick J.

    2014-01-01

    Background Tuberculosis (TB) is an infectious disease that remains a major cause of morbidity and mortality worldwide, yet the reasons why only 10% of people infected with Mycobacterium tuberculosis go on to develop clinical disease are poorly understood. Genetically determined variation in the host immune response is one factor influencing the response to M. tuberculosis. SP110 is an interferon-responsive nuclear body protein with critical roles in cell cycling, apoptosis and immunity to infection. However association studies of the gene with clinical TB in different populations have produced conflicting results. Methods To examine the importance of the SP110 gene in immunity to TB in the Vietnamese we conducted a case-control genetic association study of 24 SP110 variants, in 663 patients with microbiologically proven TB and 566 unaffected control subjects from three tertiary hospitals in northern Vietnam. Results Five SNPs within SP110 were associated with all forms of TB, including four SNPs at the C terminus (rs10208770, rs10498244, rs16826860, rs11678451) under a dominant model and one SNP under a recessive model, rs7601176. Two of these SNPs were associated with pulmonary TB (rs10208770 and rs16826860) and one with extra-pulmonary TB (rs10498244). Conclusion SP110 variants were associated with increased susceptibility to both pulmonary and extra-pulmonary TB in the Vietnamese. Genetic variants in SP110 may influence macrophage signaling responses and apoptosis during M. tuberculosis infection, however further research is required to establish the mechanism by which SP110 influences immunity to tuberculosis infection. PMID:25006821

  12. Diagnostic value of sputum adenosine deaminase (ADA) level in pulmonary tuberculosis

    PubMed Central

    Binesh, Fariba; Jalali, Hadi; Zare, Mohammad Reza; Behravan, Farhad; Tafti, Arefeh Dehghani; Behnaz, Fatemah; Tabatabaee, Mohammad; Shahcheraghi, Seyed Hossein

    2016-01-01

    Introduction Tuberculosis is still a considerable health problem in many countries. Rapid diagnosis of this disease is important, and adenosine deaminase (ADA) has been used as a diagnostic test. The aim of this study was to assess the diagnostic value of ADA in the sputum of patients with pulmonary tuberculosis. Methods The current study included 40 patients with pulmonary tuberculosis (culture positive, smear ±) and 42 patients with non tuberculosis pulmonary diseases (culture negative). ADA was measured on all of the samples. Results The median value of ADA in non-tuberculosis patients was 2.94 (4.2) U/L and 4.01 (6.54) U/L in tuberculosis patients, but this difference was not statistically significant (p=0.100). The cut-off point of 3.1 U/L had a sensitivity of 61% and a specificity of 53%, the cut-off point of 2.81 U/L had a sensitivity of 64% and a specificity of 50% and the cut-off point of 2.78 U/L had a sensitivity of 65% and a specificity of 48%. The positive predictive values for cut-off points of 3.1, 2.81 and 2.78 U/L were 55.7%, 57.44% and 69.23%, respectively. The negative predictive values for the abovementioned cut-off points were 56.75%, 57.14% and 55.88%, respectively. Conclusion Our results showed that sputum ADA test is neither specific nor sensitive. Because of its low sensitivity and specificity, determination of sputum ADA for the diagnosis of pulmonary tuberculosis is not recommended. PMID:27482515

  13. Exposure to Mycobacterium tuberculosis during Flexible Bronchoscopy in Patients with Unexpected Pulmonary Tuberculosis

    PubMed Central

    Na, Hae Jung; Eom, Jung Seop; Lee, Geewon; Mok, Jeong Ha; Kim, Mi Hyun; Lee, Kwangha; Kim, Ki Uk; Lee, Min Ki

    2016-01-01

    Objective Recent guidelines recommend the use by healthcare personnel of a fit-tested N95 particulate respirator or higher-grade respiratory precaution in a patient undergoing bronchoscopy when pulmonary tuberculosis (PTB) is suspected. However, PTB may be unexpectedly diagnosed in this setting and therefore not evaluated, resulting in the unexpected exposure to Mycobacterium tuberculosis (MTB) of healthcare workers in the bronchoscopy suite. Here, we examined the incidence of unexpected exposure to MTB during flexible bronchoscopy and determined the exposure-related factors. Methods Between 2011 and 2013, a retrospective study was conducted to evaluate unexpected diagnoses of PTB in the bronchoscopy suite. During the study period, 1650 consecutive patients for whom previous CT scans were available and who underwent bronchoscopy for respiratory disease other than PTB were included. The results of bronchial washing, bronchoalveolar lavage, and post-bronchoscopic sputum were reviewed. Results PTB was unexpectedly diagnosed in 76 patients (4.6%). The presence of anthracofibrosis [odds ratio (OR), 3.878; 95% confidence interval (CI), 1.291–11.650; P = 0.016), bronchiectasis (OR, 1.974; 95% CI, 1.095–3.557; P = 0.024), or atelectasis (OR, 1.740; 95% CI, 1.010–2.903; P = 0.046) as seen on chest CT scan was independently associated with unexpected PTB. Patients with both anthracofibrosis and atelectasis were at much higher risk of unexpected PTB (OR, 4.606; 95% CI, 1.383–15.342; P = 0.013). Conclusions The risk of MTB exposure by healthcare personnel in the bronchoscopy suite due to patients with undiagnosed PTB has been underestimated. Therefore, in geographic regions with an intermediate PTB prevalence, such as South Korea (97/100,000 persons per year), higher-grade respiratory precaution, such as a fit-tested N95 particulate respirator, should be considered to prevent occupational exposure to MTB during routine bronchoscopy, especially in patients with CT

  14. [Pulmonary tuberculosis and HIV seropositivity at the Principal Hospital of Dakar (Senegal)].

    PubMed

    Brucker-Davis, F; Le Guenno, B; Bah, A; Griffet, P; Launois, P

    1993-01-01

    In a prospective survey conducted in 1990 in the Principal Hospital of Dakar, pulmonary tuberculosis was 2.3 times more frequent in HIV seropositive patients (12.5%) than in HIV seronegative patients. We studied 22 cases of pulmonary tuberculosis in HIV+ patients and compared them with a control group of HIV- patients admitted for pulmonary tuberculosis. Tuberculosis occurred in 6 out of 22 asymptomatic HIV+ patients, in 15 out of 22 patients with clinical AIDS and in 1 patient with ARC syndrome. Clinical signs were the same as in controls, except for patients with advanced AIDS who developed cardinal signs. TB intra-dermal reactions were more often negative in HIV+ patients, notably those with HDV1, expressing immunodepression. Radiological images were typical in 81% of patients and in 86% of controls. However, concomitant infections were common in both groups, with atypical radiology and hyperleukocytosis. At light microscopy, there was no difference in the frequency of acid and alcohol fast bacilli between the two groups. The mortality rate was increased in HIV+ patients, but this was not due to tuberculosis. Relapses were frequent in both groups, due to poor compliance with treatment. PMID:8362103

  15. Analysis of Immune Responses against a Wide Range of Mycobacterium tuberculosis Antigens in Patients with Active Pulmonary Tuberculosis

    PubMed Central

    Kassa, Desta; Ran, Leonie; Geberemeskel, Wudneh; Tebeje, Mekashaw; Alemu, Amelewerk; Selase, Alemayehu; Tegbaru, Belete; Franken, Kees L. M. C.; Friggen, Annemieke H.; van Meijgaarden, Krista E.; Ottenhoff, Tom H. M.; Wolday, Dawit; Messele, Tsehaynesh

    2012-01-01

    Characterizing host immune responses to molecular targets of Mycobacterium tuberculosis is essential to develop effective immunodiagnostics and better vaccines. We investigated the immune response against a large series of M. tuberculosis antigens, including 5 classical and 64 nonclassical (39 DosR regulon-encoded, 4 resuscitation-promoting factor [RPF], and 21 reactivation-associated) antigens in active-pulmonary-tuberculosis (TB) patients. Whole blood from TB patients (n = 34) was stimulated in vitro with M. tuberculosis antigens. Gamma interferon (IFN-γ) was measured after 7 days of stimulation, using an enzyme-linked immunosorbent assay (ELISA). The majority of the study participants responded to the classical M. tuberculosis antigens TB10.4 (84.8%), early secreted antigenic target-6 kDa (ESAT-6)/CFP-10 (70.6%), and purified protein derivative (PPD) (55.9%). However, only 26.5% and 24.2% responded to HSP65 and Ag85A/B, respectively. Of the 64 nonclassical antigens, 23 (33.3%) were immunogenic (IFN-γ levels, >62 pg/ml) and 8 were strong inducers of IFN-γ (IFN-γ levels, ≥100 pg/ml). The RPF antigens were the most immunogenic. In addition, we observed distinct cytokine expression profiles in response to several M. tuberculosis antigens by multiplex immunoassay. Tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), and IL-6 were commonly detected at high levels after stimulation with 4/15 latency antigens (Rv0081, Rv2006, Rv2629, and Rv1733c) and were found especially in supernatants of the three strong IFN-γ inducers (Rv2629, Rv1009, and Rv2389c). IL-8, IL-6, and IL-17 were exclusively detected after stimulation with Rv0574c, Rv2630, Rv1998, Rv054c, and Rv2028c. In conclusion, in active-pulmonary-TB patients, we identified 23 new immunogenic M. tuberculosis antigens. The distinct expression levels of IFN-γ, TNF-α, IL-6, and IL-10 in response to specific subsets of M. tuberculosis antigens may be promising for the development of immunodiagnostics

  16. Orchestration of pulmonary T cell immunity during Mycobacterium tuberculosis infection: immunity interruptus

    PubMed Central

    Behar, Samuel M.; Carpenter, Stephen M.; Booty, Matthew G.; Barber, Daniel L.; Jayaraman, Pushpa

    2014-01-01

    Despite the introduction almost a century ago of Mycobacterium bovis BCG (BCG), an attenuated form of M. bovis that is used as a vaccine against Mycobacterium tuberculosis, tuberculosis remains a global health threat and kills more than 1.5 million people each year. This is mostly because BCG fails to prevent pulmonary disease – the contagious form of tuberculosis. Although there have been significant advances in understanding how the immune system responds to infection, the qualities that define protective immunity against M. tuberculosis remain poorly characterized. The ability to predict who will maintain control over the infection and who will succumb to clinical disease would revolutionize our approach to surveillance, control, and treatment. Here we review the current understanding of pulmonary T cell responses following M. tuberculosis infection. While infection elicits a strong immune response that contains infection, M. tuberculosis evades eradication. Traditionally, its intracellular lifestyle and alteration of macrophage function are viewed as the dominant mechanisms of evasion. Now we appreciate that chronic inflammation leads to T cell dysfunction. While this may arise as the host balances the goals of bacterial sterilization and avoidance of tissue damage, it is becoming clear that T cell dysfunction impairs host resistance. Defining the mechanisms that lead to T cell dysfunction is crucial as memory T cell responses are likely to be subject to the same subject to the same pressures. Thus, success of T cell based vaccines is predicated on memory T cells avoiding exhaustion while at the same time not promoting overt tissue damage. PMID:25311810

  17. A Comparative Study of Induced Sputum and Bronchial Washings in Diagnosing Sputum Smear Negative Pulmonary Tuberculosis

    PubMed Central

    Mandava, Venu; Namballa, Usha Rani; Makala, Sravani

    2016-01-01

    Introduction Tuberculosis is one of the most important public health problem worldwide. Detecting patients with active pulmonary Koch’s disease is an important component of tuberculosis control programs. However, at times in patients even with a compatible clinical picture, sputum smears do not reveal acid-fast bacilli and smear-negative pulmonary tuberculosis remains a common problem. Aim The present study is aimed to compare the results of induced sputum and bronchial washings smear in patients suspected to have sputum smear negative pulmonary tuberculosis. Materials and Methods A prospective study conducted from August 2014 to July 2015, comprising 120 patients fulfilling study criteria. Patients with respiratory symptoms and chest roentgenogram suspicious of pulmonary tuberculosis with no previous history of anti-tuberculosis treatment and two spontaneous sputum smear samples negative for acid fast bacilli were included. Patients with active haemoptysis and sputum positive were excluded from the study. Sputum induction was done by using 5-10 ml of 3% hypertonic saline through ultrasonic nebulizer taking safety precautions. All the patient underwent fibreoptic bronchoscopy after six hours fasting on the same day. About 20 ml of normal saline instilled into the suspected pathology area and washings were taken with gentle suction. The sample processing and fluorescent staining for acid fast bacilli was done in a designated microscopy lab. Results Out of 120 sputum smear negative pulmonary tuberculosis patients, induced sputum smear examination detected acid fast bacilli in 76 patients (63.3%) and acid fast bacilli detected from bronchial washings in 94 patients (78.3%). Smear positivity was higher in cavitary and infiltrative lesions as compared to consolidation and infrahilar pattern disease. Conclusion Even though both induced sputum and bronchial washings procedures were valuable for the diagnosis of sputum smear negative, sputum induction with hypertonic

  18. 38 CFR 3.370 - Pulmonary tuberculosis shown by X-ray in active service.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... shown by X-ray in active service. 3.370 Section 3.370 Pensions, Bonuses, and Veterans' Relief DEPARTMENT... Rating Considerations Relative to Specific Diseases § 3.370 Pulmonary tuberculosis shown by X-ray in active service. (a) Active disease. X-ray evidence alone may be adequate for grant of direct...

  19. 38 CFR 3.370 - Pulmonary tuberculosis shown by X-ray in active service.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... shown by X-ray in active service. 3.370 Section 3.370 Pensions, Bonuses, and Veterans' Relief DEPARTMENT... Rating Considerations Relative to Specific Diseases § 3.370 Pulmonary tuberculosis shown by X-ray in active service. (a) Active disease. X-ray evidence alone may be adequate for grant of direct...

  20. 38 CFR 3.370 - Pulmonary tuberculosis shown by X-ray in active service.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... shown by X-ray in active service. 3.370 Section 3.370 Pensions, Bonuses, and Veterans' Relief DEPARTMENT... Rating Considerations Relative to Specific Diseases § 3.370 Pulmonary tuberculosis shown by X-ray in active service. (a) Active disease. X-ray evidence alone may be adequate for grant of direct...

  1. 38 CFR 3.370 - Pulmonary tuberculosis shown by X-ray in active service.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... shown by X-ray in active service. 3.370 Section 3.370 Pensions, Bonuses, and Veterans' Relief DEPARTMENT... Rating Considerations Relative to Specific Diseases § 3.370 Pulmonary tuberculosis shown by X-ray in active service. (a) Active disease. X-ray evidence alone may be adequate for grant of direct...

  2. 38 CFR 3.370 - Pulmonary tuberculosis shown by X-ray in active service.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... shown by X-ray in active service. 3.370 Section 3.370 Pensions, Bonuses, and Veterans' Relief DEPARTMENT... Rating Considerations Relative to Specific Diseases § 3.370 Pulmonary tuberculosis shown by X-ray in active service. (a) Active disease. X-ray evidence alone may be adequate for grant of direct...

  3. Broncho pleuro subcutaneous fistula with subcutaneous emphysema: A rare presentation of pulmonary tuberculosis

    PubMed Central

    Saxena, Mukul; Shameem, Mohammad; Bhargava, Rakesh; Baneen, Ummul; Alam, Mohd Mazhar; Fatima, Nazish

    2012-01-01

    Subcutaneous tissue emphysema is observed in a several clinical settings but spontaneous subcutaneous emphysema in the absence of pneumothorax with broncho pleuro subcutaneous fistula is rare. We report a case of spontaneous subcutaneous emphysema secondary to cavitary pulmonary tuberculosis in the absence of pneumothorax. PMID:26029604

  4. Diagnosing pulmonary tuberculosis with the Xpert MTB/RIF test.

    PubMed

    Bodmer, Thomas; Ströhle, Angelika

    2012-01-01

    Tuberculosis (TB) due to Mycobacterium tuberculosis (MTB) remains a major public health issue: the infection affects up to one third of the world population(1), and almost two million people are killed by TB each year. Universal access to high-quality, patient-centered treatment for all TB patients is emphasized by WHO's Stop TB Strategy. The rapid detection of MTB in respiratory specimens and drug therapy based on reliable drug resistance testing results are a prerequisite for the successful implementation of this strategy. However, in many areas of the world, TB diagnosis still relies on insensitive, poorly standardized sputum microscopy methods. Ineffective TB detection and the emergence and transmission of drug-resistant MTB strains increasingly jeopardize global TB control activities. Effective diagnosis of pulmonary TB requires the availability - on a global scale - of standardized, easy-to-use, and robust diagnostic tools that would allow the direct detection of both the MTB complex and resistance to key antibiotics, such as rifampicin (RIF). The latter result can serve as marker for multidrug-resistant MTB (MDR TB) and has been reported in > 95% of the MDR-TB isolates. The rapid availability of reliable test results is likely to directly translate into sound patient management decisions that, ultimately, will cure the individual patient and break the chain of TB transmission in the community. Cepheid's (Sunnyvale, CA, U.S.A.) Xpert MTB/RIF assay meets the demands outlined above in a remarkable manner. It is a nucleic-acids amplification test for 1) the detection of MTB complex DNA in sputum or concentrated sputum sediments; and 2) the detection of RIF resistance-associated mutations of the rpoB gene. It is designed for use with Cepheid's GeneXpert Dx System that integrates and automates sample processing, nucleic acid amplification, and detection of the target sequences using real-time PCR and reverse transcriptase PCR. The system consists of an instrument

  5. Childhood pulmonary tuberculosis: old wisdom and new challenges.

    PubMed

    Marais, Ben J; Gie, Robert P; Schaaf, H Simon; Beyers, Nulda; Donald, Peter R; Starke, Jeff R

    2006-05-15

    Childhood tuberculosis is neglected in endemic areas with resource constraints, as children are considered to develop mild forms of disease and to contribute little to the maintenance of the tuberculosis epidemic. However, children contribute a significant proportion of the disease burden and suffer severe tuberculosis-related morbidity and mortality, particularly in endemic areas. This review provides an overview of well-documented concepts and principles, and demonstrates how this "old wisdom" applies to current and future challenges in the field of childhood tuberculosis; the aim was to articulate some of the most pressing issues, to provide a rational framework for discussion, and to stimulate thought and further scientific study. The prechemotherapy literature that described the natural history of disease in children identified three central concepts: (1) the need for accurate case definitions, (2) the importance of risk stratification, and (3) the diverse spectrum of disease pathology, which necessitates accurate disease classification. The relevance of these concepts and their application to pertinent issues such as the diagnosis of childhood tuberculosis are discussed. The concepts are also linked to the basic principles of antituberculosis treatment, providing a simplified approach to the diagnosis and treatment of childhood tuberculosis that is independent of resource constraints. The main challenges for future research are highlighted and in conclusion it is emphasized that the infrastructure provided by the directly observed therapy, short-course strategy, combined with well-targeted interventions, slightly improved resources, and greatly improved political commitment, may lead to a dramatic reduction in tuberculosis-related morbidity and mortality among children. PMID:16484674

  6. Characteristics of pulmonary tuberculosis in HIV seropositive and seronegative patients in a Northeastern region of Brazil.

    PubMed

    Liberato, Isabella Ramos de Oliveira; de Albuquerque, Maria de Fatima P Militão; Campelo, Antônio Roberto Leite; de Melo, Heloísa Ramos Lacerda

    2004-01-01

    The aim of this study was to analyse the clinical, epidemiological and bacteriological features present in 60 pulmonary tuberculosis patients who were also infected with human immunodeficiency virus (HIV) and to compare these with 120 TB patients who were not infected with HIV. The patients with pulmonary tuberculosis and HIV coinfection were mostly male (p = 0.001), showed a higher frequency of weight loss >10 kilos (p <0.001), had a higher rate of non-reaction result to the tuberculin skin test (p <0.001), a higher frequency of negative sputum smear examination for acid-fast bacilli (p = 0.001) and negative sputum culture for Mycobacterium tuberculosis (p = 0.001). Treatment failure was more common in those who were HIV positive (p <0.000). No higher frequency of resistance to antituberculosis drugs was found to be associated with TB/HIV coinfection (p = 0.407). Association between extrapulmonary and pulmonary tuberculosis was more frequent in those seropositive to HIV than those without HIV virus, 30% and 1.6% respectively. These findings showed a predominance of atypical clinical laboratory features in co-infected patients, and suggest that health care personnel should consider the possibility this diagnosis. PMID:15042183

  7. TLR2-targeted secreted proteins from Mycobacterium tuberculosis are protective as powdered pulmonary vaccines.

    PubMed

    Tyne, Anneliese S; Chan, John Gar Yan; Shanahan, Erin R; Atmosukarto, Ines; Chan, Hak-Kim; Britton, Warwick J; West, Nicholas P

    2013-09-13

    Despite considerable research efforts towards effective treatments, tuberculosis (TB) remains a staggering burden on global health. Suitably formulated sub-unit vaccines offer potential as safe and effective generators of protective immunity. The Mycobacterium tuberculosis antigens, cutinase-like proteins (Culp) 1 and 6 and MPT83, were conjugated directly to the novel adjuvant Lipokel (Lipotek Pty Ltd), a TLR2 ligand that delivers antigen to immune cells in a self-adjuvanting context. Protein-Lipokel complexes were formulated as dry powders for pulmonary delivery directly to the lungs of mice by intra-tracheal insufflation, leading to recruitment of neutrophils and antigen presenting cell populations to the lungs at 72 h, that persisted at 7 days post immunisation. Significant increases in the frequency of activated dendritic cells were observed in the mediastinal lymph node (MLN) at 1 and 4 weeks after homologous boosting with protein-Lipokel vaccine. This was associated with the increased recruitment of effector CD4(+) and CD8(+) T-lymphocytes to the MLN and systemic antigen-specific, IFN-γ producing T-lymphocyte and IgG responses. Notably, pulmonary immunisation with either Culp1-6-Lipokel or MPT83-Lipokel powder vaccines generated protective responses in the lungs against aerosol M. tuberculosis challenge. The successful combination of TLR2-targeting and dry powder vaccine formulation, together with important practical benefits, offers potential for pulmonary vaccination against M. tuberculosis. PMID:23880366

  8. Mycobacterium sherrisii Lung Infection in a Brazilian Patient with Silicosis and a History of Pulmonary Tuberculosis

    PubMed Central

    de Oliveira Abrão, Carolina; de Araújo Filho, João Alves

    2015-01-01

    Nontuberculous mycobacteria (NTM) diseases became relevant with the emergence and spread of HIV and are also related to lung infection in non-HIV individuals with structural lung diseases. Mycobacterium sherrisii is a NTM first characterized in 2004. Only a few cases have been reported. The aim of this case report is to describe the first detailed case of infection with M. sherrisii in a patient with silicosis and history of pulmonary tuberculosis. A 50-year-old HIV-negative white male, previous smoker, with silicosis and a history of treated pulmonary tuberculosis developed a worsening of cough and expectoration pattern, and two sputum samples were positive for acid-fast bacilli. Presumptive treatment for pulmonary tuberculosis was initiated with rifampin, isoniazid, pyrazinamide, and ethambutol, but, at month 5 of treatment, despite correct medication intake and slight improvement of symptoms, sputum bacilloscopy remained positive. Sputum cultures were positive Mycobacterium sherrisii. Treatment regimen was altered to streptomycin (for 2 months), ethambutol, clarithromycin, rifabutin, and trimethoprim-sulfamethoxazole. M. sherrisii should be considered a possible etiological agent of lung infections in patients with pneumoconiosis and history of tuberculosis. PMID:26557395

  9. Tuberculosis and pulmonary candidiasis co-infection present in a previously healthy patient

    PubMed Central

    Jiménez Borré, Gustavo; Gómez Camargo, Doris; Chalavé Jiménez, Neylor; Bellido Rodríguez, Javier; Cuadrado Cano, Bernarda; Navarro Gómez, Shirley

    2016-01-01

    Background: The coexistance among fungal pathogens and tuberculosis pulmonary is a clinical condition that generally occurs in immunosuppressive patients, however, immunocompetent patients may have this condition less frequently. Objective: We report the case of an immunocompetent patient diagnosed with coinfection Mycobacterium tuberculosis and Candida albicans. Case Description: A female patient, who is a 22-years old, with fever and a new onset of hemoptysis. Clinical findings and diagnosis: Diminished vesicular breath sounds in the apical region and basal crackling rales in the left lung base were found in the physical examination. Microbiological tests include: chest radiography and CAT scan pictograms in high resolution, Ziehl-Neelsen stain, growth medium for fungus and mycobacteria through Sabouraudís agar method with D-glucose. Medical examinations showed Candida albicans fungus and Mycobacterium tuberculosis present in the patient. Treatment and Outcome: Patient was treated with anti-tuberculosis and anti-fungal medications, which produced good responses. Clinical relevance: Pulmonary tuberculosis and fungal co-infection are not common in immunocompetent patients. However, we can suspect that there is a presence of these diseases by detecting new onset of hemoptysis in patients. PMID:27546933

  10. [Use of molecular techniques in the diagnosis of pulmonary and extrapulmonary tuberculosis].

    PubMed

    Ozyurt, Mustafa

    2012-04-01

    conventional assays for clinical follow-up of patients. This review article discusses the diagnostic value of molecular methods in the evaluation of pulmonary and extrapulmonary tuberculosis in the light of the current literature. PMID:22639322

  11. [Blood gas changes during treadmill exercise in convalescents from pulmonary tuberculosis. 1. Method of measurement].

    PubMed

    Yoshida, F

    1989-09-01

    With advances in treatment for tuberculosis, pulmonary tuberculosis has become curable. However, chronic respiratory failure has been more often observed in those who have ever had thoracic operation, and were cured with anti-tuberculous chemotherapy in spite of initially severe pulmonary tuberculosis with wide spread lesions in both lungs, particularly in the aged. Therefore it is now necessary to understand accurately the real physio-dynamic situation of respiro-circulatory impairment in these patients. For this purpose, an exercise test was newly designed, and changing curves of blood gas (O2- and CO2-partial pressure, measured transcutaneously) were drawn in 4 healthy persons and 23 recovered patients from pulmonary tuberculosis. The newly designed method was carried out by using Treadmill walk apparatus (Nihon-Denki Sanei Co., Japan), transcutaneous blood gas measurement apparatus (Radio-Meter Co., Copenhagen) and automatic blood pressure measurement apparatus (Kyorin Co., Japan). Treadmill walk exercise test was done through Bruce-Sheffield converted method. The details of this exercise test are written and illustrated in this paper. The results of the test were classified into 4 types by the changes of transcutaneously measured O2 partial pressure curve during the test: 1. unchanged, 2. slightly decreased, 3. moderately decreased, 4. markedly decreased. The significance of these 4 types will be discussed in the next report after examining more convalescents from pulmonary tuberculosis. The reproducibility of this test was examined in 6 patients, and it was almost good. In addition, in 3 out of 27 patients, odd curves contrary to our expectation, that is increase of the value of trans-cutaneously measured O2 partial pressure and/or decrease of the value of trans-cutaneously measured CO2 partial pressure immediately after the initiation of the first test were observed. But in the second test, carried out in the other day, the curve fell into one of the 4 types

  12. Treatment outcome of new smear positive pulmonary tuberculosis patients in Penang, Malaysia

    PubMed Central

    2014-01-01

    Background According to the World Health Organization’s recent report, in Malaysia, tuberculosis (TB) treatment success rate for new smear positive pulmonary tuberculosis (PTB) patients is still below the global success target of 85%. In this study, we evaluated TB treatment outcome among new smear positive PTB patients, and identified the predictors of unsuccessful treatment outcome and longer duration of treatment (i.e., > 6 months). Methods The population in this study consisted of all new smear positive PTB patients who were diagnosed at the chest clinic of Penang General Hospital between March 2010 and February 2011. During the study period, a standardized data collection form was used to obtain socio-demographic, clinical and treatment related data of the patients from their medical charts and TB notification forms (Tuberculosis Information System; TBIS). These data sources were reviewed at the time of the diagnosis of the patients and then at the subsequent follow-up visits until their final treatment outcomes were available. The treatment outcomes of the patients were reported in line with six outcome categories recommended by World Health Organization. Multiple logistic regression analysis was used to find the independent risk factors for unsuccessful treatment outcome and longer treatment duration. Data were analyzed using the PASW (Predictive Analysis SoftWare, version 19.0. Armonk, NY: IBM Corp). Results Among the 336 PTB patients (236 male and 100 female) notified during the study period, the treatment success rate was 67.26% (n = 226). Out of 110 patients in unsuccessful outcome category, 30 defaulted from the treatment, 59 died and 21 were transferred to other health care facilities. The mean duration of TB treatment was 8.19 (SD 1.65) months. In multiple logistic regression analysis, risk factors for unsuccessful treatment outcome were foreign nationality, male gender and being illiterate. Similarly, risk factors for mortality due to TB

  13. Coinfections in Intensive Care Unit with pulmonary tuberculosis and mucormycosis: A clinical dilemma.

    PubMed

    Dube, Pratibha; Saroa, Richa; Palta, Sanjeev

    2016-03-01

    Herein, we present the case report of an adult male diabetic patient who had coinfection with Mycobacterium tuberculosis and mucormycosis, which otherwise is a rare clinical entity. Diabetes mellitus may predispose a patient to tuberculosis (TB) infection which further weakens immune system thus making him susceptible to other fungal or bacterial infections which may pose various treatment difficulties. Therefore, there is a need for mycological and bacteriological investigations in patients with pulmonary TB to rule out secondary coinfections thus contributing to better management. PMID:27076735

  14. Preventing Infectious Pulmonary Tuberculosis Among Foreign-Born Residents of the United States

    PubMed Central

    Katz, Dolly; Ghosh, Smita; Blumberg, Henry; Tamhane, Ashutosh; Sevilla, Anna; Reves, Randall

    2015-01-01

    Objectives. We described risk factors associated with infectious tuberculosis (TB) and missed TB-prevention opportunities in foreign-born US residents, who account for almost two thirds of the nation’s TB patients. Methods. In a cross-sectional study at 20 US sites of foreign-born persons diagnosed with TB in 2005 through 2006, we collected results of sputum smear microscopy for acid-fast bacilli (a marker for infectiousness) and data on visa status, sociodemographics, TB-related care seeking, and latent TB infection (LTBI) diagnosis opportunities. Results. Among 980 persons with pulmonary TB who reported their visa status, 601 (61%) were legal permanent residents, 131 (13.4%) had temporary visas, and 248 (25.3%) were undocumented. Undocumented persons were more likely than permanent residents to have acid-fast bacilli–positive smears at diagnosis (risk ratio = 1.3; 95% confidence interval = 1.2, 1.4). Of those diagnosed 1 year or more after arrival, 57.3% reported LTBI screening opportunities; fewer than 25% actually were. Undocumented persons reported fewer LTBI screening opportunities and were less likely to be tested. Conclusions. Progress toward TB elimination in the United States depends upon expanding opportunities for regular medical care and promotion of LTBI screening and treatment among foreign-born persons. PMID:26180947

  15. Frequency of hypovitaminosis D and its associated risk factors in newly diagnosed pulmonary tuberculosis patients

    PubMed Central

    Azam, Fahad; Shaheen, Abida; Arshad, Rabia

    2016-01-01

    Objective: To find out the frequency of hypovitaminosis D and its associated risk factors in newly diagnosed pulmonary tuberculosis patients prior to administration of standard anti tuberculosis therapy. Methods: This cross-sectional study was carried out in Ojha Institute of Chest Diseases-DUHS. After approval from BASR and following written informed consent eighty newly diagnosed, as per WHO criteria, tuberculosis patients were enrolled. Prior to the initiation of anti tuberculosis therapy, the serum vitamin D level was determined by 25-OH Vitamin D kit using the chemiluminescent immunoassay (CLIA) method. A cut off value of >30 ng/mL of serum vitamin D was taken as normal whereas a range between 10-30 ng/mL and <10 ng/mL were considered insufficient and deficient respectively. Frequency of socio-demographic associated risk factors of hypovitaminosis D was also determined. Results: Out of eighty newly diagnosed tuberculosis patients 33 (41.25%) were males and 47(58.75%) were females with their ages ranging from 18-50 years. 54 patients (26 male and 28 female patients) were smokers. BMI of all the patients was found to be less than the normal ranges. Hypovitaminosis was present in all the cases. Vitamin D insufficiency was found in 49 participants (20 male and 29 female) whereas 31 patients (13 male and 18 female) were found to be vitamin D deficient. Conclusion: Prevalence of serum vitamin D level derangement is very high in newly diagnosed patients with pulmonary tuberculosis in our local setting which necessitates administration of adjuvant vitamin D along with standard anti tuberculosis therapy. PMID:27182266

  16. Microscopy as a diagnostic tool in pulmonary tuberculosis.

    PubMed

    Singhal, Ritu; Myneedu, Vithal Prasad

    2015-03-01

    Tuberculosis continues to cast a huge impact on humanity with its high incidence and mortality, especially in developing countries. For tuberculosis case detection, microscopy continues to be indispensible, given its low cost, rapidity, simplicity of procedure and high specificity. Modifications have attempted to improve the sensitivity of microscopy which include: concentration methods such as centrifugation, N-acetyl cysteine-sodium hydroxide, bleach, ammonium sulfate or chitin. Furthermore, classical Ziehl-Neelsen (ZN) staining has been subjected to varying carbol fuchsin concentrations or replaced by Kinyoun staining, fluorescent microscopy or immune-fluorescence. Currently, light emitting diode fluorescence is recognizably the most plausible method as an alternative to ZN staining. PMID:26655191

  17. A prospective cohort study of latent tuberculosis in adult close contacts of active pulmonary tuberculosis patients in Korea

    PubMed Central

    Park, Sun Hyo; Lee, Seung Jun; Cho, Yu Ji; Jeong, Yi Yeong; Kim, Ho Cheol; Lee, Jong Deog; Kim, Hee Jin; Menzies, Dick

    2016-01-01

    Background/Aims: The objective of this prospective study was to evaluate the diagnosis and treatment of latent tuberculosis infection (LTBI) in adult close contacts of active pulmonary tuberculosis (TB) patients in Korea. Methods: Adult close contacts of active pulmonary TB patients were recruited at a regional tertiary hospital in Korea. The participants were tested for LTBI using the tuberculin skin test (TST) and/or QuantiFERON-TB Gold (QFT-G) test. LTBI patients, who consented to treatment, were randomly assigned to receive isoniazid for 9 months (9INH) or rifampin for 4 months (4RIF). Results: We examined 189 adult close contacts (> 18 years) of 107 active pulmonary TB patients. The TST and QFT-G were positive (≥ 10 mm) in 75/183 (39.7%) and 45/118 (38.1%) tested participants, respectively. Among 88 TST or QFT-G positive LTBI participants, 45 participants were randomly assigned to receive 4RIF (n = 21) or 9INH (n = 24), respectively. The average treatment duration for the 4RIF and 9INH groups was 3.3 ± 1.3 and 6.1 ± 2.7 months, respectively. Treatment was completed in 25 participants (4RIF, n = 16; 9INH, n = 9). LTBI participants who accepted treatment were more likely to be women and have more cavitary lesions on the chest radiographs of index cases and positive TST and QFT-G results compared to those who refused treatment. Conclusions: About 40% of adult close contacts of active pulmonary TB patients had LTBI; about 50% of these LTBI participants agreed to treatment. PMID:27052266

  18. Adverse Outcomes after Non-Chest Surgeries in Patients with Pulmonary Tuberculosis: A Nationwide Study

    PubMed Central

    Lin, Chao-Shun; Yeh, Chun-Chieh; Chung, Chi-Li; Hung, Chih-Jen; Chen, Ta-Liang

    2015-01-01

    Background The association between pulmonary tuberculosis (TB) and postoperative outcomes remains unknown. This study investigated outcomes following non-chest surgeries in patients with previous pulmonary TB. Methods Using Taiwan’s National Health Insurance Research Database, we analyzed 6911 patients (aged ≥ 20 years) with preoperative diagnosis of pulmonary TB and 6911 propensity score-matched controls receiving non-chest surgeries in 2008–2010. Postoperative outcomes were compared between patients with or without pulmonary TB by calculating adjusted odds ratios (ORs) and 95% confidence intervals (CIs) in the multivariate logistic regressions. Results Surgical patients with pulmonary TB had a significantly higher postoperative complication rates than controls, including septicemia, pneumonia, acute renal failure, deep wound infection, overall complications, and 30-day postoperative mortality (OR 1.41; 95% CI 1.07–1.86). The ORs of patients with low-income status were as high as 2.27 (95% CI 1.03–5.03). Preoperative use of TB drugs and TB-related medical expenditure also associated with higher postoperative mortality among surgical patients with pulmonary TB. Conclusions Surgical patients with pulmonary TB have significantly increased risks of postoperative complications and mortality after non-chest surgeries. This study suggests the need to improve postoperative care for surgical patients with pulmonary TB. PMID:26172153

  19. DIAGNOSTIC TEST OF SPUTUM GENEXPERT MTB/RIF FOR SMEAR NEGATIVE PULMONARY TUBERCULOSIS.

    PubMed

    Reechaipichitkul, Wipa; Phetsuriyawong, Attawoot; Chaimanee, Prajuab; Ananta, Pimjai

    2016-05-01

    The objective of this study was to evaluate the performance of the Gene-Xpert MTB/RIF sputum test for diagnosing pulmonary tuberculosis (TB) among patients sputum acid-fast bacillus (AFB) smear negative results in Thailand, a country with a high prevalence of pulmonary tuberculosis. We studied 151 patients who presented to Srinagarind Hospital, Khon Kaen, Thailand with a 2 week or more history of fever and/or cough and an abnormal chest radiograph between 2010 and 2014; these patients had at least 2 negative sputum AFB smear results. Of these, 76 were diagnosed as having either confirmed or probable pulmonary TB: the 32 confirmed cases were those with a positive sputum culture for Mycobacterium tuberculosis (MTB) and the 44 probable case were those with clinical and radiographic findings consistent with TB and who had a response to anti-TB therapy. Seventy-five cases were diagnosed as not having pulmonary TB. Of the 32 patients with a positive sputum culture for MTB, 26 had a positive GeneXpert MTB/RIF sputum test. Compared to sputum culture for MTB the GeneXpert MTB/ RIF test gave a sensitivity of 83.9% (95% CI: 66.3-94.5) and a specificity of 92.1% (95% CI: 83.6-97), a positive predictive value (PPV) of 81.3% (95% CI: 63.6-92.8) and a negative predictive value (NPV) of 93.3% (95% CI: 85.1-97.8). The GeneXpert MTB/RIF test had a fair sensitivity and specificity for diagnosing smear negative pulmonary TB. It may be useful for diagnosing pulmonary TB in patients with a negative sputum AFB smear. The assay is faster than culture and can detect rifampicin resistant strains of MTB. PMID:27405129

  20. Rapid Screening of MDR-TB in Cases of Extra Pulmonary Tuberculosis Using Geno Type MTBDRplus

    PubMed Central

    Kumari, Richa; Tripathi, Rajneesh; Pandey, Alok Prakash; Banerjee, Tuhina; Sinha, Pallavi; Anupurba, Shampa

    2016-01-01

    Background Drug resistance in tuberculosis is a major public health challenge in developing countries. The limited data available on drug resistance in extra pulmonary tuberculosis stimulated us to design our study on anti-tuberculosis drug resistance pattern in cases of extra pulmonary tuberculosis in a tertiary referral hospital of North India. We performed Geno Type MTBDRplus assay in comparison with conventional drug susceptibility testing by proportion method to study the mutation patterns in rpoB, katG and inhA genes. Methods A total of 510 extra pulmonary samples were included in this study. After the smear microscopy, all the specimens were subjected for culture on Lowenstein Jensen (LJ) media. Phenotypic drug susceptibility testing (DST) was performed on LJ media for all the MTB isolates and compared with the results of Geno Type MTBDRplus assay which was performed with the DNA isolated from the culture by conventional method. Results Of 510 specimens cultured, the total culture positivity obtained was 11.8% (60) encompassing 54 (10.6%) Mycobacterium tuberculosis and 6 (1.2%) non-tubercular mycobacteria (NTM). DST results by Geno Type MTBDRplus assay and solid culture methods were compared in 51 MTB isolates excluding the two Rif indeterminate and one invalid test. Geno Type MTBDRplus accurately identified 13 of 14 rifampicin-resistant strains, 14 of 15 isoniazid-resistant strains and 13 of 14 as multi drug resistant tuberculosis (MDR-TB) in comparison with conventional method. Sensitivity and specificity were 92.86% and 97.30% respectively for detection of RIF resistance, 93.33% and 94.44% respectively for detection of INH resistance, 92.86% and 97.30% respectively for detection of MDR-TB, while the overall concordance of Geno Type MTBDRplus assay with conventional DST was 94.11%. The turn-around time for performing Geno Type MTBDRplus assay test was 48 hours. Conclusion The problem of MDR in extra pulmonary tuberculosis (EPTB) cannot be overlooked and

  1. CD14 contributes to pulmonary inflammation and mortality during murine tuberculosis

    PubMed Central

    Wieland, Catharina W; van der Windt, Gerritje J W; Wiersinga, W Joost; Florquin, Sandrine; van der Poll, Tom

    2008-01-01

    Toll-like receptors play an essential role in the innate recognition of micro-organisms by the host. CD14 is one of the extracellular adaptor proteins required for recognition of Gram-negative bacteria and possibly also Mycobacterium tuberculosis. Therefore, we intranasally infected wild-type (WT) and CD14 knock-out (KO) mice with virulent M. tuberculosis H37Rv. We found no differences in bacterial load in the main target organ lung up to 32 weeks after infection. From 20 weeks onward 57% of WT mice succumbed, whereas all CD14 KO mice survived. The improved outcome of CD14 KO mice was accompanied by reduced pulmonary inflammation; lung cell counts and percentage of inflamed lung tissue were reduced in CD14 WT mice. These data suggest that during chronic infection CD14 KO mice are protected from lethality caused by lung tuberculosis because of a reduction of the inflammatory response. PMID:18393969

  2. The pathogen recognition sensor, NOD2, is variably expressed in patients with pulmonary tuberculosis

    PubMed Central

    Lala, Sanjay; Dheda, Keertan; Chang, Jung-Su; Huggett, Jim F; Kim, Louise U; Johnson, Margaret A; Rook, Graham AW; Keshav, Satish; Zumla, Alimuddin

    2007-01-01

    Background NOD2, an intracellular pathogen recognition sensor, modulates innate defences to muropeptides derived from various bacterial species, including Mycobacterium tuberculosis (MTB). Experimentally, NOD2 attenuates two key putative mycobactericidal mechanisms. TNF-α synthesis is markedly reduced in MTB-antigen stimulated-mononuclear cells expressing mutant NOD2 proteins. NOD2 agonists also induce resistance to apoptosis, and may thus facilitate the survival of MTB in infected macrophages. To further define a role for NOD2 in disease pathogenesis, we analysed NOD2 transcriptional responses in pulmonary leucocytes and mononuclear cells harvested from patients with pulmonary tuberculosis (PTB). Methods We analysed NOD2 mRNA expression by real-time polymerase chain-reaction in alveolar lavage cells obtained from 15 patients with pulmonary tuberculosis and their matched controls. We compared NOD2 transcriptional responses, in peripheral leucocytes, before and after anti-tuberculous treatment in 10 patients. In vitro, we measured NOD2 mRNA levels in MTB-antigen stimulated-mononuclear cells. Results No significant differences in NOD2 transcriptional responses were detected in patients and controls. In some patients, however, NOD2 expression was markedly increased and correlated with toll-like-receptor 2 and 4 expression. In whole blood, NOD2 mRNA levels increased significantly after completion of anti-tuberculosis treatment. NOD2 expression levels did not change significantly in mononuclear cells stimulated with mycobacterial antigens in vitro. Conclusion There are no characteristic NOD2 transcriptional responses in PTB. Nonetheless, the increased levels of NOD2 expression in some patients with severe tuberculosis, and the increases in expression levels within peripheral leucocytes following treatment merit further studies in selected patient and control populations. PMID:17705850

  3. Kinetics of Mycobacterium tuberculosis-specific IFN-γ responses and sputum bacillary clearance in HIV-infected adults during treatment of pulmonary tuberculosis.

    PubMed

    Mzinza, David T; Sloan, Derek J; Jambo, Kondwani C; Shani, Doris; Kamdolozi, Mercy; Wilkinson, Katalin A; Wilkinson, Robert J; Davies, Geraint R; Heyderman, Robert S; Mwandumba, Henry C

    2015-07-01

    In HIV-uninfected adults with pulmonary tuberculosis (TB), anti-TB treatment is associated with changes in Mycobacterium tuberculosis (Mtb)-specific immune responses, which correlate with sputum bacillary load. It is unclear if this occurs in HIV-infected TB patients. We investigated changes in Mtb-specific immune responses and sputum bacillary clearance during anti-TB treatment in HIV-infected and HIV-uninfected adults with pulmonary TB. Sputum bacillary load was assessed by smear microscopy and culture. Mtb-specific IFN-γ secreting peripheral blood mononuclear cells were enumerated using an ELISPOT assay following stimulation with PPD, ESAT-6 and CFP-10. The baseline frequency of Mtb-specific IFN-γ secreting cells was lower in HIV-infected than HIV-uninfected patients (median PPD 32 vs. 104 Spot Forming Units (SFU), p = 0.05; CFP-10 19 vs. 74 SFU, p = 0.01). ESAT-6-specific IFN-γ secreting cells and sputum bacillary load declined progressively during treatment in both HIV-infected and HIV-uninfected patients. HIV infection did not influence the 2-month sputum culture conversion rate (Odds Ratio 0.89, p = 0.95). These findings suggest that changes in ESAT-6-specific immune responses during anti-TB treatment correspond with changes in sputum bacillary load irrespective of host HIV infection status. The utility of Mtb-specific IFN-γ responses as a proxy measure of treatment response in HIV-infected TB patients warrants further evaluation in other settings. PMID:26051653

  4. Thalidomide treatment reduces tumor necrosis factor alpha production and enhances weight gain in patients with pulmonary tuberculosis.

    PubMed Central

    Tramontana, J. M.; Utaipat, U.; Molloy, A.; Akarasewi, P.; Burroughs, M.; Makonkawkeyoon, S.; Johnson, B.; Klausner, J. D.; Rom, W.; Kaplan, G.

    1995-01-01

    BACKGROUND: The monocyte-derived cytokine, tumor necrosis factor alpha (TNF alpha), is essential for host immunity, but overproduction of this cytokine may have serious pathologic consequences. Excess TNF alpha produced in pulmonary tuberculosis may cause fevers, weakness, night sweats, necrosis, and progressive weight loss. Thalidomide (alpha-N-phthalimidoglutarimide) has recently been shown to suppress TNF alpha production by human monocytes in vitro and to reduce serum TNF alpha in leprosy patients. We have therefore conducted a two-part placebo-controlled pilot study of thalidomide in patients with active tuberculosis to determine its effects on clinical response, immune reactivity, TNF alpha levels, and weight. MATERIALS AND METHODS: 30 male patients with active tuberculosis, either human immunodeficiency virus type 1 positive (HIV-1+) or HIV-1-, received thalidomide or placebo for single or multiple 14 day cycles. Toxicity of the study drug, delayed type hypersensitivity (DTH), cytokine production, and weight gain were evaluated. RESULTS: Thalidomide treatment was well tolerated, without serious adverse events. The drug did not adversely affect the DTH response to purified protein derivative (PPD), total leukocyte, or differential cell counts. TNF alpha production was significantly reduced during thalidomide treatment while interferon-gamma (IFN gamma) production was enhanced. Daily administration of thalidomide resulted in a significant enhancement of weight gain. CONCLUSIONS: The results indicate that thalidomide is well tolerated by patients receiving anti-tuberculosis therapy. Thalidomide treatment reduces TNF alpha production both in vivo and in vitro and is associated with an accelerated weight gain during the study period. PMID:8521296

  5. Prevalence and characterization of opportunistic candidal infections among patients with pulmonary tuberculosis

    PubMed Central

    Astekar, Madhusudan; Bhatiya, Priyanka Sharma; Sowmya, GV

    2016-01-01

    Background: Although Candida albicans remains the most common cause of human candidiasis, the frequency of infection attributed to other members of the genus is also increasing. Hence, the present study was carried out to know the prevalence of opportunistic candidal infection in tuberculosis, and if positive, the species of Candida that is most commonly associated. Materials and Methods: The present study comprised sixty pulmonary tuberculosis patients who were divided into (1) fresh or untreated group, (2A) chronic or treated group having no complications and (2B) having complications, comprising twenty patients each, respectively. The collected sputum samples were initially stained with Ziehl–Neelsen stain for confirmation of presence of tubercle Bacilli. Primary isolation was done on Sabouraud Dextrose Agar (SDA). The candidal colonies were confirmed microscopically for the presence of pseudohyphae. Further speciation of the positive candidal samples was carried out using ChromAgar. Result: The total fungal prevalence among 60 patients with pulmonary tuberculosis on SDA was 33 (55%) Candida and 3 (5%) Aspergillus. The prevalence of different candidal species on ChromAgar showed C. albicans as the predominant one, followed by Candida tropicalis and Candida krusei. Freshly diagnosed or untreated group was less commonly associated with pulmonary mycoses than chronic or treated group. The prevalence of Candida had increased with treatment, duration and age, and it was more in males than females. Conclusion: The present study confirms the phenomenon of opportunistic candidal infections in pulmonary tuberculosis patients. Rapid and reliable identification of Candida species is essential as they differ in their virulence and sensitivity to antifungal drugs. PMID:27601806

  6. Rapid culture-based diagnosis of pulmonary tuberculosis in developed and developing countries.

    PubMed

    Asmar, Shady; Drancourt, Michel

    2015-01-01

    Culturing Mycobacterium tuberculosis remains the gold standard for the laboratory diagnosis of pulmonary tuberculosis, with 9 million new cases and 1.5 million deaths mainly in developing countries. Reviewing data reported over 20 years yields a state-of-the-art procedure for the routine culture of M. tuberculosis in both developed and developing countries. Useful specimens include sputum, induced sputum, and stools collected in quaternary ammonium preservative-containing sterile cans. The usefulness of other non-invasive specimens remains to be evaluated. Specimens can be collected in a diagnosis kit also containing sampling materials, instructions, laboratory requests, and informed consent. Automated direct LED fluorescence microscopy after auramine staining precedes inoculation of an egg-lecithin-containing culture solid medium under microaerophilic atmosphere, inverted microscope reading or scanning video-imaging detection of colonies and colonies identification by recent molecular methods. This procedure should result in a diagnosis of pulmonary tuberculosis as fast as 5 days. It may be implemented in both developed and developing countries with automated steps replaceable by manual steps depending on local resources. PMID:26579092

  7. [Immunotherapy of autologous focus of infiltrating lymphocytes in resection of pulmonary tuberculosis].

    PubMed

    Zhestkov, K G; Zemskov, V M; Batyrov, F A

    2001-01-01

    The development of immunotherapy modalities using active immunologically "trained" cells obtained just from a focus of tuberculous inflammation is a promising direction of the prevention and treatment of recurrent tuberculosis. Thirty patients were examined. A procedure was developed for autoimmunotherapy. The study showed it possible to obtain living, sterile, tuberculous inflammation focus-trophic lymphocytes in the amount sufficient for an immunotherapeutical effect. Autoimmunotherapy was found to reduce the number of postoperative recurrences (6% in the experimental group versus 20% in the control one), promoted prompter recovery of tuberculous bronchitis, earlier normalization of the parameters of systemic and antituberculous immunity after surgery. Densitometric analysis of X-ray films revealed a significant focal consolidation (by 1.37 times) after using focus-infiltrating lymphocytes. Autoimmunotherapy using focus-infiltrating lymphocytes makes it possible to improve the outcomes of surgical treatment of patients with pulmonary tuberculosis by reducing the risk of postoperative recurrent tuberculosis, to apply resection interventions in disseminated and bilateral pulmonary tuberculosis more extensively, to use saving resections aimed at removing the basic focus of a tuberculous lesion if there are disseminated focal seedings, and to promote the solution of a problem of the surgical management of patients with drug-resistant mycobacteria. PMID:11858084

  8. Evidence From Chile That Arsenic in Drinking Water May Increase Mortality From Pulmonary Tuberculosis

    PubMed Central

    Smith, Allan H.; Marshall, Guillermo; Yuan, Yan; Liaw, Jane; Ferreccio, Catterina; Steinmaus, Craig

    2011-01-01

    Arsenic in drinking water causes increased mortality from several cancers, ischemic heart disease, bronchiectasis, and other diseases. This paper presents the first evidence relating arsenic exposure to pulmonary tuberculosis, by estimating mortality rate ratios for Region II of Chile compared with Region V for the years 1958–2000. The authors compared mortality rate ratios with time patterns of arsenic exposure, which increased abruptly in 1958 in Region II and then declined starting in 1971. Tuberculosis mortality rate ratios in men started increasing in 1968, 10 years after high arsenic exposure commenced. The peak male 5-year mortality rate ratio occurred during 1982–1986 (rate ratio = 2.1, 95% confidence interval: 1.7, 2.6; P < 0.001) and subsequently declined. Mortality rates in women were also elevated but with fewer excess pulmonary tuberculosis deaths (359 among men and 95 among women). The clear rise and fall of tuberculosis mortality rate ratios in men following high arsenic exposure are consistent with a causal relation. The findings are biologically plausible in view of evidence that arsenic is an immunosuppressant and also a cause of chronic lung disease. Finding weaker associations in women is unsurprising, because this is true of most arsenic-caused health effects. Confirmatory evidence is needed from other arsenic-exposed populations. PMID:21190988

  9. Rapid culture-based diagnosis of pulmonary tuberculosis in developed and developing countries

    PubMed Central

    Asmar, Shady; Drancourt, Michel

    2015-01-01

    Culturing Mycobacterium tuberculosis remains the gold standard for the laboratory diagnosis of pulmonary tuberculosis, with 9 million new cases and 1.5 million deaths mainly in developing countries. Reviewing data reported over 20 years yields a state-of-the-art procedure for the routine culture of M. tuberculosis in both developed and developing countries. Useful specimens include sputum, induced sputum, and stools collected in quaternary ammonium preservative-containing sterile cans. The usefulness of other non-invasive specimens remains to be evaluated. Specimens can be collected in a diagnosis kit also containing sampling materials, instructions, laboratory requests, and informed consent. Automated direct LED fluorescence microscopy after auramine staining precedes inoculation of an egg-lecithin-containing culture solid medium under microaerophilic atmosphere, inverted microscope reading or scanning video-imaging detection of colonies and colonies identification by recent molecular methods. This procedure should result in a diagnosis of pulmonary tuberculosis as fast as 5 days. It may be implemented in both developed and developing countries with automated steps replaceable by manual steps depending on local resources. PMID:26579092

  10. Antimycobacterial drugs modulate immunopathogenic matrix metalloproteinases in a cellular model of pulmonary tuberculosis.

    PubMed

    Singh, Shivani; Kubler, Andre; Singh, Utpal K; Singh, Ajay; Gardiner, Harriet; Prasad, Rajniti; Elkington, Paul T; Friedland, Jon S

    2014-08-01

    Tuberculosis is characterized by extensive destruction and remodelling of the pulmonary extracellular matrix. Stromal cell-derived matrix metalloproteinases (MMPs) are implicated in this process and may be a target for adjunctive immunotherapy. We hypothesized that MMPs are elevated in bronchoalveolar lavage fluid of tuberculosis patients and that antimycobacterial agents may have a modulatory effect on MMP secretion. Concentrations of MMP-1, -2, -3, -7, -8, and -9 were elevated in the bronchoalveolar lavage fluid from tuberculosis patients compared to those in bronchoalveolar lavage fluid from patients with other pulmonary conditions. There was a positive correlation between MMP-3, MMP-7, and MMP-8 and a chest radiological score of cavitation and parenchymal damage. Respiratory epithelial cell-derived MMP-3 was suppressed by moxifloxacin, rifampicin, and azithromycin in a dose-dependent manner. Respiratory epithelial cell-derived MMP-1 was suppressed by moxifloxacin and azithromycin, whereas MMP-9 secretion was only decreased by moxifloxacin. In contrast, moxifloxacin and azithromycin both increased MMP-1 and -3 secretion from MRC-5 fibroblasts, demonstrating that the effects of these drugs are cell specific. Isoniazid did not affect MMP secretion. In conclusion, MMPs are elevated in bronchoalveolar lavage fluid from tuberculosis patients and correlate with parameters of tissue destruction. Antimycobacterial agents have a hitherto-undescribed immunomodulatory effect on MMP release by stromal cells. PMID:24890593

  11. Demonstration of acid-fast bacilli in buffy coat and bone marrow smear--a diagnostic tool in pulmonary tuberculosis.

    PubMed

    Sen, R; Singh, S; Singh, H P; Sen, J; Yadav, M S; Arora, B R

    1996-10-01

    Buffy coat smears prepared from peripheral blood and bone marrow aspirate obtained from proved 60 untreated cases of pulmonary tuberculosis were stained with Ziehl-Neelsen method and thoroughly screened for presence of tubercle bacilli. Acid-fast bacilli were detected in 55% cases in buffy coat, 48.3% cases in bone marrow, 38.3% cases both in buffy coat and bone marrow and 65% cases either in buffy coat or in bone marrow or in both. Considering the fact that demonstration of acid-fast bacilli may not be possible in more than 25-50% of the suspected cases of tuberculosis, these techniques are recommended for evaluation of their utility in establishing diagnosis of tuberculosis, particularly in reference to sputum negative cases of pulmonary tuberculosis and tuberculosis of inaccessible extrapulmonary sites. PMID:9141877

  12. Radiological findings of pulmonary tuberculosis in indigenous patients in Dourados, MS, Brazil*

    PubMed Central

    Lachi, Tatiana; Nakayama, Mauro

    2015-01-01

    Objective To describe the radiological findings of pulmonary tuberculosis in indigenous patients from the city of Dourados, MS, Brazil, according to age and sex. Materials and Methods Chest radiographic images of 81 patients with pulmonary tuberculosis, acquired in the period from 2007 to 2010, were retrospectively analyzed by two radiologists in consensus for the presence or absence of changes. The findings in abnormal radiographs were classified according to the changes observed and they were correlated to age and sex. The data were submitted to statistical analysis. Results The individuals’ ages ranged from 1 to 97 years (mean: 36 years). Heterogeneous consolidations, nodules, pleural involvement and cavities were the most frequent imaging findings. Most patients (55/81 or 67.9%) were male, and upper lung and right lung were the most affected regions. Fibrosis, heterogeneous consolidations and involvement of the left lung apex were significantly more frequent in males (p < 0.05). Presence of a single type of finding at radiography was most frequent in children (p < 0.05). Conclusion Based on the hypothesis that indigenous patients represent a population without genetically determined resistance to tuberculosis, the present study may enhance the knowledge about how the pulmonary form of this disease manifests in susceptible individuals. PMID:26543277

  13. Association analysis of the LTA4H gene polymorphisms and pulmonary tuberculosis in 9115 subjects

    PubMed Central

    Curtis, James; Kopanitsa, Liliya; Stebbings, Emma; Speirs, Arran; Ignatyeva, Olga; Balabanova, Yanina; Nikolayevskyy, Vladyslav; Hoffner, Sven; Horstmann, Rolf; Drobniewski, Francis; Nejentsev, Sergey

    2011-01-01

    Summary Immunoregulatory eicosanoids have been implicated in protection from mycobacterial infection in cell and animal models. Recently, a study of the zebrafish embryo demonstrated that mutants of the lta4h gene, which encodes the leukotriene A4 hydrolase (LTA4H) enzyme of the eicosanoid pathway, have hypersusceptibility to Mycobacterium marinum infection. It also reported that heterozygosity at the two single nucleotide polymorphisms rs1978331 and rs2660898 located in introns of the LTA4H gene, a human homologue of lta4h, is associated with protection from pulmonary tuberculosis. To replicate this association we genotyped six LTA4H gene polymorphisms in samples from 3703 pulmonary tuberculosis patients and 5412 healthy controls collected in Russia. We found no evidence of the protective effect of heterozygosity at the polymorphisms rs1978331 and rs2660898 (P = 0.29 and 0.49) and no association of the alleles of any of the six polymorphisms (P = 0.13–0.81). These results suggest that common polymorphisms in the LTA4H gene do not play any major role in susceptibility to clinical pulmonary tuberculosis. PMID:21112816

  14. CT-Guided Transthoracic Core Biopsy for Pulmonary Tuberculosis: Diagnostic Value of the Histopathological Findings in the Specimen

    SciTech Connect

    Fukuda, Hozumi Ibukuro, Kenji; Tsukiyama, Toshitaka; Ishii, Rei

    2004-09-15

    We evaluated the value of CT-guided transthoracic core biopsy for the diagnosis of mycobacterial pulmonary nodules. The 30 subjects in this study had pulmonary nodules that had been either diagnosed histopathologically as tuberculosis or were suspected as tuberculosis based on a specimen obtained by CT-guided transthoracic core biopsy. The histopathological findings, the existence of acid-fast bacilli in the biopsy specimens, and the clinical course of the patients after the biopsy were reviewed retrospectively. Two of the three histological findings for tuberculosis that included epithelioid cells, multinucleated giant cells and caseous necrosis were observed in 21 of the nodules which were therefore diagnosed as histological tuberculosis. Six of these 21 nodules were positive for acid-fast bacilli, confirming the diagnosis of tuberculosis. Thirteen of the 21 nodules did not contain acid-fast bacilli but decreased in size in response to antituberculous treatment and were therefore diagnosed as clinical tuberculosis. Seven nodules with only caseous necrosis were diagnosed as suspected tuberculosis, with a final diagnosis of tuberculosis being made in 4 of the nodules and a diagnosis of old tuberculosis in 2 nodules. Two nodules with only multinucleated giant cells were diagnosed as suspected tuberculosis with 1 of these nodules being diagnosed finally as tuberculosis and the other nodule as a nonspecific granuloma. When any two of the three following histopathological findings - epithelioid cells, multinucleated giant cells or caseous necrosis - are observed in a specimen obtained by CT-guided transthoracic core biopsy, the diagnosis of tuberculosis can be established without the detection of acid-fast bacilli or Mycobacterium tuberculosis.

  15. Genotypic, Phenotypic and Clinical Validation of GeneXpert in Extra-Pulmonary and Pulmonary Tuberculosis in India

    PubMed Central

    Singh, Urvashi B.; Pandey, Pooja; Mehta, Girija; Bhatnagar, Anuj K.; Mohan, Anant; Goyal, Vinay; Ahuja, Vineet; Ramachandran, Ranjani; Sachdeva, Kuldeep S.; Samantaray, Jyotish C.

    2016-01-01

    Background Newer molecular diagnostics have brought paradigm shift in early diagnosis of tuberculosis [TB]. WHO recommended use of GeneXpert MTB/RIF [Xpert] for Extra-pulmonary [EP] TB; critics have since questioned its efficiency. Methods The present study was designed to assess the performance of GeneXpert in 761 extra-pulmonary and 384 pulmonary specimens from patients clinically suspected of TB and compare with Phenotypic, Genotypic and Composite reference standards [CRS]. Results Comparison of GeneXpert results to CRS, demonstrated sensitivity of 100% and 90.68%, specificity of 100% and 99.62% for pulmonary and extra-pulmonary samples. On comparison with culture, sensitivity for Rifampicin [Rif] resistance detection was 87.5% and 81.82% respectively, while specificity was 100% for both pulmonary and extra-pulmonary TB. On comparison to sequencing of rpoB gene [Rif resistance determining region, RRDR], sensitivity was respectively 93.33% and 90% while specificity was 100% in both pulmonary and extra-pulmonary TB. GeneXpert assay missed 533CCG mutation in one sputum and dual mutation [517 & 519] in one pus sample, detected by sequencing. Sequencing picked dual mutation [529, 530] in a sputum sample sensitive to Rif, demonstrating, not all RRDR mutations lead to resistance. Conclusions Current study reports observations in a patient care setting in a high burden region, from a large collection of pulmonary and extra-pulmonary samples and puts to rest questions regarding sensitivity, specificity, detection of infrequent mutations and mutations responsible for low-level Rif resistance by GeneXpert. Improvements in the assay could offer further improvement in sensitivity of detection in different patient samples; nevertheless it may be difficult to improve sensitivity of Rif resistance detection if only one gene is targeted. Assay specificity was high both for TB detection and Rif resistance detection. Despite a few misses, the assay offers major boost to early

  16. [Intravenous chemotherapy and galvanization of damaged lung regions in patients with newly diagnosed pulmonary tuberculosis].

    PubMed

    Strelis, A K; Blinov, V Iu; Andreev, I G

    1991-01-01

    The results of a combined treatment of 179 patients with newly diagnosed destructive pulmonary tuberculosis are presented. Patients of the main group (89 subjects) were given intermittent intravenous chemotherapy with simultaneous galvanization of the affected pulmonary zone, while patients of the control group (90 subjects) received the same treatment but without galvanization. In pulmonary tuberculosis patients who had undergone intracutaneous electrophoresis, the body temperature normalized significantly more rapidly (within 2.2 +/- 0.2 weeks), weakness and weakness disappeared (within 1.2 +/- 0.2 months) and cough ceased (1.6 +/- 0.2 months); sputum expectoration disappeared or substantially reduced (within 1.5 +/- 0.1 months); leukocytosis came to an end (within 1.5 +/- 0.1 months). The basic parameters of a spirogram improved in a shorter period and to a greater degree. Bacillary excretion ceased more rapidly (within 2.2 +/- 0.4 months), so did the infiltrative phenomena resolute (within 3.0 +/- 0.1 months) and pulmonary destructive changes disappear (within 3.3 +/- 0.2 months). PMID:1803367

  17. Identification of potential biomarkers of disease progression in bovine tuberculosis.

    PubMed

    Blanco, Federico Carlos; Bigi, Fabiana; Soria, Marcelo Abel

    2014-08-15

    Bovine tuberculosis (bTB) remains an important animal and zoonotic disease in many countries. The diagnosis of bTB is based on tuberculin skin test and IFN-γ release assays (IGRA). Positive animals are separated from the herd and sacrificed. The cost of this procedure is difficult to afford for developing countries with high prevalence of bTB; therefore, the improvement of diagnostic methods and the identification of animals in different stages of the disease will be helpful to control the infection. To identify biomarkers that can discriminate between tuberculin positive cattle with and without tuberculosis lesions (ML+ and ML-, respectively), we assessed a group of immunological parameters with three different classification methods: lineal discriminant analysis (LDA), quadratic discriminant analysis (QDA) and K nearest neighbors (k-nn). For this purpose, we used data from 30 experimentally infected cattle. All the classifiers (LDA, QDA and k-nn) selected IL-2 and IL-17 as the most discriminatory variables. The best classification method was LDA using IL-17 and IL-2 as predictors. The addition of IL-10 to LDA improves the performance of the classifier to discriminate ML-individuals (93.3% vs. 86.7%). Thus, the expression of IL-17, IL-2 and, in some cases, IL-10 would serve as an additional tool to study disease progression in herds with a history of bTB. PMID:24856732

  18. Serum PCT and its Relation to Body Weight Gain in Pulmonary Tuberculosis.

    PubMed

    Rohini, K; Bhat, Surekha; Srikumar, P S; Mahesh Kumar, A

    2015-07-01

    The present study was aimed at assessing alterations in serum PCT in terms of its relation to body weight gain in pulmonary tuberculosis (PTB) patients undergoing treatment. Among patients (25-75 years) diagnosed with pulmonary tuberculosis, those that were new smear positive, showed sputum conversion at the end of 2 months and were declared clinically cured at the end of 6 months, were included in the study (n = 40). Serum procalcitonin was determined by BRAHMS PCT-Q kit. Patients were divided into two study groups-Group 1 (n = 21; serum PCT > 2 ng/ml at diagnosis), Group 2 (n = 19; serum PCT > 10 ng/ml at diagnosis). Body weights of all patients were obtained at three different time points, PTB-0 (at diagnosis), PTB-2 (after 2 months of intensive treatment) and PTB-6 (after 6 months of treatment). In both groups, mean body weights at PTB-2 and PTB-6 were significantly higher than those at PTB-0 and at PTB-6 were significantly higher than those at PTB-2. However, percentage body weight gain following 2 months of intensive treatment was higher in group 1 (4.05 % gain, p < 0.01) than in group 2 (2.75 % body weight gain, p < 0.05). Thus, the percentage gain in group 1 was tending more towards the desirable minimum gain of 5 % during intensive phase. Increase in serum PCT levels in pulmonary tuberculosis is inversely associated with body weight gain during treatment. Thus, PCT could play a role in regulation of body weight gain in anorectic conditions like tuberculosis. PMID:26089621

  19. Problems in defining a “case” of pulmonary tuberculosis in prevalence surveys*

    PubMed Central

    Narain, Raj; Nair, S. S.; Naganna, K.; Chandrasekhar, P.; Rao, G. Ramanatha; Lal, Pyare

    1968-01-01

    An analysis of data from two successive tuberculosis prevalence surveys (conducted at an interval of 18 months) in a random sample of villages in Bangalore District, South India, has shown that the term “a case of pulmonary tuberculosis” does not represent a single uniform entity, but rather embraces cases of several types, differing considerably in their mortality experience, tuberculin sensitivity, results of X-ray and sputum examinations, and in the reliability of their diagnosis. The status at the first survey of the cases found at the resurvey and that at resurvey of those found at the initial survey give an indication of changes with time. Such changes show considerable differences for the various types of cases and provide another dimension to study the differences among them. The authors consider that, in spite of the great need and importance of a single straightforward definition of a case, no such definition is suitable for all situations; there is no other option but to continue to use more than one definition. Although, theoretically, finding a single bacillus in the sputum should be adequate proof of pulmonary tuberculosis, it is shown that finding of a few bacilli, 3 or less, is probably far too often due to artefacts and should not be the basis for a diagnosis. The findings also well bear out the notion that positive radiological findings, in the absence of bacteriological confirmation, indicate, not pulmonary tuberculosis, but only a high risk of the disease. Direct microscopy appears to be a consistent index of disease but, in community surveys, has the limitations of missing a substantial proportion of cases and of adding some false cases. The extent of these limitations, so far as symptomatic patients in a community tuberculosis control programme are concerned, remains to be investigated. PMID:5306123

  20. Mannose-Binding Lectin Promoter Polymorphisms and Gene Variants in Pulmonary Tuberculosis Patients from Cantabria (Northern Spain)

    PubMed Central

    Lavín-Alconero, Lucía; Sánchez-Velasco, Pablo; Guerrero-Alonso, M.-Ángeles; Ausín, Fernando; Fariñas, M.-Carmen; Leyva-Cobián, Francisco

    2012-01-01

    Mannose-binding lectin is a central molecule of the innate immune system. Mannose-binding lectin 2 promoter polymorphisms and structural variants have been associated with susceptibility to tuberculosis. However, contradictory results among different populations have been reported, resulting in no convincing evidence of association between mannose-binding lectin 2 and susceptibility to tuberculosis. For this reason, we conducted a study in a well genetically conserved Spanish population in order to shed light on this controversial association. We analysed the six promoter and structural mannose-binding lectin 2 gene variants in 107 patients with pulmonary tuberculosis and 441 healthy controls. Only D variant and HYPD haplotype were significantly more frequents in controls which would indicate that this allele could confer protection against pulmonary tuberculosis, but this difference disappeared after statistical correction. Neither the rest of alleles nor the haplotypes were significantly associated with the disease. These results would indicate that mannose-binding lectin promoter polymorphisms and gene variants would not be associated with an increased risk to pulmonary tuberculosis. Despite the slight trend of the D allele and HYPD haplotype in conferring protection against pulmonary tuberculosis, susceptibility to this disease would probably be due to other genetic factors, at least in our population. PMID:23304495

  1. Mannose-binding lectin promoter polymorphisms and gene variants in pulmonary tuberculosis patients from cantabria (northern Spain).

    PubMed

    Ocejo-Vinyals, J-Gonzalo; Lavín-Alconero, Lucía; Sánchez-Velasco, Pablo; Guerrero-Alonso, M-Ángeles; Ausín, Fernando; Fariñas, M-Carmen; Leyva-Cobián, Francisco

    2012-01-01

    Mannose-binding lectin is a central molecule of the innate immune system. Mannose-binding lectin 2 promoter polymorphisms and structural variants have been associated with susceptibility to tuberculosis. However, contradictory results among different populations have been reported, resulting in no convincing evidence of association between mannose-binding lectin 2 and susceptibility to tuberculosis. For this reason, we conducted a study in a well genetically conserved Spanish population in order to shed light on this controversial association. We analysed the six promoter and structural mannose-binding lectin 2 gene variants in 107 patients with pulmonary tuberculosis and 441 healthy controls. Only D variant and HYPD haplotype were significantly more frequents in controls which would indicate that this allele could confer protection against pulmonary tuberculosis, but this difference disappeared after statistical correction. Neither the rest of alleles nor the haplotypes were significantly associated with the disease. These results would indicate that mannose-binding lectin promoter polymorphisms and gene variants would not be associated with an increased risk to pulmonary tuberculosis. Despite the slight trend of the D allele and HYPD haplotype in conferring protection against pulmonary tuberculosis, susceptibility to this disease would probably be due to other genetic factors, at least in our population. PMID:23304495

  2. [Commemorative lecture of receiving Imamura Memorial Prize. NK cell in pulmonary tuberculosis from basic and clinical point of view].

    PubMed

    Yoneda, T

    1996-11-01

    Although natural killer (NK) cells, which lyse certain tumors in vitro, have been shown to provide early defense mechanism against cancer growth and viral infection, possible role in the host defense against pulmonary tuberculosis remains undefined. A series of my studies have recently provided several evidence supporting the involvement of NK cells in the immunopathology of pulmonary tuberculosis. NK cell activity in patients with active pulmonary tuberculosis was significantly augmented compared with that in age-, sex- matched healthy controls, which suggests NK cells are activated in vivo in pulmonary tuberculosis. Lung NK cells from BCG-infected mice also are shown to be activated. Asialo GM 1 was demonstrated to be a novel surface marker of mice NK cells, which inhibited activation of NK cells by interferon. Chronic intractable tuberculosis was classified with a combination of NK cell activity and delayed-type hypersensitivity reaction to 2, 4-dinitrochrolbenzene. Subgroup defined with high NK cell activity and normal delayed-type hypersensitivity was characterized with moderate radiographical lesions and stable clinical course, suggesting the immune-spectrum classification was associated with clinical manifestations. Malnutrition has been suggested to be a risk factor associated with the development and reactivation of pulmonary tuberculosis. NK cell activity was significantly correlated with visceral proteins. IL-2 producing capability was significantly decreased in patients with serum albumin less than 3.5 g/dl. More recently, I established an in vitro system evaluating quantitative capability for intracellular killing by human monocytes, in which monocyte phagocytize Mycobacterium tuberculosis and subsequently inhibit intracellular replication of the organisms by adding some cytokines or cells. Purified NK cells by using discontinuous gradient centrifugation and magnetic separation technique were added to M. tuberculosis-infected monocytes monolayer

  3. Risk Factors for Multidrug-Resistant Tuberculosis among Patients with Pulmonary Tuberculosis at the Central Chest Institute of Thailand

    PubMed Central

    Chuchottaworn, Charoen; Thanachartwet, Vipa; Sangsayunh, Piamlarp; Than, Thu Zar Myint; Sahassananda, Duangjai; Surabotsophon, Manoon; Desakorn, Varunee

    2015-01-01

    There are limited data available on the risk factors for multidrug-resistant tuberculosis (MDR-TB). Therefore, we here conducted a retrospective matched case−control study among adults with pulmonary TB who received treatment at the Central Chest Institute of Thailand (CCIT) between January 2007 and December 2013, in order to determine the risk factors associated with MDR-TB among patients with pulmonary TB. We identified 145 patients with pulmonary MDR-TB (cases) and 145 patients with drug-sensitive pulmonary TB (controls). Multivariate analysis identified the independent risk factors for MDR-TB as follows: (1) ≥ 2 episodes of prior pulmonary TB (odds ratio [OR] 39.72, 95% confidence interval (95% CI) 7.86−200.66), (2) duration of illness > 60 days (OR 3.08, 95% CI 1.52−6.22), (3) sputum acid fast bacilli smear 3+ (OR 13.09, 95% CI 4.64−36.91), (4) presence of lung cavities (OR 3.82, 95% CI 1.89−7.73), and (5) presence of pleural effusion (OR 2.75, 95% CI 1.06−7.16). Prior pulmonary TB management with a non-category I regimen (P = 0.012) and having treatment failure or default as treatment outcomes (P = 0.036) were observed in a higher proportion among patients with MDR-TB. Particular characteristics of lung cavities, including the maximum diameter ≥ 30 mm (P < 0.001), the number of cavities ≥ 3 (P = 0.001), bilateral involvement (P < 0.001), and ≥ 2 lung zones involved (P = 0.001) were more commonly observed in patients with MDR-TB. In conclusion, these clinical factors and chest radiographic findings associated with MDR-TB among patients with pulmonary TB may help physicians to provide proper management of cases for prevention of the development and spread of MDR-TB in future. PMID:26444421

  4. Application of the Multistate Tuberculosis Pharmacometric Model in Patients With Rifampicin-Treated Pulmonary Tuberculosis.

    PubMed

    Svensson, R J; Simonsson, Ush

    2016-05-01

    This is the first clinical implementation of the Multistate Tuberculosis Pharmacometric (MTP) model describing fast-, slow-, and nonmultiplying bacterial states of Mycobacterium tuberculosis. Colony forming unit data from 19 patients treated with rifampicin were analyzed. A previously developed rifampicin population pharmacokinetic (PK) model was linked to the MTP model previously developed using in vitro data. Drug effect was implemented as exposure-response relationships tested at several effect sites, both alone and in combination. All MTP model parameters were fixed to in vitro estimates except Bmax . Drug effect was described by an on/off effect inhibiting growth of fast-multiplying bacteria in addition to linear increase of the stimulation of the death rate of slow- and nonmultiplying bacteria with increasing drug exposure. Clinical trial simulations predicted well three retrospective clinical trials using the final model that confirmed the potential utility of the MTP model in antitubercular drug development. PMID:27299939

  5. Application of the Multistate Tuberculosis Pharmacometric Model in Patients With Rifampicin‐Treated Pulmonary Tuberculosis

    PubMed Central

    Simonsson, USH

    2016-01-01

    This is the first clinical implementation of the Multistate Tuberculosis Pharmacometric (MTP) model describing fast‐, slow‐, and nonmultiplying bacterial states of Mycobacterium tuberculosis. Colony forming unit data from 19 patients treated with rifampicin were analyzed. A previously developed rifampicin population pharmacokinetic (PK) model was linked to the MTP model previously developed using in vitro data. Drug effect was implemented as exposure‐response relationships tested at several effect sites, both alone and in combination. All MTP model parameters were fixed to in vitro estimates except Bmax. Drug effect was described by an on/off effect inhibiting growth of fast‐multiplying bacteria in addition to linear increase of the stimulation of the death rate of slow‐ and nonmultiplying bacteria with increasing drug exposure. Clinical trial simulations predicted well three retrospective clinical trials using the final model that confirmed the potential utility of the MTP model in antitubercular drug development. PMID:27299939

  6. Delay for First Consultation and Its Associated Factors among New Pulmonary Tuberculosis Patients of Central Nepal

    PubMed Central

    Mahato, Roshan Kumar; Koju, Rajendra; Vaeteewootacharn, Kriangsak

    2016-01-01

    Tuberculosis (TB) is still a major public health challenge in Nepal and worldwide. Most transmissions occur between the onset of symptoms and the consultation with formal health care centers. This study aimed to determine the duration of delay for the first consultation and its associated factors with unacceptable delay among the new sputum pulmonary tuberculosis cases in the central development region of Nepal. An analytical cross-sectional study was conducted in the central development region of Nepal between January and May 2015. New pulmonary sputum positive tuberculosis patients were interviewed by using a structured questionnaire and their medical records were reviewed. Among a total of 374 patients, the magnitude of patient delay was 53.21% (95% CI: 48.12–58.28%) with a median delay of 32 days and an interquartile range of 11–70 days. The factors associated with unacceptable patient delay (duration ≥ 30 days) were residence in the rural area (adj. OR = 3.10, 95% CI: 1.10–8.72; p value = 0.032) and DOTS center located more than 5 km away from their residences (adj. OR = 5.53, 95% CI: 2.18–13.99; p value < 0.001). Unemployed patients were more likely to have patient delay (adj. OR = 7.79, 95% CI: 1.64–37.00; p value = 0.010) when controlled for other variables. PMID:27144020

  7. Molecular diversity of Mycobacterium tuberculosis isolates from patients with pulmonary tuberculosis in Mozambique

    PubMed Central

    2010-01-01

    Background Mozambique is one of the countries with the highest burden of tuberculosis (TB) in Sub-Saharan Africa, and information on the predominant genotypes of Mycobacterium tuberculosis circulating in the country are important to better understand the epidemic. This study determined the predominant strain lineages that cause TB in Mozambique. Results A total of 445 M. tuberculosis isolates from seven different provinces of Mozambique were characterized by spoligotyping and resulting profiles were compared with the international spoligotyping database SITVIT2. The four most predominant lineages observed were: the Latin-American Mediterranean (LAM, n = 165 or 37%); the East African-Indian (EAI, n = 132 or 29.7%); an evolutionary recent but yet ill-defined T clade, (n = 52 or 11.6%); and the globally-emerging Beijing clone, (n = 31 or 7%). A high spoligotype diversity was found for the EAI, LAM and T lineages. Conclusions The TB epidemic in Mozambique is caused by a wide diversity of spoligotypes with predominance of LAM, EAI, T and Beijing lineages. PMID:20663126

  8. A concurrent comparison of home and sanatorium treatment of pulmonary tuberculosis in South India

    PubMed Central

    1959-01-01

    In India, as in most under-development countries, the tuberculosis problem is aggravated by an acute shortage of sanatorium beds. The number of active cases of tuberculosis in the country has been estimated at 2 ½ million, but only 23 000 tuberculosis beds are available. In these circumstances great importance attaches to the possibility of applying mass domiciliary chemotherapy as a substitute for sanatorium treatment in cases of pulmonary tuberculosis. The findings of the present study, based on a comparison of the two types of treatment over a period of 12 months, show that despite the manifest advantages of sanatorium care—rest, adequate diet, nursing and supervised medicine-taking—the merits of domiciliary chemotherapy are comparable to those of sanatorium treatment, and that it would therefore be appropriate to treat the majority of patients at home, provided an adequate service were established. Imagesp135-ap136-ap137-ap138-ap139-ap140-ap141-ap142-ap143-ap144-a PMID:20604054

  9. Drug-resistant pulmonary tuberculosis in the Baja California-San Diego County border population.

    PubMed

    Peter, C R; Schultz, E; Moser, K; Cox, M; Freeman, R; Ramirez-Zetina, M; Lomeli, M R

    1998-10-01

    A study was conducted to determine the frequency of, and risk factors for, drug-resistant pulmonary tuberculosis (TB) among Baja California (BC) and San Diego County (SDC) residents. Another purpose was to document the amount of contact between pulmonary TB patients and residents of the opposite side of the the border. During the period from February 1995 to May 1996, pulmonary TB patients from BC (n = 427) and SDC (n = 331) were evaluated with cultures, drug susceptibility tests, and questionnaires. Drug resistance was found in 41% of the BC Mycobacterium tuberculosis complex (MTB) isolates and 20% of the SDC isolates. Resistance to both isoniazid (INH) and rifampin (RIF) varied from 1% of isolates from SDC patients to 17% of isolates from BC patients. Patients with a history of previous treatment had increased odds of drug-resistant disease. Older BC patients were more likely to have INH- or RIF-resistant TB. Although 42% of Tijuana TB patients reported recent contact with residents from SDC, travel to Mexico and contact with residents from Mexico were not significant risk factors for drug-resistant TB among SDC residents. However, the demonstrated contact between TB patients and residents on opposite sides of the border indicates the importance of coordinating efforts internationally to control TB. PMID:9795580

  10. Molecular mechanisms in progressive idiopathic pulmonary fibrosis.

    PubMed

    Steele, Mark P; Schwartz, David A

    2013-01-01

    There is clear evidence that environmental exposures and genetic predisposition contribute to the pathogenesis of idiopathic pulmonary fibrosis (IPF). Cigarette smoking increases the risk of developing IPF several-fold, as do other exposures such as metal-fume and wood-dust exposure. Occupations that increase the risk of IPF are agricultural work, hairdressing, and stone polishing, supporting the role of environmental exposure in disease pathogenesis. Genetic predisposition to IPF is evident from its familial aggregation and the fact that pulmonary fibrosis develops in several rare genetic disorders. Mutations in surfactant proteins lead to pulmonary fibrosis and are associated with endoplasmic reticulum stress in alveolar type II epithelial cells. Mutations in telomerase have been found in several families with IPF, and shortened telomeres are found in sporadic cases of IPF. A common variant in mucin 5B predisposes to both familial and sporadic IPF and is present in the majority of cases, indicating sporadic IPF occurs in those with genetic predisposition. PMID:23020878

  11. Pulmonary responses to pathogen-specific antigens in latent Mycobacterium tuberculosis infection.

    PubMed

    Jarvela, Jessica R; Tuscano, Lori; Lee, Hung; Silver, Richard F

    2016-01-01

    In this study, we used ELISPOT to quantify frequencies of bronchoalveolar lavage (BAL) and peripheral blood T cells capable of producing IFNγ in response to PPD, antigen 85B, and Mtb-specific antigens CFP-10 and ESAT-6 in individuals with latent tuberculosis infection (LTBI) and Mtb-naïve controls. Compared to peripheral blood, BAL cells of LTBI subjects displayed significant enrichment for T cells responding to PPD, antigen 85B, and CFP-10, but not to ESAT-6. Baseline BAL cells of LTBI subjects displayed significant production of Mig (CXCL9) in response to PPD, antigen 85B, and CFP-10 as well. These findings suggest that enrichment for Mtb-specific T cells within BAL is not unique to active pulmonary tuberculosis and may, to the contrary, contribute to protection from re-infection in Mtb immune individuals. PMID:26732045

  12. [AA-type amyloidosis secondary to multidrug resistant pulmonary tuberculosis: implications for therapy].

    PubMed

    Baux, E; Henard, S; Alauzet, C; Goehringer, F; Laurain, C; Champigneulle, J; Vaillant, P; Hardy, A; Rabaud, C; May, T

    2015-10-01

    Multidrug resistant pulmonary tuberculosis was diagnosed to a 32-year-old man. An AA-amyloidosis was subsequently diagnosed on the renal biopsy performed for nephrotic syndrome and macroscopic hematuria. A 6-drug antibiotic treatment was delivered quickly after first results of genotypic antibiogram given the renal failure, and was secondarily adapted to the phenotypic antibiogram. Multidrug therapy was fairly well tolerated. Clinical and biological improving were slow. Although tuberculosis is a classic cause of amyloidosis, this is the first case reporting an association between a multidrug resistant case and an amyloidosis in adults. This case also raises the question of MDR probabilistic treatments in situations whether a vital organ prognosis is engaged. PMID:26198876

  13. Nearest patch matching for color image segmentation supporting neural network classification in pulmonary tuberculosis identification

    NASA Astrophysics Data System (ADS)

    Rulaningtyas, Riries; Suksmono, Andriyan B.; Mengko, Tati L. R.; Saptawati, Putri

    2016-03-01

    Pulmonary tuberculosis is a deadly infectious disease which occurs in many countries in Asia and Africa. In Indonesia, many people with tuberculosis disease are examined in the community health center. Examination of pulmonary tuberculosis is done through sputum smear with Ziehl - Neelsen staining using conventional light microscope. The results of Ziehl - Neelsen staining will give effect to the appearance of tuberculosis (TB) bacteria in red color and sputum background in blue color. The first examination is to detect the presence of TB bacteria from its color, then from the morphology of the TB bacteria itself. The results of Ziehl - Neelsen staining in sputum smear give the complex color images, so that the clinicians have difficulty when doing slide examination manually because it is time consuming and needs highly training to detect the presence of TB bacteria accurately. The clinicians have heavy workload to examine many sputum smear slides from the patients. To assist the clinicians when reading the sputum smear slide, this research built computer aided diagnose with color image segmentation, feature extraction, and classification method. This research used K-means clustering with patch technique to segment digital sputum smear images which separated the TB bacteria images from the background images. This segmentation method gave the good accuracy 97.68%. Then, feature extraction based on geometrical shape of TB bacteria was applied to this research. The last step, this research used neural network with back propagation method to classify TB bacteria and non TB bacteria images in sputum slides. The classification result of neural network back propagation are learning time (42.69±0.02) second, the number of epoch 5000, error rate of learning 15%, learning accuracy (98.58±0.01)%, and test accuracy (96.54±0.02)%.

  14. High-Dose Rifapentine with Moxifloxacin for Pulmonary Tuberculosis

    PubMed Central

    Jindani, Amina; Harrison, Thomas S.; Nunn, Andrew J.; Phillips, Patrick P.J.; Churchyard, Gavin J.; Charalambous, Salome; Hatherill, Mark; Geldenhuys, Hennie; McIlleron, Helen M.; Zvada, Simbarashe P.; Mungofa, Stanley; Shah, Nasir A.; Zizhou, Simukai; Magweta, Lloyd; Shepherd, James; Nyirenda, Sambayawo; van Dijk, Janneke H.; Clouting, Heather E.; Coleman, David; Bateson, Anna L.E.; McHugh, Timothy D.; Butcher, Philip D.; Mitchison, Denny A.

    2014-01-01

    BACKGROUND Tuberculosis regimens that are shorter and simpler than the current 6-month daily regimen are needed. METHODS We randomly assigned patients with newly diagnosed, smear-positive, drug-sensitive tuberculosis to one of three regimens: a control regimen that included 2 months of ethambutol, isoniazid, rifampicin, and pyrazinamide administered daily followed by 4 months of daily isoniazid and rifampicin; a 4-month regimen in which the isoniazid in the control regimen was replaced by moxifloxacin administered daily for 2 months followed by moxifloxacin and 900 mg of rifapentine administered twice weekly for 2 months; or a 6-month regimen in which isoniazid was replaced by daily moxifloxacin for 2 months followed by one weekly dose of both moxifloxacin and 1200 mg of rifapentine for 4 months. Sputum specimens were examined on microscopy and after culture at regular intervals. The primary end point was a composite treatment failure and relapse, with noninferiority based on a margin of 6 percentage points and 90% confidence intervals. RESULTS We enrolled a total of 827 patients from South Africa, Zimbabwe, Botswana, and Zambia; 28% of patients were coinfected with the human immunodefiency virus. In the per-protocol analysis, the proportion of patients with an unfavorable response was 4.9% in the control group, 3.2% in the 6-month group (adjusted difference from control, −1.8 percentage points; 90% confidence interval [CI], −6.1 to 2.4), and 18.2% in the 4-month group (adjusted difference from control, 13.6 percentage points; 90% CI, 8.1 to 19.1). In the modified intention-to-treat analysis these proportions were 14.4% in the control group, 13.7% in the 6-month group (adjusted difference from control, 0.4 percentage points; 90% CI, −4.7 to 5.6), and 26.9% in the 4-month group (adjusted difference from control, 13.1 percentage points; 90% CI, 6.8 to 19.4). CONCLUSIONS The 6-month regimen that included weekly administration of high-dose rifapentine and

  15. [Diabetes among new cases of pulmonary tuberculosis in Hanoï, Vietnam].

    PubMed

    Thanh, Nguyen Phuong; Khue, Pham Minh; Sy, Dinh Ngoc; Strobel, M

    2015-12-01

    The aim of this study was to analyze all new pulmonary tuberculosis cases and to assess the frequency and consequences of associated diabetes mellitus. Although apparently distinct, these two diseases could be linked, as suspected since decades. The context is the persistent endemicity of tuberculosis and the recent emergence of diabetes, two major health events for developing countries. The study was conducted at National TB hospital in Hanoï, Vietnam, and retrospectively included tuberculosis patients, cases with diabetes and controls without diabetes, collected during a three-year period 2006-2008. Cases associated with HIV infection or other comorbidities potentially affecting mortality were excluded. Among 2867 new pulmonary TB cases, 254 (8.8%) had associated diabetes. Eighty-six cases and 86 matched controls were included. Among cases mean blood glucose at admission was 14.4 mmol/dl, and patients were mostly urban (50% cases vs 32.5% controls, p=0.03). Clinical symptoms were similar in both groups. However, chest X-Ray cavitary images were significantly more frequent among cases (38.3% vs 16.3%, p=0.002, OR=4.1), as did infiltrative images (78% vs 62%, p=0.017, OR=2.55) and positive sputum smears (67.4% vs 47.8%, p=0.014, OR=2.21). In Vietnam, DM is found in quasi 9% of patients with a new diagnosis of primary pulmonary TB. The diabetes-TB patients may have more severe radiologic findings and a higher smear positivity rate. We suggest that in addition to the systematic HIV screening, all new TB patients should also be screened for diabetes. PMID:26490764

  16. Control measures to trace ≤ 15-year-old contacts of index cases of active pulmonary tuberculosis

    PubMed Central

    Oliveira, Cláudia Di Lorenzo; de Melo, Angelita Cristine; de Oliveira, Lílian Ruth Silva; Froede, Emerson Lopes; Camargos, Paulo

    2015-01-01

    This was descriptive study carried out in a medium-sized Brazilian city. In ≤ 15-year-old contacts of index cases of active pulmonary tuberculosis, we assessed compliance with the Brazilian national guidelines for tuberculosis control. We interviewed 43 contacts and their legal guardians. Approximately 80% of the contacts were not assessed by the municipal public health care system, and only 21% underwent tuberculin skin testing. The results obtained with the Chi-square Automatic Interaction Detector method suggest that health care teams have a biased attitude toward assessing such contacts and underscore the need for training health professionals regarding tuberculosis control programs. PMID:26578137

  17. Surgery and pleuro-pulmonary tuberculosis: a scientific literature review

    PubMed Central

    Subotic, Dragan; Yablonskiy, Piotr; Sulis, Giorgia; Cordos, Ioan; Petrov, Danail; Centis, Rosella; D’Ambrosio, Lia; Sotgiu, Giovanni

    2016-01-01

    Tuberculosis (TB) is still a major public health concern, mostly affecting resource-constrained settings and marginalized populations. The fight against the disease is hindered by the growing emergence of drug-resistant forms whose management can be rather challenging. Surgery may play an important role to support diagnosis and treatment of the most complex cases and improve their therapeutic outcome. We conducted a non-systematic review of the literature based on relevant keywords through PubMed database. Papers in English and Russian were included. The search was focused on five main areas of intervention as follows: (I) diagnosis of complicated cases; (II) elimination of contagious persisting cavities, despite appropriate chemotherapy; (III) treatment of destroyed lung; (V) resection of tuberculomas; (VI) treatment of tuberculous pleural empyema. Although specific practical guidelines concerning surgical indications and approaches are currently unavailable, a summary of the evidence emerged from the scientific literature was elaborated to help the clinician in the management of severely compromised TB patients. The decision to proceed to surgery is usually individualized and a careful assessment of the patient’s risk profile is always recommended before performing any procedure in addition to appropriate chemotherapy. PMID:27499980

  18. Tuberculosis

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Tuberculosis KidsHealth > For Teens > Tuberculosis Print A A A Text Size What's in ... Duration When to Call the Doctor en español Tuberculosis TB Basics Tuberculosis (also known as "TB") is ...

  19. Evaluation of methods for detection and identification of Mycobacterium species in patients suspected of having pulmonary tuberculosis

    PubMed Central

    Marchi, A. M.; Juttel, I. D.; Kawacubo, E. M.; Dalmarco, E. M.; Blatt, S. L.; Cordova, C. M. M.

    2008-01-01

    Tuberculosis control is a priority for the Ministry of Health policies in Brazil. In the present work, the detection of Mycobacterium tuberculosis by the Polymerase Chain Reaction (PCR) was standardized, and the laboratory diagnosis of pulmonary tuberculosis was evaluated comparing baciloscopy, culture and PCR tests. The study was carried out with 117 sputum samples from different patients suspected of having pulmonary tuberculosis, for whom physicians had ordered a baciloscopy test. Baciloscopy was performed using the Ziehl-Neelsen method, and culture was performed by incubation of treated samples in Lowenstein-Jensen’s medium at 37°C for eight weeks. For PCR, DNA was amplified with a specific pair of primers to the M. tuberculosis complex, with a resulting product of 123 bp from the insertion element IS6110. Three (2.56%) samples presented a positive baciloscopy result and a positive PCR result (100% agreement), and nine (7.69%) presented Mycobacterium sp. growth in culture (P= 0.1384). Among six samples with positive results in culture, one was identified by PCR-RFLP as belonging to the M. tuberculosis complex and one was identified as a non-tuberculosis mycobacteria. Sensitivity and specificity of PCR compared to culture were 33.3% and 100%, respectively. PMID:24031276

  20. Evaluation of methods for detection and identification of Mycobacterium species in patients suspected of having pulmonary tuberculosis.

    PubMed

    Marchi, A M; Juttel, I D; Kawacubo, E M; Dalmarco, E M; Blatt, S L; Cordova, C M M

    2008-10-01

    Tuberculosis control is a priority for the Ministry of Health policies in Brazil. In the present work, the detection of Mycobacterium tuberculosis by the Polymerase Chain Reaction (PCR) was standardized, and the laboratory diagnosis of pulmonary tuberculosis was evaluated comparing baciloscopy, culture and PCR tests. The study was carried out with 117 sputum samples from different patients suspected of having pulmonary tuberculosis, for whom physicians had ordered a baciloscopy test. Baciloscopy was performed using the Ziehl-Neelsen method, and culture was performed by incubation of treated samples in Lowenstein-Jensen's medium at 37°C for eight weeks. For PCR, DNA was amplified with a specific pair of primers to the M. tuberculosis complex, with a resulting product of 123 bp from the insertion element IS6110. Three (2.56%) samples presented a positive baciloscopy result and a positive PCR result (100% agreement), and nine (7.69%) presented Mycobacterium sp. growth in culture (P= 0.1384). Among six samples with positive results in culture, one was identified by PCR-RFLP as belonging to the M. tuberculosis complex and one was identified as a non-tuberculosis mycobacteria. Sensitivity and specificity of PCR compared to culture were 33.3% and 100%, respectively. PMID:24031276

  1. Incidental intraoperative diagnosis of retained foreign body lung misdiagnosed as pulmonary tuberculosis.

    PubMed

    Ramchandani, Radhakrishna; Dewan, Ravindra Kumar; Ramchandani, Sarita

    2016-01-01

    Tracheobronchial foreign body aspiration (FBA) is a very common and lethal problem among children. It can easily be diagnosed with a typical history of choking crisis. Clinical examination and radiology play a secondary role in diagnosis. Acute choking episode may lead to death or else to serious sequels such as bronchiectasis, atelectasis, and recurrent pneumonia. Here, we report an interesting case of bronchiectasis in a young female initially thought to be a consequence of pulmonary tuberculosis, who was subsequently found to have retained foreign body in the left lower lobe lung which was the actual cause of her symptoms. PMID:27578942

  2. Incidental intraoperative diagnosis of retained foreign body lung misdiagnosed as pulmonary tuberculosis

    PubMed Central

    Ramchandani, Radhakrishna; Dewan, Ravindra Kumar; Ramchandani, Sarita

    2016-01-01

    Tracheobronchial foreign body aspiration (FBA) is a very common and lethal problem among children. It can easily be diagnosed with a typical history of choking crisis. Clinical examination and radiology play a secondary role in diagnosis. Acute choking episode may lead to death or else to serious sequels such as bronchiectasis, atelectasis, and recurrent pneumonia. Here, we report an interesting case of bronchiectasis in a young female initially thought to be a consequence of pulmonary tuberculosis, who was subsequently found to have retained foreign body in the left lower lobe lung which was the actual cause of her symptoms.

  3. Isolation of Mycobacterium kumamotonense from a patient with pulmonary infection and latent tuberculosis.

    PubMed

    Kontos, Fanourios; Mavromanolakis, Dimitrios Nikitas; Zande, Marina Chari; Gitti, Zoe Georgios

    2016-01-01

    Mycobacterium kumamotonense is a novel, slow-growing non-chromogenic nontuberculous mycobacterium, which belongs to Mycobacterium terrae complex. We report, for the first time in Greece, the isolation of M. kumamotonense from an immunocompetent patient with pulmonary infection and latent tuberculosis. M. kumamotonense was identified by sequencing analysis of 16S rDNA and 65-kDa heat shock protein genes while by commercial molecular assays it was misidentified as Mycobacterium celatum. Antibiotic susceptibility testing was performed by the reference broth microdilution method. The strain was susceptible to amikacin, clarithromycin, rifampin, ciprofloxacin, moxifloxacin, rifabutin, ethambutol and linezolid. PMID:27080783

  4. The contribution of the sympathetic nervous system to the immunopathology of experimental pulmonary tuberculosis.

    PubMed

    Barrios-Payán, Jorge; Revuelta, Alberto; Mata-Espinosa, Dulce; Marquina-Castillo, Brenda; Villanueva, Enrique Becerril; Gutiérrez, María Eugenia Hernández; Pérez-Sánchez, Gilberto; Pavón, Lenin; Hernandez-Pando, Rogelio

    2016-09-15

    The role of norepinephrine (NE) in the immunopathology of experimental tuberculosis (TB) was studied by measuring pulmonary NE and determining its cellular sources and targets. Functional studies were performed administrating adrenergic and anti-adrenergic drugs at different TB phases. Results showed high production of NE during early infection by adrenergic nerve terminals and lymphocytes located in the lungs and mediastinal lymph nodes, these cells highly expressed β2 adreno-receptors (β2AR) which by an autocrine mechanism promote Th-1 cell differentiation favoring protection. During advanced infection, the production of NE and β2AR sharply decreased, suggesting that adrenergic activity is less important during late TB. PMID:27609282

  5. Association of the FCN2 Gene Single Nucleotide Polymorphisms with Susceptibility to Pulmonary Tuberculosis

    PubMed Central

    Jiang, Feng; Wei, Li-Liang; Shi, Li-Ying; Yu, Xiao-Mei; Liu, Chang-Ming; Liu, Xue-Hong; Feng, Xian-Min; Ping, Ze-Peng; Jiang, Ting-Ting; Chen, Zhong-Liang; Li, Zhong-Jie; Li, Ji-Cheng

    2015-01-01

    Ficolin-2 (FCN2) is an innate immune pattern recognition molecule that can activate the complement pathway, opsonophagocytosis, and elimination of the pathogens. The present study aimed to investigate the association of the FCN2 gene single nucleotide polymorphisms (SNPs) with susceptibility to pulmonary tuberculosis (TB). A total of seven SNPs in exon 8 (+6359 C>T and +6424 G>T) and in the promoter region (-986 G>A, -602 G>A, -557 A>G, -64 A>C and -4 A>G) of the FCN2 gene were genotyped using the PCR amplification and DNA sequencing methods in the healthy controls group (n = 254) and the pulmonary TB group (n = 282). The correlation between SNPs and pulmonary TB was analyzed using the logistic regression method. The results showed that there were no significant differences in the distribution of allelic frequencies of seven SNPs between the pulmonary TB group and the healthy controls group. However, the frequency of the variant homozygous genotype (P = 0.037, -557 A>G; P = 0.038, -64 A>C; P = 0.024, +6424 G>T) in the TB group was significantly lower than the control group. After adjustment for age and gender, these variant homozygous genotypes were found to be recessive models in association with pulmonary TB. In addition, -64 A>C (P = 0.047) and +6424 G>T (P = 0.03) were found to be codominant models in association with pulmonary TB. There was strong linkage disequilibrium (r2 > 0.80, P < 0.0001) between 7 SNPs except the -602 G>A site. Therefore, -557 A>G, -64 A>C and +6424 G>T SNPs of the FCN2 gene were correlated with pulmonary TB, and may be protective factors for TB. This study provides a novel idea for the prevention and control of TB transmission from a genetics perspective. PMID:26379154

  6. High Prevelance of Rifampin-Monoresistant Tuberculosis: A Retrospective Analysis among Iranian Pulmonary Tuberculosis Patients

    PubMed Central

    Velayati, Ali Akbar; Farnia, Parissa; Mozafari, Mohadese; Sheikholeslami, Maryam Fatemeh; Karahrudi, Mona Afraei; Tabarsi, Payam; Hoffner, Sven

    2014-01-01

    We determined the prevalence of rifampin-monoresistant tuberculosis (RMR-TB) in Iran. Because development of RMR-TB is not common, we also identified the major risk factors associated with RMR-TB reported from different provinces of Iran. Data for 3,020 TB patients who remained or became smear positive after two, four, six, and nine months of standard first-line chemotherapy were retrospectively analyzed. Of 3,020 patients, 1,242 patients (41.1%) were culture and DNA positive for Mycobacterium tuberculosis. Of these patients, 73 (7.4%) patients had monoresistant isolates to rifampin, which was significantly higher than that for multidrug-resistant TB (5.8%). The average rate of RMR-TB in the studied population ranged from 5% to 10%. Classical investigation showed that 33.6% of patients had either a previous or family history of TB. Molecular epidemiology methods (i.e., spoligotyping and Mycobacterium intespersed repetitive unit–variable number tandem repeat), defined transmission link in three clusters (13%). These results outline the urgent need for a comprehensive plan for detection and treatment of RMR-TB cases. PMID:24189362

  7. Deregulated tyrosine-phenylalanine metabolism in pulmonary tuberculosis patients.

    PubMed

    Das, Mrinal Kumar; Bishwal, Subasa Chandra; Das, Aleena; Dabral, Deepti; Badireddy, Vinod Kumar; Pandit, Bhaswati; Varghese, George M; Nanda, Ranjan Kumar

    2015-04-01

    Metabolic profiling of biofluids from tuberculosis (TB) patients would help us in understanding the disease pathophysiology and may also be useful for the development of novel diagnostics and host-directed therapy. In this pilot study we have compared the urine metabolic profiles of two groups of subjects having similar TB symptoms and categorized as active TB (ATB, n = 21) and non-TB (NTB, n = 21) based on GeneXpert test results. Silylation, gas chromatography mass spectrometry, and standard chemometric methods were employed to identify the important molecules and deregulated metabolic pathways. Eleven active TB patients were followed up on longitudinally for comparative urine metabolic profiling with healthy controls (n = 11). A set of 42 features qualified to have a variable importance parameter score of > 1.5 of a partial least-squares discriminate analysis model and fold change of > 1.5 at p value < 0.05 between ATB and NTB. Using these variables, a receiver operating characteristics curve was plotted and the area under the curve was calculated to be 0.85 (95% CI: 0.72-0.96). Several of these variables that represent norepinephrine, gentisic acid, 4-hydroxybenzoic acid, hydroquinone, and 4-hydroxyhippuric acid are part of the tyrosine-phenylalanine metabolic pathway. In the longitudinal study we observed a treatment-dependent trend in the urine metabolome of follow-up samples, and subjects declared as clinically cured showed similar metabolic profile as those of asymptomatic healthy subjects. The deregulated tyrosine-phenylalanine axis reveals a potential target for diagnostics and intervention in TB. PMID:25693719

  8. Ayurvedic management of pulmonary tuberculosis: A systematic review

    PubMed Central

    Samal, Janmejaya

    2016-01-01

    Background: Tuberculosis (TB) is a global public health crisis. 25% of world’s TB cases are found in India. Ayurveda, an ancient medical science may offer some solution to this problem. Hence, a systematic review was carried out to assess the role of Ayurveda for the management of TB. Methodology: A systematic review was carried out using published literature obtained through “PubMed” until April 2015. The key words used for literature search include “Ayurveda, role and TB.” Results and Discussion: It was observed that a couple of single and compound drugs have been used for the management of TB. However, none of the studies could reflect the true anti-TB activities of any drug, both single and compound. Two of the studies revealed in vitro anti-TB properties of some herbs which can potentially be brought into the realm of a clinical trial to test their efficacy in a human subject. Most of these Ayurvedic therapeutic preparations studied in different clinical settings primarily reflected their adjunct properties for the management of TB. These studies revealed that Ayurvedic therapeutics was able to reduce associated symptoms and the adverse drug effects of ATDs (anti-TB drugs). Furthermore, some of the preparations showed potential hepato-protective properties that can be simultaneously administered with ATDs. Conclusion: Distressingly research on the role of Ayurveda in the management of TB is very scanty and mostly limited to adjunct or supportive therapy. Being a global public health crisis, it is highly recommended to carry out clinical trials on TB patients using Ayurvedic drugs and therapeutic regimens. PMID:27069721

  9. Inflammasome genetics contributes to the development and control of active pulmonary tuberculosis.

    PubMed

    Souza de Lima, D; Ogusku, M M; Sadahiro, A; Pontillo, A

    2016-07-01

    Tuberculosis (TB) continues to be a major public health problem. An estimated one-third of the world's population is infected with Mycobacterium tuberculosis (Mtb) but remains asymptomatic (latent TB) and only 5% to 10% of these latent individuals will develop active pulmonary TB. Factors affecting the balance between latent and active TB are mostly unknown, even if host genome has been shown to contribute to the outcome of Mtb response. Acute inflammation and Th1 response are important in the early clearance of the bacteria as it was emphasized by the association between immune genes (i.e.: HLA, IFNG, TNF, NRPAM1, IL10) variants and the development of active pulmonary TB. Recently, the role of the inflammasome in experimental TB has been demonstrated, however, to our knowledge, no data still exist about the contribution of inflammasome genetics to Mtb susceptibility and/or to the development of active TB. For this reason, selected polymorphisms in inflammasome genes were analysed in a case/control cohort of individuals with active pulmonary TB from an endemic area of Brazil Amazon. Our data evidence the novel association between polymorphisms in NLRP3-inflammasome encoding genes and active pulmonary TB, and replicated the association between P2X7 and TB observed in other populations. These results emphasize the role of NLRP3-inflammasome also in human TB, and contribute to our knowledge about pathways involved in the development of active TB, even if deeper investigation are needed to fully elucidate the role of the complex in Mtb infection. PMID:27101784

  10. NF-κB Repressing Factor Inhibits Chemokine Synthesis by Peripheral Blood Mononuclear Cells and Alveolar Macrophages in Active Pulmonary Tuberculosis

    PubMed Central

    Huang, Kuo-Hsiung; Wang, Chun-Hua; Lee, Kang-Yun; Lin, Shu-Min

    2013-01-01

    NF-κB repressing factor (NRF) is a transcriptional silencer implicated in the basal silencing of specific NF-κB targeting genes, including iNOS, IFN-β and IL-8/CXCL8. IP-10/CXCL10 and IL-8/CXCL8 are involved in neutrophil and lymphocyte recruitment against M. tuberculosis (MTb) and disease progression of pulmonary tuberculosis (TB). Alveolar macrophages (AM) and peripheral blood mononuclear cells (PBMC) were used to study the regulatory role of NRF in pulmonary TB. AM and PBMC were purified from 19 TB patients and 15 normal subjects. To study the underlying mechanism, PBMC were exposed to heated TB bacilli. The regulation role of NRF in IP-10/CXCL10 and IL-8/CXCL8 was determined by NRF knock-down or over-expression. NRF binding capabilities in promoter sites were measured by chromatin immunoprecipitation (ChIP) assay. The levels of IP-10/CXCL10, IL-8/CXCL8 and NRF were significantly higher in AM and PBMC in patients with active TB. NRF played an inhibitory role in IP-10/CXCL10 and IL-8/CXCL8 inductions. We delineate the role of NRF in pulmonary TB, which inhibits the expressions of IP-10/CXCL10 and IL-8/CXCL8 in AM and PBMC of patients with high bacterial load. NRF may serve as an endogenous repressor to prevent robust increase in IP-10/CXCL10 and IL-8/CXCL8 when TB bacterial load is high. PMID:24223729

  11. Pulmonary but Not Subcutaneous Delivery of BCG Vaccine Confers Protection to Tuberculosis-Susceptible Mice by an Interleukin 17-Dependent Mechanism.

    PubMed

    Aguilo, Nacho; Alvarez-Arguedas, Samuel; Uranga, Santiago; Marinova, Dessislava; Monzón, Marta; Badiola, Juan; Martin, Carlos

    2016-03-01

    Some of the most promising novel tuberculosis vaccine strategies currently under development are based on respiratory vaccination, mimicking the natural route of infection. In this work, we have compared pulmonary and subcutaneous delivery of BCG vaccine in the tuberculosis-susceptible DBA/2 mouse strain, a model in which parenterally administered BCG vaccine does not protect against tuberculosis. Our data show that intranasally but not subcutaneously administered BCG confers robust protection against pulmonary tuberculosis challenge. In addition, our results indicate that pulmonary vaccination triggers a Mycobacterium tuberculosis-specific mucosal immune response orchestrated by interleukin 17A (IL-17A). Thus, IL-17A neutralization in vivo reduces protection and abrogates M. tuberculosis-specific immunoglobulin A (IgA) secretion to respiratory airways and lung expression of polymeric immunoglobulin receptor induced following intranasal vaccination. Together, our results demonstrate that pulmonary delivery of BCG can overcome the lack of protection observed when BCG is given parenterally, suggesting that respiratory tuberculosis vaccines could have an advantage in tuberculosis-endemic countries, where intradermally administered BCG has inefficient effectiveness against pulmonary tuberculosis. PMID:26494773

  12. The effects of SP110's associated genes on fresh cavitary pulmonary tuberculosis in Han Chinese population.

    PubMed

    Jiang, Shi-Yao; Li, Lin-Lin; Yue, Jun; Chen, Wen-Zhong; Yang, Chao; Wan, Chun-Ling; He, Lin; Cai, Lei; Deng, Shao-Li

    2016-05-01

    SP110 is a promising anti-Mycobacterium tuberculosis (MTB) gene. To investigate the effects of SP110 and its associated genes, i.e., MYBBP1A and RELA, on pathological progression of MTB infection, an association study with 424 patients of fresh pulmonary tuberculosis (PTB) and 424 healthy controls was performed. Moreover, classification and regression tree and multifactor dimensionality reduction were employed to explore the effects of gene-gene interactions on cavitary PTB. The results indicated that both the heterozygous genotype GC and homozygous genotype CC in rs3809849 had significant effects on the risk of PTB (OR 1.42, 95 % CI 1.06-1.92, p 0.019; OR 1.55, 95 % CI 1.04-2.33, p = 0.033, respectively), and heterozygous genotype CT in rs9061 also had similar effects (OR 1.43, 95 % CI 1.07-1.90, p = 0.014). The rs3809849 and rs9905742 in MYBBP1A were also significantly associated with cavitary PTB (p = 0.00046 and 0.039, respectively), while rs9061 in SP110 had no such association (p = 0.06931) except its significant association with non-cavitary PTB (p = 0.0093). The interaction of MYBBP1A and RELA had significant effect on cavitary PTB (OR 4.24, 95 % CI 1.44-12.49, p = 0.005). These suggest that MYBBP1A instead of SP110 may be a genetic risk factor for cavitary PTB and play important effects on its whole progress. PMID:25612917

  13. A new model of progressive pulmonary fibrosis in rats

    SciTech Connect

    Last, J.A.; Gelzleichter, T.R.; Pinkerton, K.E.; Walker, R.M.; Witschi, H. )

    1993-08-01

    Sprague-Dawley rats were exposed for 6 h daily to 0.8 ppm of ozone and 14.4 ppm of nitrogen dioxide. Approximately 7 to 10 wk after the initiation of exposure, animals began to demonstrate respiratory insufficiency and severe weight loss. About half of the rats died between Days 55 and 78 of exposure; no overt ill effects were observed in animals exposed to filtered air, to ozone alone, or to nitrogen dioxide. Biochemical findings in animals exposed to ozone and nitrogen dioxide included increased lung content of DNA, protein, collagen, and elastin, which was about 300% higher than the control values. The collagen-specific crosslink hydroxy-pyridinium, a biomarker for mature collagen in the lung, was decreased by about 40%. These results are consistent with extensive breakdown and remodeling of the lung parenchyma and its associated vasculature. Histopathologic evaluation showed severe fibrosis, alveolar collapse, honeycombing, macrophage and mast cell accumulation, vascular smooth muscle hypertrophy, and other indications of severe progressive interstitial pulmonary fibrosis and end-stage lung disease. This unique animal model of progressive pulmonary fibrosis resembles the final stages of human idiopathic pulmonary fibrosis and should facilitate studying underlying mechanisms and potential therapy of progressive pulmonary fibrosis.

  14. Risk factors for treatment delay in pulmonary tuberculosis in Recife, Brazil

    PubMed Central

    dos Santos, Martinho APS; Albuquerque, Maria FPM; Ximenes, Ricardo AA; Lucena-Silva, Norma LCL; Braga, Cynthia; Campelo, Antônio RL; Dantas, Odimariles MS; Montarroyos, Ulisses R; Souza, Wayner V; Kawasaki, Alexandre M; Rodrigues, Laura C

    2005-01-01

    Background Tuberculosis is still a great challenge to public health in Brazil and worldwide. Early detection followed by effective therapy is extremely important in controlling the disease. Recent studies have investigated reasons for delays in treatment, but there is no agreed definition of what constitutes an "acceptable" delay. This study investigates factors associated with total delay in treatment of tuberculosis. Methods A cohort of adult cases of pulmonary tuberculosis diagnosed over a two-year period was studied. Patients were interviewed on entry, reporting the duration of symptoms before the start of treatment, and sputum and blood samples were collected. It was decided that sixty days was an acceptable total delay. Associations were investigated using univariable and multivariable analysis and the population attributable fraction was estimated. Results Of 1105 patients, 62% had a delay of longer than 60 days. Age, sex, alcoholism and difficulty of access were not associated with delays, but associations were found in the case of unemployment, having given up smoking, having lost weight and being treated in two of the six health districts. The proportion attributable to: not being an ex-smoker was 31%; unemployment, 18%; weight loss, 12%, and going to the two worst health districts, 25%. Conclusion In this urban area, delays seem to be related to unemployment and general attitudes towards health. Although they reflect the way health services are organized, delays are not associated with access to care. PMID:15777473

  15. Neutrophil-Derived MMP-8 Drives AMPK-Dependent Matrix Destruction in Human Pulmonary Tuberculosis.

    PubMed

    Ong, Catherine W M; Elkington, Paul T; Brilha, Sara; Ugarte-Gil, Cesar; Tome-Esteban, Maite T; Tezera, Liku B; Pabisiak, Przemyslaw J; Moores, Rachel C; Sathyamoorthy, Tarangini; Patel, Vimal; Gilman, Robert H; Porter, Joanna C; Friedland, Jon S

    2015-05-01

    Pulmonary cavities, the hallmark of tuberculosis (TB), are characterized by high mycobacterial load and perpetuate the spread of M. tuberculosis. The mechanism of matrix destruction resulting in cavitation is not well defined. Neutrophils are emerging as key mediators of TB immunopathology and their influx are associated with poor outcomes. We investigated neutrophil-dependent mechanisms involved in TB-associated matrix destruction using a cellular model, a cohort of 108 patients, and in separate patient lung biopsies. Neutrophil-derived NF-kB-dependent matrix metalloproteinase-8 (MMP-8) secretion was up-regulated in TB and caused matrix destruction both in vitro and in respiratory samples of TB patients. Collagen destruction induced by TB infection was abolished by doxycycline, a licensed MMP inhibitor. Neutrophil extracellular traps (NETs) contain MMP-8 and are increased in samples from TB patients. Neutrophils lined the circumference of human pulmonary TB cavities and sputum MMP-8 concentrations reflected TB radiological and clinical disease severity. AMPK, a central regulator of catabolism, drove neutrophil MMP-8 secretion and neutrophils from AMPK-deficient patients secrete lower MMP-8 concentrations. AMPK-expressing neutrophils are present in human TB lung biopsies with phospho-AMPK detected in nuclei. These data demonstrate that neutrophil-derived MMP-8 has a key role in the immunopathology of TB and is a potential target for host-directed therapy in this infectious disease. PMID:25996154

  16. Fixed-dose combinations of drugs versus single-drug formulations for treating pulmonary tuberculosis

    PubMed Central

    Gallardo, Carmen R; Rigau Comas, David; Valderrama Rodríguez, Angélica; Roqué i Figuls, Marta; Parker, Lucy Anne; Caylà, Joan; Bonfill Cosp, Xavier

    2016-01-01

    Background People who are newly diagnosed with pulmonary tuberculosis (TB) typically receive a standard first-line treatment regimen that consists of two months of isoniazid, rifampicin, pyrazinamide, and ethambutol followed by four months of isoniazid and rifampicin. Fixed-dose combinations (FDCs) of these drugs are widely recommended. Objectives To compare the efficacy, safety, and acceptability of anti-tuberculosis regimens given as fixed-dose combinations compared to single-drug formulations for treating people with newly diagnosed pulmonary tuberculosis. Search methods We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL, published in the Cochrane Library, Issue 11 2015); MEDLINE (1966 to 20 November 2015); EMBASE (1980 to 20 November 2015); LILACS (1982 to 20 November 2015); the metaRegister of Controlled Trials; and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), without language restrictions, up to 20 November 2015. Selection criteria Randomized controlled trials that compared the use of FDCs with single-drug formulations in adults (aged 15 years or more) newly diagnosed with pulmonary TB. Data collection and analysis Two review authors independently assessed studies for inclusion, and assessed the risk of bias and extracted data from the included trials. We used risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data with 95% confidence intervals (CIs). We attempted to assess the effect of treatment for time-to-event measures with hazard ratios and their 95% CIs. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used the fixed-effect model when there was little heterogeneity and the random-effects model with moderate heterogeneity. We used an I² statistic value of 75% or greater to denote significant heterogeneity, in which case we did not perform a

  17. Tuberculosis as a three-act play: A new paradigm for the pathogenesis of pulmonary tuberculosis.

    PubMed

    Hunter, Robert L

    2016-03-01

    Lack of access to human tissues with untreated tuberculosis (TB) has forced generations of researchers to use animal models and to adopt a paradigm that granulomas are the characteristic lesion of both primary and post primary TB. An extended search of studies of human lung tissues failed to find any reports that support this paradigm. We found scores of publications from gross pathology in 1804 through high resolution CT scans in 2015 that identify obstructive lobular pneumonia, not granulomas, as the characteristic lesion of developing post-primary TB. This paper reviews this literature together with other relevant observations to formulate a new paradigm of TB with three distinct stages: a three-act play. First, primary TB, a war of attrition, begins with infection that spreads via lymphatics and blood stream before inducing systemic immunity that contains and controls the organisms within granulomas. Second, post-primary TB, a sneak attack, develops during latent TB as an asymptomatic obstructive lobular pneumonia in persons with effective systemic immunity. It is a paucibacillary process with no granulomas that spreads via bronchi and accumulates mycobacterial antigens and host lipids for 1-2 years before suddenly undergoing caseous necrosis. Third, the fallout, is responsible for nearly all clinical post primary disease. It begins with caseous necrotic pneumonia that is either retained to become the focus of fibrocaseous disease or is coughed out to leave a cavity. This three-stage paradigm suggests testable hypotheses and plausible answers to long standing questions of immunity to TB. PMID:26980490

  18. Tuberculosis

    MedlinePlus

    Tuberculosis (TB) is a disease caused by bacteria called Mycobacterium tuberculosis. The bacteria usually attack the lungs, but they can also damage other parts of the body. TB spreads through the air when a person with ...

  19. Adjunctive Phosphodiesterase-4 Inhibitor Therapy Improves Antibiotic Response to Pulmonary Tuberculosis in a Rabbit Model

    PubMed Central

    Subbian, Selvakumar; Tsenova, Liana; Holloway, Jennifer; Peixoto, Blas; O'Brien, Paul; Dartois, Véronique; Khetani, Vikram; Zeldis, Jerome B.; Kaplan, Gilla

    2016-01-01

    Objectives Adjunctive host-directed therapy is emerging as a new potential approach to improve the outcome of conventional antimicrobial treatment for tuberculosis (TB). We tested the ability of a phosphodiesterase-4 inhibitor (PDE4i) CC-11050, co-administered with the first-line anti-TB drug isoniazid (INH), to accelerate bacillary killing and reduce chronic inflammation in the lungs of rabbits with experimental Mycobacterium tuberculosis (Mtb) infection. Methods A rabbit model of pulmonary TB that recapitulates the pathologic manifestations seen in humans was used. Rabbits were infected with virulent Mtb by aerosol exposure and treated for eight weeks with INH with or without CC-11050, starting at four weeks post infection. The effect of CC-11050 treatment on disease severity, pathology, bacillary load, T cell proliferation and global lung transcriptome profiles were analyzed. Results Significant improvement in bacillary clearance and reduced lung pathology and fibrosis were noted in the rabbits treated for eight weeks with INH + CC-11050, compared to those treated with INH or CC-11050 only. In addition, expression of host genes associated with tissue remodeling, tumor necrosis factor alpha (TNF-α) regulation, macrophage activation and lung inflammation networks was dampened in CC-11050-treated, compared to the untreated rabbits. Conclusions Adjunctive CC-11050 therapy significantly improves the response of rabbits with experimental pulmonary TB to INH treatment. We propose that CC-11050 may be a promising candidate for host directed therapy of patients with pulmonary TB, reducing the duration and improving clinical outcome of antibiotic treatment. PMID:26981575

  20. Potential and development of inhaled RNAi therapeutics for the treatment of pulmonary tuberculosis.

    PubMed

    Man, Dede K W; Chow, Michael Y T; Casettari, Luca; Gonzalez-Juarrero, Mercedes; Lam, Jenny K W

    2016-07-01

    Tuberculosis (TB), caused by the infection of Mycobacterium tuberculosis (Mtb), continues to pose a serious threat to public health, and the situation is worsening with the rapid emergence of multidrug resistant (MDR) TB. Current TB regimens require long duration of treatment, and their toxic side effects often lead to poor adherence and low success rates. There is an urgent need for shorter and more effective treatment for TB. In recent years, RNA interference (RNAi) has become a powerful tool for studying gene function by silencing the target genes. The survival of Mtb in host macrophages involves the attenuation of the antimicrobial responses mounted by the host cells. RNAi technology has helped to improve our understanding of how these bacilli interferes with the bactericidal effect and host immunity during TB infection. It has been suggested that the host-directed intervention by modulation of host pathways can be employed as a novel and effective therapy against TB. This therapeutic approach could be achieved by RNAi, which holds enormous potential beyond a laboratory to the clinic. RNAi therapy targeting TB is being investigated for enhancing host antibacterial capacity or improving drug efficacy on drug resistance strains while minimizing the associated adverse effects. One of the key challenges of RNAi therapeutics arises from the delivery of the RNAi molecules into the target cells, and inhalation could serve as a direct administration route for the treatment of pulmonary TB in a non-invasive manner. However, there are still major obstacles that need to be overcome. This review focuses on the RNAi candidates that are currently explored for the treatment of TB and discusses the major barriers of pulmonary RNAi delivery. From this, we hope to stimulate further studies of local RNAi therapeutics for pulmonary TB treatment. PMID:27108702

  1. Intravesical BCG therapy as cause of miliary pulmonary tuberculosis.

    PubMed

    Rosati, Yuri; Fabiani, Andrea; Taccari, Tommaso; Ranaldi, Renzo; Mammana, Gabriele; Tubaldi, Alberto

    2016-03-01

    Immunotherapy with intravesical bacillus Calmette-Guérin (BCG) is considered the most effective adjuvant to endoscopic resection of bladder urothelial carcinoma in the therapeutic management of non-muscle invasive (NMIBC) at intermediate and high risk of recurrence and progression (pTa - pT1 and high-grade carcinoma in situ, CIS). Despite its proven efficacy, this type of treatment can determine local and systemic side effects of moderate or severe gravity, with the histological diagnosis of epithelioid granulomas in different organs, even in the absence of microbiological positivity of BCG. The immunotherapy with BCG is usually well tolerated and the virulence of the attenuated BCG is very low in immuno-competent patients, although only 16% of patients are able to receive all the instillations of the maintenance period (3 years) of treatment provided by the protocols, precisely because of side effects. Minor side effects usually resolve within a few hours or days. They develop in 3-5% of patients and usually consist of local infectious complications. Manifestations of BCG dissemination, such as vascular and ocular complications, are much less common, while BCG-disseminated infections, with granulomatous pneumonia or hepatitis present, are quite rare, representing 0.5-2% of the complications recorded. We present the clinical case of granulomatous lung and possibly liver infection caused by BCG in a patient aged 56 years being treated for several weeks with intravesical BCG for NIMBC pT1 high grade associated with CIS. PMID:26616461

  2. Spatial analysis of deaths from pulmonary tuberculosis in the city of São Luís, Brazil*

    PubMed Central

    Santos-Neto, Marcelino; Yamamura, Mellina; Garcia, Maria Concebida da Cunha; Popolin, Marcela Paschoal; Silveira, Tatiane Ramos dos Santos; Arcêncio, Ricardo Alexandre

    2014-01-01

    OBJECTIVE: To characterize deaths from pulmonary tuberculosis, according to sociodemographic and operational variables, in the city of São Luís, Brazil, and to describe their spatial distribution. METHODS: This was an exploratory ecological study based on secondary data from death certificates, obtained from the Brazilian Mortality Database, related to deaths from pulmonary tuberculosis. We included all deaths attributed to pulmonary tuberculosis that occurred in the urban area of São Luís between 2008 and 2012. We performed univariate and bivariate analyses of the sociodemographic and operational variables of the deaths investigated, as well as evaluating the spatial distribution of the events by kernel density estimation. RESULTS: During the study period, there were 193 deaths from pulmonary tuberculosis in São Luís. The median age of the affected individuals was 52 years. Of the 193 individuals who died, 142 (73.60%) were male, 133 (68.91%) were Mulatto, 102 (53.13%) were single, and 64 (33.16%) had completed middle school. There was a significant positive association between not having received medical care prior to death and an autopsy having been performed (p = 0.001). A thematic map by density of points showed that the spatial distribution of those deaths was heterogeneous and that the density was as high as 8.12 deaths/km2. CONCLUSIONS: The sociodemographic and operational characteristics of the deaths from pulmonary tuberculosis evaluated in this study, as well as the identification of priority areas for control and surveillance of the disease, could promote public health policies aimed at reducing health inequities, allowing the optimization of resources, as well as informing decisions regarding the selection of strategies and specific interventions targeting the most vulnerable populations. PMID:25410843

  3. Diagnostic delay of pulmonary tuberculosis in patients with acute respiratory distress syndrome associated with aspiration pneumonia: Two case reports and a mini-review from Japan

    PubMed Central

    Nakao, Makoto; Sone, Kazuki; Kagawa, Yusuke; Kurokawa, Ryota; Sato, Hidefumi; Kunieda, Takefumi; Muramatsu, Hideki

    2016-01-01

    Diagnosing active tuberculosis in elderly patients presents problems due to nonspecific symptoms and complications such as aspiration pneumonia. The current study presents two cases of pulmonary tuberculosis with bilateral pulmonary infiltrates associated with aspiration pneumonia. The two elderly patients developed acute respiratory distress syndrome as a result of aspiration pneumonia. The diagnoses of pulmonary tuberculosis were delayed in both cases, as the patients were diagnosed with active tuberculosis following discharge from hospital. The sputum test for acid-fast bacillus at the time of administration was smear-negative/culture-positive in these patients. They were treated with isoniazid, rifampicin and ethambutol, and nosocomial transmission of tuberculosis from these patients was not reported. The number of elderly patients with aspiration pneumonia is predicted to increase rapidly, and aspiration pneumonia combined with pulmonary tuberculosis is a major medical and healthcare concern in Japan. The present study concludes that physicians should always consider the complication of pulmonary tuberculosis when treating pneumonia patients, in particular in treating elderly patients with pulmonary infiltrates.

  4. Health system delay in pulmonary tuberculosis treatment in a country with an intermediate burden of tuberculosis: a cross-sectional study

    PubMed Central

    2013-01-01

    Background Delayed diagnosis and treatment of tuberculosis increase both the severity of the disease and the duration of infectivity. A number of studies have addressed the issue of health system delays in the treatment of tuberculosis, but mostly in countries with a high or low incidence of the disease. Our understanding of delay is quite limited in settings with an intermediate burden of tuberculosis. We explore the duration and factors associated with delays in the Croatian health system which has free health care and a sufficient network of health services providing tuberculosis diagnosis and care. Methods A total of 241 consecutive adults with culture-confirmed pulmonary tuberculosis were interviewed in seven randomly selected Croatian counties and their medical records were evaluated. A health system delay was defined as the number of days from the first consultation with a physician to the initiation of anti-tuberculosis treatment. A long delay was defined as a period exceeding the median delay, while an extreme delay was considered to be above the 75th percentile delay. Results The median health system delay was 15 days while the 75th percentile was 42 days (the 5th and 95th percentile being 1 and 105 days respectively). Almost 30% of tuberculosis patients remained undiagnosed for more than 30 days after the initial health care visit. Female patients (p = 0.005), patients with a negative sputum smear (p = 0.002) and patients having symptoms other than the usual ones (0.027) were found to be in significant correlation with a long delay. In a multivariate model, a long delay remained associated with the same variables (p = 0.008, p = 0.003, and p = 0.037, respectively). A significant association was demonstrated between both the female gender (p = 0.042) and a negative sputum smear (p < 0.001) and extreme delay, while only a negative sputum smear (p < 0.001) remained significant in the multivariate analysis. Conclusions Our

  5. Prevalence, Risk Factors and Social Context of Active Pulmonary Tuberculosis among Prison Inmates in Tajikistan

    PubMed Central

    Winetsky, Daniel E.; Almukhamedov, Olga; Pulatov, Dilshod; Vezhnina, Natalia; Dooronbekova, Aizhan; Zhussupov, Baurzhan

    2014-01-01

    Setting Tuberculosis (TB) is highly prevalent in prisons of the former Soviet Union. Objective To understand the behavioral, demographic and biological factors placing inmates in Tajikistan at risk for active TB. Design We administered a behavioral and demographic survey to 1317 inmates in two prison facilities in Sughd province, Tajikistan along with radiographic screening for pulmonary TB. Suspected cases were confirmed bacteriologically. Inmates undergoing TB treatment were also surveyed. In-depth interviews were conducted with former prisoners to elicit relevant social and behavioral characteristics. Results We identified 59 cases of active pulmonary TB (prevalence 4.5%). Factors independently associated with increased prevalence of active TB were: HIV-infection by self-report (PR 7.88; 95%CI 3.40–18.28), history of previous TB (PR 10.21; 95%CI 6.27–16.63) and infrequent supplemental nutrition beyond scheduled meals (PR 3.00; 95%CI 1.67–5.62). Access to supplemental nutrition was associated with frequency of visits from friends and family and ability to rely on other inmates for help. Conclusion In prison facilities of Tajikistan, HIV-infection, injection drug use and low access to supplemental nutrition were associated with prevalent cases of active pulmonary TB. Policies that reduce HIV transmission among injection drug users and improve the nutritional status of socially isolated inmates may alleviate the TB burden in Tajikistan’s prisons. PMID:24465861

  6. Health System Delay among the Pulmonary Tuberculosis Patients Presenting in the DOTS Centers of Nepal

    PubMed Central

    Mahato, Roshan Kumar; Koju, Rajendra

    2016-01-01

    Introduction Health system delay is the time for complete diagnosis of the disease after patient approaches a health care provider. Aim The study aims to identify the characteristics and the determinants of unacceptable health system delay (≥ 7 days delay from health system) in diagnosis of new pulmonary tuberculosis patients attending in Direct Observation Treatment Short course (DOTS) centers of Nepal. Materials and Methods An analytical cross-sectional study was conducted by administrating a structured questionnaire interview and reviewing the medical record of the new sputum smear positive pulmonary tuberculosis cases during January–May 2015. The generalized linear model (GLM) was applied to control the clustering effects. Multiple logistic regressions were performed to identify the association between variables with ≥ 7 days of unacceptable health system delay. Results Of the 374 new sputum smear positive pulmonary tuberculosis cases, the factors that were associated with unacceptable health system delay (time ≥ 7 days) were doing business (adj.OR= 1.61, 95% CI: 1.22-2.11; p-value <0.001) and unemployed (adj.OR= 3.04, 95% CI: 1.53-6.04; p-value <0.001) had chances of health system delay. However, getting support from parents (adj.OR= 0.55, 95% CI: 0.44-0.68; p-value <0.001), consultation with the private practitioners/ pharmacists (adj.OR= 0.24, 95% CI: 0.07-0.81; p-value 0.021), visiting government health facilities (adj.OR= 0.31, 95% CI: 0.13-0.73; p-value 0.008), using X-ray (adj.OR= 0.69, 95% CI: 0.49-0.97; p-value 0.032) and advance technologies for diagnosis of TB (adj.OR= 0.60, 95% CI: 0.39-0.94; p-value 0.024) were found contributing to reduce health system delay while controlling socio-economic, knowledge, presence of symptoms and attitude factors. Conclusion About a quarter of new TB patients faced health system delay problems. Socioeconomic factors, unemployment, influences the health system delay when controlled for other covariates. PMID

  7. A Novel Scoring System to Measure Radiographic Abnormalities and Related Spirometric Values in Cured Pulmonary Tuberculosis

    PubMed Central

    Báez-Saldaña, Renata; López-Arteaga, Yesenia; Bizarrón-Muro, Alma; Ferreira-Guerrero, Elizabeth; Ferreyra-Reyes, Leticia; Delgado-Sánchez, Guadalupe; Cruz-Hervert, Luis Pablo; Mongua-Rodríguez, Norma; García-García, Lourdes

    2013-01-01

    Background Despite chemotherapy, patients with cured pulmonary tuberculosis may result in lung functional impairment. Objective To evaluate a novel scoring system based on the degree of radiographic abnormalities and related spirometric values in patients with cured pulmonary tuberculosis. Methods One hundred and twenty seven patients with cured pulmonary tuberculosis were prospectively enrolled in a referral hospital specializing in respiratory diseases. Spirometry was performed and the extent of radiographic abnormalities was evaluated twice by each of two readers to generate a novel quantitative score. Scoring reproducibility was analyzed by the intra-class correlation coefficient (ICC) and the Bland-Altman method. Multiple linear regression models were performed to assess the association of the extent of radiographic abnormalities with spirometric values. Results The intra-observer agreement for scoring of radiographic abnormalities (SRA) showed an ICC of 0.81 (CI:95%, 0.67–0.95) and 0.78 (CI:95%, 0.65–0.92), for reader 1 and 2, respectively. Inter-observer reproducibility for the first measurement was 0.83 (CI:95%, 0.71–0.95), and for the second measurement was 0.74 (CI:95%, 0.58–0.90). The Bland-Altman analysis of the intra-observer agreement showed a mean bias of 0.87% and -0.55% and an inter-observer agreement of -0.35% and -1.78%, indicating a minor average systematic variability. After adjustment for age, gender, height, smoking status, pack-years of smoking, and degree of dyspnea, the scoring degree of radiographic abnormalities was significantly and negatively associated with absolute and percent predicted values of FVC: -0.07 (CI:95%, -0.01 to -0.04); -2.48 (CI:95%, -3.45 to -1.50); and FEV1 -0.07 (CI:95%, -0.10 to -0.05); -2.92 (CI:95%, -3.87 to -1.97) respectively, in the patients studied. Conclusion The extent of radiographic abnormalities, as evaluated through our novel scoring system, was inversely associated with spirometric values, and

  8. Alleles of HLA-DRB1*04 Associated with Pulmonary Tuberculosis in Amazon Brazilian Population

    PubMed Central

    Porto dos Santos, Maisa; de Melo Silva, Cláudia Maria; Alves de Almeida, Vanessa; Assumpção Antunes, Irineide

    2016-01-01

    Immunogenetic host factors are associated with susceptibility or protection to tuberculosis (TB). Strong associations of HLA class II genes with TB are reported. We analyzed the HLA-DRB1*04 alleles to identify subtypes associated with pulmonary TB and their interaction with risk factors such as alcohol, smoking, and gender in 316 pulmonary TB patients and 306 healthy individuals from the Brazilian Amazon. The HLA-DRB1*04 was prevalent in patients with pulmonary TB (p<0.0001; OR = 2.94; 95% CI = 2.12 to 4.08). Direct nucleotide sequencing of DRB1 exon 2 identified nine subtypes of HLA-DRB1*04. The subtype HLA-DRB1*04:11:01 (p = 0.0019; OR = 2.23; 95% CI = 1.34 to 3.70) was associated with susceptibility to pulmonary TB while DRB1*04:07:01 (p<0.0001; OR = 0.02; 95% CI = 0.001 to 0.33) to protection. Notably, the interaction between alcohol and HLA-DRB1*04:11:01 increased the risk for developing pulmonary TB (p = 0.0001; OR = 51.3; 95% CI = 6.81 to 386). Multibacillary pulmonary TB, the clinical presentation of disease transmission, was strongly associated with interaction to alcohol (p = 0.0026; OR = 11.1; 95% CI = 3.99 to 30.9), HLA-DRB1*04:11:01 (p = 0.0442; OR = 2.01; 95% CI = 1.03 to 3.93) and DRB1*04:92 (p = 0.0112; OR = 8.62; 95% CI = 1.63 to 45.5). These results show that HLA-DRB1*04 are associated with pulmonary TB. Interestingly, three subtypes, DRB1*04:07:01, DRB1*04:11:01 and DRB1*04:92 of the HLA-DRB1*04 could be potential immunogenetic markers that may help to explain mechanisms involved in disease development. PMID:26901036

  9. Evaluation of antigen-specific immunoglobulin g responses in pulmonary tuberculosis patients and contacts.

    PubMed

    Hur, Yun-Gyoung; Kim, Ahreum; Kang, Young Ae; Kim, An Sik; Kim, Dae Yeon; Kim, Yeun; Kim, Youngmi; Lee, Hyeyoung; Cho, Sang-Nae

    2015-03-01

    This study aimed to evaluate the serodiagnostic potential of immunoglobulin G (IgG) responses to Mycobacterium tuberculosis antigens in pulmonary tuberculosis (TB) patients, recent TB contacts with latent TB infection (LTBI), and healthy subjects. Infections were assessed using tuberculin skin tests, QuantiFERON-TB Gold In-Tube tests, drug susceptibility testing, and molecular genotyping of clinical isolates. Serum IgG responses to selective M. tuberculosis antigens, including the 38-kDa and 16-kDa antigens, lipoarabinomannan (LAM), and recombinant early secreted antigen target 6 kDa (ESAT-6) and culture filtrate protein 10 kDa (CFP-10), were determined. We found that the serum IgG responses to all antigens might differentiate between active TB and LTBI, with LAM having the highest diagnostic value (area under the curve [AUC] of 0.7756, P < 0.001). Recurrent TB cases showed significantly higher IgG responses to 38 kDa, CFP-10 (P < 0.01), and LAM (P < 0.05) than new cases, and male patients had higher levels of antigen-specific IgG than females (P < 0.05). Conversely, drug resistance and patient body mass index did not affect IgG responses (P > 0.05). LAM-specific IgG responses differentiated between acid-fast bacillus (AFB) smear-positive and -negative patients (P < 0.01), whereas antigen-specific IgG responses did not vary with the M. tuberculosis genotype (P > 0.05). Significantly higher IgG responses to 38 kDa and 16 kDa were observed in AFB smear-negative patients than in controls. These results suggest that assessment of serum IgG responses to selective purified M. tuberculosis antigens may help improve the diagnosis of active TB, particularly for sputum smear-negative patients or recurrent cases, and these may also help to differentiate between active TB and LTBI. PMID:25588651

  10. [Four cases of pulmonary tuberculosis resembling pulmonary abscess with a so-called niveau-like shadow in a medical school hospital: discussion concerning the formation mechanism of niveau-like shadows].

    PubMed

    Kobashi, Y; Niki, Y; Kawane, H; Matsushima, T

    1996-04-01

    Four cases of pulmonary tuberculosis resembling pulmonary abscess radiographically were reviewed from their clinical features, chest X-ray and chest CT, and the mechanism of formation of so-called niveau-like shadows was discussed. Only one case showed a newly formed tuberculous cavity with air fluid level on chest X-ray, however, even in this case, the possibility of the infection with tubercle bacilli of an emphysematous bulla of the lung could not be completely excluded as several bulla were found on chest CT. The remaining three cases showed a slightly different mechanism of the formation of niveau-like shadows. Namely, mycobacterium tuberculosis spread into an existed bulla and a tubercle bacilli infected bulla was formed. Regarding the clinical features, no remarkable findings were detected and we could find no differences with common tuberculosis. Based on these experiences, the presence of pulmonary tuberculosis resembling the shadow of pulmonary abscess should be emphasized. PMID:8683908

  11. Calcified Pulmonary Nodules Identified in a 350-Year-Old-Joseon Mummy: the First Report on Ancient Pulmonary Tuberculosis from Archaeologically Obtained Pre-modern Korean Samples

    PubMed Central

    2016-01-01

    We found calcified pulmonary nodules in a middle-aged female mummy discovered from 350-yr-old Joseon tomb of Korea. In the CT scan, we found six radiopaque nodules in right lung, through the levels of thoracic vertebrae 1 to 6. We also found presumptive pleural adhesions in right thoracic cavity of CT images. We re-confirmed radiological findings by our post-factum dissection on the same mummy. By the differential diagnosis, we speculate that the radiopaque calcification nodules and associated pleural adhesion could have been caused by tuberculosis. This is the first-ever report on the pulmonary tuberculosis identified in archaeologically obtained, pre-modern Korean samples. PMID:26770051

  12. Mouse model of pulmonary cavitary tuberculosis and expression of matrix metalloproteinase-9.

    PubMed

    Ordonez, Alvaro A; Tasneen, Rokeya; Pokkali, Supriya; Xu, Ziyue; Converse, Paul J; Klunk, Mariah H; Mollura, Daniel J; Nuermberger, Eric L; Jain, Sanjay K

    2016-07-01

    Cavitation is a key pathological feature of human tuberculosis (TB), and is a well-recognized risk factor for transmission of infection, relapse after treatment and the emergence of drug resistance. Despite intense interest in the mechanisms underlying cavitation and its negative impact on treatment outcomes, there has been limited study of this phenomenon, owing in large part to the limitations of existing animal models. Although cavitation does not occur in conventional mouse strains after infection with Mycobacterium tuberculosis, cavitary lung lesions have occasionally been observed in C3HeB/FeJ mice. However, to date, there has been no demonstration that cavitation can be produced consistently enough to support C3HeB/FeJ mice as a new and useful model of cavitary TB. We utilized serial computed tomography (CT) imaging to detect pulmonary cavitation in C3HeB/FeJ mice after aerosol infection with M. tuberculosis Post-mortem analyses were performed to characterize lung lesions and to localize matrix metalloproteinases (MMPs) previously implicated in cavitary TB in situ A total of 47-61% of infected mice developed cavities during primary disease or relapse after non-curative treatments. Key pathological features of human TB, including simultaneous presence of multiple pathologies, were noted in lung tissues. Optical imaging demonstrated increased MMP activity in TB lesions and MMP-9 was significantly expressed in cavitary lesions. Tissue MMP-9 activity could be abrogated by specific inhibitors. In situ, three-dimensional analyses of cavitary lesions demonstrated that 22.06% of CD11b+ signal colocalized with MMP-9. C3HeB/FeJ mice represent a reliable, economical and tractable model of cavitary TB, with key similarities to human TB. This model should provide an excellent tool to better understand the pathogenesis of cavitation and its effects on TB treatments. PMID:27482816

  13. Prevalence and Risk Factors for Adult Pulmonary Tuberculosis in a Metropolitan City of South India

    PubMed Central

    Dhanaraj, Baskaran; Papanna, Mohan Kumar; Adinarayanan, Srividya; Vedachalam, Chandrasekaran; Sundaram, Vijayaraj; Shanmugam, Shivakumar; Sekar, Gomathi; Menon, Pradeep Aravindan; Wares, Fraser; Swaminathan, Soumya

    2015-01-01

    Background The present study measured the community prevalence and risk factors of adult pulmonary tuberculosis (PTB) in Chennai city, and also studied geographical distribution and the presence of different M. tuberculosis strains in the survey area. Methods A community-based cross sectional survey was carried out from July 2010 to October 2012 in Chennai city. Prevalence of bacteriologically positive PTB was estimated by direct standardization method. Univariate and multivariate analyses were carried out to identify significant risk factors. Drug susceptibility testing and spoligotyping was performed on isolated M. tuberculosis strains. Mapping of PTB cases was done using geographic positioning systems. Results Of 59,957 eligible people, 55,617 were screened by X-ray and /or TB symptoms and the prevalence of smear, culture, and bacteriologically positive PTB was estimated to be 228 (95% CI 189–265), 259 (95% CI 217–299) and 349 (95% CI 330–428) per 100,000 population, respectively. Prevalence of smear, culture, and bacteriologically positive PTB was highest amongst men aged 55–64 years. Multivariate analysis showed that occurrence of both culture and bacteriologically positive PTB disease was significantly associated with: age >35 years, past history of TB treatment, BMI <18.5 Kgs/m2, solid cooking fuel, and being a male currently consuming alcohol. The most frequent spoligotype family was East African Indian. Spatial distribution showed that a high proportion of patients were clustered in the densely populated north eastern part of the city. Conclusion Our findings demonstrate that TB is a major public health problem in this urban area of south India, and support the use of intensified case finding in high risk groups. Undernutrition, slum dwelling, indoor air pollution and alcohol intake are modifiable risk factors for TB disease. PMID:25905900

  14. Prevalence and clinical predictors of pulmonary tuberculosis among isolated inpatients: a prospective study.

    PubMed

    Lagrange-Xélot, M; Porcher, R; Gallien, S; Wargnier, A; Pavie, J; de Castro, N; Molina, J-M

    2011-04-01

    Guidelines help to prevent the transmission of Mycobacterium tuberculosis in healthcare settings, but may also result in the unnecessary isolation of many patients. We performed a prospective study to assess the prevalence and identify clinical predictors of culture-proven tuberculosis among inpatients isolated for suspected pulmonary tuberculosis (PTB) at our hospital. We also wished to validate a pre-existing clinical decision rule to improve our isolation policy. From August 2005 to January 2007, 134 patients isolated on admission to the ward for suspicion of PTB were prospectively enrolled. The admitting team made the decision to isolate patients on the basis of clinical and radiological findings, without the use of the clinical decision rule, and graded the overall suspicion of PTB. Twenty-six of the 134 isolated patients had PTB (prevalence: 19.4%), as well as one patient not isolated at admission. Univariate analysis revealed that PTB was significantly associated with young age, lack of human immunodeficiency virus (HIV) infection, weight loss, night sweats, fever, upper lobe disease and, especially, cavitary lesions on chest X-ray (adjusted OR 25.4, p <0.0001). Low suspicion of PTB by the admitting team and low clinical decision rule score had negative predictive values of 98.5% and 95.8% for PTB, respectively. Use of the clinical decision rule in addition to the team assessment would have led to the isolation of the patient with PTB not isolated on admission, and avoided 16 (14.8%) unnecessary isolations. In conclusion, the prevalence of PTB among isolated inpatients was high, and the use of a clinical decision rule in addition to clinical impression might improve isolation decisions. PMID:20459437

  15. True status of smear-positive pulmonary tuberculosis defaulters in Malawi.

    PubMed Central

    Kruyt, M. L.; Kruyt, N. D.; Boeree, M. J.; Harries, A. D.; Salaniponi, F. M.; van Noord, P. A.

    1999-01-01

    The article reports the results of a study to determine the true outcome of 8 months of treatment received by smear-positive pulmonary tuberculosis (PTB) patients who had been registered as defaulters in the Queen Elizabeth Central Hospital (QECH) and Mlambe Mission Hospital (MMH), Blantyre, Malawi. The treatment outcomes were documented from the tuberculosis registers of all patients registered between 1 October 1994 and 30 September 1995. The true treatment outcome for patients who had been registered as defaulters was determined by making personal inquiries at the treatment units and the residences of patients or relatives and, in a few cases, by writing to the appropriate postal address. Interviews were carried out with patients who had defaulted and were still alive and with matched, fully compliant PTB patients who had successfully completed the treatment to determine the factors associated with defaulter status. Of the 1099 patients, 126 (11.5%) had been registered as defaulters, and the true treatment outcome was determined for 101 (80%) of the latter; only 22 were true defaulters, 31 had completed the treatment, 31 had died during the treatment period, and 17 had left the area. A total of 8 of the 22 true defaulters were still alive and were compared with the compliant patients. Two significant characteristics were associated with the defaulters; they were unmarried; and they did not know the correct duration of antituberculosis treatment. Many of the smear-positive tuberculosis patients who had been registered as defaulters in the Blantyre district were found to have different treatment outcomes, without defaulting. The quality of reporting in the health facilities must therefore be improved in order to exclude individuals who are not true defaulters. PMID:10361755

  16. Mouse model of pulmonary cavitary tuberculosis and expression of matrix metalloproteinase-9

    PubMed Central

    Ordonez, Alvaro A.; Tasneen, Rokeya; Pokkali, Supriya; Xu, Ziyue; Converse, Paul J.; Klunk, Mariah H.; Mollura, Daniel J.; Nuermberger, Eric L.

    2016-01-01

    ABSTRACT Cavitation is a key pathological feature of human tuberculosis (TB), and is a well-recognized risk factor for transmission of infection, relapse after treatment and the emergence of drug resistance. Despite intense interest in the mechanisms underlying cavitation and its negative impact on treatment outcomes, there has been limited study of this phenomenon, owing in large part to the limitations of existing animal models. Although cavitation does not occur in conventional mouse strains after infection with Mycobacterium tuberculosis, cavitary lung lesions have occasionally been observed in C3HeB/FeJ mice. However, to date, there has been no demonstration that cavitation can be produced consistently enough to support C3HeB/FeJ mice as a new and useful model of cavitary TB. We utilized serial computed tomography (CT) imaging to detect pulmonary cavitation in C3HeB/FeJ mice after aerosol infection with M. tuberculosis. Post-mortem analyses were performed to characterize lung lesions and to localize matrix metalloproteinases (MMPs) previously implicated in cavitary TB in situ. A total of 47-61% of infected mice developed cavities during primary disease or relapse after non-curative treatments. Key pathological features of human TB, including simultaneous presence of multiple pathologies, were noted in lung tissues. Optical imaging demonstrated increased MMP activity in TB lesions and MMP-9 was significantly expressed in cavitary lesions. Tissue MMP-9 activity could be abrogated by specific inhibitors. In situ, three-dimensional analyses of cavitary lesions demonstrated that 22.06% of CD11b+ signal colocalized with MMP-9. C3HeB/FeJ mice represent a reliable, economical and tractable model of cavitary TB, with key similarities to human TB. This model should provide an excellent tool to better understand the pathogenesis of cavitation and its effects on TB treatments. PMID:27482816

  17. Detection and Quantification of Mycobacterium tuberculosis in the Sputum of Culture-Negative HIV-infected Pulmonary Tuberculosis Suspects: A Proof-of-Concept Study

    PubMed Central

    Madico, Guillermo; Mpeirwe, Moses; White, Laura; Vinhas, Solange; Orr, Beverley; Orikiriza, Patrick; Miller, Nancy S.; Gaeddert, Mary; Mwanga-Amumpaire, Juliet; Palaci, Moises; Kreiswirth, Barry; Straight, Joe; Dietze, Reynaldo; Boum, Yap; Jones-López, Edward C.

    2016-01-01

    Rationale Rapid diagnosis of pulmonary tuberculosis (TB) is critical for timely initiation of treatment and interruption of transmission. Yet, despite recent advances, many patients remain undiagnosed. Culture, usually considered the most sensitive diagnostic method, is sub-optimal for paucibacillary disease. Methods We evaluated the Totally Optimized PCR (TOP) TB assay, a new molecular test that we hypothesize is more sensitive than culture. After pre-clinical studies, we estimated TOP’s per-patient sensitivity and specificity in a convenience sample of 261 HIV-infected pulmonary TB suspects enrolled into a TB diagnostic study in Mbarara, Uganda against MGIT culture, Xpert MTB/RIF and a composite reference standard. We validated results with a confirmatory PCR used for sequencing M. tuberculosis. Measurements and Results Using culture as reference, TOP had 100% sensitivity but 35% specificity. Against a composite reference standard, the sensitivity of culture (27%) and Xpert MTB/RIF (27%) was lower than TOP (99%), with similar specificity (100%, 98% and 87%, respectively). In unadjusted analyses, culture-negative/TOP-positive patients were more likely to be older (P<0·001), female (P<0·001), have salivary sputum (P = 0·05), sputum smear-negative (P<0.001) and less advanced disease on chest radiograph (P = 0.05). M. tuberculosis genotypes identified in sputum by DNA sequencing exhibit differential growth in culture. Conclusions These findings suggest that the TOP TB assay is accurately detecting M. tuberculosis DNA in the sputum of culture-negative tuberculosis suspects. Our results require prospective validation with clinical outcomes. If the operating characteristics of the TOP assay are confirmed in future studies, it will be justified as a “TB rule out” test. PMID:27391604

  18. Prevalence and treatment outcome of pulmonary and extrapulmonary pediatric tuberculosis in southwestern Iran

    PubMed Central

    Alavi, Seyed Mohammad; Salmanzadeh, Shokrollah; Bakhtiyariniya, Pejman; Albagi, Ali; Hemmatnia, Fatemeh; Alavi, Leila

    2015-01-01

    Background: Knowledge about childhood tuberculosis (TB) in Iran is limited. This study aimed to determine the proportion of tuberculosis in children living in Khuzestan in southwest of Iran and its treatment outcomes. Methods: In this retrospective study, the child’s medical records registered in national TB program (NTP) unit of Khuzestan Health Center (KHC) for TB treatment from 2005 to 2010 were studied. Data including demographic, clinical presentation, laboratory test results, and treatment outcomes were extracted from the files and were analyzed. Results: Of total 4104 new TB cases registered in KHC, 203 (4.9%) were children. The mean age was 10.7±4.3 years, and 75.7% of them were females. More than 84% of TB children cases were 10 years or older, whereas, young children (< 5 years old) accounted for 5.6%. Of the total studied cases, 57.1% were pulmonary TB and 42.9% were extra pulmonary, 91.7% were successfully treated and 8.3% had poor treatment outcome. The main risk factors for poor treatment outcome were: age <5 years (OR: 0.17, 95% CI, 0.04-0.76), low body weight (OR: 0.08, 95% CI, 0.01-0.60), household contact with cases of TB treatment failure (OR: 0.13, 95% CI, 0.03-0.52), and exposure to cigarette smoke odor inside the home (OR: 0.17, 95% CI, 0.05-0.56). Conclusion: The proportion of pediatric TB in the region was lower than expected. The treatment success rate was higher than the rate defined in NTP. Special attention should be given to children aged less than five years, low body weight, contact with TB treatment failure cases, and exposure to cigarette smoke. PMID:26644895

  19. Interleukin 17-Producing γδ T Cells Increased in Patients with Active Pulmonary Tuberculosis

    PubMed Central

    Peng, Meiyu; Wang, Zhaohua; Yao, Chunyan; Jiang, Lina; Jin, Qili; Wang, Jing; Li, Baiqing

    2008-01-01

    Although it has been known that γδ T cells may play an important role in the immune response to infection of Mycobacterium tuberculosis (M. tb), the mechanisms by which the γδ T cells participate in the innate and/or acquired immunity to tuberculosis (TB) have not been full elucidated. In the present study, 27 patients with active pulmonary TB and 16 healthy donors (HD) were performed. We found that proportion of IL-17-producing cells among lymphocyte was similar between TB patients and HD, whereas the proportions of γδ T cells in IL-17-producing cells (59.2%) and IL-17-producing cells in γδ T cells (19.4%) in peripheral blood were markedly increased in TB patients when compared to those in HD (43.9% and 7.7%, respectively). In addition, the proportions of IFN-γ-producing γδ T cells in TB patients were obviously lower than that in HD. Upon re-stimulated with M. tb heat-treated antigen (M. tb-HAg) in vitro, fewer IL-17-producing γδ T cells were generated from HD and TB patients, whereas IFN-γ-producing γδ T cells were increased in TB patients compared to that in HD. Our findings in TB patients and healthy human were consistent with other murine investigation that the IL-17-producing γδ T cells were main source of IL-17 in mouse model of BCG infection, suggesting that γδ T cells might be involved in the formation of tubercular granuloma in pulmonary TB patients, but need further identification. PMID:18582402

  20. MicroRNAs as potential targets for progressive pulmonary fibrosis

    PubMed Central

    Rajasekaran, Subbiah; Rajaguru, P.; Sudhakar Gandhi, P. S.

    2015-01-01

    Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and devastating disorder. It is characterized by alveolar epithelial cell injury and activation, infiltration of inflammatory cells, initiation of epithelial mesenchymal transition (EMT), aberrant proliferation and activation of fibroblasts, exaggerated deposition of extracellular matrix (ECM) proteins, and finally leading to the destruction of lung parenchyma. MicroRNAs (miRNAs) are endogenous small non-coding RNA molecules that post-transcriptionally regulate gene expression in diverse biological and pathological processes, including cell proliferation, differentiation, apoptosis and metastasis. As a result, miRNAs have emerged as a major area of biomedical research with relevance to pulmonary fibrosis. In this context, the present review discusses specific patterns of dysregulated miRNAs in patients with IPF. Further, we discuss the current understanding of miRNAs involvement in regulating lung inflammation, TGF-β1-mediated EMT and fibroblast differentiation processes, ECM genes expression, and in the progression of lung fibrosis. The possible future directions that might lead to novel therapeutic strategies for the treatment of pulmonary fibrosis are also reviewed. PMID:26594173

  1. A genome-wide association study of pulmonary tuberculosis in Morocco.

    PubMed

    Grant, A V; Sabri, A; Abid, A; Abderrahmani Rhorfi, I; Benkirane, M; Souhi, H; Naji Amrani, H; Alaoui-Tahiri, K; Gharbaoui, Y; Lazrak, F; Sentissi, I; Manessouri, M; Belkheiri, S; Zaid, S; Bouraqadi, A; El Amraoui, N; Hakam, M; Belkadi, A; Orlova, M; Boland, A; Deswarte, C; Amar, L; Bustamante, J; Boisson-Dupuis, S; Casanova, J L; Schurr, E; El Baghdadi, J; Abel, L

    2016-03-01

    Although epidemiological evidence suggests a human genetic basis of pulmonary tuberculosis (PTB) susceptibility, the identification of specific genes and alleles influencing PTB risk has proven to be difficult. Previous genome-wide association (GWA) studies have identified only three novel loci with modest effect sizes in sub-Saharan African and Russian populations. We performed a GWA study of 550,352 autosomal SNPs in a family-based discovery Moroccan sample (on the full population and on the subset with PTB diagnosis at <25 years), which identified 143 SNPs with p < 1 × 10(-4). The replication study in an independent case/control sample identified four SNPs displaying a p < 0.01 implicating the same risk allele. In the combined sample including 556 PTB subjects and 650 controls these four SNPs showed suggestive association (2 × 10(-6) < p < 4 × 10(-5)): rs358793 and rs17590261 were intergenic, while rs6786408 and rs916943 were located in introns of FOXP1 and AGMO, respectively. Both genes are involved in the function of macrophages, which are the site of latency and reactivation of Mycobacterium tuberculosis. The most significant finding (p = 2 × 10(-6)) was obtained for the AGMO SNP in an early (<25 years) age-at-onset subset, confirming the importance of considering age-at-onset to decipher the genetic basis of PTB. Although only suggestive, these findings highlight several avenues for future research in the human genetics of PTB. PMID:26767831

  2. Effect of vitamin D3 on chemokine levels and regulatory T-cells in pulmonary tuberculosis.

    PubMed

    Harishankar, M; Anbalagan, S; Selvaraj, P

    2016-05-01

    1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] the active form of vitamin D3 acts as an immunomodulator in various immune cells. The present study is aimed to study the effect of 1,25(OH)2D3 on chemokine levels and regulatory T-cells in 51 healthy controls (HCs) and 50 pulmonary tuberculosis (PTB) patients. Peripheral blood mononuclear cells were cultured with culture filtrate antigen (CFA) of Mycobacterium tuberculosis in the presence or absence of 1,25(OH)2D3 at 10(-7)M concentration for 72h and the percentage positive regulatory T-cell subsets were studied using flow cytometry. The chemokine levels were estimated in the culture supernatants by ELISA. 1,25(OH)2D3 significantly upregulated the frequency of regulatory T-cell subsets while suppressed the production of chemokine levels in CFA stimulated cultures of HCs and PTB patients (p<0.05). Correlation analysis revealed a significant negative correlation between CD4+Foxp3+ regulatory T-cells and MCP-1, MIP-1β and IP-10 in CFA stimulated with 1,25(OH)2D3 treated cells (p<0.05). The results suggested that 1,25(OH)2D3 upregulated regulatory T-cells and act as anti-inflammatory by downregulating chemokine levels which could be beneficial to protect the host from inflammation and tissue damage during infection. PMID:26927615

  3. IMPACT OF CIGARETTE SMOKING ON RATES AND CLINICAL PROGNOSIS OF PULMONARY TUBERCULOSIS IN SOUTHERN MEXICO

    PubMed Central

    Bonacci, Robert A.; Cruz-Hervert, Luis Pablo; García-García, Lourdes; Reynales-Shigematsu, Luz Myriam; Ferreyra-Reyes, Leticia; Bobadilla-del-Valle, Miriam; Canizales-Quintero, Sergio; Ferreira-Guerrero, Elizabeth; Báez-Saldaña, Renata; Téllez-Vázquez, Norma; Mongua-Rodríguez, Norma; Montero-Campos, Rogelio; Delgado-Sánchez, Guadalupe; Martínez-Gamboa, Rosa Areli; Cano-Arellano, Bulmaro; Sifuentes-Osornio, José; de León, Alfredo Ponce

    2012-01-01

    Objectives To examine the relationship between cigarette smoking and incidence and mortality rates of pulmonary tuberculosis (TB) and treatment outcomes. Materials From 1995-2010, we analyzed data from 1062 patients with TB and from 2001-2004, 2951 contacts in Southern Mexico. Patients with acid-fast bacilli or Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and mycobacteriological evaluation and received treatment by the local DOTS program. Results Consumers of 1-10 (LS) or 11 or more (HS) cigarettes per day incidence (1.75 and 11.79) and mortality (HS,17.74) smoker-nonsmoker rate ratios were significantly higher for smokers. Smoker population was more likely to experience unfavorable treatment outcomes (HS, adjusted OR 2.36) and retreatment (LS and HS, adjusted hazard ratio (HR) 2.14 and 2.37). Contacts that smoked had a higher probability of developing active TB (HR 2.38) during follow up. Conclusions Results indicate the need of incorporating smoking prevention and cessation, especially among men, into international TB control strategies. PMID:22982014

  4. Prolonged survival of scavenger receptor class A-deficient mice from pulmonary Mycobacterium tuberculosis infection

    PubMed Central

    Sever-Chroneos, Zvjezdana; Tvinnereim, Amy; Hunter, Robert L.; Chroneos, Zissis C.

    2016-01-01

    SUMMARY The present study tested the hypothesis that the scavenger receptor SR-A modulates granuloma formation in response to pulmonary infection with Mycobacterium tuberculosis (MTB). To test this hypothesis, we monitored survival and histopathology in WT and SR-A-deficient mice following aerosol infection with MTB Rv. SR-A-deficient (SR-A−/−) mice infected with MTB survived significantly longer than WT mice; the mean survival of SR-A−/− mice exceeded 430 days compared to 230 days for WT mice. Early granuloma formation was not impaired in SR-A−/− mice. The extended survival of SR-A−/− mice was associated with 13- and 3-fold higher number of CD4+ lymphocytes and antigen presenting cells in SR-A−/− lungs compared to WT mice 280 after infection. The histopathology of chronically infected SR-A−/− lungs, however, was marked by abundant cholesterol clefts in parenchymal lesions containing infection in multinucleated giant cells. The present study indicates SR-A as a candidate gene of the innate immune system influencing the chronic phase of M. tuberculosis infection. PMID:22088322

  5. Association of TAP1 and TAP2 genes with susceptibility to pulmonary tuberculosis in Koreans.

    PubMed

    Roh, Eun Youn; Yoon, Jong Hyun; Shin, Sue; Song, Eun Young; Park, Myoung Hee

    2015-06-01

    Tuberculosis remains an important public health problem in Koreans. However, very few studies have reported on the genetic factors associated with TB susceptibility in Koreans. The aim of this study was to elucidate the genetic factors associated with susceptibility to pulmonary tuberculosis (PTB). We investigated the transporter associated with antigen processing -1 (TAP1) and TAP2 gene polymorphisms in 160 Korean PTB patients (categorized according to extent of lesion and TB medication history) and 210 controls. TAP2*C/E frequency was significantly increased in the PTB (pc = 0.004, OR = 2.28). TAP2*Bky2/C/E were enriched in the retreated, far-advanced and total PTB compared with the controls (pc = 0.015, OR = 3.27; pc = 0.019, OR = 2.56; pc = 2.8 × 10(-4) , OR = 2.42, respectively). In the comparison of TAP2 gene with the DRB1*08:03, which is associated with TAP2*Bky2 and PTB in Koreans, we demonstrated the hierarchy of these association factors. TAP2*C/E is independent factors as strong as DRB1*08:03, and TAP2*C/E interacts with DRB1*08:03, resulting in a striking combined association. Our results suggest that TAP2 gene has an association with PTB susceptibility, the extent of the lesion or recurrence. These associations are independent from and additive with DRB1*08:03. PMID:25846714

  6. Comparative Study of GeneXpert with ZN Stain and Culture in Samples of Suspected Pulmonary Tuberculosis

    PubMed Central

    Bajaj, Ashish; Bhatia, Vinay; Dutt, Sarjana

    2016-01-01

    Introduction Tuberculosis remains one of the deadliest communicable diseases. There are number of tests available for the diagnosis of tuberculosis but conventional microscopy has low sensitivity and culture although gold standard, but takes longer time for positivity. On the other side, Nucleic acid amplification techniques due to its rapidity and sensitivity not only help in early diagnosis and management of tuberculosis especially in patients with high clinical suspicion like immunocompromised patients, history of contact with active tuberculosis patient etc., but also curtail the transmission of the disease. Aim To evaluate the sensitivity, specificity, positive predictive value and negative predictive value of Nucleic acid amplification assay (GeneXpert) using respiratory samples in patients with suspected pulmonary tuberculosis and compare with AFB smear microscopy (Ziehl Neelsen stain) and Acid Fast Bacilli (AFB) culture. Materials and Methods We retrospectively reviewed the respiratory samples of suspected pulmonary tuberculosis (including Bronchoalveolar lavage and sputum) of 170 patients from Jan 2015 to Nov 2015 for ZN stain, culture and GeneXpert (Xpert® MTB/Rif assay). The sensitivity, specificity, PPV and NPV of GeneXpert and ZN microscopy were calculated using Liquid culture of Mycobacterium tuberculosis as gold standard. Results A total of 170 patient samples were evaluated in final analysis. Of these, 14 samples were positive by all three methods used in our study. The overall sensitivity, specificity, PPV and NPV of GeneXpert were 86.8%, 93.1%, 78.5% and 96% respectively and for BAL sample, 81.4%, 93.4%, 73.3% and 95.7% respectively. The overall sensitivity and specificity of AFB smear microscopy were 22.2%, % and 78.5% respectively and for BAL sample 22.2% and 100% respectively. For AFB negative samples sensitivity and specificity were 79.1% and 93.1% respectively. Conclusion GeneXpert has a higher sensitivity than AFB smear microscopy in

  7. Pulmonary tuberculosis

    MedlinePlus

    ... unclean living conditions Have poor nutrition The following factors can increase the rate of TB infection in a population: Increase in HIV infections Increase in number of homeless people (poor environment and nutrition) Drug-resistant strains of TB

  8. Pulmonary tuberculosis

    MedlinePlus

    ... MD, PhD, Assistant Professor in Medicine, Harvard Medical School; Assistant in Medicine, Division of Infectious Disease, Department ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  9. Vitamin D status and incidence of tuberculosis infection conversion in contacts of pulmonary tuberculosis patients: a prospective cohort study.

    PubMed

    Arnedo-Pena, A; Juan-Cerdán, J V; Romeu-García, M A; García-Ferrer, D; Holguín-Gómez, R; Iborra-Millet, J; Pardo-Serrano, F

    2015-06-01

    The objective of this study was to estimate the relationship between serum vitamin D (VitD) status and tuberculosis (TB) infection conversion (TBIC), measured by the tuberculin skin test (TST) and an interferon-gamma release assay, the QuantiFERON-TB Gold In-Tube (QFT-GIT) test, in the contacts of pulmonary TB patients in Castellon (Spain) in a prospective cohort study from 2010 to 2012. Initially, the participants were negative to latent TB infection after a screening that included TST and QFT-GIT tests, and other examinations. A baseline determination of 25-hydroxyvitamin D [25(OH)D] was obtained by chemiluminescence immunoassay. After 8-10 weeks, participants were screened for a second time to determine TB infection conversion (TBIC). Poisson regression models were used in the statistical analysis. Of the 247 participants in the cohort, 198 (80·2%) were screened twice and 18 (9·1%) were TBIC cases. The means of VitD concentration in the TBIC cases and the non-cases were 20·7±11·9 and 27·2±11·4 ng/ml (P = 0·028), respectively. Adjusted for high exposure and TB sputum acid-fast bacilli (AFB)-positive index case, higher serum VitD concentration was associated with low incidence of TBIC (P trend = 0·005), and an increase of 1 ng/ml VitD concentration decreased the incidence of TBIC by 6% (relative risk 0·94, 95% confidence interval 0·90-0·99, P = 0·015). The results suggest that sufficient VitD level could be a protective factor of TBIC. PMID:25274036

  10. A retired shipyard worker with rapidly progressive pulmonary interstitial fibrosis.

    PubMed Central

    Moy, E V; Hu, H; Christiani, D C

    1999-01-01

    We present a case of progressive interstitial fibrosis in a retired shipyard worker who was exposed to asbestos during the postwar era of the late 1940s and 1950s, when asbestos exposures in the workplace were not regulated. Forty years later, at 63 years of age, the patient presented with restrictive lung disease. The patient was diagnosed with asbestos-related pleural disease and parenchymal asbestosis. He remained stable for the next 7 years, but then he began to manifest rapid clinical progression, which raised the possibility of an unusual variant of asbestosis, a concomitant interstitial process, or an unrelated disease. Lung biopsy was not undertaken because of the patient's low pulmonary reserve and limited treatment options. An empiric trial of oral steroids was initiated, but his pulmonary status continued to deteriorate and he died of pulmonary failure at 72 years of age. Many diseases result in pulmonary interstitial fibrosis. Ideally, open lung biopsy should be performed, but this procedure inevitably causes complications in many patients with end-stage restrictive lung disease. Furthermore, while the presence of asbestos bodies in tissue sections is a sensitive and specific marker of asbestos exposure, neither this finding nor any other charge is a marker indicative of asbestosis or the severity of asbestosis. With the enactment of the Asbestos Standard in the United States, asbestos exposures have been decreasing in this country. However, industries that produce asbestos products and wastes continue to expand in developing countries. Prevention of asbestos-related lung disease should be a global endeavor, and asbestos exposures should be regulated in both developed and developing countries. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:10090713

  11. Pulmonary tuberculosis in severely-malnourished or HIV-infected children with pneumonia: a review.

    PubMed

    Chisti, Mohammod Jobayer; Ahmed, Tahmeed; Pietroni, Mark A C; Faruque, Abu S G; Ashraf, Hasan; Bardhan, Pradip K; Hossain, Iqbal; Das, Sumon Kumar; Salam, Mohammed Abdus

    2013-09-01

    Presentation of pulmonary tuberculosis (PTB) as acute pneumonia in severely-malnourished and HIV-positive children has received very little attention, although this is very important in the management of pneumonia in children living in communities where TB is highly endemic. Our aim was to identify confirmed TB in children with acute pneumonia and HIV infection and/or severe acute malnutrition (SAM) (weight-for-length/height or weight-for-age z score <-3 of the WHO median, or presence of nutritional oedema). We conducted a literature search, using PubMed and Web of Science in April 2013 for the period from January 1974 through April 2013. We included only those studies that reported confirmed TB identified by acid fast bacilli (AFB) through smear microscopy, or by culture-positive specimens from children with acute pneumonia and SAM and/or HIV infection. The specimens were collected either from induced sputum (IS), or gastric lavage (GL), or broncho-alveolar lavage (BAL), or percutaneous lung aspirates (LA). Pneumonia was defined as the radiological evidence of lobar or patchy consolidation and/or clinical evidence of severe/ very severe pneumonia according to the WHO criteria of acute respiratory infection. A total of 17 studies met our search criteria but 6 were relevant for our review. Eleven studies were excluded as those did not assess the HIV status of the children or specify the nutritional status of the children with acute pneumonia and TB. We identified only 747 under-five children from the six relevant studies that determined a tubercular aetiology of acute pneumonia in children with SAM and/or positive HIV status. Three studies were reported from South Africa and one each from the Gambia, Ethiopia, and Thailand where 610, 90, 35, and 12 children were enrolled and 64 (10%), 23 (26%), 5 (14%), and 1 (8%) children were identified with active TB respectively, with a total of 93 (12%) children with active TB. Among 610 HIV-infected children in three studies

  12. PULMONARY RESECTION FOR EXTENSIVELY DRUG-RESISTANT TUBERCULOSIS IN DURBAN, SOUTH AFRICA

    PubMed Central

    Iddriss, Adam; Padayachi, Nesri; Reddy, Darshan; Reddi, Anu

    2013-01-01

    Background Extensively-drug resistant tuberculosis (XDR-TB) has been reported in 58 countries around the world and has emerged as a major public health challenge. This is the first report to describe pulmonary resection for XDR-TB management in Africa. Methods We conducted a retrospective case review of XDR-TB patients who underwent pulmonary resection between January 2007 and December 2009. Results Two pneumonectomies and two right upper lobectomies were performed. No operative mortality or major morbidity was noted. All patients achieved sputum conversion and were ultimately regarded as either a “cure” or “probable cure”. Conclusions Although the initial cohort of XDR-TB patients from Tugela Ferry demonstrated near complete mortality, our results demonstrate the potential of adjuvant surgical methods in XDR-TB treatment. With appropriate neoadjuvant chemotherapy and timeous surgery, patients with disease localized to lobe or lung XDR-TB may achieve a “cure” with low morbidity and mortality. Consequently, this approach may be the most cost effective treatment for patients suitable for lung resection. PMID:22633500

  13. Gender-Dependent Differences in Plasma Matrix Metalloproteinase-8 Elevated in Pulmonary Tuberculosis

    PubMed Central

    Sathyamoorthy, Tarangini; Sandhu, Gurjinder; Tezera, Liku B.; Thomas, Richard; Singhania, Akul; Woelk, Christopher H.; Dimitrov, Borislav D.; Agranoff, Dan; Evans, Carlton A. W.; Friedland, Jon S.; Elkington, Paul T.

    2015-01-01

    Tuberculosis (TB) remains a global health pandemic and greater understanding of underlying pathogenesis is required to develop novel therapeutic and diagnostic approaches. Matrix metalloproteinases (MMPs) are emerging as key effectors of tissue destruction in TB but have not been comprehensively studied in plasma, nor have gender differences been investigated. We measured the plasma concentrations of MMPs in a carefully characterised, prospectively recruited clinical cohort of 380 individuals. The collagenases, MMP-1 and MMP-8, were elevated in plasma of patients with pulmonary TB relative to healthy controls, and MMP-7 (matrilysin) and MMP-9 (gelatinase B) were also increased. MMP-8 was TB-specific (p<0.001), not being elevated in symptomatic controls (symptoms suspicious of TB but active disease excluded). Plasma MMP-8 concentrations inversely correlated with body mass index. Plasma MMP-8 concentration was 1.51-fold higher in males than females with TB (p<0.05) and this difference was not due to greater disease severity in men. Gender-specific analysis of MMPs demonstrated consistent increase in MMP-1 and -8 in TB, but MMP-8 was a better discriminator for TB in men. Plasma collagenases are elevated in pulmonary TB and differ between men and women. Gender must be considered in investigation of TB immunopathology and development of novel diagnostic markers. PMID:25635689

  14. Risk Factors for Death during Pulmonary Tuberculosis Treatment in Korea: A Multicenter Retrospective Cohort Study

    PubMed Central

    2014-01-01

    The data regarding risk factors for death during tuberculosis (TB) treatment are inconsistent, and few studies examined this issue in Korea. The purpose of this study was to evaluate baseline prognostic factors for death during treatment of adult patients with pulmonary TB in Korea. A multicenter retrospective cohort study of 2,481 patients who received TB treatment at eight hospitals from January 2009 to December 2010 was performed. Successful treatment included cure (1,129, 45.5%) and treatment completion (1,204, 48.5%) in 2,333 patients (94.0%). Unsuccessful treatment included death (85, 3.4%) and treatment failure (63, 2.5%) occurred in 148 patients (6.0%). In multivariate analysis, male sex, anemia, dyspnea, chronic heart disease, malignancy, and intensive care unit (ICU) admission were significant risk factors for death during TB treatment. Therefore, male sex, anemia, dyspnea, chronic heart disease, malignancy, and ICU admission could be baseline prognostic factors for death during treatment of adult patients with pulmonary TB in Korea. Graphical Abstract PMID:25246740

  15. Transfer factors as immunotherapy and supplement of chemotherapy in experimental pulmonary tuberculosis

    PubMed Central

    FABRE, R A; PÉREZ, T M; AGUILAR, L D; RANGEL, M J; ESTRADA-GARCÌA, I; HERNÁNDEZ-PANDO, R; ESTRADA PARRA, S

    2004-01-01

    Problems of logistics, compliance and drug resistance point to an urgent need for immunotherapeutic strategies capable of shortening the current six month antibiotic regimens used to treat tuberculosis. One potential immunotherapeutic agent is transfer factors. Transfer factors (TF) are low molecular weight dialysable products from immune cells which transmit the ability to express delayed-type hypersensitivity (DTH) and cell mediated immunity from sensitized donors to nonimmune recipients. In this study we determined the efficiency of TF as immunotherapy to treat experimental tuberculosis. When BALB/c mice are infected via the trachea with Mycobacterium tuberculosis H37Rv there is an initial phase of partial resistance dominated by Th-1 type cytokines plus tumour necrosis factor-alpha (TNFα) and the inducible isoform of nitric oxide synthase (iNOS), followed by a phase of progressive disease characterized by increasing expression of IL-4, diminished expression of TNFα and iNOS, and low DTH. Animals in this late progressive phase of the disease (day 60) were treated with different doses of TF (one injection per week) obtained from spleen cells when the peak of immune protection in this animal model is reached (day 21), or with different doses of TF from peripheral leucocytes of PPD + healthy subjects. We show here that the treatment with murine or human TF restored the expression of Th-1 cytokines, TNFα and iNOS provoking inhibition of bacterial proliferation and significant increase of DTH and survival. This beneficial effect was dose dependent. Interestingly, murine TF in combination with conventional chemotherapy had a synergistic effect producing significant faster elimination of lung bacteria loads than chemotherapy alone. PMID:15086383

  16. Oral Tolerance to Environmental Mycobacteria Interferes with Intradermal, but Not Pulmonary, Immunization against Tuberculosis

    PubMed Central

    Price, Dominique N.; Kusewitt, Donna F.; Lino, Christopher A.; McBride, Amber A.; Muttil, Pavan

    2016-01-01

    Bacille Calmette–Guérin (BCG) is currently the only approved vaccine against tuberculosis (TB) and is administered in over 150 countries worldwide. Despite its widespread use, the vaccine has a variable protective efficacy of 0–80%, with the lowest efficacy rates in tropical regions where TB is most prevalent. This variability is partially due to ubiquitous environmental mycobacteria (EM) found in soil and water sources, with high EM prevalence coinciding with areas of poor vaccine efficacy. In an effort to elucidate the mechanisms underlying EM interference with BCG vaccine efficacy, we exposed mice chronically to Mycobacterium avium (M. avium), a specific EM, by two different routes, the oral and intradermal route, to mimic human exposure. After intradermal BCG immunization in mice exposed to oral M. avium, we saw a significant decrease in the pro-inflammatory cytokine IFN-γ, and an increase in T regulatory cells and the immunosuppressive cytokine IL-10 compared to naïve BCG-vaccinated animals. To circumvent the immunosuppressive effect of oral M. avium exposure, we vaccinated mice by the pulmonary route with BCG. Inhaled BCG immunization rescued IFN-γ levels and increased CD4 and CD8 T cell recruitment into airways in M. avium-presensitized mice. In contrast, intradermal BCG vaccination was ineffective at T cell recruitment into the airway. Pulmonary BCG vaccination proved protective against Mtb infection regardless of previous oral M. avium exposure, compared to intradermal BCG immunization. In conclusion, our data indicate that vaccination against TB by the pulmonary route increases BCG vaccine efficacy by avoiding the immunosuppressive interference generated by chronic oral exposure to EM. This has implications in TB-burdened countries where drug resistance is on the rise and health care options are limited due to economic considerations. A successful vaccine against TB is necessary in these areas as it is both effective and economical. PMID:27153120

  17. Prevalence of latent tuberculosis infection among health care workers in a hospital for pulmonary diseases

    PubMed Central

    Schablon, Anja; Beckmann, Gudrun; Harling, Melanie; Diel, Roland; Nienhaus, Albert

    2009-01-01

    Background Little is known about the prevalence of latent tuberculosis infections (LTBI) in health care workers (HCW) in low-incidence countries especially in hospitals for pulmonary diseases. With Interferon-gamma release assays (IGRA), a new method for diagnosis of LTBI is available which is more specific than the tuberculin skin test (TST). Objectives The study was designed to estimate prevalence of LTBI among 270 HCW in a Hospital of Pulmonary Diseases routinely screened for TB. Methods LTBI was assessed by the QuantiFERON-Gold In Tube (QFT-IT). Information on gender, age, workplace, job title, BCG vaccination and history of both TB and TST were collected using a standardised questionnaire. Adjusted odds ratios for potential risk factors for LTBI were calculated. Results The prevalence of LTBI was 7.2%. In HCW younger than 30 years LTBI prevalence was 3.5% and in those older than 50 years 22%. Physicians and nurses showed a higher prevalence rate than other professions (10.8% to 4.5%). The putative risk factors for LTBI were age (>50 year OR 9.3, 95%CI 2.5–33.7), working as physicians/nurses (OR 3. 95%CI 1.2–10.4) and no previous TST in medical history (OR 4.4, 95%CI 1.01–18.9) when compared to those with a negative TST. Conclusion Prevalence of LTBI assessed by QFT-IT is low, this indicates a low infection risk even in hospitals for pulmonary diseases. No statement can be made regarding the occupational risk as compared to the general population because there are no LTBI prevalence data from Germany available. The higher LTBI prevalence rate in older HCWs might be due to the cohort effect or the longer time at risk. PMID:19134168

  18. Oral Tolerance to Environmental Mycobacteria Interferes with Intradermal, but Not Pulmonary, Immunization against Tuberculosis.

    PubMed

    Price, Dominique N; Kusewitt, Donna F; Lino, Christopher A; McBride, Amber A; Muttil, Pavan

    2016-05-01

    Bacille Calmette-Guérin (BCG) is currently the only approved vaccine against tuberculosis (TB) and is administered in over 150 countries worldwide. Despite its widespread use, the vaccine has a variable protective efficacy of 0-80%, with the lowest efficacy rates in tropical regions where TB is most prevalent. This variability is partially due to ubiquitous environmental mycobacteria (EM) found in soil and water sources, with high EM prevalence coinciding with areas of poor vaccine efficacy. In an effort to elucidate the mechanisms underlying EM interference with BCG vaccine efficacy, we exposed mice chronically to Mycobacterium avium (M. avium), a specific EM, by two different routes, the oral and intradermal route, to mimic human exposure. After intradermal BCG immunization in mice exposed to oral M. avium, we saw a significant decrease in the pro-inflammatory cytokine IFN-γ, and an increase in T regulatory cells and the immunosuppressive cytokine IL-10 compared to naïve BCG-vaccinated animals. To circumvent the immunosuppressive effect of oral M. avium exposure, we vaccinated mice by the pulmonary route with BCG. Inhaled BCG immunization rescued IFN-γ levels and increased CD4 and CD8 T cell recruitment into airways in M. avium-presensitized mice. In contrast, intradermal BCG vaccination was ineffective at T cell recruitment into the airway. Pulmonary BCG vaccination proved protective against Mtb infection regardless of previous oral M. avium exposure, compared to intradermal BCG immunization. In conclusion, our data indicate that vaccination against TB by the pulmonary route increases BCG vaccine efficacy by avoiding the immunosuppressive interference generated by chronic oral exposure to EM. This has implications in TB-burdened countries where drug resistance is on the rise and health care options are limited due to economic considerations. A successful vaccine against TB is necessary in these areas as it is both effective and economical. PMID:27153120

  19. The Influence of Smoking on Pulmonary Tuberculosis in Diabetic and Non-Diabetic Patients

    PubMed Central

    Bai, Kuan-Jen; Lee, Jen-Jyh; Chien, Shun-Tien; Suk, Chi-Won; Chiang, Chen-Yuan

    2016-01-01

    Background Both smoking and diabetes can increase the risk and influence the manifestations and outcomes of tuberculosis (TB). It is not clear whether the influence of smoking on pulmonary TB differs between non-diabetic and diabetic patients. Herein, we assessed the manifestations and outcomes of TB in relation to smoking in both diabetic and non-diabetic TB patients. Methodology/Principal Findings All diabetic culture-positive pulmonary TB patients notified from 2005–2010 at three teaching hospitals in Taiwan were enrolled. A culture-positive pulmonary TB patient without DM who was notified to the health authority immediately prior to each diabetic TB patient was selected for comparison. The 972 patients in this study cohort included 365 (37.6%) non-diabetic non-smokers, 149 (15.3%) non-diabetic smokers, 284 (29.2%) diabetic non-smokers, and 174 (17.9%) diabetic smokers. The adjusted relative risk of a pretreatment positive smear for a smoker compared with a non-smoker was 2.19 (95% CI 1.38–3.47) in non-diabetic patients and 2.23 (95% CI 1.29–3.87) in diabetic culture-positive pulmonary TB patients. The adjusted relative risk for a positive smear among diabetic smokers was 5.61 (95% CI 3.35–9.41) compared with non-diabetic non-smokers. Smoking was significantly associated with an increased frequency of bilateral lung parenchyma involvement (AdjOR 1.84, 95% CI 1.16–2.93), far-advanced pulmonary TB (AdjOR 1.91, 95% CI 1.04–3.50), cavitary lesions (AdjOR 2.03, 95% CI 1.29–3.20), and unfavorable outcomes of TB (AdjOR 2.35, 95% CI 1.02–5.41) in non-diabetic patients. However, smoking was not associated with cavitary lung parenchyma lesions regarding the location, number or size of the cavity in diabetic TB patients. Conclusions/Significance Smoking and diabetes have joint effects on a pretreatment positive smear. Diabetic smokers had more than a 5-fold increased risk of a pretreatment positive smear than did non-diabetic non-smokers, indicating

  20. Pulmonary Langerhans cell histiocytosis with cervical lymph node involvement, and coexistence with pulmonary tuberculosis and right pneumothorax: a case report and review of literature

    PubMed Central

    Gao, Limin; Li, Huifang; Li, Gandi; Liu, Weiping; Li, Jinnan; Zhang, Wenyan

    2015-01-01

    We report an uncommon 22-year-old male Pulmonary Langerhans Cell Histiocytosis (PLCH) case which co-existed with pulmonary tuberculosis (TB). Unlike the common PLCH cases, this PLCH case has cervical lymph node involvement and right pneumothorax. The diagnosis was established by the imaging of lung and the biopsies of the lung and left neck lymph node. Imaging of the chest showed characteristic small nodules and thin-walled cysts and right pneumothorax. The LCH cells in the lung and left neck lymph node were characterized by large convoluted nuclei with cerebriform indentations of the nuclear envelope and longitudinal grooves. The nuclei contained small eosinophilic nucleoli and moderate amount cytoplasm. Immunohistochemically, the histiocytoid cells were positive for Langerin, CD1a and S-100. Acid-fast bacilli were found in sputum and lung biopsy tissue. To the best of our knowledge, this is the first case of PLCH with cervical lymph node involvement, and coexisted with pulmonary tuberculosis, right pneumothorax. A contribution of this case and review three of the five cases of PLCH with extrapulmonary involvement to lymph nodes resolved spontaneously after smoking cessation constitute a novel addition that it is inappropriate to regard pulmonary/nodal LCH as multi-organ or disseminated disease, and the treatment methods are the same whether the PLCH patient with lymph node involvement or not. PMID:25973117

  1. Pulmonary Langerhans cell histiocytosis with cervical lymph node involvement, and coexistence with pulmonary tuberculosis and right pneumothorax: a case report and review of literature.

    PubMed

    Gao, Limin; Li, Huifang; Li, Gandi; Liu, Weiping; Li, Jinnan; Zhang, Wenyan

    2015-01-01

    We report an uncommon 22-year-old male Pulmonary Langerhans Cell Histiocytosis (PLCH) case which co-existed with pulmonary tuberculosis (TB). Unlike the common PLCH cases, this PLCH case has cervical lymph node involvement and right pneumothorax. The diagnosis was established by the imaging of lung and the biopsies of the lung and left neck lymph node. Imaging of the chest showed characteristic small nodules and thin-walled cysts and right pneumothorax. The LCH cells in the lung and left neck lymph node were characterized by large convoluted nuclei with cerebriform indentations of the nuclear envelope and longitudinal grooves. The nuclei contained small eosinophilic nucleoli and moderate amount cytoplasm. Immunohistochemically, the histiocytoid cells were positive for Langerin, CD1a and S-100. Acid-fast bacilli were found in sputum and lung biopsy tissue. To the best of our knowledge, this is the first case of PLCH with cervical lymph node involvement, and coexisted with pulmonary tuberculosis, right pneumothorax. A contribution of this case and review three of the five cases of PLCH with extrapulmonary involvement to lymph nodes resolved spontaneously after smoking cessation constitute a novel addition that it is inappropriate to regard pulmonary/nodal LCH as multi-organ or disseminated disease, and the treatment methods are the same whether the PLCH patient with lymph node involvement or not. PMID:25973117

  2. Detection of Mycobacterium tuberculosis (MTB) in Fecal Specimens From Adults Diagnosed With Pulmonary Tuberculosis Using the Xpert MTB/Rifampicin Test

    PubMed Central

    Kokuto, Hiroyuki; Sasaki, Yuka; Yoshimatsu, Shoji; Mizuno, Kazue; Yi, Lina; Mitarai, Satoshi

    2015-01-01

    Background. The Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) is a fully automated diagnostic test that allows for the detection of MTB including its RIF resistance. Although the test is used for the diagnosis of tuberculosis (TB) in sputum samples worldwide, studies using fecal specimens are scarce. We therefore evaluated the efficacy of the Xpert MTB/RIF test for detection of MTB in fecal specimens obtained from adult pulmonary TB patients, confirmed by culture and/or molecular diagnostic methods. Methods. We conducted a retrospective case-control study to provide proof-of-concept regarding the efficacy of the Xpert MTB/RIF test using fecal samples for diagnosing pulmonary TB via detection of MTB in adult patients (≥20 years) at the Fukujuji Hospital in Tokyo, Japan. Results. Fecal specimens were obtained from 56 active pulmonary TB patients (including 48 sputum smear-positive and 8 sputum smear-negative patients), 10 non-TB patients (including 4 Myocobacterium avium complex infections), and 27 healthy individuals who were exposed to active pulmonary TB patients. The sensitivity of the fecal Xpert MTB/RIF was 100% (81.7%–100%) for detection of MTB in specimens from sputum smear-positive (1+ to 3+) patients, 81.0% (58.1%–94.6%) in specimens from sputum smear scanty positive patients, and 50.0% (15.7%–84.3%) in specimens from sputum smear-negative patients. Meanwhile, each of the fecal specimens from the non-TB group was negative for MTB (specificity 100%; 95% confidence interval, 86.2–100). Conclusions. The fecal Xpert MTB/RIF test could detect MTB in a large proportion of smear-positive pulmonary TB patients, without frequent false-positive results at a TB referral hospital in Japan. PMID:26125035

  3. [The prevention of neurotoxic reactions during the treatment of pulmonary tuberculosis in middle-aged and elderly patients].

    PubMed

    Markova, E F

    1990-10-01

    To prevent and control neurotoxic reactions in the treatment of pulmonary tuberculosis in elderly and old patients the author used dipromonium (derivative of pangamic acid). Use of this agent at the beginning of the treatment course reduced the incidence of side-effects of neurotoxic character. In case of development of reactions of the central and peripheral nervous system dipromonium treatment resulted in their weakening or liquidation. PMID:2080583

  4. Effect of Active Case Finding on Prevalence and Transmission of Pulmonary Tuberculosis in Dhaka Central Jail, Bangladesh

    PubMed Central

    Banu, Sayera; Rahman, Md. Toufiq; Uddin, Mohammad Khaja Mafij; Khatun, Razia; Khan, Md. Siddiqur Rahman; Rahman, Md. Mojibur; Uddin, Syed Iftekhar; Ahmed, Tahmeed; Heffelfinger, James D.

    2015-01-01

    Background Understanding tuberculosis (TB) transmission dynamics is essential for establishing effective TB control strategies in settings where the burden and risk of transmission are high. The objectives of this study were to evaluate the effect of active screening on controlling TB transmission and also to characterize Mycobacterium tuberculosis strains for investigating transmission dynamics in a correctional setting. Methods The study was carried out in Dhaka Central Jail (DCJ), from October 2005 to February 2010. An active case finding strategy for pulmonary TB was established both at the entry point to the prison and inside the prison. Three sputum specimens were collected from all pulmonary TB suspects and subjected to smear microscopy, culture, and drug susceptibility testing as well as genotyping which included deletion analysis, spoligotyping and analysis of mycobacterial interspersed repetitive units (MIRU). Results A total of 60,585 inmates were screened during the study period. We found 466 inmates with pulmonary TB of whom 357 (77%) had positive smear microscopy results and 109 (23%) had negative smear microscopy results but had positive results on culture. The number of pulmonary TB cases declined significantly, from 49 cases during the first quarter to 8 cases in the final quarter of the study period (p=0.001). Deletion analysis identified all isolates as M. tuberculosis and further identified 229 (70%) strains as ‘modern’ and 100 (30%) strains as ‘ancestral’. Analysis of MIRU showed that 347 strains (85%) exhibited unique patterns, whereas 61 strains (15%) clustered into 22 groups. The largest cluster comprised eight strains of the Beijing M. tuberculosis type. The rate of recent transmission was estimated to be 9.6%. Conclusions Implementation of active screening for TB was associated with a decline in TB cases in DCJ. Implementation of active screening in prison settings might substantially reduce the national burden of TB in Bangladesh

  5. Mycobacterium tuberculosis Lineage 7 Strains Are Associated with Prolonged Patient Delay in Seeking Treatment for Pulmonary Tuberculosis in Amhara Region, Ethiopia

    PubMed Central

    Norheim, Gunnstein; Namouchi, Amine; Zegeye, Ephrem D.; Kinander, Wibeke; Tønjum, Tone; Bekele, Shiferaw; Mannsåker, Turid; Bjune, Gunnar; Aseffa, Abraham; Holm-Hansen, Carol

    2015-01-01

    Recent genotyping studies of Mycobacterium tuberculosis in Ethiopia have reported the identification of a new phylogenetically distinct M. tuberculosis lineage, lineage 7. We therefore investigated the genetic diversity and association of specific M. tuberculosis lineages with sociodemographic and clinical parameters among pulmonary TB patients in the Amhara Region, Ethiopia. DNA was isolated from M. tuberculosis-positive sputum specimens (n = 240) and analyzed by PCR and 24-locus mycobacterial interspersed repetitive unit–variable-number tandem-repeat (MIRU-VNTR) analysis and spoligotyping. Bioinformatic analysis assigned the M. tuberculosis genotypes to global lineages, and associations between patient characteristics and genotype were evaluated using logistic regression analysis. The study revealed a high diversity of modern and premodern M. tuberculosis lineages, among which approximately 25% were not previously reported. Among the M. tuberculosis strains (n = 138) assigned to seven subgroups, the largest cluster belonged to the lineage Central Asian (CAS) (n = 60; 26.0%), the second largest to lineage 7 (n = 36; 15.6%), and the third largest to the lineage Haarlem (n = 35; 15.2%). Four sublineages were new in the MIRU-VNTRplus database, designated NW-ETH3, NW-ETH1, NW-ETH2, and NW-ETH4, which included 24 (10.4%), 18 (7.8%), 8 (3.5%), and 5 (2.2%) isolates, respectively. Notably, patient delay in seeking treatment was significantly longer among patients infected with lineage 7 strains (Mann-Whitney test, P < 0.008) than in patients infected with CAS strains (adjusted odds ratio [AOR], 4.7; 95% confidence interval [CI], 1.6 to 13.5). Lineage 7 strains also grew more slowly than other M. tuberculosis strains. Cases of Haarlem (OR, 2.8; 95% CI, 1.2 to 6.6) and NW-ETH3 (OR, 2.8; 95% CI, 1.0 to 7.3) infection appeared in defined clusters. Intensified active case finding and contact tracing activities in the study region are needed to expedite diagnosis and

  6. Progress in targeting cell envelope biogenesis in Mycobacterium tuberculosis

    PubMed Central

    Jackson, Mary; McNeil, Michael R; Brennan, Patrick J

    2013-01-01

    Most of the newly discovered compounds showing promise for the treatment of TB, notably multidrug-resistant TB, inhibit aspects of Mycobacterium tuberculosis cell envelope metabolism. This review reflects on the evolution of the knowledge that many of the front-line and emerging products inhibit aspects of cell envelope metabolism and in the process are bactericidal not only against actively replicating M. tuberculosis, but contrary to earlier impressions, are effective against latent forms of the disease. While mycolic acid and arabinogalactan synthesis are still primary targets of existing and new drugs, peptidoglycan synthesis, transport mechanisms and the synthesis of the decaprenyl-phosphate carrier lipid all show considerable promise as targets for new products, older drugs and new combinations. The advantages of whole cell- versus target-based screening in the perpetual search for new targets and products to counter multidrug-resistant TB are discussed. PMID:23841633

  7. Tuberculosis.

    PubMed

    Dheda, Keertan; Barry, Clifton E; Maartens, Gary

    2016-03-19

    Although the worldwide incidence of tuberculosis has been slowly decreasing, the global disease burden remains substantial (∼9 million cases and ∼1·5 million deaths in 2013), and tuberculosis incidence and drug resistance are rising in some parts of the world such as Africa. The modest gains achieved thus far are threatened by high prevalence of HIV, persisting global poverty, and emergence of highly drug-resistant forms of tuberculosis. Tuberculosis is also a major problem in health-care workers in both low-burden and high-burden settings. Although the ideal preventive agent, an effective vaccine, is still some time away, several new diagnostic technologies have emerged, and two new tuberculosis drugs have been licensed after almost 50 years of no tuberculosis drugs being registered. Efforts towards an effective vaccine have been thwarted by poor understanding of what constitutes protective immunity. Although new interventions and investment in control programmes will enable control, eradication will only be possible through substantial reductions in poverty and overcrowding, political will and stability, and containing co-drivers of tuberculosis, such as HIV, smoking, and diabetes. PMID:26377143

  8. IL-10 Dependent Suppression of Type 1, Type 2 and Type 17 Cytokines in Active Pulmonary Tuberculosis

    PubMed Central

    Kumar, Nathella Pavan; Gopinath, Venugopal; Sridhar, Rathinam; Hanna, Luke E.; Banurekha, Vaithilingam V.; Jawahar, Mohideen S.; Nutman, Thomas B.; Babu, Subash

    2013-01-01

    Background Although Type 1 cytokine responses are considered protective in pulmonary tuberculosis (PTB), their role as well as those of Type 2, 17 and immunoregulatory cytokines in tuberculous lymphadenitis (TBL) and latent tuberculosis (LTB) have not been well studied. Aim and Methods To identify cytokine responses associated with pulmonary tuberculosis (TB), TB lymphadenitits and latent TB, we examined mycobacterial antigen-specific immune responses of PTB, TBL and LTB individuals. More specifically, we examined ESAT-6 and CFP-10 induced Type 1, Type 2 and Type 17 cytokine production and their regulation using multiplex ELISA. Results PTB individuals exhibited a significantly lower baseline as well as antigen-specific production of Type 1 (IFNγ, TNFα and IL-2); Type 2 (IL-4) and Type 17 (IL-17A and IL-17F) cytokines in comparison to both TBL and LTB individuals. TBL individuals exhibited significantly lower antigen-specific IFNγ responses alone in comparison to LTB individuals. Although, IL-10 levels were not significantly higher, neutralization of IL-10 during antigen stimulation resulted in significantly enhanced production of IFNγ, IL-4 and IL-17A in PTB individuals, indicating that IL-10 mediates (at least partially) the suppression of cytokine responses in PTB. Conclusion Pulmonary TB is characterized by an IL-10 dependent antigen-specific suppression of Type 1, Type 2 and Type 17 cytokines, reflecting an important association of these cytokines in the pathogenesis of active TB. PMID:23544075

  9. The Role of Video-Assisted Thoracoscopic Therapeutic Resection for Medically Failed Pulmonary Tuberculosis.

    PubMed

    Tseng, Yau-Lin; Chang, Jia-Ming; Liu, Yi-Sheng; Cheng, Lili; Chen, Ying-Yuan; Wu, Ming-Ho; Lu, Chung-Lan; Yen, Yi-Ting

    2016-05-01

    There are few reports regarding video-assisted thoracoscopic therapeutic resection for medically failed pulmonary tuberculosis (TB). We reviewed our surgical results of video-assisted thoracoscopic surgery (VATS) therapeutic resection for pulmonary TB with medical failure, and its correlation with image characteristics on chest computed tomography (CT) scan.Between January 2007 and December 2012, among the 203 patients who had surgery for TB, the medical records of 89 patients undergoing therapeutic resection for medically failed pulmonary TB were reviewed. Clinical information and the image characteristics of CT scan were investigated and analyzed.Forty-six of the 89 patients undergoing successful VATS therapeutic resection had significantly lower grading in pleural thickening (P < 0.001), peribronchial lymph node calcification (P < 0.001), tuberculoma (P = 0.015), cavity (P = 0.006), and aspergilloma (P = 0.038); they had less operative blood loss (171.0 ± 218.7 vs 542.8 ± 622.8 mL; P < 0.001) and shorter hospital stay (5.2 ± 2.2 vs 15.6 ± 15.6 days; P < 0.001). They also had a lower percentage of anatomic resection (73.9% vs 93.0%; P = 0.016), a higher percentage of sublobar resection (56.5% vs 32.6%; P = 0.023), and a lower disease relapse rate (4.3% vs 23.3%; P = 0.009). Eighteen of the 38 patients with multi-drug resistant pulmonary tuberculosis (MDRTB) who successfully underwent VATS had significantly lower grading in pleural thickening (P = 0.001), peribronchial lymph node calcification (P = 0.019), and cavity (P = 0.017). They were preoperatively medicated for a shorter period of time (221.6 ± 90.8 vs 596.1 ± 432.5 days; P = 0.001), and had more sublobar resection (44.4% vs 10%), less blood loss (165.3 ± 148.3 vs 468.0 ± 439.9 mL; P = 0.009), and shorter hospital stay (5.4 ± 2.6 vs 11.8 ± 6.9 days; P = 0.001).Without multiple cavities

  10. The Role of Video-Assisted Thoracoscopic Therapeutic Resection for Medically Failed Pulmonary Tuberculosis

    PubMed Central

    Tseng, Yau-Lin; Chang, Jia-Ming; Liu, Yi-Sheng; Cheng, Lili; Chen, Ying-Yuan; Wu, Ming-Ho; Lu, Chung-Lan; Yen, Yi-Ting

    2016-01-01

    Abstract There are few reports regarding video-assisted thoracoscopic therapeutic resection for medically failed pulmonary tuberculosis (TB). We reviewed our surgical results of video-assisted thoracoscopic surgery (VATS) therapeutic resection for pulmonary TB with medical failure, and its correlation with image characteristics on chest computed tomography (CT) scan. Between January 2007 and December 2012, among the 203 patients who had surgery for TB, the medical records of 89 patients undergoing therapeutic resection for medically failed pulmonary TB were reviewed. Clinical information and the image characteristics of CT scan were investigated and analyzed. Forty-six of the 89 patients undergoing successful VATS therapeutic resection had significantly lower grading in pleural thickening (P < 0.001), peribronchial lymph node calcification (P < 0.001), tuberculoma (P = 0.015), cavity (P = 0.006), and aspergilloma (P = 0.038); they had less operative blood loss (171.0 ± 218.7 vs 542.8 ± 622.8 mL; P < 0.001) and shorter hospital stay (5.2 ± 2.2 vs 15.6 ± 15.6 days; P < 0.001). They also had a lower percentage of anatomic resection (73.9% vs 93.0%; P = 0.016), a higher percentage of sublobar resection (56.5% vs 32.6%; P = 0.023), and a lower disease relapse rate (4.3% vs 23.3%; P = 0.009). Eighteen of the 38 patients with multi-drug resistant pulmonary tuberculosis (MDRTB) who successfully underwent VATS had significantly lower grading in pleural thickening (P = 0.001), peribronchial lymph node calcification (P = 0.019), and cavity (P = 0.017). They were preoperatively medicated for a shorter period of time (221.6 ± 90.8 vs 596.1 ± 432.5 days; P = 0.001), and had more sublobar resection (44.4% vs 10%), less blood loss (165.3 ± 148.3 vs 468.0 ± 439.9 mL; P = 0.009), and shorter hospital stay (5.4 ± 2.6 vs 11.8 ± 6.9 days; P = 0.001). Without multiple