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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. 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

  3. Pulmonary tuberculosis presenting with oral aphthae

    PubMed Central

    Bayraktar, Kevser; Gürer, Gülcan

    2015-01-01

    Tuberculosis is caused by the Mycobacterium tuberculosis bacterium. Tuberculosis primarily affects the lungs. Patients mainly complain of cough, sputum, night sweating, weight loss, and fever. However, there may be cases of atypical presentations. Although aphthous mouth ulcers are mostly present in the oral cavity in primary tuberculosis patients, our literature search showed only one case report of pulmonary tuberculosis with oral aphthae. Here we report a case of a patient with pulmonary tuberculosis admitted to the hospital with the complaint of oral aphthae.

  4. Collapsing glomerulopathy associated with pulmonary tuberculosis

    PubMed Central

    Srinivasaprasad, N. D.; Chandramohan, G.; Praveen, V.; Fernando, M. E.

    2016-01-01

    Collapsing glomerulopathy (CG) usually presents with reduced glomerular filtration rate, heavy proteinuria and has unfavorable prognosis. Numerous associations with CG are found. We encountered a case of CG associated with pulmonary tuberculosis presenting with proteinuria and dialysis-requiring severe renal failure. Our patient made partial recovery of his renal function and became dialysis-independent after antituberculous therapy and oral steroids. Long-term follow-up is needed to assess the progression of the disease. PMID:27795635

  5. 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

  6. Hyperferritinemia in pulmonary tuberculosis.

    PubMed

    D'Souza, Benedicta; Sinha, Sulekha; Manjrekar, Poornima; D'Souza, Vivian

    2013-07-01

    High ferritin levels have been found to be associated with non infectious as well as infectious causes including tuberculosis. This is one case report of 41 year old male who presented with cough with expectoration. The patient had Multi drug resistant tuberculosis (MDRTB) and type 2 diabetes mellitus. The laboratory findings showed Iron 280 μg/dl, Total iron binding capacity (TIBC) 61 μg/dl, and ferritin 92,945 ng/ml which indicates that iron is an essential nutrient for the survival of the pathogen Mycobacterium tuberculosis.

  7. 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

  8. 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

  9. [Treatment of extrapulmonary tuberculosis and complicated forms of pulmonary tuberculosis].

    PubMed

    2008-09-01

    Tuberculosis is one of the most important health problems worldwide. In developed countries there is an increased number of cases due to different reasons. The most likely determinant cause is from immigrants coming from high endemic areas. This phenomenon is a direct cause of the increase in extrapulmonary and complicated pulmonary forms of tuberculosis. There are only a few controlled clinical trials evaluating therapies for extrapulmonary tuberculosis. Consequently, documented evidence is scarce, particularly in paediatrics. The majority of therapeutic recommendations are based on series of cases or expert opinions, with a lack of uniformity provided by the different consensus of the main scientific societies. The main objective of this fourth consensus by the Tuberculosis Study Group of the Spanish Society of Paediatric Infectious Diseases (Sociedad Española de Infectología Pediátrica, SEIP) is to perform a thorough revision of the data obtained from scientific literature, in order to establish recommendations for the treatment of extrapulmonary tuberculosis and complicated forms of pulmonary tuberculosis, adapted to the characteristics and drugs available in Spain.

  10. [Hemophagocytic syndrome secondary to cavitary pulmonary tuberculosis].

    PubMed

    Rakotoson, J L; Rakotonirainy, O H; Moroyandsa, F; Rakotoharivelo, H; Rakotomizao, J R; Andrianarisoa, A C F

    2012-01-01

    Hemophagocytic syndrome is due to the activation and nonmalignant proliferation of macrophages and T lymphocytes. The purpose of this report is to describe a 25-year-old man who presented with fever, coughing, and weight loss over the past month. Laboratory findings demonstrated pancytopenia, hyperferritinemia, and cytolysis. The myelogram showed a hemophagocytic syndrome, and tuberculosis bacilli were found in the sputum. Chest radiography and thoracic computed tomography depicted a cavitary lesion suggestive of pulmonary tuberculosis. Treatment of tuberculosis alone, without an immunosuppressant agent, was effective and led to improvement. In a country where tuberculosis is highly endemic, hemophagocytic syndrome should be considered in the differential diagnosis of patients with active tuberculosis complicated by pancytopenia.

  11. [Pulmonary manifestations of tuberculosis in children].

    PubMed

    Olivier, C

    1997-12-01

    The occurrence of tuberculosis in children is dependent on a contagious bacillus carrying adult. Among 500 cases notified annually, perhaps 5 or 6% of the total infectious reservoir in France, 75% have parenchymal pulmonary disease and/or lymph nodes. These tuberculous diseases only represent 10% of the pulmonary disorders: 90% remain primary infections (PI active) or latent infections. These are most often asymptomatic (PI Latent) or of low grade activity (PI active). The CT scanner and fibreoptic bronchoscopy are indispensable complementary investigations in tuberculous disease. Whatever the clinical picture the diagnosis rests on bacteriological confirmation (but only 30% of cultures are positive) and most often rests on a body of evidence: for example a contagious adult living in proximity or a contagious family, or other risk factors are present. The evidence of a child with whatever form of pulmonary tuberculosis, even a latent primary infection, requires treatment which is adapted in such a way to enable a cure and to protect against subsequent endogenous re-activation. A coherent system of co-operation between the hospital and community service and between paediatricians and adult physicians is indispensable to find the index adult case to break the chain of contagion. There are two specific aspects in children, first congenital tuberculosis when a diagnosis is difficult and secondly tuberculosis in a child who is HIV positive when the management can be delicate. PMID:9496592

  12. Rapid diagnosis of pulmonary tuberculosis

    PubMed Central

    Sarmiento, José Mauricio Hernández; Restrepo, Natalia Builes; Mejía, Gloria Isabel; Zapata, Elsa; Restrepo, Mary Alejandra; Robledo, Jaime

    2014-01-01

    Introduction World Health Organization had estimated 9.4 million tuberculosis cases on 2009, with 1.7 million of deaths as consequence of treatment and diagnosis failures. Improving diagnostic methods for the rapid and timely detection of tuberculosis patients is critical to control the disease. The aim of this study was evaluating the accuracy of the cord factor detection on the solid medium Middlebrook 7H11 thin layer agar compared to the Lowenstein Jensen medium for the rapid tuberculosis diagnosis. Methods Patients with suspected tuberculosis were enrolled and their sputum samples were processed for direct smear and culture on Lowenstein Jensen and BACTEC MGIT 960, from which positive tubes were subcultured on Middlebrook 7H11 thin layer agar. Statistical analysis was performed comparing culture results from Lowenstein Jensen and the thin layer agar, and their corresponding average times for detecting Mycobacterium tuberculosis. The performance of cord factor detection was evaluated determining its sensitivity, specificity, positive and negative predictive value. Results 111 out of 260 patients were positive for M. tuberculosis by Lowenstein Jensen medium with an average time ± standard deviation for its detection of 22.3 ± 8.5 days. 115 patients were positive by the MGIT system identifying the cord factor by the Middlebrook 7H11 thin layer agar which average time ± standard deviation was 5.5 ± 2.6 days. Conclusion The cord factor detection by Middlebrook 7H11 thin layer agar allows early and accurate tuberculosis diagnosis during an average time of 5 days, making this rapid diagnosis particularly important in patients with negative sputum smear. PMID:25419279

  13. 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

  14. 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

  15. [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

  16. 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

  17. [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

  18. [Diagnosis delay of pleural and pulmonary tuberculosis].

    PubMed

    Cherif, J; Mjid, M; Ladhar, A; Toujani, S; Mokadem, S; Louzir, B; Mehiri, N; Béji, M

    2014-08-01

    Tuberculosis (TB) is still being endemic in our country. Time until management determines both evolution and prognosis of this condition. The aim of this work is to evaluate the delay in diagnosis of TB in a respiratory unit from a university hospital series. The authors conducted a cross-sectional study including patients with pulmonary TBC and/or pleural. An evaluation of time management was conducted from the beginning of symptoms and various consultations with reference to the date of hospitalization and treatment set up. One hundred patients were included (pulmonary TB: 68 cases, pleural TB 23 cases, miliary pulmonary TB: 4 cases, pulmonary TB associated with other extrathoracic locations: 5 cases). The mean time of patient delay and total delay institution were respectively 43.6, 25.7 and 69.3 days. Variables responsible for long delays were: number of consultations more than 3 before hospitalization, empirical antibiotic therapy, of a regional hospital first consultation and the presence of extra-respiratory impairment. The patient delay was considered long. A reorganization of the TB control program, in particular by partial decentralization of care and health education is imperative in order to improve the quality of tuberculosis management in our country.

  19. The Transcriptional Signature of Active Tuberculosis Reflects Symptom Status in Extra-Pulmonary and Pulmonary Tuberculosis

    PubMed Central

    Blankley, Simon; Graham, Christine M.; Turner, Jacob; Berry, Matthew P. R.; Bloom, Chloe I.; Xu, Zhaohui; Pascual, Virginia; Banchereau, Jacques; Chaussabel, Damien; Breen, Ronan; Santis, George; Blankenship, Derek M.; Lipman, Marc; O’Garra, Anne

    2016-01-01

    Background Mycobacterium tuberculosis infection is a leading cause of infectious death worldwide. Gene-expression microarray studies profiling the blood transcriptional response of tuberculosis (TB) patients have been undertaken in order to better understand the host immune response as well as to identify potential biomarkers of disease. To date most of these studies have focused on pulmonary TB patients with gene-expression profiles of extra-pulmonary TB patients yet to be compared to those of patients with pulmonary TB or sarcoidosis. Methods A novel cohort of patients with extra-pulmonary TB and sarcoidosis was recruited and the transcriptional response of these patients compared to those with pulmonary TB using a variety of transcriptomic approaches including testing a previously defined 380 gene meta-signature of active TB. Results The 380 meta-signature broadly differentiated active TB from healthy controls in this new dataset consisting of pulmonary and extra-pulmonary TB. The top 15 genes from this meta-signature had a lower sensitivity for differentiating extra-pulmonary TB from healthy controls as compared to pulmonary TB. We found the blood transcriptional responses in pulmonary and extra-pulmonary TB to be heterogeneous and to reflect the extent of symptoms of disease. Conclusions The transcriptional signature in extra-pulmonary TB demonstrated heterogeneity of gene expression reflective of symptom status, while the signature of pulmonary TB was distinct, based on a higher proportion of symptomatic individuals. These findings are of importance for the rational design and implementation of mRNA based TB diagnostics. PMID:27706152

  20. 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

  1. The imaging spectrum of pulmonary tuberculosis.

    PubMed

    Cardinale, Luciano; Parlatano, Daniela; Boccuzzi, Francesco; Onoscuri, Maurizio; Volpicelli, Giovanni; Veltri, Andrea

    2015-05-01

    Tuberculosis has still an important impact on public health because it is an important cause of death, particularly in developing countries. On the other hand recent studies have shown that tuberculosis is again becoming concentrated in big cities of Western Europe, especially among immigrants, drug addicts, poor people, and the homeless, despite progress in reducing national rates of the disease. Diagnostic imaging is challenging for radiologists because signs of tuberculosis may easily mimic other diseases such as neoplasms or sarcoidosis. Clinical signs and symptoms in affected adults can be non-specific and a high level of pre-test clinical suspicion based on history is fundamental in the diagnostic work-up. Impact of tuberculosis in the world is extremely important considering the high incidence estimated during 2011 that was 8.7 million cases. This article gives a review of imaging patterns of chest tuberculosis as may be detected on conventional radiography and computerized tomography (CT). The main aim is to improve radiologist's familiarity with the spectrum of imaging features of this disease and facilitate timely diagnosis. Furthermore, we consider the emerging role of alternative methods of imaging, such as magnetic resonance imaging (MRI), that can be helpful and highly accurate for a better definition of some signs of tuberculosis. PMID:24833643

  2. [The chest CT findings and pathologic findings of pulmonary tuberculosis].

    PubMed

    Ogata, Hideo

    2009-08-01

    The past research of the radiologic manifestations of pulmonary tuberculosis in Japan was based on morphological pathology of the untreated patient autopsy. I would like to show the chest CT scan of tuberculosis diseases with caseous granuloma at its exudative reaction, proliferative reaction, productive reaction, cirrhotic reaction until self cure. This progress reflects the normal cell mediated immunological responses. Also I would like to show the cavitation of granuloma, which results from liquefaction of caseous materials during the course and results in the formation of the source of infection. And finally I would like to show the morphological differences of acinous lesion, acino-nodular lesion and caseous lobular pneumonia. These differences reflect the amount of bacilli disseminated in the peripheral parts under the lobules. In this study, I do not show old age cases and HIV positive cases, who do not form typical granuloma due to the decreased cell mediated immnunity and whose X ray findings are atypical.

  3. 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

  4. [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

  5. [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.

  6. [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

  7. 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

  8. Tuberculosis, Pulmonary Cavitation, and Matrix Metalloproteinases

    PubMed Central

    Ong, Catherine W. M.; Elkington, Paul T.

    2014-01-01

    Tuberculosis (TB), a chronic infectious disease of global importance, is facing the emergence of drug-resistant strains with few new drugs to treat the infection. Pulmonary cavitation, the hallmark of established disease, is associated with very high bacillary burden. Cavitation may lead to delayed sputum culture conversion, emergence of drug resistance, and transmission of the infection. The host immunological reaction to Mycobacterium tuberculosis is implicated in driving the development of TB cavities. TB is characterized by a matrix-degrading phenotype in which the activity of proteolytic matrix metalloproteinases (MMPs) is relatively unopposed by the specific tissue inhibitors of metalloproteinases. Proteases, in particular MMPs, secreted from monocyte-derived cells, neutrophils, and stromal cells, are involved in both cell recruitment and tissue damage and may cause cavitation. MMP activity is augmented by proinflammatory chemokines and cytokines, is tightly regulated by complex signaling paths, and causes matrix destruction. MMP concentrations are elevated in human TB and are closely associated with clinical and radiological markers of lung tissue destruction. Immunomodulatory therapies targeting MMPs in preclinical and clinical trials are potential adjuncts to TB treatment. Strategies targeting patients with cavitary TB have the potential to improve cure rates and reduce disease transmission. PMID:24713029

  9. Tuberculosis, pulmonary cavitation, and matrix metalloproteinases.

    PubMed

    Ong, Catherine W M; Elkington, Paul T; Friedland, Jon S

    2014-07-01

    Tuberculosis (TB), a chronic infectious disease of global importance, is facing the emergence of drug-resistant strains with few new drugs to treat the infection. Pulmonary cavitation, the hallmark of established disease, is associated with very high bacillary burden. Cavitation may lead to delayed sputum culture conversion, emergence of drug resistance, and transmission of the infection. The host immunological reaction to Mycobacterium tuberculosis is implicated in driving the development of TB cavities. TB is characterized by a matrix-degrading phenotype in which the activity of proteolytic matrix metalloproteinases (MMPs) is relatively unopposed by the specific tissue inhibitors of metalloproteinases. Proteases, in particular MMPs, secreted from monocyte-derived cells, neutrophils, and stromal cells, are involved in both cell recruitment and tissue damage and may cause cavitation. MMP activity is augmented by proinflammatory chemokines and cytokines, is tightly regulated by complex signaling paths, and causes matrix destruction. MMP concentrations are elevated in human TB and are closely associated with clinical and radiological markers of lung tissue destruction. Immunomodulatory therapies targeting MMPs in preclinical and clinical trials are potential adjuncts to TB treatment. Strategies targeting patients with cavitary TB have the potential to improve cure rates and reduce disease transmission.

  10. 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

  11. 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

  12. Tuberculosis incidence among contacts of active pulmonary tuberculosis

    PubMed Central

    Cailleaux-Cezar, M.; de A. Melo, D.; Xavier, G. M.; de Salles, C. L. G.; de Mello, F. C. Q.; Ruffino-Netto, A.; Golub, J. E.; Efron, A.; Chaisson, R. E.; Conde, M. B.

    2013-01-01

    SUMMARY BACKGROUND Treatment of latent tuberculosis (TB) infection (LTBI) in Brazil is recommended only in the case of contacts of pulmonary smear-positive TB patients aged ≤15 years with a tuberculin skin test (TST) ≥10 mm and no previous bacille Calmette-Guérin (BCG) vaccination or with a TST ≥15 mm regardless of previous BCG vaccination. OBJECTIVE To evaluate the 2-year incidence and predictors of TB among contacts who did not meet the Brazilian criteria for LTBI treatment. DESIGN Retrospective cohort study. Contacts aged between 12 and 15 years and those aged >15 years who did not meet the Brazilian criteria for LTBI treatment were enrolled in the study. RESULTS TB incidence was 3.2% (22/667), with an estimated TB rate of 1649 per 100 000 population. Risk of TB was greater among the 349 contacts with TST ≥5 mm (5.4%) compared to the 318 contacts with TST < 5 mm (0.9%; RR 6.04, 95%CI 1.7–20.6). CONCLUSION The high incidence of TB among contacts who did not meet the Brazilian criteria for LTBI treatment strongly suggests that these criteria should be reviewed. Furthermore, even among BCG-vaccinated contacts, TST induration ≥5 mm was the only variable that predicted the development of TB disease within 2 years. PMID:19146746

  13. [Four cases of pulmonary tuberculosis among deep-sea fishermen].

    PubMed

    Ono, Hidemaro; Murakami, Reiko; Tsuruwaka, Mia; Suzuki, Yoshihiko

    2003-06-01

    Pulmonary tuberculosis among deep-sea fishermen was reported. Four pulmonary tuberculosis cases among fishing boat members engaged in deep-sea fishing were registered at the Kesennuma Health Center during three years period from 2000 to 2002. Crew engaging in deep-sea fishing live together in a narrow cabin with inadequate airconditioning for a long period of time, about 1 year. It is difficult to consult with a medical institution in an open sea. If a tuberculosis patient breaks out in a boat, the risk of transmission of tuberculosis to other members is high. In boats of all four cases in this report, about 30 to 70 percent of crew were Indonesian. Indonesia is one of the high burden countries of tuberculosis in the world. The Japanese fishing boat members have received the medical checkup every year. Indonesians have also received the pre-employment medical checkup, however, the improvement in the quality of this medical checkup is required.

  14. DNA fingerprinting of Mycobacterium tuberculosis strains from patients with pulmonary tuberculosis in Honduras.

    PubMed Central

    Pineda-Garcia, L; Ferrera, A; Hoffner, S E

    1997-01-01

    Mycobacterium tuberculosis isolates from 84 patients with pulmonary tuberculosis in Honduras were characterized by restriction fragment length polymorphism analysis. Seventy-three different IS6110 patterns were found; 63 of these were unique and 10 were shared by two to three strains each. Thus, no ongoing spread of any specific clone of bacteria could be demonstrated. PMID:9276422

  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. [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%).

  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. 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

  19. 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.

  20. Clinical value of the measurement of Mycobacterium tuberculosis specific antibody in pulmonary tuberculosis.

    PubMed Central

    Bothamley, G H; Rudd, R; Festenstein, F; Ivanyi, J

    1992-01-01

    BACKGROUND: A serological test that could help to diagnose tuberculosis, especially smear negative disease, would contribute to patient management. METHODS: Levels of antibody to distinct antigens of Mycobacterium tuberculosis were assessed for their value in the diagnosis and management of pulmonary tuberculosis. Serum was taken from 52 patients who were smear positive, from 27 patients who were smear negative but with evidence of active tuberculosis (sputum culture positive in 16, response to antituberculosis chemotherapy in 11), from 11 patients with old healed tuberculosis (pre-antibiotic era), and from 39 healthy subjects vaccinated with BCG. RESULTS: In smear positive tuberculosis an enzyme linked immunosorbent assay using a single 38 kDa antigen gave a diagnostic sensitivity of 80% with a 100% specificity. In smear negative pulmonary tuberculosis, however, combination of the 19 kDa antigen, lipoarabinomannan (ML 34 epitope), and hsp 65 (TB 78 epitope) was needed to achieve a sensitivity of 64% with a specificity of 95%. Recurrent and extensive radiographic disease with a poor prognosis was associated with high anti-38 kDa and low anti-14 kDa antibody levels in patients with active disease. Patients with less pulmonary cavitation had high anti-19 kDa titres. Bacteriological relapse during treatment was indicated by a rise in anti-14 kDa (TB68 epitope) antibodies. Four patients with non-tuberculous mycobacterial infection showed no anti-38 kDa antibody. CONCLUSION: Antigen or epitope specific serology may help in the diagnosis, assessment of prognosis, and monitoring of chemotherapy in patients with pulmonary tuberculosis. PMID:1585290

  1. 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...

  2. 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

  3. A rare case of pulmonary tuberculosis with simultaneous pulmonary and skin sarcoidosis: a case report

    PubMed Central

    2010-01-01

    Background Tuberculosis and sarcoidosis are chronic diseases that rarely occur concomitantly. Sarcoidosis is a multisystem granulomatous disorder characterized pathologically by the presence of non-caseating granulomas in involved tissues. Tuberculosis is infectious disease caused by Mycobacterium tuberculosis characterized by granulomas with caseous necrosis. Case presentation We present a case of 43-year-old female refugee from Kosovo with microbiological confirmation of pulmonary tuberculosis and pulmonary and skin sarcoidosis at the same time. Three weeks after corticosteroid therapy for pulmonary sarcoidosis was introduced, positive finding of mycobacterium culture of bronchial aspirate was observed. Based on these results, corticosteroid therapy was excluded and antituberculous therapy was introduced for six months. In the meantime, new nodes on face and nose appeared and skin sarcoidosis was diagnosed. The patient was given corticosteroids and colchicine according to the skin and pulmonary sarcoidosis therapy recommendation. Conclusion The authors of this study suggest that in cases when there is a dilemma in diagnosis between tuberculosis and sarcoidosis we should advance with corticosteroid therapy until we have microbiological confirmation of mycobacterium culture. This case is remarkable because this is a third described case of sarcoidosis and tuberculosis together (the first reported in Asia, the second in South Africa), and to authors knowledge, this is a first case report in Europe. PMID:20205764

  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. 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

  6. 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

  7. 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...

  8. Experience with pulmonary resection for extensively drug-resistant tuberculosis.

    PubMed

    Shiraishi, Yuji; Katsuragi, Naoya; Kita, Hidefumi; Toishi, Masayuki; Onda, Takahito

    2008-12-01

    Extensively drug-resistant tuberculosis is becoming a global threat. It is a relatively new phenomenon, and its optimal management remains undetermined. We report our experience in using pulmonary resection for treating patients with this disease. Records were reviewed of 54 consecutive patients undergoing a pulmonary resection for multidrug-resistant tuberculosis at Fukujuji Hospital between 2000 and 2006. These patients were identified using the definition approved by the World Health Organization Global Task Force on extensively drug-resistant tuberculosis in October 2006. Five (9%) patients (3 men and 2 women) aged 31-60 years met the definition. None of the patients was HIV-positive. Although the best available multidrug regimens were initiated, no patient could achieve sputum conversion. Adjuvant resectional surgery was considered because the patients had localized disease. Procedures performed included pneumonectomy (2) and upper lobectomy (3). There was no operative mortality or morbidity. All patients attained sputum-negative status after the operation, and they were maintained on multidrug regimens for 12-25 months postoperatively. All patients remained free from disease at the time of follow-up. Pulmonary resection under cover of state-of-the-art chemotherapy is safe and effective for patients with localized extensively drug-resistant tuberculosis.

  9. The clinical significance of CA-125 in pulmonary tuberculosis.

    PubMed

    Kim, Eun Sun; Park, Kyoung Un; Song, JungHan; Lim, Hyo-Jeong; Cho, Young-Jae; Yoon, Hoil; Lee, JaeHo; Lee, Choon-Taek; Park, Jong Sun

    2013-03-01

    Cancer antigen 125 (CA-125) is usually elevated in ovarian cancer. However, there are several reports that serum CA-125 is elevated in tuberculosis. This study investigated the clinical significance of serum CA-125 measurements in patients with active pulmonary tuberculosis (TB). Between September 2008 and March 2011, Serum CA-125 was measured in patients with active pulmonary TB before treatment (baseline), and 6 and 12 months after initiation of anti-TB treatment. Patients with pulmonary TB confirmed by culture or polymerase chain reaction for Mycobacterium tuberculosis (TB-PCR) were included. The study enrolled 100 patients. The mean serum CA-125 was 38.9 ± 41.4 U/ml (reference value, <35 U/ml). Thirty-eight patients showed elevated CA-125. Significantly more of those with elevated CA-125 were female (p < 0.001), and had a positive sputum smear for acid-fast bacilli (AFB) (p = 0.030). They also significantly more showed extensive pulmonary lesions on chest X-ray (p = 0.004). Elevated CA-125 was independently associated with female gender (OR = 12.5, 95% CI: 3.4-45.2), positive acid-fast staining of sputum (OR = 6.0, 95% CI: 1.8-19.7), cavitary lung lesion (OR = 4.0, 95% CI: 1.2-12.9), and involvement of more than one lung on chest X-ray (OR = 9.4, 95% CI: 2.2-40.1). The CA-125 level decreased with anti-TB treatment (p = 0.001). Serum CA-125 was related to the activity and severity of pulmonary TB, and it may be useful in the monitoring of therapeutic responses in certain cases of active pulmonary TB, especially in female patients of active pulmonary TB. PMID:23414674

  10. 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

  11. [Alcohol sales and pulmonary tuberculosis mortality in the Republic of Belarus in 1981 to 2001].

    PubMed

    Razvodovskiĭ, Iu E

    2006-01-01

    The fact that there is an association of alcohol abuse with pulmonary tuberculosis is well documented. The effect of alcohol sales per capita on tuberculosis mortality rates is considerably less known. The aim of the study was to evaluate the beverage-specific effect of alcohol on pulmonary tuberculosis mortality rates. Trends in pulmonary tuberculosis mortality rates in Belarus from 1981 to 2001 were analyzed in relation to those in the level of sales of various alcoholic beverages per capita, by applying the time series analysis. The analysis demonstrated a positive and statistically significant effect of changes in per capita alcohol sale levels on pulmonary tuberculosis mortality rates. It suggests that a 1% increase in alcohol sales per capita might cause 0.49 and 0.36% increases in pulmonary tuberculosis mortality rates in males and females, respectively. This study also indicates that tuberculosis prevention programs should place more emphasis on alcohol problems.

  12. Immunophenotypical characterization of the lymphocyte infiltrate in caprine pulmonary tuberculosis.

    PubMed

    Seva, J; Hernández, D; Bernabé, A; Pallarés, F J; Navarro, J A

    2000-01-01

    A study was made of the immunophenotype of the lymphocytes associated with natural caprine pulmonary tuberculosis at four stages of the disease. Regardless of the stage, CD4(+)and CD8(+)T lymphocytes predominated in lung and mediastinal lymph node lesions, but gamma/delta T and B (IgM(+)) cells were seen only rarely. At the primary complex stage, CD4(+)cells outnumbered CD8(+)cells. At the stage of generalized tuberculosis, however, and still more at the post-primary stage, CD8(+)cells outnumbered CD4(+)cells. At the final stage (tuberculous pneumonia), CD4(+)and CD8(+)cells were present in low but approximately equal numbers.

  13. Immunological aspects of pulmonary tuberculosis in children.

    PubMed

    Lagrange, P H; Wargnier, A

    1995-01-01

    In recent years new information has been collected about the immunological responses to pathogenic mycobacteria. More information on cellular and molecular responses of cells in murine and human tuberculosis has been produced and T cells' role in the production of selected cytokines has been clarified. Studies in mice have provided insight into the phases of the T cell response to virulent M. tuberculosis, the role of various T cell subsets, and the repertoire of antigens recognized by these cells. However, despite this new information, some of which has been confirmed in humans, large gaps remain in our knowledge about the immune response to this infection, particularly concerning cellular or molecular mechanisms involved in acquired protection. Even if some extrapolations from adult data can be made, large gaps in our knowledge exist on the potential immune defects in young infants who are prone to develop tuberculosis soon after infection.

  14. Outbreak of pulmonary tuberculosis in children.

    PubMed

    Bosley, A R; George, G; George, M

    1986-05-17

    A case of miliary tuberculosis in a 4-year-old child led to contact tracing, revealing 32 children with evidence of tuberculous infection. 3 adult cases were also identified. The source case was a mother who passed on the infection at two Christmas parties. Limited exposure to the organism caused infection, suggesting a virulent strain and a susceptible subgroup. A range of complications of primary tuberculosis in children was seen. Minor side-effects of the chemotherapeutic agents occurred in most children but only 3 suffered substantial toxic effects. The limited range of agents marketed in a presentation suitable for young children was a serious difficulty.

  15. 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

  16. Pulmonary mucormycosis mimicking as pulmonary tuberculosis: a case report.

    PubMed

    Garg, Rajiv; Marak, Rungmei Sk; Verma, Sanjay Kumar; Singh, Jagdeep; Sanjay; Prasad, Rajendra

    2008-07-01

    Pulmonary Mucormycosis is an uncommon disease caused by fungi of class Zygomycetes. It occurs predminantly in an immunodeficient host most common risk factor being diabetes mellitus. The lesions are localized in the lungs or the mediastinum. We are reporting a case of 70 years old male, having cough, haemoptysis, fever and chest pain. He was on antituberculosis treatment (RHEZ) for last 10 days and was later found to have Pulmonary Mucormycosis on further evaluation.

  17. 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

  18. 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

  19. [Progress in management of severe tuberculosis or tuberculosis with severe complication].

    PubMed

    Kimura, Hiroshi; Imaizumi, Kazuyoshi

    2014-05-01

    The management and therapy of miliary tuberculosis: Nobuharu OHSHIMA (Asthma and Allergy Center, National Hospital Organization Tokyo National Hospital). Treatment and management of severe pulmonary tuberculosis: Yuta HAYASHI, Kenji OGAWA (Department of Respiratory Medicine, National Hospital Organization Higashi Nagoya National Hospital). Death of a young (non-elderly) patient may become a large psychological burden not only for patient's family but also for medical staff. We analyzed non-elderly cases with severe pulmonary tuberculosis by comparing 13 patients who died of tuberculosis in the hospital (death group) and 31 patients who survived and were discharged from hospital (survivor group). The mean age was older and there were more patients who were out of employment in the death group compared to the survivor group. Among the factors related to the general condition evaluated on the admission, disturbance of consciousness, respiratory insufficiency, impairment in the ADL, poor dietary intake, and decubitus ulcer were more observed in the death group. Chest X-ray finding was not a predictive factor of poor prognosis. Among the laboratory findings, the numbers of peripheral blood lymphocytes, red blood cells, and thrombocytes significantly decreased in the death group. Serum level of total cholesterol, cholinesterase, and albumin were also significantly lower in the death group, indicating that malnutrition was related to the death of severe tuberculosis. Further studies are needed to establish the optimal nutritional management and evaluate the effectiveness of adjunctive use of steroid for severe tuberculosis patients. Invasive fungal infection complicated with pulmonary tuberculosis: Akira WATANABE, Katsuhiko KAMEI (Division of Clinical Research, Medical Mycology Research Center, Chiba University). Among the invasive mycoses, chronic pulmonary aspergillosis (CPA) is the most frequent disease as a sequel to pulmonary tuberculosis. However, identifying CPA

  20. Rifampin-containing chemotherapy for pulmonary tuberculosis associated with coal workers' pneumoconiosis

    SciTech Connect

    Jones, F.L. Jr.

    1982-06-01

    The outcomes of 20 anthracite miners with coal workers' pneumoconiosis and culture-proved pulmonary tuberculosis treated with rifampin-containing chemotherapeutic regimens were determined by a retrospective review. Their mean age was 65 yr, and the duration of underground dust exposure averaged 27 yr. Nine miners had simple pneumoconiosis, 11 had progressive massive fibrosis, and 13 had cavitary disease; 3 also had extrapulmonary disease. All patients were given rifampin (mean, 12 months in survivors) plus one or more other effective agents; the mean duration of treatment with 2 or more drugs was 17 months. Follow-up averaged 46 months in those surviving more than 1 yr. Sputum cultures became negative and remained so within 3 months in 17 patients and within 5 months in the remainder. Eighteen patients survived more than 1 yr after completing chemotherapy. No clinical, radiologic, or bacteriologic relapses were observed during follow-up, but 5 patients died of nontuberculous causes. These results are superior to those reported previously in patients with coal workers' pneumoconiosis treated for pulmonary tuberculosis with regimens not containing rifampin. They suggest that treatment of tuberculosis in coal workers, even in the presence of progressive massive fibrosis and cavitary disease, can yield results as favorable as in nonpneumoconiotic patients provided the initial treatment regimen includes rifampin plus one or more other effective agents.

  1. 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

  2. Assessment of Hematological Parameters in Pulmonary Tuberculosis Patients.

    PubMed

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

    2016-07-01

    The aim of the study was the assessment of hematological parameters in pulmonary tuberculosis patients. Forty patients diagnosed with tuberculosis were recruited from the Institute of Thoracic Medicine on the basis of history, clinical examination, chest radiography, sputum examination and related laboratory parameters and were compared with age and sex matched healthy volunteers (n = 40). Hematological parameters and CRP in tuberculosis patients were determined. The mean values for serum hemoglobin level, RBC count and platelet count in PTB was found to be less (p < 0.001). Erythrocyte sedimentation rate (ESR), plasma C-reactive protein, WBC count in PTB subjects was increased (p < 0.001 for ESR & CRP, p < 0.05 for WBCs) and all were statistically significant. This study demonstrated that serum hemoglobin level, RBC count and platelet count was decreased in tuberculosis patients whereas ESR, CRP and WBC count was increased when compared with healthy controls. PMID:27382206

  3. Genetic diversity and dynamic distribution of Mycobacterium tuberculosis isolates causing pulmonary and extrapulmonary tuberculosis in Thailand.

    PubMed

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

    2014-12-01

    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.

  4. [Factors affecting the treatment results with pulmonary tuberculosis patients].

    PubMed

    Berezovskiĭ, B A; Salobaĭ, R Iu; Marchak, V V; Popova, I I; Zakopaĭlo, G G; Kucher, V A; Vasylyk, V U; Mikheĭ, L V

    1991-12-01

    A study is presented of the effect of social factors on the outcomes of pulmonary tuberculosis in patients with freshly detected disease mainly in rural localities in 1985-1989. The outcomes of treatment depended mainly on the form and extension of the pathological process and terms of treatment. It was also established that the outcomes of tuberculosis are also influenced by unfavourable social factors which are more pronounced in persons with an extensive process. Treatment results were better in women with higher education than in similarly educator men. Among agricultural workers treatment efficacy was worse than among office workers and housewives. Life in the family effects more favourably treatment results than single life. Treatment results were worse in those living in unsatisfactory conditions, engaged in hard physical work, suffering of concomitant diseases and bad habits.

  5. Pulmonary langerhans cell histiocytosis masquerading as tuberculosis in an infant.

    PubMed

    Senanayake, M P; Mettananda, S; De Silva, M V C

    2011-01-01

    A 4-month-old infant presented with continued fever, unresolving bronchopneumonia and household contact with sputum-smear-positive tuberculosis (TB) and showed marginal improvement on anti-TB chemotherapy. Recurrent pneumothorax prompted the clinical diagnosis of TB to be revised. High-resolution CT scan of the chest and open lung biopsy confirmed the diagnosis of pulmonary Langerhans cell histiocytosis. Treatment with prednisolone and vinblastin resulted in settling of fever and resolution of respiratory symptoms and signs. In communities where the prevalence of TB is high, unusual presentations should prompt consideration of alternative diagnoses. PMID:22041471

  6. Breath tests in diagnosis of pulmonary tuberculosis.

    PubMed

    Cheepsattayakorn, Attapon; Cheepsattayakorn, Ruangrong

    2014-01-01

    Since the time of Hippocrates, physicians have known that the odour of human breath can provide clues to diagnosis. In the past, hydrogen peroxide which is a marker of inflammatory diseases and oxidative stress was the most studied substance in the exhaled breath which was detectable in the liquid that obtained by condensing or cooling. The advantages of breath analysis are that it is convenient, non-invasive, and could be performed with children as well as mechanically ventilated patients. Today, exhaled nitric oxide has been studied extensively, especially in relation to asthma. More than a thousand different volatile organic compounds have been observed in low concentrations in normal human breath. Alkanes and methylalkanes have been increasingly used by physicians as a novel method to diagnose many diseases without discomforts of invasive procedures. Although the limitations of measurement of exhaled nitric oxide in direct diagnosis of infectious pulmonary TB, it may have potential development as a cost-effective replacement of chest radiological examination in screening algorithms. None of the individual exhaled volatile organic compound alone is specific for disease. Exhaled breath analysis techniques may be available to diagnose and monitor the diseases in home setting when their sensitivity and specificity are expected to improve in the future. Here, we also discussed some patents related to the topic. PMID:25185981

  7. 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

  8. 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

  9. Impairments of Antigen-Presenting Cells in Pulmonary Tuberculosis.

    PubMed

    Sakhno, Ludmila V; Shevela, Ekaterina Ya; Tikhonova, Marina A; Nikonov, Sergey D; Ostanin, Alexandr A; Chernykh, Elena R

    2015-01-01

    The phenotype and functional properties of antigen-presenting cells (APC), that is, circulating monocytes and generated in vitro macrophages and dendritic cells, were investigated in the patients with pulmonary tuberculosis (TB) differing in lymphocyte reactivity to M. tuberculosis antigens (PPD-reactive versus PPD-anergic patients). We revealed the distinct impairments in patient APC functions. For example, the monocyte dysfunctions were displayed by low CD86 and HLA-DR expression, 2-fold increase in CD14(+)CD16(+) expression, the high numbers of IL-10-producing cells, and enhanced IL-10 and IL-6 production upon LPS-stimulation. The macrophages which were in vitro generated from peripheral blood monocytes under GM-CSF were characterized by Th1/Th2-balance shifting (downproduction of IFN-γ coupled with upproduction of IL-10) and by reducing of allostimulatory activity in mixed lymphocyte culture. The dendritic cells (generated in vitro from peripheral blood monocytes upon GM-CSF + IFN-α) were characterized by impaired maturation/activation, a lower level of IFN-γ production in conjunction with an enhanced capacity to produce IL-10 and IL-6, and a profound reduction of allostimulatory activity. The APC dysfunctions were found to be most prominent in PPD-anergic patients. The possible role of APC impairments in reducing the antigen-specific T-cell response to M. tuberculosis was discussed. PMID:26339660

  10. Case-finding for pulmonary tuberculosis in Penang.

    PubMed

    Hooi, L N

    1994-09-01

    The process of case-finding was studied in 100 consecutive patients with pulmonary tuberculosis treated by the Chest Clinic, Penang Hospital. The median time from the onset of the illness until the initial medical consultation was two weeks (patient's delay). This delay was longer in males, patients with lower than secondary education and drug abusers. Only 47% of patients were put on treatment with a correct diagnosis within one month of the first consultation (doctor's delay). Almost all patients had at least one symptom suggestive of tuberculosis at presentation and the mean number of consultations before diagnosis was three. Patients who first visited government medical facilities had shorter doctor's delay than those who first saw private practitioners, and patients who first consulted a private practitioner were the least likely to be appropriately investigated by sputum examination and chest radiography. The median total delay was three months and at the time of diagnosis, 95% of patients had moderate or far advanced disease radiologically. In order to shorten doctor's delay, all medical practitioners, especially those in the private sector, should be made aware of the importance of early diagnosis and the proper management of tuberculosis. Health education campaigns for the public should also be undertaken to shorten patient's delay.

  11. Vaccine development for tuberculosis: current progress.

    PubMed

    Orme, Ian M

    2013-07-01

    Very substantial efforts have been made over the past decade or more to develop vaccines against tuberculosis. Historically, this began with a view to replace the current vaccine, Bacillus Calmette Guérin (BCG), but more recently most candidates are either new forms of this bacillus, or are designed to boost immunity in children given BCG as infants. Good progress is being made, but very few have, as yet, progressed into clinical trials. The leading candidate has advanced to phase IIb efficacy testing, with disappointing results. This article discusses the various types of vaccines, including those designed to be used in a prophylactic setting, either alone or BCG-boosting, true therapeutic (post-exposure) vaccines, and therapeutic vaccines designed to augment chemotherapy. While there is no doubt that progress is still being made, we have a growing awareness of the limitations of our animal model screening processes, further amplified by the fact that we still do not have a clear picture of the immunological responses involved, and the precise type of long-lived immunity that effective new vaccines will need to induce.

  12. Vaccine development for tuberculosis: current progress

    PubMed Central

    Orme, Ian M.

    2013-01-01

    Very substantial efforts have been made over the past decade or more to develop vaccines against tuberculosis. Historically, this began with a view to replace the current vaccine, BCG, but more recently most candidates are either new forms of this bacillus, or are designed to boost immunity in children given BCG as infants. Good progress is being made, but very few have as yet progressed into clinical trials. The leading candidate has advanced to Phase IIb efficacy testing, with disappointing results. This article discusses the various types of vaccines, including those designed to be used in a prophylactic setting, either alone or BCG-boosting, true therapeutic [post-exposure] vaccines, and therapeutic vaccines designed to augment chemotherapy. While there is no doubt that progress is still being made, we have a growing awareness of the limitations of our animal model screening processes, further amplified by the fact that we still do not have a clear picture of the immunological responses involved, and the precise type of long lived immunity we will need effective new vaccines to induce. PMID:23794129

  13. 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

  14. Surgical treatment of complications of pulmonary tuberculosis, including drug-resistant tuberculosis.

    PubMed

    Madansein, Rajhmun; Parida, Shreemanta; Padayatchi, Nesri; Singh, Nalini; Master, Iqbal; Naidu, Kantharuben; Zumla, Alimuddin; Maeurer, Markus

    2015-03-01

    Surgery for drug-resistant tuberculosis has been shown to be safe and effective, with similar level of mortalities associated with surgical intervention observed with that for lung cancer. While surgery has been an option to treat TB in the pre-antibiotic era, it is now increasingly used to treat complications of pulmonary TB, particularly in patients with drug-resistant TB who do not respond to medical treatment. The two most frequent indications for lung resection in drug- resistant TB, are i) failed medical treatment with persistent sputum positivity or ii) patients who have had medical treatment and are sputum negative, but with persistent localized cavitary disease or bronchiectasis. Massive hemoptysis is a potentially life-threatening complication of TB. Lung resection is potentially curative in patients with massive hemoptysis and cavitary or bronchiectatic disease. Bronchial artery embolization in these patients has a high success rate but bears also the risk of recurrence. Lung resection can be safely undertaken in selected patients with HIV co-infection and pulmonary complications of TB. Ambulatory drainage is a novel, safe, affordable and effective method of draining a chronic TB associated empyema thoracis. We review here the current surgical treatment of the complications of pulmonary TB and discuss the experience from the Durban Cardiothoracic Surgery Unit for the surgical treatment of patients with complicated pulmonary TB. PMID:25809758

  15. [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.

  16. Blood transcriptomic diagnosis of pulmonary and extrapulmonary tuberculosis

    PubMed Central

    Roe, Jennifer K; Thomas, Niclas; Gil, Eliza; Best, Katharine; Tsaliki, Evdokia; Morris‑Jones, Stephen; Stafford, Sian; Simpson, Nandi; Witt, Karolina D; Chain, Benjamin; Miller, Robert F; Martineau, Adrian

    2016-01-01

    BACKGROUND. Novel rapid diagnostics for active tuberculosis (TB) are required to overcome the time delays and inadequate sensitivity of current microbiological tests that are critically dependent on sampling the site of disease. Multiparametric blood transcriptomic signatures of TB have been described as potential diagnostic tests. We sought to identify the best transcript candidates as host biomarkers for active TB, extend the evaluation of their specificity by comparison with other infectious diseases, and to test their performance in both pulmonary and extrapulmonary TB. METHODS. Support vector machine learning, combined with feature selection, was applied to new and previously published blood transcriptional profiles in order to identify the minimal TB‑specific transcriptional signature shared by multiple patient cohorts including pulmonary and extrapulmonary TB, and individuals with and without HIV-1 coinfection. RESULTS. We identified and validated elevated blood basic leucine zipper transcription factor 2 (BATF2) transcript levels as a single sensitive biomarker that discriminated active pulmonary and extrapulmonary TB from healthy individuals, with receiver operating characteristic (ROC) area under the curve (AUC) scores of 0.93 to 0.99 in multiple cohorts of HIV-1–negative individuals, and 0.85 in HIV-1–infected individuals. In addition, we identified and validated a potentially novel 4-gene signature comprising CD177, haptoglobin, immunoglobin J chain, and galectin 10 that discriminated active pulmonary and extrapulmonary TB from other febrile infections, giving ROC AUCs of 0.94 to 1. CONCLUSIONS. Elevated blood BATF2 transcript levels provide a sensitive biomarker that discriminates active TB from healthy individuals, and a potentially novel 4-gene transcriptional signature differentiates between active TB and other infectious diseases in individuals presenting with fever. FUNDING. MRC, Wellcome Trust, Rosetrees Trust, British Lung Foundation, NIHR

  17. Particulate air pollution and susceptibility to the development of pulmonary tuberculosis disease in North Carolina: an ecological study

    PubMed Central

    Schoenbach, Victor J.; Richardson, David B.; Gammon, Marilie D.

    2015-01-01

    Although Mycobacterium tuberculosis is the causative agent of pulmonary tuberculosis (PTB), environmental factors may influence disease progression. Ecologic studies conducted in countries outside the USA with high levels of air pollution and PTB have suggested a link between active disease and ambient air pollution. The present investigation is the first to examine the ambient air pollution/PTB association in a country, where air pollution levels are comparatively lower. We used Poisson regression models to examine the association of outdoor air pollutants, PM10 and PM2.5 with rates of PTB in North Carolina residents during 1993–2007. Results suggest a potential association between long-term exposure to particulate matter (PM) and PTB disease. In view of the high levels of air pollution and high rates of PTB worldwide, a potential association between ambient air pollution and tuberculosis warrants further study. PMID:24387197

  18. Particulate air pollution and susceptibility to the development of pulmonary tuberculosis disease in North Carolina: an ecological study.

    PubMed

    Smith, Genee S; Schoenbach, Victor J; Richardson, David B; Gammon, Marilie D

    2014-04-01

    Although Mycobacterium tuberculosis is the causative agent of pulmonary tuberculosis (PTB), environmental factors may influence disease progression. Ecologic studies conducted in countries outside the USA with high levels of air pollution and PTB have suggested a link between active disease and ambient air pollution. The present investigation is the first to examine the ambient air pollution-PTB association in a country, where air pollution levels are comparatively lower. We used Poisson regression models to examine the association of outdoor air pollutants, PM10 and PM2.5 with rates of PTB in North Carolina residents during 1993-2007. Results suggest a potential association between long-term exposure to particulate matter (PM) and PTB disease. In view of the high levels of air pollution and high rates of PTB worldwide, a potential association between ambient air pollution and tuberculosis warrants further study.

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. T Cell Functional Disturbances in Patients with Pulmonary Tuberculosis.

    PubMed

    Ostanin, Alexander A.; Khonina, Nataliya A.; Norkin, Maxim N.; Leplina, Olga Yu.; Nikonov, Sergey D.; Ogirenko, Anatoly P.; Chernykh, Helen R.

    2000-04-01

    The investigations of 38 patients with pulmonary tuberculosis (PT) revealed combined T cell and monocyte functional disturbances. Indeed, the percentages of CD4(+) and CD8(+) T lymphocytes, proliferative response and IL-2 production, as well as the percentages of HLA DR(+) monocytes and IL-1beta production were significantly decreased in PT patients as compared with normal individuals. Herewith the absolute T lymphocyte number did not undergo the pronounced changes. The decrease of T cell proliferative response was not mediated through immunosuppressive action of monocytes or T lymphocytes since removing of "adherent" cells from patient's peripheral blood mononuclear cells (PBMC) or pretreatment of PBMC with indomethacin and cyclophosphan failed to recover mitogenic reactivity in vitro. The patient's sera also did not significantly influence on PBMC proliferation. The decrease of IL-2 production and the stimulation of T cell proliferative response via TcR-CD3 complex, i.e. through the classic pathway of activation, indicated the anergy of T lymphocyte in tuberculosis patients. Furthermore, T lymphocytes were characterized by enhanced apoptosis. It should be noted, that patient's sera (especially in the patients with an initially high apoptosis) promoted significant anti-apoptotic activity. It is likely that this mechanism may be an explanation, why absolute T lymphopenia is absent during tuberculosis infection. Our findings suggest, that T lymphocyte dysfunctions in patients with PT are caused by impairments of T cell activation process, which lead to predominance of "negative" response (induction anergy, apoptosis) and to a lesser degree connected with direct suppressive mechanisms mediated by monocytes, T lymphocytes or serum factors.

  5. 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

  6. Microscopic examination and smear negative pulmonary tuberculosis in Ethiopia

    PubMed Central

    Keflie, Tibebe Seyoum; Ameni, Gobena

    2014-01-01

    Introduction Tuberculosis causes illness among millions of people each year and ranks as the second leading cause of death from infectious disease worldwide. The aim of this study was to investigate the detection rate of microscopic examination and estimate risk of transmission of TB by smear negative pulmonary TB patients. Methods A cross-sectional study and retrospective data analysis on TB were undertaken in Northwest Shewa, Ethiopia. Microscopic examination, bacterial culture and PCR were performed. The statistical analysis was made by using STATA software version 10. Results A total of 92 suspected TB cases was included in the study. Of these, 27.17% (25/92) were positive for microscopic examination and 51% (47/92) for culture. The sensitivity and specificity of microscopic examination with 95% CI were 48.94% (34.08% to 63.93%) and 95.56% (84.82 to 99.33%), respectively. The positive and negative predictive values were 92% (73.93% to 98.78%) and 64.18% (51.53% to 75.53%), respectively. Of 8150 pulmonary TB cases in the retrospective study, 58.9% was smear negative. The proportion of TB-HIV co-infection was 28.66% (96/335). Conclusion The sensitivity of microscopic examination was 48.94% which was very low. The poor sensitivity of this test together with the advent of HIV/AIDS elevated the prevalence of smear negative pulmonary TB. This in turn increased the risk of TB transmission. PMID:25810798

  7. 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

  8. A case of multifocal lupus vulgaris that preceded pulmonary tuberculosis in an immune compromised patient.

    PubMed

    Hamada, Manabu; Urabe, Kazunori; Moroi, Yoichi; Koga, Tetsuya; Takeishi, Masaaki; Fujita, Masaki; Nakanishi, Yoichi; Furue, Masutaka

    2004-02-01

    We describe the rare case of a Japanese male with multifocal lupus vulgaris that preceded asymptomatic pulmonary tuberculosis and adult T-cell leukemia/lymphoma (ATL). He visited our hospital with multiple reddish plaques and erythema of 4-12 months duration. A skin biopsy revealed non-caseating epithelioid granulomas. Mycobacterium tuberculosis was detected by polymerase chain reaction (PCR)-hybridization from a skin biopsy specimen and was also isolated from a culture of the skin biopsy sample. The result of chest roentogenography was compatible with pulmonary tuberculosis. In addition, the diagnosis of ATL was based upon the presence of atypical lymphocytes with convoluted nuclei in his peripheral blood and a positive anti-ATL antibody reaction. Cases of cutaneous tuberculosis presenting with unusual clinical features may be on the increase, accompanying the spread of tuberculosis in immunosuppressed patients, including those with ATL and acquired immunodeficiency syndrome (AIDS).

  9. The role of prostaglandin E2 in the immunopathogenesis of experimental pulmonary tuberculosis

    PubMed Central

    Moreno, Javier Rangel; García, Iris Estrada; de la Luz García Hernández, María; Leon, Diana Aguilar; Marquez, Ricardo; Pando, Rogelio Hernández

    2002-01-01

    Prostaglandins (PG) are potent mediators of intercellular communication, and PGE2 at high concentration is immunosuppressive for T-cell-mediated immunity. We studied the kinetics of PGE2 production and the expression of the enzymes related to its synthesis during the course of experimental pulmonary tuberculosis. Secondly, we analysed the pathological and immunological changes produced by the pharmacological suppression of PG production. In BALB/c mice infected via the trachea with Mycobacterium tuberculosis H37Rv there is an initial phase of partial resistance, dominated by type 1 cytokines plus tumour necrosis factor-α (TNF-α) and expression of the inducible form of nitric oxide synthase (iNOS), followed by a phase of progressive disease. During the early phase of the infection some activated macrophages located in the alveolar-capillary interstitium and in granulomas showed strong PGE2 immunostaining. However, PGE2 concentrations were relatively low and stable. Animals in this early phase of infection were treated with niflumic acid, a potent and specific blocker of cyclo-oxygenase 2, the rate-limiting enzyme of PG production. In comparison with control animals, the suppression of PG synthesis produced higher inflammation and expression of TNF-α, interleukin-1α and interferon-γ (IFN-γ), but almost complete disappearance of iNOS expression, which coexisted with a significant increment of bacterial load. The late progressive phase in this experimental model is characterized by progressive pneumonia, small granulomas and diminished expression of IFN-γ, TNF-α and iNOS in coexistence with high expression of IL-4. Strong PGE2 immunostaining was seen in foamy macrophages localized in the pneumonic areas, and the PGE2 concentration was four-fold higher in this late phase of infection than during the early phase. When PG production was suppressed in animals suffering advanced phase infection, a significant reduction of pneumonia and bacillus load with striking

  10. 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

  11. Use of PCR in routine diagnosis of treated and untreated pulmonary tuberculosis.

    PubMed Central

    Yuen, K Y; Chan, K S; Chan, C M; Ho, B S; Dai, L K; Chau, P Y; Ng, M H

    1993-01-01

    AIMS--To assess the routine use of a polymerase chain reaction (PCR) assay for the direct detection of Mycobacterium tuberculosis in expectorated sputum specimens. METHODS--A pair of primers (20-mer) were designed to amplify the 38 kilodalton protein of M tuberculosis. The specificity of the assay was evaluated in 31 M tuberculosis strains, 15 atypical mycobacterium species, and several commensal bacteria of the upper respiratory tract. The assay was subsequently applied to 519 sputum specimens from 85 inpatients of a chest hospital in Hong Kong. RESULTS--An amplified product of 239 base pairs was found in all M tuberculosis strains, standard strains of M bovis, and M africanum but not in the other bacterial strains tested. For the 51 patients with pulmonary radiographic lesions, the diagnosis of pulmonary tuberculosis was subsequently confirmed by both culture and PCR in 41 of them. Five patients who were treated before admission were positive by PCR alone. All but one patient in the control group (patients with acute exacerbation of chronic obstructive airway diseases) or those with atypical mycobacterial diseases were PCR negative. The PCR remained positive after four weeks of anti-tuberculosis treatment in 29 patients, 16 of whom had become culture negative. CONCLUSION--This PCR assay is a useful technique for the diagnosis of untreated and recently treated cases of pulmonary tuberculosis. Images PMID:8496388

  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. Hyponatremia Due to Pulmonary Tuberculosis: Review of 200 Cases

    PubMed Central

    Jonaidi Jafari, Nematollah; Izadi, Morteza; Sarrafzadeh, Farhad; Heidari, Amir; Ranjbar, Reza; Saburi, Amin

    2012-01-01

    Background Pulmonary Tuberculosis (PTB) is one of the common diseases with high prevalence of mortality and morbidity in developing countries. Various complications have been reported along with PTB. The subclinical electrolyte imbalances are customary in cases with PTB. Objectives The aim of this study was the evaluation of patients with PTB and hyponatremia. Patients and Methods We evaluated patients with diagnosis of secondary PTB who have been admitted to Baqiyatallah hospital, Tehran, Iran from 2005 till 2010. The diagnosis of PTB was based on the appearance of acid fast bacilli in sputum smears or sputum cultures, without any evidence of miliary TB. Demographic and laboratory characteristics relative to electrolytes were recorded according inclusion and exclusion criteria. Results The mean age was 59.22 ± 20.57 years and 91 (45.5%) patients were male. The mean serum sodium concentration was 134.54 ± 4.95 mmol/L and more than half of subjects (51%) have shown hyponatremia. The mean age difference between hyponatremic and eunatremic groups was statistically significant (61.95 versus 56.02 years) (P = 0.047). No significant relationship was found between hyponatremia and gender, anti-TB medications and co-morbidity conditions. Conclusions In this study, an older age was suggested as an important predisposing factor for hyponatremia in patients with PTB which had been observed as less of a determinant. We recommend further evaluations for hyponatremia in patients presenting with PTB, particularly for those who are older. PMID:23577332

  14. Immunophenotyping of macrophages in human pulmonary tuberculosis and sarcoidosis

    PubMed Central

    Stanton, Lee-Anne; Fenhalls, Gael; Lucas, Andrew; Gough, Peter; Greaves, David R; Mahoney, James A; Helden, Paul Van; Gordon, Siamon

    2003-01-01

    Classic studies of tuberculosis (TB) revealed morphologic evidence of considerable heterogeneity of macrophages (MØs), but the functional significance of this heterogeneity remains unknown. We have used newly available specific antibodies for selected membrane and secretory molecules to examine the phenotype of MØs in situ in a range of South African patients with TB, compared with sarcoidosis. Patients were human immunodeficiency virus-negative adults and children, and the examined biopsy specimens included lung and lymph nodes. Mature pulmonary MØs (alveolar, interstitial, epithelioid and multinucleated giant cells) selectively expressed scavenger receptor type A and a novel carboxypeptidase-like antigen called carboxypeptidase-related vitellogenin-like MØ molecule (CPVL). CPVL did not display enhanced expression in sarcoidosis, vs. TB patients, as observed with angiotensin-converting enzyme (ACE), a related molecule. Immunocytochemical studies with surfactant proteins (SP)-A and -D showed that type II alveolar cells expressed these collectins, as did MØs, possibly after binding of secreted proteins. Studies with an antibody specific for the C-terminus of fractalkine, a tethered CX3C chemokine, confirmed synthesis of this molecule by bronchiolar epithelial cells and occasional endothelial cells. These studies provide new marker antigens and extend previous studies on MØ differentiation, activation and local interactions in chronic human granulomatous inflammation in the lung. PMID:14748748

  15. 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

  16. 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

  17. [Role of computerized tomography in the diagnosis of cirrhotic pulmonary tuberculosis].

    PubMed

    Lazareva, Ia V

    1999-01-01

    Computed tomography (CT) revealed cirrhotic tuberculosis in 52 patients. In most patients, cirrhosis resulted from infiltrative and fibrocavernous tuberculosis, less frequently from tuberculous bronchoadenitis, disseminated and focal tuberculosis, caseous pneumonia. Segmental cirrhosis was present in 15 patients, multisegmental and lobar cirrhosis in 19, and bilateral lung cirrhosis in 2. In 8 patients, pulmonary cirrhosis was accompanied by tuberculous empyema; in 8 more patients lobar cirrhosis was the metatuberculous syndrome of fibrocavernous tuberculosis. Evaluation of the diagnostic potentialities of CT in cirrhotic pulmonary tuberculosis revealed that the major CT semiotics of this clinical type was identical to the basic skialogic signs of routine X-ray study. However, unlike the latter that assesses mainly indirect X-ray signs of the cirrhotic transformation of lung tissue, such as reduced lung volumes, chest deformity, CT objectively detects morphological changes in cirrhosis, the presence and magnitude of specific and metatuberculous changes, interprets clinical and X-ray variants of this form of tuberculosis and its related pulmonary vascular alterations.

  18. 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

  19. Diagnosis of Pulmonary Tuberculosis in Children: Assessment of the 2012 National Institutes of Health Expert Consensus Criteria

    PubMed Central

    Zar, Heather J.; Workman, Lesley J.; Little, Francesca; Nicol, Mark P.

    2015-01-01

    Background. The 2012 National Institutes of Health (NIH) consensus criteria for standardized diagnostic categories of pulmonary tuberculosis in children have not been validated. We aimed to assess the NIH diagnostic criteria in children with culture-confirmed pulmonary tuberculosis and those in whom tuberculosis has been excluded. Methods. We performed a retrospective analysis of consecutive children hospitalized with suspected pulmonary tuberculosis in Cape Town, South Africa, who were enrolled in a diagnostic study. Children were categorized as definite tuberculosis (culture positive), probable tuberculosis (chest radiograph consistent), possible tuberculosis (chest radiograph inconsistent), or not tuberculosis (improved without tuberculosis treatment). We applied the NIH diagnostic categories to the cohort and evaluated their performance specifically in children with definite tuberculosis and not tuberculosis. Results. Four hundred sixty-four children (median age, 25.1 months [interquartile range, 13.5–61.5 months]) were included; 96 (20.7%) were HIV infected. Of these, 165 (35.6%) were definite tuberculosis, and 299 (64.4%) were not tuberculosis. If strict NIH symptom criteria were applied, 100 (21.6%) were unclassifiable including 21 (21.0%) with definite pulmonary tuberculosis, as they did not meet the NIH criteria due to short duration of symptoms; 71 (71%) had cough <14 days, 48 (48%) had recent weight loss, and 39 (39%) had fever <7 days. Of 364 classifiable children, there was moderate agreement (κ = 0.48) with 100% agreement for definite tuberculosis and moderate agreement for not tuberculosis (220 [60.4%] vs 89 [24.5%]). Conclusions. Entry criteria for diagnostic studies should not be restrictive. Data from this analysis have informed revision of the NIH definitions. PMID:26409280

  20. Comparison of bronchial brushing and sputum in detection of pediatric pulmonary tuberculosis.

    PubMed

    Chen, Qiao-Pei; Ren, Shi-Feng; Wang, Xin-Feng; Wang, Mao-Shui

    2016-01-27

    The retrospective study aimed to evaluate the diagnostic value of bronchial brushing and sputum using acid fast bacilli smear, mycobacterial culture and real-time PCR in detection of pediatric pulmonary tuberculosis, sensitivity and specificity of bronchial brushing and sputum examined by the three methods were calculated and compared to each other. Data showed there were no significant difference in sensitivity between bronchial brushing and matched sputum using each method. But the specificity of real-time PCR on bronchial brushing was lower than on sputum. Compared with bronchial brushing, sputum was better specimen in detection of pediatric pulmonary tuberculosis.

  1. [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

  2. 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

  3. The association of some genetic factors with pulmonary tuberculosis in Georgian and Azeri ethno groups.

    PubMed

    Khukhunaishvili, R; Tskvitinidze, S; Nagervadze, M; Akhvlediani, L; Koridze, M

    2014-06-01

    Pulmonary Tuberculosis (TB) is still one of the major public health problems. Over the last half decade the significant problem is an increased ratio of drug-resistant TB cases. TB is as well the most significant infectious disease in the country of Georgia. Pulmonary tuberculosis is assessed as a complex infectious disease affected by both, environmental and genetic factors. Present study was undertaken to find out the correlation between pulmonary tuberculosis and erythrocyte blood groups antigens determinant alleles (ABO - r, p, q; Rh D+, Rh D- and MN - p, q) in two different, Georgian and Azeri, ethno groups. Immune-serological methods, direct reaction of universal monoclonal antibodies were used. Materials processed by biostatistician methods. The study had shown different correlation of pulmonary tuberculosis to erythrocyte blood groups determinant alleles in Georgian and Azeri ethno groups. In Georgian ethno group pulmonary TB correlates with ABO-r and p, Rh-D,+' and MN-p alleles, whether ABO-q, Rh-D,-' and MN-p in Azeri ethno group. PMID:25020171

  4. 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

  5. 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

  6. 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

  7. [Clinical diagnosis of HIV infection in patients with acute surgical diseases of the abdominal cavity organs and pulmonary tuberculosis].

    PubMed

    Nguen, V Kh; Stroganov, P V; Geshelin, S A

    2011-09-01

    The results of treatment of 81 patients, suffering tuberculosis and operated in emergency for an acute surgical diseases of the abdominal cavity organs, are adduced, in 29 of them--nonspecific diseases of nontuberculosis genesis were diagnosed. In 52 patients the indication for emergency operation performance were complications of abdominal tuberculosis (perforation of the tuberculosis ulcers of small intestine--in 37, the tuberculosis mesadenitis--in 15), of them in 34--pulmonary tuberculosis was in inactive phase, that's why the HIV presence was supposed. In 26 patients the diagnosis was confirmed, basing on serologic analysis data. The presence of intraabdominal catastrophe, caused by abdominal tuberculosis complications on inactive pulmonary tuberculosis background witnesses with 85.3% probability the HIV-infectioning of the patient.

  8. 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

  9. 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

  10. [The effect of thymogen on the state of immunity in destructive pulmonary tuberculosis].

    PubMed

    Medus, A I; Pisarevskaia, L I; Nikishina, E V

    1999-10-01

    The article shows that the immunocorrector timoguen stimulates T-cell link in patients with destructive forms of pulmonary tuberculosis, increases tolerance for ethiotropics, makes intoxication syndromes disappear and heals decomposition cavities and stops the bacteria discharge. It recommends 2 courses of timoguen immunostimulation (1% solution by 1 ml injection N 10 in 2 days for 2 and 4 mouths' treatment course).

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  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. [Use of essential oil of peppermint (Mentha piperita) in the complex treatment of patients with infiltrative pulmonary tuberculosis].

    PubMed

    Shkurupiĭ, V A; Odintsova, O A; Kazarinova, N V; Tkrachenko, K G

    2006-01-01

    The paper describes the effects of peppermint (Mentha piperita) essential oil inhaled by patients with infiltrative pulmonary tuberculosis in the penitentiary system. This procedure is shown to be most effective in infiltrative pulmonary tuberculosis in the phase of resorption of infiltrates and/or closure of decay cavities. The efficiency is determined by the rapid positive changes in a tuberculous process, which appear as a rapider regression of tuberculous inflammation, causing small residual changes. This procedure may be used to prevent recurrences and exacerbations of pulmonary tuberculosis.

  18. Relationship between human LTA4H polymorphisms and extra-pulmonary tuberculosis in an ethnic Han Chinese population in Eastern China.

    PubMed

    Yang, Jinghui; Chen, Jin; Yue, Jun; Liu, Lirong; Han, Min; Wang, Hongxiu

    2014-12-01

    Two single nucleotide polymorphisms in Leukotriene A4 hydrolase (LTA4H) gene were reported to be associated with protection from pulmonary tuberculosis in Vietnamese population. But these associations were not found in the Russians. To investigate the association of LTA4H polymorphisms with tuberculosis in a Han Chinese population in Eastern China, we genotyped 5 SNPs of LTA4H gene in 743 of pulmonary tuberculosis patients, 372 of extra-pulmonary tuberculosis patients and 888 of healthy controls individuals. The CC and TT homozygotes of rs1978331 and rs2540474 were identified to have higher rates (P < 0.01) and be risk factors in the patients with extra-pulmonary tuberculosis (OR = 1.412; 95% CI = 1.104-1.804 and(OR = 1.380; 95% CI = 1.080-1.764). However, no significant association was found between any of the SNPs and pulmonary tuberculosis. In the extra-pulmonary tuberculosis subgroups. LTA4H gene were significantly associated with tuberculous meningitis, lymph node tuberculosis, bone tuberculosis and other extra-pulmonary tuberculosis except for pleural tuberculosis. The present findings suggest that polymorphisms in the LTA4H gene may affect susceptibility to extra-pulmonary tuberculosis and change the risk of developing the disease in the Han nationality in the East China.

  19. Vitamin D deficiency in Malawian adults with pulmonary tuberculosis: risk factors and treatment outcomes

    PubMed Central

    Mwandumba, H. C.; Kamdolozi, M.; Shani, D.; Chisale, B.; Dutton, J.; Khoo, S. H.; Allain, T. J.; Davies, G. R.

    2015-01-01

    SUMMARY SETTING: Vitamin D deficiency is common in African adults with tuberculosis (TB), and may be exacerbated by the metabolic effects of anti-tuberculosis drugs and antiretroviral therapy (ART). It is unclear whether vitamin D deficiency influences response to anti-tuberculosis treatment. OBJECTIVES: To describe risk factors for baseline vitamin D deficiency in Malawian adults with pulmonary TB, assess the relationship between serum 25-hydroxy vitamin D (25[OH]D) concentration and treatment response, and evaluate whether the administration of anti-tuberculosis drugs and ART is deleterious to vitamin D status during treatment. DESIGN: A prospective longitudinal cohort study. RESULTS: The median baseline 25(OH)D concentration of the 169 patients (58% human immunodeficiency virus [HIV] infected) recruited was 57 nmol/l; 47 (28%) had vitamin D deficiency (<50 nmol/l). Baseline 25(OH)D concentrations were lower during the cold season (P < 0.001), with food insecurity (P = 0.034) or in patients who consumed alcohol (P = 0.019). No relationship between vitamin D status and anti-tuberculosis treatment response was found. 25(OH)D concentrations increased during anti-tuberculosis treatment, irrespective of HIV status or use of ART. CONCLUSIONS: Vitamin D deficiency is common among TB patients in Malawi, but this does not influence treatment response. Adverse metabolic effects of drug treatment may be compensated by the positive impact of clinical recovery preventing exacerbation of vitamin D deficiency during anti-tuberculosis treatment. PMID:26162355

  20. Progressive intraparenchymal lung nodules dissemination in a heavy smoker and seropositive rheumatoid arthritis suspected of tuberculosis relapse.

    PubMed

    Arghir, Oana Cristina; Niţu, Mimi; Trenchea, Mihaela; Ciobotaru, Camelia

    2013-01-01

    Anthony Caplan first described rheumatoid lung nodules associated with pneumoconiosis in coal-miners (Caplan, 1953). Intraparenchymal lung nodules were later described in rheumatoid arthritis (RA) patients who were never exposed to coal dust and/or without pneumoconiosis. Rheumatoid lung nodules are usually detected in unselected patients: 0.2% in chest radiography and 4% in high-resolution computed tomography (Nannini et al., 2008). Patients could be reluctant to perform surgical lung biopsy for an accurate histopathological diagnosis. We present a peculiar association between a seropositive RA and a presumptive active tuberculosis (TB) disease in a 59-year-old male patient, ex-smoker with a previously healed pulmonary TB disease. The purpose of this report is to describe an unusual case of a presumptive relapse of the nodular TB disease, which progressed to an extensive nodular bilateral dissemination under anti-tuberculosis therapy, mimicking a metastatic carcinoma. The diagnosis of rheumatoid necrobiotic lung nodules was confirmed after open biopsy left pulmonary was performed. Formalin-fixed paraffin-embedded pulmonary rheumatoid nodules were processed for histology and stained with Masson's trichrome. Central structure of the removed pulmonary nodules is typical of a rheumatoid nodule with central necrosis surrounded by a palisade of macrophages. The accumulation of anthracotic pigment was noticed inside the pulmonary nodules in a RA patient without professional exposure to coal or mineral dust. This rare entity is an appearance of the rheumatoid nodules lung syndrome and anthracosis in a heavy tobacco former smoker.

  1. 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

  2. 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

  3. 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

  4. [Use of alpha-tocopherol acetate in the treatment of hemodynamic disorders in patients with pulmonary tuberculosis].

    PubMed

    Ditiatkov, A E; Tikhonov, V A; Radzevich, A E; Zholnin, P A

    2005-01-01

    Examination of 101 patients with pulmonary tuberculosis established the impact of specific intoxication on central hemodynamics in 51 patients. Specific treatment was found to have a certain positive effect on impaired hemodynamics. However, there were no significant changes in patients with severe tuberculosis. Hemodynamics substantially improved when alpha-tocopherol acetate was supplemented to antibacterial therapy.

  5. 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

  6. 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

  7. [Immunomodulator Intensification of Etioropic Therapy in Patients with Advanced Pulmonary Tuberculosis].

    PubMed

    Kolomiets, V M; Abramov, A V; Rachina, N V; Rubleva, N V

    2015-01-01

    The study was aimed at possible increase of the therapy efficacy in patients with advanced tuberculosis by including immunomodulators to the treatment schemes. The data concerning 6034 patients with advanced tuberculosis, mainly fibrocavernous tuberculosis of the lungs, were analysed. Four groups of the patients were randomized. In group 1 the management of the patients included etiotropic therapy and some treatment and rehabilitation measures with the use of Cycloferon. The group 2 patients in addition to the etiotropic therapy and some treatment and rehabilitation measures were given Omega-3. In group 3 the management included the etiotropic therapy and some treatment and rehabilitation measures. In group 4 the etioropic therapy was used alone. The analysis showed that 3419 patients had primary pulmonary tuberculosis, 340 patients had relapsing tuberculosis and 2275 patients had long-term process. The etiotropic therapy efficacy was estimated after an intensive phase of not more than 3 months. In the cases with Mycobacterium tuberculosis drug resistance and some other unfavourable factors it was estimated after a 5-month intensive phase. The results confirmed that inclusion of immunomodulators to the treatment schemes allowed to increase the therapy efficacy and the patients' adherence to the treatment, as well as to shorten the period of the bacteria carriage. Thus, the use of Cycloferon in the schemes of the treatment of the patients with fibrocavernous pulmonary tuberculosis allowed to shorten the period of the pathogen carriage (as well as the drug resistant forms) in 94.1 ± 3.33% of the patients in spite of concomitant diseases. The effect of Cycloferon in such cases was likely due to both its direct immunoprotective action and the improvement of the general state of the patients and their higher adherence to the treatment.

  8. 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

  9. Comparison of the immune response against Mycobacterium tuberculosis antigens between a group of patients with active pulmonary tuberculosis and healthy household contacts.

    PubMed Central

    Torres, M; Mendez-Sampeiro, P; Jimenez-Zamudio, L; Teran, L; Camarena, A; Quezada, R; Ramos, E; Sada, E

    1994-01-01

    The mycobacterial antigens and the factors related to protection for the development of active tuberculosis are not known. In a natural model of tuberculosis, we studied 10 patients with active pulmonary tuberculosis (non-protective immune response) and 38 healthy household contacts (protective immune response). We tested the lymphocyte proliferative response by T cell Western blotting to eight different antigen fractions and to two purified mycobacterial antigens of 30 and 64 kD. Patients with active tuberculosis recognized fractions with molecular weights of 80-114, 60-80, 28-41 and 14-19 kD. Household contacts recognized the same fractions except the 14-19 kD. The response to the 64-kD antigen was not significantly different between groups. In contrast, 10% of the patients with active tuberculosis and 73% of the household contacts responded to the 30-kD antigen. The humoral response against the 30-kD antigen by ELISA showed a significantly higher production of antibodies in tuberculosis patients compared with household contacts. We conclude that patients with active pulmonary tuberculosis develop an immune response characterized by poor proliferative response to the 30-kD antigen with a strong humoral response, whereas the opposite occurs in healthy subjects infected by Mycobacterium tuberculosis. PMID:8149670

  10. 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

  11. 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

  12. Intracellular levels and extracellular release of lysosomal enzymes from peripheral blood monocytes in pulmonary tuberculosis patients.

    PubMed

    Jaswal, S; Dhand, R; Sethi, A K; Kohli, K K; Ganguly, N K

    1993-01-01

    The intracellular activity and extracellular release (basal and latex-stimulated) of B-glucuronidase (BG) and N-acetylglucosaminidase (NAG), measured fluorimetrically, were observed to be significantly (P < 0.05) higher in blood monocytes (BM) of untreated pulmonary tuberculosis (TB) patients compared to those of age- and sex-matched controls and Mantoux-positive subjects without any evidence of active disease. After completion of antituberculous therapy, BG and NAG activities declined appreciably (P < 0.05) and their levels became comparable to those in control subjects. The present results suggest the potentiation of the oxygen-independent defense mechanism of BM in pulmonary TB. PMID:8457326

  13. 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

  14. [Pulmonary tuberculosis of occupational origin in a funeral director: a case report].

    PubMed

    Witkowska, Anna; Wiszniewska, Marta; Krakowiak, Anna; Walusiak-Skorupa, Jolanta

    2014-01-01

    In Poland the incidence rate of tuberculosis is higher than the average for countries of the European Union, Norway or Iceland. On the other hand, occupational tuberculosis is still rarely recognized in our country. In this paper we present the first in Poland--to our best knowledge--case of pulmonary manifestation of this disease acquired at work in a funeral director. The recognition of the occupational etiology of the discussed illness gave rise to an array of diagnostic problems and became feasible after a thorough analysis of the patient's history and literature data, which allowed finding the relationship between infection and performed job. We speculated that the transfer of the dead body and handling of cadavers may expel residual air from the lungs of the deceased. Although tuberculosis occurs frequently in the general population, the recognition of work-related cases of this disease is still rare, especially among funeral directors.

  15. A case of pulmonary Serratia marcescens granuloma radiologically mimicking metastatic malignancy and tuberculosis infection.

    PubMed

    Das, Joyutpal; Layton, Benjamin; Lamb, Harriet; Sinnott, Nicola; Leahy, Bernard C

    2015-11-01

    Serratia marcescens is a saprophytic gram-negative bacillus capable of causing a wide range of infections. A 57-year-old female was admitted to our hospital for four weeks with community acquired pneumonia. A chest x-ray, six weeks after discharge, demonstrated multiple, bilateral 'cannon ball'-like opacities and mediastinal lymphadenopathy which were highly suspicious of disseminated malignancy or tuberculosis. The only symptom that this patient had was a productive cough. She had multiple commodities, but no specific immunodeficiency disorder. Interestingly, her sputum and bronchial washing samples grew S. marcescens. The computed tomography-guided lung biopsy demonstrated necrotic granulomatous changes. There was no pathological evidence of tuberculosis or fungal infection, malignancy or vasculitis. There are only a handful of reported cases of Serratia granulomas. Thus, we are reporting a rare instance of pulmonary Serratia marcescens granuloma radiologically mimicking metastatic malignancy and tuberculosis infection.

  16. 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.

  17. Pulmonary hyalinizing granuloma detected in a family member after confirmation of tuberculosis in his father.

    PubMed

    Matsuoka, Katsunari; Imanishi, Naoko; Matsuoka, Takahisa; Nagai, Shinjiro; Ueda, Mitsuhiro; Miyamoto, Yoshihiro

    2014-01-01

    Pulmonary hyalinizing granuloma (PHG) is an uncommon lung disease that usually presents as bilateral multiple nodules, and more rarely as a solitary nodule. An exaggerated immune response to antigenic stimuli resulting from infection or an autoimmune process has been suggested as the cause of PHG. Here, we describe a rare case of solitary PHG that was detected in a family member after tuberculosis had been confirmed in his father, without any background of infectious disease or autoimmune abnormality. PMID:23903707

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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

  3. Evidence from Chile that arsenic in drinking water may increase mortality from pulmonary tuberculosis.

    PubMed

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

    2011-02-15

    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.

  4. 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

  5. [The clinical and morphological features of pulmonary tuberculosis under the conditions of the Far North].

    PubMed

    Vinokurov, I I; Argunov, V A; Nikolaev, Iu Ia; Plotnikova, N V

    2006-01-01

    The clinical and morphological features of pulmonary tuberculomas were studied in 205 patients among the naives and newcomers of the Far North. It was established that the lymphohematogenous spread of tuberculosis involving mainly the lymphatic system into the inflammatory process predominates in the genesis of tuberculomas under the conditions of the Far North. At the same time the lymphatic genesis of tuberculosis was found to affect the development of pulmonary tuberculomas in 60% of cases among the native patients. In most patients, the afflicted intrathoracic lymph nodes became a source of retrograde dissemination of tuberculosis in the lung. Tuberculomas were chiefly unilateral and in 56.7% of cases they were located in the lower portions of the lung in the presence of significant fibrosis. The lymphohematogenous spread of tuberculous infection was a cause of pulmonary tuberculomas in most (72.9%) newcomers on adapting to the conditions of the Far North. In most cases, tuberculomas were formed from a newly appeared tuberculous focus in the presence of intact lung tissue and located in the upper portions of both lungs. The formed tuberculomas had no extensive focal dissemination and were present within the anatomic structure of one or two segments of the lung.

  6. 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.

  7. The ABO and rhesus blood groups in patients with pulmonary tuberculosis.

    PubMed

    Viskum, K

    1975-12-01

    During the 3 year period 1970-1972 a total of 554 patients were notified for the first time as having bacillary or abacillary pulmonary tuberculosis in the Municipality of Copenhagen; 99 per cent of these patients were typed according to the ABO and rhesus system. The bacillary patients showed an excess of group O and AB and a deficit of A and B as compared to the general population. The deviations were statistically highly significant for group O and A. The distribution according to the rhesus system did not deviate from the expected pattern. The ABO and rhesus distribution of the abacillary patients did not differ significantly from the expected pattern. During a follow-up period of 2-5 years after the initial diagnosis 104 bacillary patients died; the ABO pattern among the survivors was now closer to the normal; this resulted from a high number of deaths from tuberculosis among patients of group O and a low number among those belonging to group A. More rhesus negative patients died from tuberculosis than rhesus positive. It is concluded that a study of the ABO and rhesus pattern among the tuberculosis patients becomes biased if a break-down by bacteriological findings and history is not made. It is also important that the study covers all patients who contract tuberculosis within a certain period, as the longevity of the patients is apparently to some extent dependent on their blood group.

  8. Mycobacterium tuberculosis strains exhibit differential and strain-specific molecular signatures in pulmonary epithelial cells.

    PubMed

    Mvubu, Nontobeko Eunice; Pillay, Balakrishna; Gamieldien, Junaid; Bishai, William; Pillay, Manormoney

    2016-12-01

    Although pulmonary epithelial cells are integral to innate and adaptive immune responses during Mycobacterium tuberculosis infection, global transcriptomic changes in these cells remain largely unknown. Changes in gene expression induced in pulmonary epithelial cells infected with M. tuberculosis F15/LAM4/KZN, F11, F28, Beijing and Unique genotypes were investigated by RNA sequencing (RNA-Seq). The Illumina HiSeq 2000 platform generated 50 bp reads that were mapped to the human genome (Hg19) using Tophat (2.0.10). Differential gene expression induced by the different strains in infected relative to the uninfected cells was quantified and compared using Cufflinks (2.1.0) and MeV (4.0.9), respectively. Gene expression varied among the strains with the total number of genes as follows: F15/LAM4/KZN (1187), Beijing (1252), F11 (1639), F28 (870), Unique (886) and H37Rv (1179). A subset of 292 genes was commonly induced by all strains, where 52 genes were down-regulated while 240 genes were up-regulated. Differentially expressed genes were compared among the strains and the number of induced strain-specific gene signatures were as follows: F15/LAM4/KZN (138), Beijing (52), F11 (255), F28 (55), Unique (186) and H37Rv (125). Strain-specific molecular gene signatures associated with functional pathways were observed only for the Unique and H37Rv strains while certain biological functions may be associated with other strain signatures. This study demonstrated that strains of M. tuberculosis induce differential gene expression and strain-specific molecular signatures in pulmonary epithelial cells. Specific signatures induced by clinical strains of M. tuberculosis can be further explored for novel host-associated biomarkers and adjunctive immunotherapies. PMID:27497873

  9. 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

  10. Mycobacterium tuberculosis strains exhibit differential and strain-specific molecular signatures in pulmonary epithelial cells.

    PubMed

    Mvubu, Nontobeko Eunice; Pillay, Balakrishna; Gamieldien, Junaid; Bishai, William; Pillay, Manormoney

    2016-12-01

    Although pulmonary epithelial cells are integral to innate and adaptive immune responses during Mycobacterium tuberculosis infection, global transcriptomic changes in these cells remain largely unknown. Changes in gene expression induced in pulmonary epithelial cells infected with M. tuberculosis F15/LAM4/KZN, F11, F28, Beijing and Unique genotypes were investigated by RNA sequencing (RNA-Seq). The Illumina HiSeq 2000 platform generated 50 bp reads that were mapped to the human genome (Hg19) using Tophat (2.0.10). Differential gene expression induced by the different strains in infected relative to the uninfected cells was quantified and compared using Cufflinks (2.1.0) and MeV (4.0.9), respectively. Gene expression varied among the strains with the total number of genes as follows: F15/LAM4/KZN (1187), Beijing (1252), F11 (1639), F28 (870), Unique (886) and H37Rv (1179). A subset of 292 genes was commonly induced by all strains, where 52 genes were down-regulated while 240 genes were up-regulated. Differentially expressed genes were compared among the strains and the number of induced strain-specific gene signatures were as follows: F15/LAM4/KZN (138), Beijing (52), F11 (255), F28 (55), Unique (186) and H37Rv (125). Strain-specific molecular gene signatures associated with functional pathways were observed only for the Unique and H37Rv strains while certain biological functions may be associated with other strain signatures. This study demonstrated that strains of M. tuberculosis induce differential gene expression and strain-specific molecular signatures in pulmonary epithelial cells. Specific signatures induced by clinical strains of M. tuberculosis can be further explored for novel host-associated biomarkers and adjunctive immunotherapies.

  11. 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.

  12. Influence of M. tuberculosis Lineage Variability within a Clinical Trial for Pulmonary Tuberculosis

    PubMed Central

    Nahid, Payam; Bliven, Erin E.; Kim, Elizabeth Y.; Mac Kenzie, William R.; Stout, Jason E.; Diem, Lois; Johnson, John L.; Gagneux, Sebastien; Hopewell, Philip C.; Kato-Maeda, Midori

    2010-01-01

    Recent studies suggest that M. tuberculosis lineage and host genetics interact to impact how active tuberculosis presents clinically. We determined the phylogenetic lineages of M. tuberculosis isolates from participants enrolled in the Tuberculosis Trials Consortium Study 28, conducted in Brazil, Canada, South Africa, Spain, Uganda and the United States, and secondarily explored the relationship between lineage, clinical presentation and response to treatment. Large sequence polymorphisms and single nucleotide polymorphisms were analyzed to determine lineage and sublineage of isolates. Of 306 isolates genotyped, 246 (80.4%) belonged to the Euro-American lineage, with sublineage 724 predominating at African sites (99/192, 51.5%), and the Euro-American strains other than 724 predominating at non-African sites (89/114, 78.1%). Uneven distribution of lineages across regions limited our ability to discern significant associations, nonetheless, in univariate analyses, Euro-American sublineage 724 was associated with more severe disease at baseline, and along with the East Asian lineage was associated with lower bacteriologic conversion after 8 weeks of treatment. Disease presentation and response to drug treatment varied by lineage, but these associations were no longer statistically significant after adjustment for other variables associated with week-8 culture status. PMID:20505778

  13. Influence of M. tuberculosis lineage variability within a clinical trial for pulmonary tuberculosis.

    PubMed

    Nahid, Payam; Bliven, Erin E; Kim, Elizabeth Y; Mac Kenzie, William R; Stout, Jason E; Diem, Lois; Johnson, John L; Gagneux, Sebastien; Hopewell, Philip C; Kato-Maeda, Midori

    2010-05-20

    Recent studies suggest that M. tuberculosis lineage and host genetics interact to impact how active tuberculosis presents clinically. We determined the phylogenetic lineages of M. tuberculosis isolates from participants enrolled in the Tuberculosis Trials Consortium Study 28, conducted in Brazil, Canada, South Africa, Spain, Uganda and the United States, and secondarily explored the relationship between lineage, clinical presentation and response to treatment. Large sequence polymorphisms and single nucleotide polymorphisms were analyzed to determine lineage and sublineage of isolates. Of 306 isolates genotyped, 246 (80.4%) belonged to the Euro-American lineage, with sublineage 724 predominating at African sites (99/192, 51.5%), and the Euro-American strains other than 724 predominating at non-African sites (89/114, 78.1%). Uneven distribution of lineages across regions limited our ability to discern significant associations, nonetheless, in univariate analyses, Euro-American sublineage 724 was associated with more severe disease at baseline, and along with the East Asian lineage was associated with lower bacteriologic conversion after 8 weeks of treatment. Disease presentation and response to drug treatment varied by lineage, but these associations were no longer statistically significant after adjustment for other variables associated with week-8 culture status.

  14. [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

  15. [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

  16. [Pulmonary actinomycosis and tuberculosis. A comorbidity pediatric case].

    PubMed

    Bisero, Elsa D; Luque, Graciela F; Rizzo, Cristina N; Zapata, Alejandra E; Cuello, María S

    2016-08-01

    La actinomicosis es una infección supurativa crónica, producida por bacterias Gram-positivas anaeróbicas o especies Actinomyces microaerófilas. Es rara en niños y adolescentes; es más común en inmunodeprimidos. El Mycobacterium tuberculosis colabora en el desarrollo de la enfermedad. La afectación pulmonar aparece como un cuadro de condensación crónica que no mejora con el tratamiento antibiótico convencional. Las complicaciones clásicas de afectación de la pared torácica con fistulización y supuración en «granulo de azufre» son descritas con menor frecuencia en la actualidad. El diagnóstico es un verdadero desafío y se establece mediante el aislamiento de las especies de Actinomyces. El tratamiento de elección para todas las formas clínicas de la enfermedad es el uso prolongado de antibióticos. Objetivo. Presentar un caso pediátrico de comorbilidad entre tuberculosis y actinomicosis. Resaltar la importancia de la sospecha diagnóstica de actinomicosis frente a todo proceso supurado crónico.

  17. 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

  18. 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

  19. [Chronic renal failure: unexpected late sequela of pulmonary tuberculosis after 30 years].

    PubMed

    Zümrütdal, Ayşegül; Yıldız, Ismail; Ozelsancak, Rüya; Canpolat, Tuba

    2011-04-01

    Tuberculosis-related chronic granulomatous tubulointerstitial nephritis (GTN) and chronic renal dysfunction as a consequence of GTN is a rarely seen clinical condition, with a few case reports in the literature. In this report, a case with end stage renal failure as an unexpected late extrapulmonary sequela of tuberculosis has been presented. A 60 years old female patient was admitted to hospital with the complaints of fever, malaise and nausea. Her history revealed that she had pulmonary tuberculosis 30 years ago and received antituberculosis therapy for nine months. The laboratory results on admission were as follows: blood urea nitrogen 90 mg/dl, serum creatinine 9 mg/dl, sodium 116 mEq/L, potassium 6.6 mEq/L, albumine 2.9 g/dl, hemoglobin, 8.4 g/dl, white blood cell count 10.800/mm3, C-reactive protein 187 mg/L and erythrocyte sedimentation rate 110 mm/hour. Urinalysis showed 8.1 g/L protein, 10-12 leukocytes, 1-2 erythrocytes, while 24-hours urinalysis yielded proteinuria with 8 ml/minutes creatinine clearance value. Urine and blood cultures of the patient revealed neither bacteria or mycobacteria. PPD skin test was negative. Acid-resistant bacilli (ARB) were not detected in sequential urine samples obtained on three consecutive days. Since sputum samples could not be obtained, diagnostic procedures for sputum were not performed. Abdomen ultrasonography yielded bilateral edema and grade II echogenity in kidneys. Computed tomography of the chest showed bilateral pulmonary nodules, chronic sequela lesions, pleural scarring and calcifications, as well as minimal interstitial infiltrate. Transthoracic lung biopsy showed chronic inflammation and fibrosis, while amyloid was negative. Renal biopsy showed GTN with central caseified necrosis and granulomas, multinuclear giant cells, tubular atrophy and interstitial fibrosis. Amyloid was negative and ARB were not detected in renal biopsy sample. Definitive diagnosis was achieved by the demonstration of Mycobacterium

  20. 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

  1. 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

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

    PubMed Central

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

    1998-01-01

    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

  3. [CORRECTION OF METABOLIC DISTURBANCES IN PATIENTS WITH PULMONARY TUBERCULOSIS AND CONCOMITANT DISEASES].

    PubMed

    2010-01-01

    Metabolic disturbances were corrected using the oral specialized formula Nutrien-phthisio (ZAO "Company Nutritec", Russia) in 53 patients with pulmonary tuberculosis and concomitant diseases. In the whole group, tuberculosis was first detected in 21 patients; 32 had a chronic process. Chemotherapy was discontinued in all the patients due to the intolerance phenomena caused by comorbidity (erosive gastritis, gastroduodenal peptic ulcer, hepatitis B and C, chronic pyelonephritis) in 24 patients, by adverse reactions in 19, and by a combination of both factors in 10. The criteria for objectively monitoring the efficiency of nutritional support (in combination with specific treatment) were body mass index, general blood analysis, by taking into account the percentage and absolute count of lymphocytes and the protein metabolism from the serum levels of total protein, albumin, and transferrin. The study determined clinical and laboratory indications for the use of Nutrien-phthisio and the favorable impact of nutritional support on the course of a tuberculous process and concomitant diseases.

  4. 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)%.

  5. A registry-based cohort study of pulmonary tuberculosis treatment outcomes in Istanbul, Turkey.

    PubMed

    Babalik, Aylin; Kilicaslan, Zeki; Caner, S Sevkan; Gungor, Gokay; Ortakoylu, M Gonenc; Gencer, Serap; McCurdy, Stephen A

    2013-01-01

    The aim of this study is to evaluate the treatment outcomes and identify factors associated with adverse tuberculosis treatment outcomes for bacteriologically confirmed pulmonary tuberculosis. Treatment outcomes of pulmonary tuberculosis were evaluated retrospectively among 11,186 smear- and/or culture-positive patients treated between 2006 and 2009 in Istanbul, Turkey. Adverse treatment outcomes were identified in 1,010 (9.0%) patients including death (1.8%), treatment default (6.1%), and treatment failure (1.1%). Factors associated with adverse treatment outcomes included being born abroad (odds ratios [OR], 5.38; 95% confidence intervals [CI], 3.67-7.91), history of tuberculosis treatment (OR, 3.77; 95% CI, 3.26-4.36), age > 65 years (OR, 2.79; 95% CI, 2.21-3.53), and male gender (OR, 1.91; 95% CI, 1.59-2.27). Death was most strongly associated with age > 65 years (OR, 45.1; 95% CI, 27.0-75.6), followed by treatment default with history of interrupted treatment (OR, 11.6; 95% CI, 8.94-15.1), and treatment failure with prior history of treatment failure (OR, 17.1; 95% CI, 6.97-41.6). Multidrug resistance was strongly associated with adverse treatment outcomes (OR, 10.8; 95% CI, 8.02-14.6). Age > 65 years, male sex, being born abroad, and history of treatment failure were found to be risk factors for adverse treatment outcomes. Hence, patients with any of these characteristics should be carefully monitored and treated aggressively.

  6. 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

  7. 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

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

    PubMed

    Oliveira, Cláudia Di Lorenzo; Melo, Angelita Cristine de; Oliveira, Lílian Ruth Silva de; 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.

  9. 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

  10. Mapping the epidemiology and trends of extra-pulmonary tuberculosis in Saudi Arabia.

    PubMed

    Varghese, Bright; Al-Hajoj, Sahal

    2015-12-01

    An extra-pulmonary tuberculosis (EPTB) infection rate of 30% in Saudi Arabia remains above the global rate. A variable rate of infection in each province has been reported and the involvement of most organs has been cited. Nationwide collective data on the current trends of infection are scarce and the factors behind the increased rate of EPTB are perplexing. This review endeavors to shed light into the epidemiology of EPTB, various types of infections sites, geographical differences in the infection rate, known risk factors, and challenges in the diagnosis and management of EPTB in Saudi Arabia.

  11. 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

  12. 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

  13. 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. PMID:27578942

  14. 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

  15. 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

  16. [A case of pulmonary tuberculosis with diminished lung function whose paradoxical reaction led to death].

    PubMed

    Omura, Harutaka; Kajiki, Akira; Nagata, Nobuhiko; Kitahara, Yoshinari; Wakamatsu, Kentarou; Minami, Takahiro; Taguchi, Kazuhito; Katahira, Katsuyuki

    2011-05-01

    Paradoxical reaction in tuberculosis treatment is not generally fatal. On rare occasion it can lead a patient with diminished lung function and poor general condition to death. A 60-year-old man with history of left upper lobe resection from tuberculosis was referred to our hospital due to the recurrence of tuberculosis. Sputum examination showed a positive smear with a Gaffky score of 10, and the chest X-ray and CT revealed pulmonary infiltrate with many cavities (bII2) on the whole left lung field. Anti-tuberculosis drugs (isoniazid, rifampicin, ethambutol and pyrazinamide) were administered, but his high fever persisted, and the infiltrate on the chest X-ray deteriorated. While the positive sputum smear persisted, the culture became negative after one month. The tuberculous bacilli were susceptible to all anti-tuberculosis drugs in vitro. Though we performed examinations and trial treatments for non-tuberculous conditions such as pneumonia and drug-induced pneumonia, the patient died after 6 months. A necropsy specimen taken from the worsening lesion (the right upper lobe) as shown on the chest X-ray revealed many epithelioid granulomas. The patient had malnutrition, diabetes, alcoholic hepatic disorder, and insanity. It is supposed that although antituberculosis drugs were effective, a large quantity of killed organisms was continuously excreted from many cavities in the left lung toward the right lung. Lesions in the right lung thus newly produced in this paradoxical reaction seemed to reduce the remaining lung function. In addition, poorly controlled diabetes caused deteriorated heart function. These multiple factors contributed to the poor prognosis of the patient and his ultimate death.

  17. 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

  18. [Bronchopleurocutaneous Fistula: A Rare Complication of Pulmonary Tuberculosis].

    PubMed

    Montez, Ana Sofia José; Coutinho, Daniel; Velez, Jorge; Freitas, Filomena; Oliveira, Célia

    2015-01-01

    Introdução: A tuberculose pulmonar pode cursar com diversas complicações. As fístulas bronco-pleuro-cutâneas consistem em comunicações anormais entre o brônquio, o espaço pleural e a pele.Caso Clínico: Apresentamos o caso de um homem, 47 anos, esquizofrénico, enviado ao Serviço de Urgência por toracalgia esquerda, tosse produtiva e emagrecimento. Apresentava-se caquético, sendo evidente um orifício cutâneo torácico latero-anterior esquerdo com drenagem purulenta, na qual o exame direto revelou bacilos ácido-álcool resistentes. A radiografia torácica evidenciava infiltrado heterogéneo bilateral. Foi internado com o diagnóstico de tuberculose pulmonar fistulizada. Na expetoração, a pesquisa de bacilos ácido-álcool resistentes foi igualmente positiva, sendo evidenciado Mycobacterium tuberculosis por reação de polimerase em cadeia e exame cultural. Iniciou terapêutica antituberculosa quádrupla apresentando evolução clínica favorável.Conclusões: A formação de fístulas bronco-pleuro-cutâneas é atualmente e em países desenvolvidos, uma complicação rara de tuberculose pulmonar. Assim, apesar da tuberculose ser frequente em Portugal, a raridade deste tipo de complicações torna pertinente a apresentação deste caso clínico.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. Immunization with extracellular proteins of Mycobacterium tuberculosis induces cell-mediated immune responses and substantial protective immunity in a guinea pig model of pulmonary tuberculosis.

    PubMed Central

    Pal, P G; Horwitz, M A

    1992-01-01

    We have studied the capacity of a selected fraction of Mycobacterium tuberculosis extracellular proteins (EP) released into broth culture by mid-logarithmic-growth-phase organisms to induce cell-mediated immune responses and protective immunity in a guinea pig model of pulmonary tuberculosis. Guinea pigs infected with M. tuberculosis by aerosol but not uninfected control guinea pigs exhibit strong cell-mediated immune responses to EP, manifest by dose-dependent cutaneous delayed-type hypersensitivity and splenic lymphocyte proliferation. Guinea pigs immunized subcutaneously with EP but not sham-immunized control guinea pigs also develop strong cell-mediated immune responses to EP, manifest by dose-dependent cutaneous delayed-type hypersensitivity and splenic lymphocyte proliferation. EP is nonlethal and nontoxic to guinea pigs upon subcutaneous immunization. Guinea pigs immunized with EP and then challenged with aerosolized M. tuberculosis exhibit protective immunity. In five independent experiments, EP-immunized guinea pigs were consistently protected against clinical illness, including weight loss. Compared with EP-immunized guinea pigs, sham-immunized control guinea pigs lost 12.9 +/- 2.0% (mean +/- SE) of their total weight. EP-immunized guinea pigs also had a 10-fold reduction in viable M. tuberculosis bacilli in their lungs and spleens (P = 0.004 and 0.001, respectively) compared with sham-immunized control animals. In the two experiments in which some guinea pigs died after aerosol challenge, EP-immunized animals were protected from death. Whereas all 12 (100%) EP-immunized guinea pigs survived challenge with aerosolized M. tuberculosis, only 6 of 12 (50%) sham-immunized control guinea pigs survived challenge (P = 0.007, Fisher exact test). This study demonstrates that actively growing M. tuberculosis cells release immunoprotective molecules extracellularly, that a subunit vaccine against tuberculosis is feasible, and that extracellular molecules of M

  4. 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 ...

  5. 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.

  6. 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

  7. 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.

  8. Treatment Outcomes with Fluoroquinolone-Containing Regimens for Isoniazid-Resistant Pulmonary Tuberculosis

    PubMed Central

    Lee, Hyun; Jeong, Byeong-Ho; Park, Hye Yun; Jeon, Kyeongman; Huh, Hee Jae; Lee, Nam Yong

    2015-01-01

    Resistance to isoniazid (INH) is the most common form of drug resistance in pulmonary tuberculosis (TB). Although fluoroquinolones (FQs) are recommended to strengthen treatment regimens for INH-resistant pulmonary TB, few studies have evaluated the clinical efficacy of FQ-containing regimens in patients with INH-resistant pulmonary TB. A retrospective cohort study of 140 patients with INH-resistant pulmonary TB was performed between 2005 and 2012. We evaluated whether FQ-containing regimens yielded improved treatment outcomes for patients with INH-resistant pulmonary TB. Overall, favorable outcomes were achieved in 128 (91.4%) patients. Unfavorable outcomes occurred in 12 patients (8.6%), including 7 with treatment failure (5.0%) and 5 with relapse after initial treatment completion (3.6%). FQs, such as levofloxacin and moxifloxacin, were given to 75 (53.6%) patients. Favorable treatment outcomes were more frequent for patients who received FQs (97.3% [73/75 patients]) than for those who did not receive FQs (84.6% [55/65 patients]) (P = 0.007). Patients who did not receive FQs were more likely to develop treatment failure (9.2% [6/65 patients] versus 1.3% [1/75 patients]) (P = 0.049) than patients who received FQs. The adjusted proportion of unfavorable outcomes was significantly higher among patients who did not receive FQs (8.8%; 95% confidence interval [CI], 3.3 to 21.5%) than among those who did receive FQs (1.5%; 95% CI, 0.3 to 7.7%) (P = 0.037). These results suggest that the addition of FQs can improve treatment outcomes for patients with INH-resistant pulmonary TB. PMID:26525801

  9. Use of conventional PCR and smear microscopy to diagnose pulmonary tuberculosis in the Amazonian rainforest area.

    PubMed

    Carniel, F; Dalla Costa, E R; Lima-Bello, G; Martins, C; Scherer, L C; Rossetti, M L

    2014-12-01

    The diagnostic usefulness of Ziehl-Neelsen (ZN)-stained sputum smears combined with conventional polymerase chain reaction (ZN/PCR) to amplify IS6110 region DNA extracted from ZN slides was evaluated. The objective was to verify if this association could improve tuberculosis (TB) diagnosis in patients at remote sites. The study was carried out in 89 patients with culture-confirmed pulmonary TB as defined by the Brazilian Manual for TB Treatment. The participants were recruited in a reference unit for TB treatment in Rondônia, a state in the Amazonian area in northern Brazil. ZN, PCR, and culture performed in the sputum samples from these patients were analyzed in different combinations (i.e., ZN plus PCR and ZN plus culture). The prevalence rates of pulmonary TB in these patients were 32.6 and 28.1% considering culture and ZN/PCR, respectively. The sensitivity and specificity of ZN/PCR were 86 and 93%, respectively. ZN/PCR was able to detect more TB cases than ZN alone. This method could offer a new approach for accurate tuberculosis diagnosis, especially in remote regions of the world where culture is not available.

  10. Applying patient centered approach in management of pulmonary tuberculosis: A case report from Malaysia.

    PubMed

    Atif, M; Sulaiman, Sas; Shafi, Aa; Muttalif, Ar; Ali, I; Saleem, F

    2011-06-01

    A 24 year university student with history of productive cough was registered as sputum smear confirmed case of pulmonary tuberculosis. During treatment, patient suffered from itchiness associated with anti tuberculosis drugs and was treated with chlorpheniramine (4mg) tablet. Patient missed twenty eight doses of anti tuberculosis drugs in continuation phase claiming that he was very busy in his studies and assignments. Upon questioning he further explained that he was quite healthy after five months and unable to concentrate on his studies after taking prescribed medicines. His treatment was stopped based on clinical improvement, although he did not complete six months therapy. Two major reasons; false perception of being completely cured and side effects associated with anti TB drugs might be responsible for non adherence. Non sedative anti histamines like fexofenadine, citrizine or loratidine should be preferred over first generation anti histamines (chlorpheniramine) in patients with such lifestyle. Patient had not completed full course of chemotherapy, which is preliminary requirement for a case to be classified as "cure" and "treatment completed". Moreover, patient had not defaulted for two consecutive months. Therefore, according to WHO treatment outcome categories, this patient can neither be classified as "cure" or "treatment completed" nor as "defaulter". Further elaboration of WHO treatment outcome categories is required for adequate classification of patients with similar characteristics. Likelihood of non adherence can be significantly reduced by applying the WHO recommended "Patient Centered Approach" strategy. Close friend, class mate or family member can be selected as treatment supporter to ensure adherence to treatment. PMID:24826012

  11. Applying patient centered approach in management of pulmonary tuberculosis: A case report from Malaysia.

    PubMed

    Atif, M; Sulaiman, Sas; Shafi, Aa; Muttalif, Ar; Ali, I; Saleem, F

    2011-06-01

    A 24 year university student with history of productive cough was registered as sputum smear confirmed case of pulmonary tuberculosis. During treatment, patient suffered from itchiness associated with anti tuberculosis drugs and was treated with chlorpheniramine (4mg) tablet. Patient missed twenty eight doses of anti tuberculosis drugs in continuation phase claiming that he was very busy in his studies and assignments. Upon questioning he further explained that he was quite healthy after five months and unable to concentrate on his studies after taking prescribed medicines. His treatment was stopped based on clinical improvement, although he did not complete six months therapy. Two major reasons; false perception of being completely cured and side effects associated with anti TB drugs might be responsible for non adherence. Non sedative anti histamines like fexofenadine, citrizine or loratidine should be preferred over first generation anti histamines (chlorpheniramine) in patients with such lifestyle. Patient had not completed full course of chemotherapy, which is preliminary requirement for a case to be classified as "cure" and "treatment completed". Moreover, patient had not defaulted for two consecutive months. Therefore, according to WHO treatment outcome categories, this patient can neither be classified as "cure" or "treatment completed" nor as "defaulter". Further elaboration of WHO treatment outcome categories is required for adequate classification of patients with similar characteristics. Likelihood of non adherence can be significantly reduced by applying the WHO recommended "Patient Centered Approach" strategy. Close friend, class mate or family member can be selected as treatment supporter to ensure adherence to treatment.

  12. Initial Presentations Predict Mortality in Pulmonary Tuberculosis Patients - A Prospective Observational Study

    PubMed Central

    Feng, Jia-Yih; Su, Wei-Juin; Chiu, Yu-Chi; Huang, Shiang-Fen; Lin, Yung-Yang; Huang, Ruay-Ming; Lin, Ching-Hsiung; Hwang, Jhi-Jhu; Lee, Jen-Jyh; Yu, Ming-Chih; Yu, Kwok-Woon; Lee, Yu-Chin

    2011-01-01

    Background Despite effective anti-TB treatments, tuberculosis remains a serious threat to public health and is associated with high mortality. Old age and multiple co-morbidities are known risk factors for death. The association of clinical presentations with mortality in pulmonary tuberculosis patients remains an issue of controversy. Methods This prospective observational study enrolled newly diagnosed, culture-proven pulmonary tuberculosis patients from five medical centers and one regional hospital, which were referral hospitals of TB patients. Radiographic findings and clinical symptoms were determined at the time of diagnosis. Patients who died for any reason during the course of anti-TB treatment were defined as mortality cases and death that occurred within 30 days of initiating treatment was defined as early mortality. Clinical factors associated with overall mortality and early mortality were investigated. Results A total of 992 patients were enrolled and 195 (19.7%) died. Nearly one-third (62/195, 31.8%) of the deaths occurred before or within 30 days of treatment initiation. Older age (RR = 1.04, 95%CI: 1.03–1.05), malignancy (RR = 2.42, 95%CI: 1.77–3.31), renal insufficiency (RR = 1.77, 95%CI: 1.12–2.80), presence of chronic cough (RR = 0.63, 95%CI: 0.47–0.84), fever (RR = 1.45, 95%CI: 1.09–1.94), and anorexia (RR = 1.49, 95%CI: 1.07–2.06) were independently associated with overall mortality. Kaplan-Meier survival analysis demonstrated significantly higher mortality in patients present with fever (p<0.001), anorexia (p = 0.005), and without chronic cough (p<0.001). Among patients of mortality, those with respiratory symptoms of chronic cough (RR = 0.56, 95%CI: 0.33–0.98) and dyspnea (HR = 0.51, 95%CI: 0.27–0.98) were less likely to experience early mortality. The radiological features were comparable between survivors and non-survivors. Conclusions In addition to demographic characteristics, clinical

  13. 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

  14. Mycobacterial Etiology of Pulmonary Tuberculosis and Association with HIV Infection and Multidrug Resistance in Northern Nigeria

    PubMed Central

    El-Kamary, Samer S.; Abimiku, Alash'le; Ezati, Nicholas; Mosunmola, Iwakun; Brown, Clayton; Tracy, Kathleen J.; Obasanya, Joshua; Blattner, William

    2013-01-01

    Objective. Data on pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) complex in Nigeria are limited. We investigated species of MTB complex in TB cases from northern Nigeria. Methods. New TB suspects were enrolled, screened for HIV and their sputum samples were cultured after routine microscopy. Genotypes MTBC and MTBDRplus were used to characterize the MTB complex species and their resistance to isoniazid and rifampicin. Results. Of the 1,603 patients enrolled, 375 (23%) had MTB complex infection: 354 (94.4%) had Mycobacterium tuberculosis; 20 (5.3%) had Mycobacterium africanum; and one had Mycobacterium bovis (0.3%). Cases were more likely to be male (AOR = 1.87, 95% CI : 1.42–2.46; P ≤ 0.001), young (AOR = 2.03, 95% CI : 1.56–2.65; P ≤ 0.001) and have HIV (AOR = 1.43, 95% CI : 1.06–1.92; P = 0.032). In 23 patients (6.1%), the mycobacterium was resistant to at least one drug, and these cases were more likely to have HIV and prior TB treatment (AOR = 3.62, 95% CI : 1.51–8.84; P = 0.004; AOR : 4.43; 95% CI : 1.71–11.45 P = 0.002 resp.), compared to cases without any resistance. Conclusion. Mycobacterium tuberculosis remained the predominant specie in TB in this setting followed by Mycobacterium africanum while Mycobacterium bovis was rare. The association of TB drug resistance with HIV has implications for TB treatment. PMID:23970967

  15. 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

  16. 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.

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

    PubMed

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

    2016-01-01

    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.

  18. 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

  19. P2X7 and NRAMP1/SLC11 A1 gene polymorphisms in Mexican mestizo patients with pulmonary tuberculosis

    PubMed Central

    Niño-Moreno, P; Portales-Pérez, D; Hernández-Castro, B; Portales-Cervantes, L; Flores-Meraz, V; Baranda, L; Gómez-Gómez, A; Acuña-Alonzo, V; Granados, J; González-Amaro, R

    2007-01-01

    Tuberculosis remains one of the most important infectious diseases worldwide. Several studies have suggested that genetic factors may affect susceptibility to tuberculosis, but the specific genes involved have not yet been fully characterized. NRAMP1/SLC11 A1 and P2X7 genes have been linked to increased risk for tuberculosis in some African and Asiatic populations. To explore the potential role of these genes in the susceptibility to pulmonary tuberculosis in a Mexican mestizo population, we evaluated the association of D543N and 3′-UTR polymorphisms in NRAMP1/SLC11 A1 and − 762 and A1513C polymorphisms in P2X7 genes with the risk for tuberculosis. Polymerase chain reaction (PCR) amplification of genomic DNA followed by restriction fragment length polymorphism analysis, and allelic-specific PCR was employed. We found no significant differences in allelic frequency in NRAMP1/SLC11 A1 gene polymorphisms in 94 patients with tuberculosis compared to 100 healthy contacts. Similarly, no significant association of the P2X7−762 gene polymorphism with tuberculosis was detected. In contrast, the P2X7 A1513C polymorphism was associated significantly with tuberculosis (P= 0·02, odds ratio = 5·28, 95% CI, 0·99–37·69), an association that had not been reported previously. However, when the function of P2X7 was assessed by an l-selectin loss assay, we did not find significant differences in patients compared to healthy contacts or between PPD+ and PPD– control individuals. This study further supports the complex role of P2X7 gene in host regulation of Mycobacterium tuberculosis infection, and demonstrates that different associations of gene polymorphisms and tuberculosis are found in distinct racial populations. PMID:17493019

  20. Pulmonary tuberculosis and tuberculous arthritis of knee joint associated with rheumatoid arthritis treated with anti-tumor necrosis factor (TNF)-alpha medication: a case report.

    PubMed

    Nalbant, Selim; Özyurt, Mustafa; Yıldırım, Murat; Kuskucu, Mesih

    2012-09-01

    Tuberculosis infection (TB) is one of the most important problems for the rheumatoid arthritis (RA) patients treated with anti-TNF agents. Pulmonary tuberculosis is the most common clinic form of the TB in these patients. However, tuberculosis arthritis is very rare. We present here a 72-year-old Caucasian woman with seropositive RA, treated with etanercept/adalimumab for the last 2 years, who presented with resistant knee pain and joint effusion. We believe that this treatment caused the tuberculosis in this patient, which is the most worried complication. Interestingly, tuberculosis was in the knee joint at this time.

  1. 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

  2. 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 ...

  3. 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

  4. Scaling up interventions to achieve global tuberculosis control: progress and new developments.

    PubMed

    Raviglione, Mario; Marais, Ben; Floyd, Katherine; Lönnroth, Knut; Getahun, Haileyesus; Migliori, Giovanni B; Harries, Anthony D; Nunn, Paul; Lienhardt, Christian; Graham, Steve; Chakaya, Jeremiah; Weyer, Karin; Cole, Stewart; Kaufmann, Stefan H E; Zumla, Alimuddin

    2012-05-19

    Tuberculosis is still one of the most important causes of death worldwide. The 2010 Lancet tuberculosis series provided a comprehensive overview of global control efforts and challenges. In this update we review recent progress. With improved control efforts, the world and most regions are on track to achieve the Millennium Development Goal of decreasing tuberculosis incidence by 2015, and the Stop TB Partnership target of halving 1990 mortality rates by 2015; the exception is Africa. Despite these advances, full scale-up of tuberculosis and HIV collaborative activities remains challenging and emerging drug-resistant tuberculosis is a major threat. Recognition of the effect that non-communicable diseases--such as smoking-related lung disease, diet-related diabetes mellitus, and alcohol and drug misuse--have on individual vulnerability, as well as the contribution of poor living conditions to community vulnerability, shows the need for multidisciplinary approaches. Several new diagnostic tests are being introduced in endemic countries and for the first time in 40 years a coordinated portfolio of promising new tuberculosis drugs exists. However, none of these advances offer easy solutions. Achievement of international tuberculosis control targets and maintenance of these gains needs optimum national health policies and services, with ongoing investment into new approaches and strategies. Despite growing funding in recent years, a serious shortfall persists. International and national financial uncertainty places gains at serious risk. Perseverance and renewed commitment are needed to achieve global control of tuberculosis, and ultimately, its elimination. PMID:22608339

  5. 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

  6. The impact of pulmonary tuberculosis treatment on the prevalence of allergic rhinitis.

    PubMed

    Lin, Carren Teh Sui; Gopala, Krishnan; Manuel, Anura Michelle

    2013-08-01

    Atopy is a syndrome characterized by immediate hypersensitivity reactions to common environmental antigens. The "hygiene hypothesis" stipulates that childhood infections are associated with a lower risk of allergies. Not much has been published about the effects that the treatment of pulmonary tuberculosis (TB) has on allergies, specifically allergic rhinitis. We conducted a study to investigate the prevalence of allergic rhinitis in patients with pulmonary TB before and after treatment of their TB. Our initial study group was made up of 121 patients with confirmed pulmonary TB who were followed up by questionnaire. In addition to demographic data, they provided information about their personal and family history of atopy and their current status with regard to allergic rhinitis. After providing informed consent, all patients underwent skin-prick testing with Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Blomia tropicalis allergens before and after TB treatment. Stool samples were obtained to identify patients with worm infestation, and they were excluded from the study. In all, 94 patients completed treatment and follow-up, and their data were included in the final analysis. Of this group, 31 patients (33.0%) exhibited symptoms of allergic rhinitis prior to TB treatment, and 26 (27.7%) had a positive skin-prick test. Following treatment, only 12 patients (12.8%) reported allergic rhinitis symptoms (p = 0.004), but there was no significant reduction in the number of patients with a positive skin-prick test (n = 20 [21.3%]; p = 0.555). We conclude that the treatment of pulmonary TB results in significant relief of atopy, particularly allergic rhinitis symptoms.

  7. [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

  8. 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

  9. Prevalence of smear-positive pulmonary tuberculosis among prisoners in Malawi: a national survey.

    PubMed

    Banda, H T; Gausi, F; Harries, A D; Salaniponi, F M

    2009-12-01

    A cross-sectional cell-to-cell survey was conducted in 18 of 22 prisons in Malawi to determine the period prevalence of smear-positive pulmonary tuberculosis (PTB). In each prison, prisoners were interviewed using a structured questionnaire. Prisoners with cough of >1 week's duration were investigated by sputum smear examination. Of 7661 prisoners, 3887 had cough of > or =1 week, of whom 3794 submitted three sputum specimens: 54 (0.7%) had smear-positive PTB. The prevalence of PTB was higher in large urban prisons (1.1%) than in district prisons (0.3%, P < 0.001). More needs to be done to improve TB control in urban prisons.

  10. 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

  11. Isolated perianal tuberculosis.

    PubMed

    Akgun, E; Tekin, F; Ersin, S; Osmanoglu, H

    2005-03-01

    Perianal tuberculosis, without the presence of any previous or active pulmonary infection, is extremely rare. A case of isolated perianal tuberculosis without gastrointestinal or pulmonary spread will be discussed here with an evaluation of the clinical features. PMID:15813425

  12. Pulmonary tuberculosis space-time clustering and spatial variation in temporal trends in Portugal, 2000-2010: an updated analysis.

    PubMed

    Areias, C; Briz, T; Nunes, C

    2015-11-01

    Portugal, a medium- to low-level endemic country (21·6 cases/100 000 population in 2012), has one of the highest European Union tuberculosis (TB) incidences. Although incidence is declining progressively, the country's heterogeneity in both regional endemics and their evolution suggests the importance of a better understanding of subnational epidemiology to customize TB control efforts. We aimed to update knowledge on municipality-years pulmonary TB incidence clustering, identify areas with different time trends, and show the potential of combining complementary clustering methods in control of infectious diseases. We used national surveillance municipality-level data (mainland Portugal, 2000-2010). Space-time clustering and spatial variation in temporal trends methods were applied. Space-time critical clusters identified (P < 0·001) were still the Lisbon and Oporto regions. The global incidence declined at a 5·81% mean annual percentage change, with high space-time heterogeneity and distinct time trend clusters (P < 0·001). Municipalities with incidences declining more rapidly belonged to critical areas. In particular, the Oporto trend cluster had a consistent -8·98% mean annual percentage change. Large space-time heterogeneities were identified, with critical incidences in the greater Lisbon and Oporto regions, but declining more rapidly in these regions. Oporto showed a consistent, steeper decrease and could represent a good example of local control strategy. Combining results from these approaches gives promise for prospects for infectious disease control and the design of more effective, focused interventions.

  13. Increased specific T cell cytokine responses in patients with active pulmonary tuberculosis from Central Africa.

    PubMed

    Winkler, Stefan; Necek, Magdalena; Winkler, Heidi; Adegnika, Ayola A; Perkmann, Thomas; Ramharter, Michael; Kremsner, Peter G

    2005-07-01

    An understanding of T cell responses that are crucial for control of Mycobacterium tuberculosis (MTB) has major implications for the development of immune-based interventions. We studied the frequency of purified protein derivative (PPD)-specific CD3) cells expressing interleukin-2 (IL)-2, gamma interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and IL-10 in HIV-negative pulmonary tuberculosis patients (TB, n=30) as well as in healthy individuals (controls, n=21) from Central Africa. Increased frequencies of PPD-stimulated CD3+ cells expressing IL-2, IFN-gamma, and TNF-alpha in TB were seen when compared with frequencies of controls. The presence of type 1 cytokine biased responses in TB patients was supported by a shift in the distribution pattern of cytokine expression from exclusively IL-2 or TNF-alpha expression seen in controls towards an increased frequency of IFN-gamma/IL-2 or IFN-gamma/TNF-alpha co-expression in TB. Higher levels of PPD-induced IFN-gamma in the supernatants from TB patients than from controls were found, which correlated with its intracellular expression. PPD was a weak inducer of IL-10 in T cells and insufficient in promoting cytokine production in TCRgammadelta+CD3+ cells. Non-specific stimulation with PMA and ionomycin revealed increased frequencies of CD4+ cells expressing IFN-gamma in controls, while expression of IL-2, IL-4, IL-10, IL-13, and TNF-alpha was not different. Non-specific cytokine responses of TCRgammadelta+CD3+ cells were similar in all groups. Pulmonary TB in Central Africa is associated with enhanced expression and secretion of specifically induced cytokines that are frequently implicated in host defense against MTB.

  14. 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

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

    PubMed

    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.

  17. A Prediction Rule to Stratify Mortality Risk of Patients with Pulmonary Tuberculosis

    PubMed Central

    Osório, Nuno S.; Castro, António Gil; Ramos, Angélica; Carvalho, Teresa; Meira, Leonor; Araújo, David; Almeida, Leonor; Boaventura, Rita; Fragata, Patrícia; Chaves, Catarina; Costa, Patrício; Portela, Miguel; Ferreira, Ivo; Magalhães, Sara Pinto; Rodrigues, Fernando; Sarmento-Castro, Rui; Duarte, Raquel; Guimarães, João Tiago; Saraiva, Margarida

    2016-01-01

    Tuberculosis imposes high human and economic tolls, including in Europe. This study was conducted to develop a severity assessment tool for stratifying mortality risk in pulmonary tuberculosis (PTB) patients. A derivation cohort of 681 PTB cases was retrospectively reviewed to generate a model based on multiple logistic regression analysis of prognostic variables with 6-month mortality as the outcome measure. A clinical scoring system was developed and tested against a validation cohort of 103 patients. Five risk features were selected for the prediction model: hypoxemic respiratory failure (OR 4.7, 95% CI 2.8–7.9), age ≥50 years (OR 2.9, 95% CI 1.7–4.8), bilateral lung involvement (OR 2.5, 95% CI 1.4–4.4), ≥1 significant comorbidity—HIV infection, diabetes mellitus, liver failure or cirrhosis, congestive heart failure and chronic respiratory disease–(OR 2.3, 95% CI 1.3–3.8), and hemoglobin <12 g/dL (OR 1.8, 95% CI 1.1–3.1). A tuberculosis risk assessment tool (TReAT) was developed, stratifying patients with low (score ≤2), moderate (score 3–5) and high (score ≥6) mortality risk. The mortality associated with each group was 2.9%, 22.9% and 53.9%, respectively. The model performed equally well in the validation cohort. We provide a new, easy-to-use clinical scoring system to identify PTB patients with high-mortality risk in settings with good healthcare access, helping clinicians to decide which patients are in need of closer medical care during treatment. PMID:27636095

  18. 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.

  19. 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

  20. A Prediction Rule to Stratify Mortality Risk of Patients with Pulmonary Tuberculosis.

    PubMed

    Bastos, Helder Novais; Osório, Nuno S; Castro, António Gil; Ramos, Angélica; Carvalho, Teresa; Meira, Leonor; Araújo, David; Almeida, Leonor; Boaventura, Rita; Fragata, Patrícia; Chaves, Catarina; Costa, Patrício; Portela, Miguel; Ferreira, Ivo; Magalhães, Sara Pinto; Rodrigues, Fernando; Sarmento-Castro, Rui; Duarte, Raquel; Guimarães, João Tiago; Saraiva, Margarida

    2016-01-01

    Tuberculosis imposes high human and economic tolls, including in Europe. This study was conducted to develop a severity assessment tool for stratifying mortality risk in pulmonary tuberculosis (PTB) patients. A derivation cohort of 681 PTB cases was retrospectively reviewed to generate a model based on multiple logistic regression analysis of prognostic variables with 6-month mortality as the outcome measure. A clinical scoring system was developed and tested against a validation cohort of 103 patients. Five risk features were selected for the prediction model: hypoxemic respiratory failure (OR 4.7, 95% CI 2.8-7.9), age ≥50 years (OR 2.9, 95% CI 1.7-4.8), bilateral lung involvement (OR 2.5, 95% CI 1.4-4.4), ≥1 significant comorbidity-HIV infection, diabetes mellitus, liver failure or cirrhosis, congestive heart failure and chronic respiratory disease-(OR 2.3, 95% CI 1.3-3.8), and hemoglobin <12 g/dL (OR 1.8, 95% CI 1.1-3.1). A tuberculosis risk assessment tool (TReAT) was developed, stratifying patients with low (score ≤2), moderate (score 3-5) and high (score ≥6) mortality risk. The mortality associated with each group was 2.9%, 22.9% and 53.9%, respectively. The model performed equally well in the validation cohort. We provide a new, easy-to-use clinical scoring system to identify PTB patients with high-mortality risk in settings with good healthcare access, helping clinicians to decide which patients are in need of closer medical care during treatment. PMID:27636095

  1. 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

  2. Surgical interventions for pulmonary tuberculosis in Mumbai, India: surgical outcomes and programmatic challenges

    PubMed Central

    Shirodkar, S.; Anande, L.; Dalal, A.; Desai, C.; Corrêa, G.; Laxmeshwar, C.; Mansoor, H.; Remartinez, D.; Trelles, M.; Isaakidis, P.

    2016-01-01

    Setting: While surgery for pulmonary tuberculosis (PTB) is considered an important adjunct for specific cases, including drug-resistant tuberculosis, operational evidence on its feasibility and effectiveness is limited. Objective: To describe surgical outcomes and programmatic challenges of providing surgery for PTB in Mumbai, India. Design: A descriptive study of routinely collected data of surgical interventions for PTB from 2010 to 2014 in two Mumbai hospitals, one public, one private. Results: Of 85 patients, 5 (6%) died and 17 (20%) had complications, with wound infection being the most frequent. Repeat operation was required in 12 (14%) patients. Most procedures were performed on an emergency basis, and eligibility was established late in the course of treatment. Median time from admission to surgery was 51 days. Drug susceptibility test (DST) patterns and final treatment outcomes were not systematically collected. Conclusion: In a high-burden setting such as Mumbai, important data on surgery for PTB were surprisingly limited in both the private and public sectors. Eligibility for surgery was established late, culture and DST were not systematically offered, the interval between admission and surgery was long and TB outcomes were not known. Systematic data collection would allow for proper evaluation of surgery as adjunctive therapy for all forms of TB under programmatic conditions. PMID:27695683

  3. Surgical interventions for pulmonary tuberculosis in Mumbai, India: surgical outcomes and programmatic challenges

    PubMed Central

    Shirodkar, S.; Anande, L.; Dalal, A.; Desai, C.; Corrêa, G.; Laxmeshwar, C.; Mansoor, H.; Remartinez, D.; Trelles, M.; Isaakidis, P.

    2016-01-01

    Setting: While surgery for pulmonary tuberculosis (PTB) is considered an important adjunct for specific cases, including drug-resistant tuberculosis, operational evidence on its feasibility and effectiveness is limited. Objective: To describe surgical outcomes and programmatic challenges of providing surgery for PTB in Mumbai, India. Design: A descriptive study of routinely collected data of surgical interventions for PTB from 2010 to 2014 in two Mumbai hospitals, one public, one private. Results: Of 85 patients, 5 (6%) died and 17 (20%) had complications, with wound infection being the most frequent. Repeat operation was required in 12 (14%) patients. Most procedures were performed on an emergency basis, and eligibility was established late in the course of treatment. Median time from admission to surgery was 51 days. Drug susceptibility test (DST) patterns and final treatment outcomes were not systematically collected. Conclusion: In a high-burden setting such as Mumbai, important data on surgery for PTB were surprisingly limited in both the private and public sectors. Eligibility for surgery was established late, culture and DST were not systematically offered, the interval between admission and surgery was long and TB outcomes were not known. Systematic data collection would allow for proper evaluation of surgery as adjunctive therapy for all forms of TB under programmatic conditions.

  4. Incidence of pulmonary tuberculosis in garments workers of Dhaka City, Bangladesh.

    PubMed

    Hassan, M R; Bennoor, K S; Rahman, M F; Mahmud, A M; Hossain, M A; Habib, G M M; Kabir, M H; Kamaluddin, A F M; Ali, T; Shamsul Huq, A K M

    2005-04-01

    This study was conducted to find out the incidence of Pulmonary Tuberculosis (PT) in garments workers of Dhaka city and to find-out the relationship between the incidence of PT and socio-demographic factors of the respondents. From all garments factories of Dhaka city, 30 factories were included by stratified random sampling method. Then workers were selected by simple random sampling technique. Following selection, detailed history was taken and recorded in a pre-tested questionnaire. Chest X-ray, Sputum for AFB, M.T and ESR were done in the suspected cases. PT was diagnosed when any patient fulfilled predefined inclusion criteria. Out of 2400 selected workers, 2281 workers were studied finally. A total of 22 (9.6 per 1000) definite PT cases were identified. Sputum positive were 4/2281 (1.75 per 1000) cases. All were diagnosed as new cases; none had received any treatment of tuberculosis in the past. The study concludes that PT among the garments workers is a more alarming health issue than among the general population of Bangladesh. Improved and regular health check-up system and 'directly observed treatment shortcourse' (DOTS) should be implemented in the working places particularly where clusters of workers are working together.

  5. 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

  6. 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

  7. Transmission dynamics of pulmonary tuberculosis between autochthonous and immigrant sub-populations

    PubMed Central

    2009-01-01

    Background The overall incidence of tuberculosis (TB) in Western Europe has been declining since the 19th Century. However, immigrant sub-groups from high-prevalence countries are slowing down this trend. The aim of this study was to describe how immigration influences TB transmission in Germany. For that we prospectively investigated the dynamics of TB transmission between TB high-prevalence immigrant and TB low-prevalence local populations with molecular epidemiological methods and conventional contact investigations. Besides, we assessed transmission in relation to social mixing using an innovative tool that measures the integration of immigrants into the local social environment. Methods A prospective study of confirmed culture positive cases of pulmonary TB and their contacts was carried out in a German federal state from 2003 to 2005. Data for the study included: 1) case data routinely collected by the local public health staff and transmitted to the state health office and the national surveillance centre, 2) a study questionnaire designed to capture social interactions of relevance for TB transmission and 3) molecular genotyping data (IS6110 DNA fingerprint and spoligotyping). The proportion of German cases caused by foreign-born cases, and vice versa, was estimated and an integration index was computed using a selected set of questions from the study questionnaire. Results A total of 749 cases of culture-positive pulmonary tuberculosis voluntarily enrolled in the study, representing 57.8% of all registered cases diagnosed over the study period. Data that included study questionnaire and DNA fingerprinting were available for 41% (n = 308) of the study participants. Forty-seven clusters, defined as a least two cases infected by the same TB strains, were identified by molecular methods and included 132 (17%) of the study participants. Epidemiological links were identified for 28% of the clusters by conventional epidemiological data. In mixed clusters, defined

  8. Pulmonary tuberculosis among tribals in India: A systematic review & meta-analysis

    PubMed Central

    Thomas, Beena E.; Adinarayanan, Srividya; Manogaran, C.; Swaminathan, Soumya

    2015-01-01

    Background & objectives: There has been limited investigation on the prevalence of tuberculosis (TB) in tribal communities in India, a vulnerable section of Indian society. The lack of a population-based estimate prompted us to conduct a meta-analysis of existing studies to provide a single, population-based estimate of the TB prevalence for tribals. Methods: Literature search was conducted in PubMed using the keywords - “tuberculosis”, “tribals”, “India”, “prevalence”, and “survey”. References cited in the articles retrieved were also reviewed, and those found relevant were selected. TB prevalence rates estimated by the studies were used for our calculation of a pooled-estimate. Results: The pooled estimate, based on the random effects model, was 703 per 100,000 population with a 95 % CI of 386-1011. The associated heterogeneity measures in terms of Cochran's Q was significant (P=0 0.08 <0.1) and I2 was moderate at 48 per cent. Interpretation & conclusions: The meta-analysis demonstrated a large variability in pulmonary TB prevalence estimates among the different studies with poor representation of the various tribal groups. The moderate level of heterogeneity found across the studies suggests that the pooled-estimate needs to be treated with caution. Our findings also highlight the need to assess the pulmonary TB burden in India. PMID:26139779

  9. 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.

  10. 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

  11. Progress in the control of bovine tuberculosis in Spanish wildlife.

    PubMed

    Gortazar, Christian; Vicente, Joaquín; Boadella, Mariana; Ballesteros, Cristina; Galindo, Ruth C; Garrido, Joseba; Aranaz, Alicia; de la Fuente, José

    2011-07-01

    Despite the compulsory test and slaughter campaigns in cattle, bovine tuberculosis (bTB) is still present in Spain, and the role of wildlife reservoirs is increasingly recognized. We provide an update on recent progress made in bTB control in Spanish wildlife, including aspects of epidemiology, surveillance, host-pathogen interaction and wildlife vaccination. At the high densities and in the particular circumstances of Mediterranean environments, wild ungulates, mainly Eurasian wild boar and red deer, are able to maintain Mycobacterium bovis circulation even in absence of domestic livestock. Infection is widespread among wild ungulates in the south of the country, local infection prevalence being as high as 52% in wild boar and 27% in red deer. Risk factors identified include host genetic susceptibility, abundance, spatial aggregation at feeders and waterholes, scavenging, and social behaviour. An increasing trend of bTB compatible lesions was reported among wild boar and red deer inspected between 1992 and 2004 in Southwestern Spain. Sporadic cases of badger TB have been detected, further complicating the picture. Gene expression profiles were characterized in European wild boar and Iberian red deer naturally infected with M. bovis. The comparative analysis of gene expression profiles in wildlife hosts in response to infection advanced our understanding of the molecular mechanisms of infection and pathogenesis, revealed common and distinctive host responses to infection and identified candidate genes associated with resistance to bTB and for the characterization of host response to infection and vaccination. Ongoing research is producing valuable knowledge on vaccine delivery, safety and efficacy issues. Baits for the oral delivery of BCG vaccine preparations to wild boar piglets were developed and evaluated. The use of selective feeders during the summer was found to be a potentially reliable bait-deployment strategy. Safety experiments yielded no isolation of M

  12. Treatment delay among pulmonary tuberculosis patients in pastoralist communities in Bale Zone, Southeast Ethiopia

    PubMed Central

    2012-01-01

    Background Tuberculosis (TB) is a major public health problem in Africa with Ethiopia being the most affected. Treatment delay is an important indicator of access to TB diagnosis and treatment. However, little is known about factors associated with treatment delay of pulmonary TB among pastoralists. Health facility based cross sectional study was conducted on 129 pulmonary TB patients in pastoralist community. The study was conducted in three health centers and a hospital. Time between onset of TB symptoms and first visit to a professional health care provider (patient delay), and the time between first visits to the professional health care provider to the date of diagnosis (provider's delay) were analyzed using SPSS 16.0 statistical software. Findings A total of 129 new smear positive pulmonary TB patients participated in the study. The median total delay was 97 days. The median patient and health provider delays were 63 and 34 days, respectively. Ninety six percent of the patients were delayed for more than the twenty one days cutoff point. Patient delay was positively associated with first visit to traditional healer/private clinic/drug shop, rural residence, being illiterate, living in more than 10 kilometers from health facility; severity of illness at first presentation to health facility. Provider delay was positively associated with rural residence, being illiterate, patient with good functional status, patients in contact with more than two health providers, and place of first visit being traditional healer/private clinic/drug shop. Conclusions This study showed that majority of smear positive patients delayed either for diagnosis or treatment, thus continue to serve as reservoirs of infection. This indicates that there is a need for intervention to decrease patient and provider delays. Effort to reduce delays in pastoralist communities should focus on improving access to services in rural communities, engaging traditional and private health providers and

  13. 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

  14. 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.

  15. 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

  16. 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

  17. Seasonal Variation of Newly Notified Pulmonary Tuberculosis Cases from 2004 to 2013 in Wuhan, China

    PubMed Central

    Yang, Xiaobing; Duan, Qionghong; Wang, Jianjie; Zhang, Zhengbin; Jiang, Gaofeng

    2014-01-01

    Background Although there was a report about the seasonal variation in Wuhan city, it only analyzed the prevalence data of pulmonary tuberculosis (TB) cases, and just studied the seasonality by subgroup of smear positive and negative from 2006 to 2010 by spectral analysis. In this study, we investigated the seasonality of the total newly notified pulmonary TB cases by subgroups such as time period, sex, age, occupation, district, and sputum smear result from 2004 to 2013 in Wuhan by a popular seasonal adjustment model (TRAMO-SEATS). Methods Monthly pulmonary TB cases from 2004 to 2013 in Wuhan were analyzed by the TRAMO-SEATS seasonal adjustment program. Seasonal amplitude was calculated and compared within the subgroups. Results From 2004 to 2013, there were 77.76 thousand newly notified pulmonary TB cases in Wuhan, China. There was a dominant peak spring peak (March) with seasonal amplitude of 56.81% and a second summer peak (September) of 43.40%, compared with the trough month (December). The spring seasonal amplitude in 2004–2008 was higher than that of 2009–2013(P<0.05). There were no statistical differences for spring seasonal amplitude within subgroups of gender, age, district, and sputum smear result (P>0.05). However, there were significant differences in spring seasonal amplitude by occupation, with amplitude ranging from 59.37% to 113.22% (P<0.05). The summer seasonal amplitude in 2004–2008 was higher than that of 2009–2013(P<0.05). There were no statistical differences in summer seasonal amplitude within subgroups of gender, district, sputum smear result(P>0.05). There were significant differences in summer seasonal amplitude by age, with amplitude ranging from 36.05% to 100.09% (P<0.05). Also, there were significant differences in summer seasonal amplitude by occupation, with amplitude ranging from 43.40% to 109.88% (P<0.05). Conclusions There was an apparent seasonal variation in pulmonary TB cases in Wuhan. We speculated that spring peak in

  18. 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

  19. Abdominal tuberculosis.

    PubMed Central

    Ahmed, M. E.; Hassan, M. A.

    1994-01-01

    The abdomen is involved in 10% to 30% of patients with pulmonary tuberculosis. The diagnosis is not difficult in societies where the disease is common and clinicians are aware of it. While previously rare in Western countries, the incidence is now rising among immigrants, and patients with AIDS. In HIV-infected patients, the disease is of a rapidly progressive nature, often fatal through usually treatable, but the diagnosis is difficult and often delayed. Treatment is essentially medical but occasionally surgical operation is necessary. PMID:8154817

  20. 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

  1. 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

  2. TB-SA antibody test for diagnosis and monitoring treatment outcome of sputum smear negative pulmonary tuberculosis patients.

    PubMed

    Li, Xinxu; Xu, Hancheng; Jiang, Shiwen; Jing, Kuanhe; Wang, Li; Liu, Xiaoqiu; Li, Weibin; Zhang, Hui; Wang, Lixia

    2011-09-01

    The objectives of this study were to evaluate the suitability of the TB-SA antibody test to diagnose tuberculosis in sputum smear negative (SS-) pulmonary tuberculosis (TB) patients and its applicability for monitoring treatment outcomes in these patients. This study was conducted in three counties/districts in Chongqing Municipality, Liaoning Province, China between June 2005 and June 2007. A total of 432 SS suspected pulmonary TB patients were recruited and their blood was collected prior to treatment, at the end of 1 month of treatment, 2 months of treatment and 6 months of treatment (E6MT). The serum samples were analyzed with a TB-SA antibody test kit. Of the 432 SS suspected pulmonary TB patients, serum samples were obtained at all time points in 316 patients and analyzed. The 316 patients were divided into three groups according to sputum smear and sputum culture results and the chest X-ray results before treatment and at E6MT. Ten point four percent were SS-/culture positive (C+), 73.1% were SS-/culture negative (C-) with X-rays abnormalities, and 16.5% were SS-/C- without X-rays abnormalities. The positive rates for TB-SA antibody in the three groups were 57.6, 44.6 and 44.2%, respectively, before treatment, and 18.2, 19.1 and 26.9%, respectively, at E6MT. There was a significant decrease in TB-SA antibody positivity with treatment for all 3 groups. The TB-SA antibody test may be a useful adjunct to diagnose tuberculosis in SS- pulmonary TB patients, and may be useful for monitoring treatment outcomes of SS- pulmonary TB patients. PMID:22299440

  3. Genetic polymorphisms of IL-17A, IL-17F, TLR4 and miR-146a in association with the risk of pulmonary tuberculosis.

    PubMed

    Wang, Min; Xu, Guisheng; Lü, Lingshuang; Xu, Kun; Chen, Yongzhong; Pan, Hongqiu; Burstrom, Bo; Burstrom, Kristina; Wang, Jianming

    2016-01-01

    Genetic factors affect host susceptibility to pathogens. In this population-based case control study, we explored the genetic polymorphisms of IL-17, TLR4 and miR-146a in association with pulmonary tuberculosis in a Chinese Han population. We recruited 1601 pulmonary tuberculosis patients matched with 1526 healthy controls and genotyped twelve functional single nucleotide polymorphisms (SNPs). After the correction for multiple comparisons, two SNPs (rs10759932 and rs2737190) in the TLR4 gene remained significant. Individuals carrying the rs2737190-AG genotype (vs. AA) had a significantly increased risk of either clinical tuberculosis (OR: 1.31, 95% CI: 1.11-1.53) or sputum smear-positive tuberculosis (OR: 1.35, 95% CI: 1.13-1.61). Stratification analysis revealed that the effects of genetic variations on tuberculosis were more evident among non-smokers. People with haplotype TLR4 rs10983755G-rs10759932C had a significantly increased risk of tuberculosis (OR: 3.43, 95% CI: 2.34-5.05). Moreover, we found that SNPs of rs3819024 in IL-17A and rs763780 in IL-17F were weakly related to a prognosis of tuberculosis. Our results suggest that genetic polymorphisms of IL-17 and TLR4 may play a role in host susceptibility to tuberculosis in the Chinese Han population. More work is necessary to identify specific causative variants of tuberculosis underlying the observed associations. PMID:27339100

  4. Genetic polymorphisms of IL-17A, IL-17F, TLR4 and miR-146a in association with the risk of pulmonary tuberculosis

    PubMed Central

    Wang, Min; Xu, Guisheng; Lü, Lingshuang; Xu, Kun; Chen, Yongzhong; Pan, Hongqiu; Burstrom, Bo; Burstrom, Kristina; Wang, Jianming

    2016-01-01

    Genetic factors affect host susceptibility to pathogens. In this population-based case control study, we explored the genetic polymorphisms of IL-17, TLR4 and miR-146a in association with pulmonary tuberculosis in a Chinese Han population. We recruited 1601 pulmonary tuberculosis patients matched with 1526 healthy controls and genotyped twelve functional single nucleotide polymorphisms (SNPs). After the correction for multiple comparisons, two SNPs (rs10759932 and rs2737190) in the TLR4 gene remained significant. Individuals carrying the rs2737190-AG genotype (vs. AA) had a significantly increased risk of either clinical tuberculosis (OR: 1.31, 95% CI: 1.11–1.53) or sputum smear-positive tuberculosis (OR: 1.35, 95% CI: 1.13–1.61). Stratification analysis revealed that the effects of genetic variations on tuberculosis were more evident among non-smokers. People with haplotype TLR4 rs10983755G–rs10759932C had a significantly increased risk of tuberculosis (OR: 3.43, 95% CI: 2.34–5.05). Moreover, we found that SNPs of rs3819024 in IL-17A and rs763780 in IL-17F were weakly related to a prognosis of tuberculosis. Our results suggest that genetic polymorphisms of IL-17 and TLR4 may play a role in host susceptibility to tuberculosis in the Chinese Han population. More work is necessary to identify specific causative variants of tuberculosis underlying the observed associations. PMID:27339100

  5. Clinical and Radiographic Manifestations of Sputum Culture-Negative Pulmonary Tuberculosis

    PubMed Central

    Nguyen, Minh-Vu H.; Jenny-Avital, Elizabeth R.; Burger, Susanne; Leibert, Eric M.; Achkar, Jacqueline M.

    2015-01-01

    Intervention at the earliest possible stage of pulmonary tuberculosis (PTB) reduces morbidity for the individual and transmission for the community. We characterize the clinical and radiographic manifestations of sputum culture-negative (Cx-) PTB in order to facilitate awareness of this under recognized and likely early disease state. In this cross-sectional sub-study, we reviewed the medical records of HIV-uninfected PTB patients enrolled from 2006–2014 within the context of a TB biomarker study in New York City. Cx- PTB was defined as clinical and/or radiographic presentation consistent with PTB, three initial mycobacterial sputum cultures negative, and no evidence of other respiratory disease. Diagnosis was confirmed by clinical and radiographic improvement on antituberculous treatment and/or culture, nucleic acid, or histological confirmation from a specimen other than the initial three sputa. Cx+ PTB was defined as above but with M. tuberculosis growth in at least one of the first three sputum cultures. Demographics, symptoms, and radiographic findings on initial presentation were compared between the two groups. Of 99 subjects diagnosed with PTB, 21 met the criteria of Cx- PTB. Cx- compared to Cx+ subjects presented with a significantly lower frequency of cough (70% vs. 91%, P = 0.02), sputum production (30% vs. 64%, P < 0.01), weight loss (25% vs. 54%, P = 0.02), and frequency of cavitation on chest CT (12% vs. 68%, P < 0.01). Our findings should raise awareness that neither a positive culture nor the hallmark symptoms are invariably associated with early TB disease. PMID:26448182

  6. Glucose Metabolism Disorder Is Associated with Pulmonary Tuberculosis in Individuals with Respiratory Symptoms from Brazil

    PubMed Central

    Castro, Simone; Cafezeiro, Aparecida S.; Daltro, Carla; Netto, Eduardo M.; Kornfeld, Hardy; Andrade, Bruno B.

    2016-01-01

    Background Diabetes mellitus (DM) has been associated with increased risk for pulmonary tuberculosis (PTB) in endemic settings but it is unknown whether PTB risk is also increased by pre-DM. Here, we prospectively examined the association between glucose metabolism disorder (GMD) and PTB in patients with respiratory symptoms at a tuberculosis primary care reference center in Brazil. Methods Oral glucose tolerance test was performed and levels of fasting plasma glucose and glycohemoglobin (HbA1c) were measured in a cohort of 892 individuals presenting with respiratory symptoms of more than two weeks duration. Patients were also tested for PTB with sputum cultures. Prevalence of pre-DM and DM (based on HbA1c) was estimated and tested for association with incident PTB. Other TB risk factors including smoking history were analyzed. Results The majority of the study population (63.1%) exhibited GMD based on HbA1c ≥5.7%. Patients with GMD had higher prevalence of PTB compared to normoglycemic patients. Individuals with DM exhibited increased frequency of TB-related symptoms and detection of acid-fast bacilli in sputum smears. Among patients with previous DM diagnosis, sustained hyperglycemia (HbA1c ≥7.0%) was associated with increased TB prevalence. Smoking history alone was not significantly associated with TB in our study population but the combination of smoking and HbA1c ≥7.0% was associated with 6 times higher odds for PTB. Conclusions Sustained hyperglycemia and pre-DM are independently associated with active PTB. This evidence raises the question whether improving glycemic control in diabetic TB patients would reduce the risk of TB transmission and simultaneously reduce the clinical burden of disease. A better understanding of mechanisms underlying these associations, especially those suggesting that pre-DM may be a factor driving susceptibility to TB is warranted. PMID:27078026

  7. Adenosine deaminase in CSF and pleural fluid for diagnosis of tubercular meningitis and pulmonary tuberculosis.

    PubMed

    Nepal, A K; Gyawali, N; Poudel, B; Mahato, R V; Lamsal, M; Gurung, R; Baral, N; Majhi, S

    2012-12-01

    Tuberculosis (TB) is one of the most common infectious diseases in developing countries including Nepal. Delay in diagnosis and treatment of tuberculosis results in poor prognosis of the disease. This study was conducted to estimate diagnostic cut off values of Adenosine Deaminase (ADA) in cerebrospinal fluid (CSF) and pleural fluid and to evaluate the sensitivity, specificity, positive and negative predictive values ofADA in pleural fluid and CSF from patients with tuberculous and non-tuberculous disease. A total of 98 body fluid (CSF: 24, Pleural fluid: 74) specimens were received for the estimation of ADA. ADA activity was measured at 37 degrees C by spectrophotometric method of Guisti and Galanti, 1984 at 625nm wavelength. Among the patients enrolled for the study subjects for which CSF were received (n = 24) included 8 tuberculous meningitis (TBM), and 16 non-tubercular meningitis (NTM). Pleural fluid samples (n = 74) were received from 19 pulmonary TB with pleural effusion, 17 PTB without pleural effusion and 37 of non-tuberculous disease patients. CSF ADA activity were (11. 1 +/- 2.03 IU/L) and (5.3 +/- +1.89 IU/L) (p <00001) in TM and non-NTM groups and Pleural fluid ADA activity were (10 +/- 22.18 IU/L) and (23.79 +/- 11.62 IU/L) (p < 0.001) in PTB and non-TB groups respectively. ADA test in body fluids, which is simple, cost-effective and sensitive, specific for the tubercular disease is recommended to perform before forwarding the cumbersome and expensive procedures like culture and PCR for TB diagnosis. PMID:24579533

  8. Plasma melatonin and urinary 6-hydroxymelatonin levels in patients with pulmonary tuberculosis.

    PubMed

    Ozkan, Esin; Yaman, Halil; Cakir, Erdinc; Deniz, Omer; Oztosun, Muzaffer; Gumus, Seyfettin; Akgul, Emin Ozgur; Agilli, Mehmet; Cayci, Tuncer; Kurt, Yasemin Gulcan; Aydin, Ibrahim; Arslan, Yakup; Ilhan, Nevin; Ilhan, Necip; Erbil, Mehmet Kemal

    2012-08-01

    Tuberculosis (TB) is the second most frequent cause of death in the world, after AIDS. Delay in diagnosing TB is an important worldwide problem. It seriously threatens public health. Cell-mediated immune responses play an important role in the pathogenesis of TB infection. The course of Mycobacterium tuberculosis (MTb) infection is regulated by two distinct T cell cytokine patterns. Melatonin is a biomolecule (mainly secreted by the pineal gland) with free radical scavenging, antioxidant and immunoregulatory properties. Melatonin has both its direct and indirect immunomodulatory effects on the immune system. In this study, we measured plasma melatonin and urine 6-hydroxy melatonin sulphate (6-HMS) concentrations in patients with newly diagnosed TB for the purpose of investigating whether there was a relationship between their levels and MTb infection. Thirty-one newly diagnosed patients presenting with active TB and 31 healthy subjects as the control group were included in this study. Blood and 24-h urine samples were collected from all individuals. Plasma melatonin levels and urine 6-HMS were measured. Our results show that in patients with TB, mean melatonin and 6-HMS concentrations were significantly lower than in the control subjects (p = 0.037, p < 0.001, respectively). We believe that the treatment of TB patients with melatonin might result in a wide range of health benefits including improved quality of life and reduced severity of infection in these patients. Supplementation with melatonin may be considered as an adjunctive therapy to classic treatment of pulmonary TB, especially during the acute phase of infection.

  9. Meandering right pulmonary vein associated with severe and progressive "idiopathic-like" pulmonary hypertensive vascular disease.

    PubMed

    Cuenca, Sofia; Bret, Montserrat; del Cerro, Maria Jesus

    2016-03-01

    Congenital anomalies of the pulmonary veins are rare. Meandering right pulmonary vein, considered a part of the Scimitar syndrome spectrum, is often an incidental finding during chest imaging. We present the case of a 4-year-old girl diagnosed with meandering pulmonary vein, who developed pulmonary hypertensive disease with an aggressive course, in spite of absence of hypoxia or elevated pulmonary wedge pressure.

  10. Immune Inflammation and Disease Progression in Idiopathic Pulmonary Fibrosis.

    PubMed

    Balestro, Elisabetta; Calabrese, Fiorella; Turato, Graziella; Lunardi, Francesca; Bazzan, Erica; Marulli, Giuseppe; Biondini, Davide; Rossi, Emanuela; Sanduzzi, Alessandro; Rea, Federico; Rigobello, Chiara; Gregori, Dario; Baraldo, Simonetta; Spagnolo, Paolo; Cosio, Manuel G; Saetta, Marina

    2016-01-01

    The clinical course in idiopathic pulmonary fibrosis (IPF) is highly heterogeneous, with some patients having a slow progression and others an accelerated clinical and functional decline. This study aims to clinically characterize the type of progression in IPF and to investigate the pathological basis that might account for the observed differences in disease behavior. Clinical and functional data were analyzed in 73 IPF patients, followed long-time as candidates for lung transplantation. The forced vital capacity (FVC) change/year (< or ≥10% predicted) was used to define "slow" or "rapid" disease progression. Pathological abnormalities were quantified in the explanted lung of 41 out of 73 patients undergoing lung transplantation. At diagnosis, slow progressors (n = 48) showed longer duration of symptoms and lower FVC than rapid progressors (n = 25). Eleven slow and 3 rapid progressors developed an acute exacerbation (AE) during follow-up. Quantitative lung pathology showed a severe innate and adaptive inflammatory infiltrate in rapid progressors, markedly increased compared to slow progressors and similar to that observed in patients experiencing AE. The extent of inflammation was correlated with the yearly FVC decline (r = 0.52, p = 0.005). In conclusion an innate and adaptive inflammation appears to be a prominent feature in the lung of patients with IPF and could contribute to determining of the rate of disease progression. PMID:27159038

  11. 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.

  12. 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

  13. Quality of outcome reporting in phase II studies in pulmonary tuberculosis.

    PubMed

    Bonnett, Laura Jayne; Davies, Geraint Rhys

    2015-01-01

    Tuberculosis (TB) remains a major killer amongst the infectious diseases. Current treatment involves a four-drug regimen for at least 6 months. New drugs and regimens are required to shorten treatment duration, reduce toxicity and combat drug resistance, but the optimal methodology to define the critical path for novel regimens is not well defined. We undertook a systematic review to summarise outcomes reported in Phase II trials of patients with newly diagnosed pulmonary TB to assess the need for a core outcome set. A systematic search of databases (PubMed, MEDLINE, EMBASE and LILACs) was conducted on 1 May 2015 to retrieve relevant peer-reviewed articles. Reference lists of included studies were also searched. This systematic review considered all reported outcomes. Risk of bias was considered via sequence generation, allocation concealment, blinding, reasons for exclusions, and selective reporting. Of 55 included studies, 20 were Phase IIB studies based on culture conversion, 32 were Phase IIA studies based on quantitative bacteriology, and three considered alternative outcomes. Large variation in reported outcomes and trial characteristics was observed across the included studies. Bacteriological results were as often expressed in terms of positivity as negativity, with varying definitions of culture conversion. Variation in reporting was particularly marked for Phase IIA studies, where multiple time intervals were typically selected for analysis and sometimes resulted in differing interpretations of the efficacy of drugs or regimens. Within both Phase IIA and IIB studies, there was variation in the time points at which the study participants were sampled, as well as in the bacteriological media and methods used. For successful future meta-analysis of early-phase studies, the findings of this review suggest that development of a core outcome set would be desirable. This would enable trial results to be more easily compared and combined, potentially leading to

  14. Variability of Infectious Aerosols Produced during Coughing by Patients with Pulmonary Tuberculosis

    PubMed Central

    Jones-López, Edward C.; Ayakaka, Irene; Kim, Soyeon; Menyha, Harriet; Kirenga, Bruce; Muchwa, Christopher; Joloba, Moses; Dryden-Peterson, Scott; Reilly, Nancy; Okwera, Alphonse; Elliott, Alison M.; Smith, Peter G.; Mugerwa, Roy D.; Eisenach, Kathleen D.; Ellner, Jerrold J.

    2012-01-01

    Rationale: Mycobacterium tuberculosis is transmitted by infectious aerosols, but assessing infectiousness currently relies on sputum microscopy that does not accurately predict the variability in transmission. Objectives: To evaluate the feasibility of collecting cough aerosols and the risk factors for infectious aerosol production from patients with pulmonary tuberculosis (TB) in a resource-limited setting. Methods: We enrolled subjects with suspected TB in Kampala, Uganda and collected clinical, radiographic, and microbiological data in addition to cough aerosol cultures. A subset of 38 subjects was studied on 2 or 3 consecutive days to assess reproducibility. Measurements and Main Results: M. tuberculosis was cultured from cough aerosols of 28 of 101 (27.7%; 95% confidence interval [CI], 19.9–37.1%) subjects with culture-confirmed TB, with a median 16 aerosol cfu (range, 1–701) in 10 minutes of coughing. Nearly all (96.4%) cultivable particles were 0.65 to 4.7 μm in size. Positive aerosol cultures were associated with higher Karnofsky performance scores (P = 0.016), higher sputum acid-fast bacilli smear microscopy grades (P = 0.007), lower days to positive in liquid culture (P = 0.004), stronger cough (P = 0.016), and fewer days on TB treatment (P = 0.047). In multivariable analyses, cough aerosol cultures were associated with a salivary/mucosalivary (compared with purulent/mucopurulent) appearance of sputum (odds ratio, 4.42; 95% CI, 1.23–21.43) and low days to positive (per 1-d decrease; odds ratio, 1.17; 95% CI, 1.07–1.33). The within-test (kappa, 0.81; 95% CI, 0.68–0.94) and interday test (kappa, 0.62; 95% CI, 0.43–0.82) reproducibility were high. Conclusions: A minority of patients with TB (28%) produced culturable cough aerosols. Collection of cough aerosol cultures is feasible and reproducible in a resource-limited setting. PMID:22798319

  15. 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

  16. Quantification of Pulmonary Inflammatory Processes Using Chest Radiography: Tuberculosis as the Motivating Application

    PubMed Central

    Giacomini, Guilherme; Miranda, José R.A.; Pavan, Ana Luiza M.; Duarte, Sérgio B.; Ribeiro, Sérgio M.; Pereira, Paulo C.M.; Alves, Allan F.F.; de Oliveira, Marcela; Pina, Diana R.

    2015-01-01

    Abstract The purpose of this work was to develop a quantitative method for evaluating the pulmonary inflammatory process (PIP) through the computational analysis of chest radiography exams in posteroanterior (PA) and lateral views. The quantification procedure was applied to patients with tuberculosis (TB) as the motivating application. A study of high-resolution computed tomography (HRCT) examinations of patients with TB was developed to establish a relation between the inflammatory process and the signal difference-to-noise ratio (SDNR) measured in the PA projection. A phantom essay was used to validate this relation, which was implemented using an algorithm that is able to estimate the volume of the inflammatory region based solely on SDNR values in the chest radiographs of patients. The PIP volumes that were quantified for 30 patients with TB were used for comparisons with direct HRCT analysis for the same patient. The Bland–Altman statistical analyses showed no significant differences between the 2 quantification methods. The linear regression line had a correlation coefficient of R2 = 0.97 and P < 0.001, showing a strong association between the volume that was determined by our evaluation method and the results obtained by direct HRCT scan analysis. Since the diagnosis and follow-up of patients with TB is commonly performed using X-rays exams, the method developed herein can be considered an adequate tool for quantifying the PIP with a lower patient radiation dose and lower institutional cost. Although we used patients with TB for the application of the method, this method may be used for other pulmonary diseases characterized by a PIP. PMID:26131814

  17. Assessment of treatment interruption among pulmonary tuberculosis patients: A cross-sectional study

    PubMed Central

    Gorityala, Satya Bhgath; Mateti, Uday Venkat; Konuru, Venkateswarlu; Martha, Srinivas

    2015-01-01

    Background: Multi-drug resistant tuberculosis (TB) is a rising peril of the TB control in India caused mostly by incomplete treatment. Aim: The aim was to assess the treatment interruption among pulmonary TB (PTB) patients. Materials and Methods: A cross-sectional study was carried out for a period of 9 months among PTB patients. Patients admitted with active pulmonary Koch's and history of anti-TB treatment (ATT) for 1-month or more from any source and who returns to treatment after not taking ATT consecutively for 2 months or more were included in the study. The data were collected from the patients or their caretakers to obtain the source of treatment given previously before default, number of treatment interruptions, phase and reasons for treatment interruption treatment. Results: A total of 107 defaulters were identified during the study period. In the present study, 62.6% of the patients interrupted treatment only once, 55.34% of the patient's early continuation (3–4 months) treatment, and 47.66% of the patient's only one reason for the treatment interruptions during the course of the treatment. The most common reason for the treatment interruptions were felt well with TB treatment (29.53%) followed by side effects (16.06%), lack of money (8.29%), and other reasons. Conclusion: The study revealed that most of the defaulters were in the age group between 35 and 60 years, male gender, illiterates, daily wage labor, and married. The treatment interruptions were minimized by putting the efforts to improve direct supervision; pretreatment counseling and retrieve treatment interrupters were recommended. PMID:26229358

  18. Prevalence of chronic pulmonary aspergillosis in patients with tuberculosis from Iran.

    PubMed

    Hedayati, M T; Azimi, Y; Droudinia, A; Mousavi, B; Khalilian, A; Hedayati, N; Denning, D W

    2015-09-01

    In patients with preexisting lung disease, especially a cavity, Aspergillus can infect the surface of the cavity, causing chronic cavitary pulmonary aspergillosis (CCPA), and may form an aspergilloma, collectively called chronic pulmonary aspergillosis (CPA). In the present study, we assessed tuberculosis (TB) patients for CPA based on culture and serological methods. During a period of 1 year (from March 2013 to March 2014), we studied 124 patients with TB (94 with current TB and 30 with previous TB) at Masih Daneshvari Hospital in Tehran, Iran. Sputum specimens were analyzed by direct microscopic examination (DME) and fungal culture. The clinical and radiological features of all patients were recorded, to categorize the patients into CCPA and aspergilloma. All patients were screened for serum-specific IgG against A. fumigatus, by enzyme-linked immunosorbent assay (ELISA). Out of 124 patients with TB (66 male, age range: 10-91 years), 48 patients (38.7 %) exhibited residual cavities. Eighteen (14.5 %) patients had cavities with pleural thickening. A round-shaped mass lesion was detected in six patients (6.8 %). DME was positive in ten patients for septate fungal hyphae. A. fumigatus was grown from 14 samples. Fifty-five (44.3 %) cases were positive for serum-specific IgG against A. fumigatus. Of 124 patients with TB, 3 (2.4 %) met criteria for aspergilloma and 14 (11.3 %) for CCPA. CPA is a common clinical presentation in individuals with healed TB in Iran, as reported by previous studies from other countries. PMID:26003310

  19. Post-Inhaled Corticosteroid Pulmonary Tuberculosis Increases Lung Cancer in Patients with Asthma

    PubMed Central

    Lin, Frank Cheau-Feng; Nfor, Oswald Ndi; Jhang, Kai-Ming; Ku, Wen-Yuan; Ho, Chien-Chang; Lung, Chia-Chi; Pan, Hui-Hsien; Wu, Min-Chen; Wu, Ming-Fang; Liaw, Yung-Po

    2016-01-01

    Purpose To evaluate the association between post-inhaled corticosteroid (ICS) pulmonary tuberculosis (TB), pneumonia and lung cancer in patients with asthma. Methods The study samples were collected from the National Health Insurance Database. Asthmatic patients who were first-time users of ICS between 2003 and 2005 were identified as cases. For each case, 4 control individuals were randomly matched for sex, age and date of ICS use. Cases and matched controls were followed up until the end of 2010. Cox proportional hazard regression was used to determine the hazard ratio for pulmonary infections and lung cancer risk in the ICS users and non-users. Results A total of 10,904 first-time users of ICS were matched with 43,616 controls. The hazard ratios for lung cancer were: 2.52 (95% confidence interval [CI], 1.22–5.22; p = 0.012) for individuals with post-ICS TB, 1.28 (95%CI, 0.73–2.26; p = 0.389) for post-ICS pneumonia, 2.31(95%CI, 0.84–6.38; p = 0.105) for post-ICS pneumonia+TB, 1.08 (95%CI, 0.57–2.03; p = 0.815) for TB, 0.99 (95%CI, 0.63–1.55; p = 0.970) for pneumonia, and 0.32 (95%CI, 0.05–2.32; p = 0.261) for pneumonia+ TB, respectively. Conclusions Post-ICS TB increased lung cancer risk in patients with asthma. Because of the high mortality associated with lung cancer, screening tests are recommended for patients with post-ICS TB. PMID:27448321

  20. Biomarkers of progression of chronic obstructive pulmonary disease (COPD)

    PubMed Central

    Vaughan, Annalicia; Dent, Annette G.; O’Hare, Phoebe E.; Goh, Felicia; Bowman, Rayleen V.; Fong, Kwun M.; Yang, Ian A.

    2014-01-01

    Disease progression of chronic obstructive pulmonary disease (COPD) is variable, with some patients having a relatively stable course, while others suffer relentless progression leading to severe breathlessness, frequent acute exacerbations of COPD (AECOPD), respiratory failure and death. Radiological markers such as CT emphysema index, bronchiectasis and coronary artery calcification (CAC) have been linked with increased mortality in COPD patients. Molecular changes in lung tissue reflect alterations in lung pathology that occur with disease progression; however, lung tissue is not routinely accessible. Cell counts (including neutrophils) and mediators in induced sputum have been associated with lung function and risk of exacerbations. Examples of peripheral blood biological markers (biomarkers) include those associated with lung function (reduced CC-16), emphysema severity (increased adiponectin, reduced sRAGE), exacerbations and mortality [increased CRP, fibrinogen, leukocyte count, IL-6, IL-8, and tumor necrosis factor α (TNF-α)] including increased YKL-40 with mortality. Emerging approaches to discovering markers of gene-environment interaction include exhaled breath analysis [volatile organic compounds (VOCs), exhaled breath condensate], cellular and systemic responses to exposure to air pollution, alterations in the lung microbiome, and biomarkers of lung ageing such as telomere length shortening and reduced levels of sirtuins. Overcoming methodological challenges in sampling and quality control will enable more robust yet easily accessible biomarkers to be developed and qualified, in order to optimise personalised medicine in patients with COPD. PMID:25478195

  1. Longitudinal Lung Function Decrease in Subjects with Spontaneous Healed Pulmonary Tuberculosis

    PubMed Central

    Lee, Seung Heon; Kwon, Amy M.; Yang, Hae-Chung; Lee, Seung Ku; Kim, Young; Choi, Jong Hyun; Kim, Je Hyeong; Shin, Chol

    2016-01-01

    Objective We compared the longitudinal course of post-bronchodilator Forced Expiratory Volume in 1 second (pFEV1) over a 10-year period in subjects with spontaneous healed pulmonary tuberculosis (SHPTB) with that in normal subjects. Methods We prospectively investigated 339 subjects with SHPTB and 3211 normal subjects. pFEV1 values measured biannually over 10 years were analyzed using mixed effects model. Results At baseline, there were no differences in gender, smoking amount, and mean height, except mean age (50.0 ± 8.1 VS. 48.1 ± 7.3, P< 0.001) between the SHPTB and normal group. 52% of the 339 participants with SHPTB and 56% of the 3211 normal participants participated till the end of study. According to the final model, the SHPTB group showed significantly larger decrease in the average pFEV1 over the time than the normal group (P< 0.001) adjusted for gender, age, height, smoking pack years, and time effects. Especially, the interaction effect between time and group was statistically significant (P = 0.036). Conclusion The average lung function in terms of pFEV1 decreases faster in subjects with SHPTB than in normal individuals over time. PMID:27706203

  2. The Poor Survival among Pulmonary Tuberculosis Patients in Chiapas, Mexico: The Case of Los Altos Region.

    PubMed

    Nájera-Ortiz, J C; Sánchez-Pérez, H J; Ochoa-Díaz-López, H; Leal-Fernández, G; Navarro-Giné, A

    2012-01-01

    Objective. To analyse survival in patients with pulmonary tuberculosis (PTB) and factors associated with such survival. Design. Study of a cohort of patients aged over 14 years diagnosed with PTB from January 1, 1998 to July 31, 2005. During 2004-2006 a home visit was made to each patient and, during 2008-2009, they were visited again. During these visits a follow-up interview was administered; when the patient had died, a verbal autopsy was conducted with family members. Statistical analysis consisted of survival tests, Kaplan-Meier log-rank test and Cox regression. Results. Of 305 studied patients, 68 had died due to PTB by the time of the first evaluation, 237 were followed-up for a second evaluation, and 10 of them had died of PTB. According to the Cox regression, age (over 45 years) and treatment duration (under six months) were associated with a poorer survival. When treatment duration was excluded, the association between poorer survival with age persisted, whereas with having been treated via DOTS strategy, was barely significant. Conclusions. In the studied area it is necessary that patients receive a complete treatment scheme, and to give priority to patients aged over 45 years.

  3. High social anxiety and poor quality of life in patients with pulmonary tuberculosis.

    PubMed

    Kibrisli, Erkan; Bez, Yasin; Yilmaz, Ahmet; Aslanhan, Hamza; Taylan, Mahsuk; Kaya, Halide; Tanrikulu, Abdullah Cetin; Abakay, Ozlem

    2015-01-01

    Pulmonary tuberculosis (PT) has been previously related with various psychosocial adverse consequences including stigmatization and social isolation.Social anxiety is a psychiatric condition that may be associated with social isolation and fear of social exclusion.To date no study has investigated social anxiety and its impact on quality of life (QoL) among patients with PT. Therefore, we aimed to determine the severity of social anxiety in a group of patients with PT.Among patients who were recently discharged from hospital with the diagnosis of PT 94 patients and 99 healthy control subjects who had similar demographical features have been included in the study. A psychiatrist interviewed all participants and a semistructured interview form, which was prepared by the authors, Liebowitz Social Anxiety Scale (LSAS), and Short Form-36 were administered to them.Patients with PT showed higher levels of performance avoidance and social avoidance than healthy control subjects. They reported lower QoL scores across all dimensions. Among patients women showed higher levels of LSAS subscale scores and total score. Fear of social exclusion was predicted by perceived illness severity and emotional role difficulty. On the other hand, perceived illness severity was predicted by fear of exclusion and sedimentation level.PT patients seem to experience higher levels of social anxiety and associated fear of social exclusion that add to their worse QoL during the earlier months of their disease. Among them fear of social exclusion is related with perceived illness severity.

  4. Evaluation of GeneXpert MTB/RIF assay for direct diagnosis of pulmonary tuberculosis

    PubMed Central

    Moussa, Husseiny Sh.; Bayoumi, Faten S.; Ali, Ahmed M.

    2016-01-01

    Objectives: To evaluate the performance of GeneXpert MTB/RIF assay for direct diagnosis of pulmonary tuberculosis (PTB). Methods: This is a cross-sectional study conducted between October 2013 and February 2016 at Abbassaia Chest Hospital and Ain Shams University Hospital, Cairo, Egypt. Inclusion criteria were adults between 18 and 60 years with suspected PTB and classified into 5 clinical categories based on their clinical, radiological, and laboratory findings: confirmed TB, probable TB, possible TB, unlikely TB, and not TB. Two sputum samples from each participant were analyzed by GX and the results were compared by conventional culture. Results: In total, 218 participants were enrolled: 71 had confirmed TB; 112, highly probable TB; 20, probable TB; 10, unlikely TB; and 5, no TB. The sensitivity and specificity of the GX assay were 93% and 98.3% respectively. GeneXpert was positive in 93% of confirmed TB and 2.2% of probable TB cases. Conclusions: GeneXpert is a rapid and promising technique with good sensitivity (93%) and specificity (98.3%), but it cannot be used as a standalone PTB diagnostic tool. There is a need for more GX evaluation studies in countries with low TB incidence. PMID:27652357

  5. Validation of an Automated Cough Detection Algorithm for Tracking Recovery of Pulmonary Tuberculosis Patients

    PubMed Central

    Larson, Sandra; Comina, Germán; Gilman, Robert H.; Tracey, Brian H.; Bravard, Marjory; López, José W.

    2012-01-01

    Background A laboratory-free test for assessing recovery from pulmonary tuberculosis (TB) would be extremely beneficial in regions of the world where laboratory facilities are lacking. Our hypothesis is that analysis of cough sound recordings may provide such a test. In the current paper, we present validation of a cough analysis tool. Methodology/Principal Findings Cough data was collected from a cohort of TB patients in Lima, Peru and 25.5 hours of recordings were manually annotated by clinical staff. Analysis software was developed and validated by comparison to manual scoring. Because many patients cough in bursts, coughing was characterized in terms of cough epochs. Our software correctly detects 75.5% of cough episodes with a specificity of 99.6% (comparable to past results using the same definition) and a median false positive rate of 4 false positives/hour, due to the noisy, real-world nature of our dataset. We then manually review detected coughs to eliminate false positives, in effect using the algorithm as a pre-screening tool that reduces reviewing time to roughly 5% of the recording length. This cough analysis approach provides a foundation to support larger-scale studies of coughing rates over time for TB patients undergoing treatment. PMID:23071550

  6. A real-time PCR signature to discriminate between tuberculosis and other pulmonary diseases.

    PubMed

    Laux da Costa, Lucas; Delcroix, Melaine; Dalla Costa, Elis R; Prestes, Isaías V; Milano, Mariana; Francis, Steve S; Unis, Gisela; Silva, Denise R; Riley, Lee W; Rossetti, Maria L R

    2015-07-01

    The goal of this study was to identify a host gene signature that can distinguish tuberculosis (TB) from other pulmonary diseases (OPD). We conducted real-time PCR on whole blood samples from patients in Brazil. TB and OPD patients (asthma and non-TB pneumonia) differentially expressed granzyme A (GZMA), guanylate binding protein 5 (GBP5) and Fc gamma receptor 1A (CD64). Receiver operating characteristic, tree classification and random forest analyses were applied to evaluate the discriminatory power of the three genes and find the gene panel most predictive of patients' disease classification. Tree classification produced a model based on GBP5 and CD64 expression. In random forest analysis, the combination of the three genes provided a robust biosignature to distinguish TB from OPD with 95% specificity and 93% sensitivity. Our results suggest that GBP5 and CD64 in tandem may be the most predictive combination. However, GZMA contribution to the prediction model requires further investigation. Regardless, these three genes show promise as a rapid diagnostic marker separating TB from OPD. PMID:26025597

  7. The Poor Survival among Pulmonary Tuberculosis Patients in Chiapas, Mexico: The Case of Los Altos Region

    PubMed Central

    Nájera-Ortiz, J. C.; Sánchez-Pérez, H. J.; Ochoa-Díaz-López, H.; Leal-Fernández, G.; Navarro-Giné, A.

    2012-01-01

    Objective. To analyse survival in patients with pulmonary tuberculosis (PTB) and factors associated with such survival. Design. Study of a cohort of patients aged over 14 years diagnosed with PTB from January 1, 1998 to July 31, 2005. During 2004–2006 a home visit was made to each patient and, during 2008-2009, they were visited again. During these visits a follow-up interview was administered; when the patient had died, a verbal autopsy was conducted with family members. Statistical analysis consisted of survival tests, Kaplan-Meier log-rank test and Cox regression. Results. Of 305 studied patients, 68 had died due to PTB by the time of the first evaluation, 237 were followed-up for a second evaluation, and 10 of them had died of PTB. According to the Cox regression, age (over 45 years) and treatment duration (under six months) were associated with a poorer survival. When treatment duration was excluded, the association between poorer survival with age persisted, whereas with having been treated via DOTS strategy, was barely significant. Conclusions. In the studied area it is necessary that patients receive a complete treatment scheme, and to give priority to patients aged over 45 years. PMID:22701170

  8. Multiple oesophago-respiratory fistulae: sequelae of pulmonary tuberculosis in retroviral infection

    PubMed Central

    Low, Soo Fin; Ngiu, Chai Soon; Hing, Erica Yee; Abu Bakar, Norzailin

    2014-01-01

    Pulmonary tuberculosis (PTB) is a common infectious disease worldwide. However, mediastinal tuberculous lymphadenitis complicated by oesophageal involvement and oesophago-respiratory fistula is now uncommon due to improved anti-tuberculous regimes and better general awareness. The overall incidence of acquired oesophago-respiratory fistula due to infection is low, and therefore, the lesion is not often a frontrunner in differential diagnosis. Still, tuberculous oesophago-respiratory fistulae can potentially occur in patients with retroviral disease, as they tend to have atypical and more virulent manifestations. In this study, we report the case of multiple oesophago-respiratory fistulae in a patient with PTB and retroviral disease, and highlight the computed tomography features of these lesions as an atypical presentation of PTB in retroviral disease. Clinicians should suspect oesophago-respiratory fistulae if patients present with Ono’s sign, and remain particularly vigilant for patients with underlying PTB and retroviral disease, as early diagnosis and treatment could help to reduce mortality. PMID:24347038

  9. Pulmonary Tuberculosis in Severely-malnourished or HIV-infected Children with Pneumonia: A Review

    PubMed Central

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

    2013-01-01

    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

  10. Real-time fluorescence Loop-Mediated Isothermal Amplification (LAMP) for rapid and reliable diagnosis of pulmonary tuberculosis.

    PubMed

    Cao, Donglin; Hu, Liangshan; Lin, Maorui; Li, Mingyou; Ye, Zebing; Sun, Hongtao; Huang, Jiwei; Yang, Huawen; Tian, Junzhang

    2015-02-01

    A reliable, simple and rapid diagnostic method that can be helpful in pulmonary tuberculosis diagnosis is urgently needed. Loop-mediated Isothermal Amplification (LAMP) allows DNA to be amplified rapidly at a constant temperature. In this study, real-time fluorescence LAMP was evaluated to rapidly detect Mycobacterium tuberculosis in sputum and was compared to the performance of real-time fluorescence quantitative PCR (Q-PCR). All the standard MTB strains were successfully detected and limit of detection (LOD) was 10(2)CFU/mL by real-time fluorescence LAMP within 20min. In light of MTB in sputum, the real-time fluorescence LAMP method yielded a sensitivity of 98.0% and a specificity of 78.3%, compared to Q-PCR assay, which yielded a sensitivity of 96.0% and a specificity of 82.6% for PTB diagnosis. There was an excellent overall agreement between LAMP and Q-PCR for PTB (κ=0.315) and non-PTB (κ=0.862). Therefore, the real-time fluorescence LAMP assay is a rapid, sensitive, and specific method to detect pulmonary tuberculosis.

  11. Potential yield of pulmonary tuberculosis cases by direct microscopy of sputum in a district of South India*

    PubMed Central

    Baily, G. V. J.; Savič, D.; Gothi, G. D.; Naidu, V. B.; Nair, S. S.

    1967-01-01

    In the District Tuberculosis Programme in India, which is part of a national programme, case-finding and treatment of pulmonary tuberculosis are integrated into the general health services. With such an integration, it is desirable, in order to forecast possible achievements, to understand the additional work-load that the programme will impose upon the existing health institutions and to assess the potential of these institutions for case-finding and treatment. The operational study described in this paper was made under programme conditions in a district in South India and is an examination of the case-finding potential of rural health institutions, using direct microscopy of sputum for diagnosis, and of the additional work-load involved by such case-finding. Under the conditions found in the course of the study, it is clear that a substantial proportion (at least 65%) of pulmonary tuberculosis cases prevalent in the district can be detected by the existing staffs with an easily manageable work-load. PMID:5301646

  12. The Progress of Therapeutic Vaccination with Regard to Tuberculosis

    PubMed Central

    Cardona, Pere-Joan

    2016-01-01

    A major problem with tuberculosis (TB) control is the long duration of drug therapy–both for latent and for active TB. Therapeutic vaccination has been postulated to improve this situation, and to this end there are several candidates already in clinical phases of development. These candidates follow two main designs, namely bacilli-directed therapy based on inactivated -whole or -fragmented bacillus (Mycobacterium w and RUTI) or fusion proteins that integrate non-replicating bacilli -related antigens (H56 vaccine), and host-directed therapy to reduce the tissue destruction. The administration of inactivated Mycobacterium vaccae prevents the “Koch phenomenon” response, and oral administration of heat-killed Mycobacterium manresensis prevents excessive neutrophilic infiltration of the lesions. This review also tries to explain the success of Mycobacterium tuberculosis by reviewing its evolution from infection to disease, and highlights the lack of a definitive understanding of the natural history of TB pathology and the need to improve our knowledge on TB immunology and pathogenesis. PMID:27733848

  13. Tuberculous liver abscess in an immunocompetent child with pulmonary tuberculosis as a cause of fever of unknown origin.

    PubMed

    Çalışkan, Bahar; Somer, Ayper; Hatipoğlu, Nevin; Keser, Melike; Yekeler, Ensar; Gün, Feryal; Güllüoğlu, Mine; Salman, Tansu; Salman, Nuran

    2015-01-01

    Infectious diseases are the leading cause of FUO. A case of prolonged fever with hepatic and pulmonary tuberculosis as a final diagnosis is herein presented. A 4-year-old, otherwise healthy boy presented with an axillary temperature of up to 39.5ºC for the previous 3 weeks. His medical history revealed an occasional increase in body temperature up to 38.5ºC for the last 6 months. Physical examination revealed coarse breath sounds on the basal lung area. Chest X-ray showed mediastinal lymphadenomegaly and computed tomography revealed paratracheal conglomerated lymph nodes and a groundglass appearance on the right lung. There were multiple contrast-enhanced, hypoechoic nodules with central necrosis in the liver parenchyma on abdominal magnetic resonance imaging. Open liver biopsy yielded chronic granulomatous inflammation compatible with pathological findings of tuberculosis infection. The culture specimen was positive for Mycobacterium tuberculosis. The patient improved rapidly after antituberculous therapy was initiated. Tuberculosis, especially in its disseminated form, poses a distinct diagnostic challenge in cases of prolonged fever with unproven etiology, and thus persistence should be exercised in disclosing the cause of such fevers. PMID:26613227

  14. Impact of Educational Intervention on Patients Behavior with Smear-positive Pulmonary Tuberculosis: A Study Using the Health Belief Model

    PubMed Central

    Jadgal, Khair Mohammad; Nakhaei-Moghadam, Tayebeh; Alizadeh-Seiouki, Hadi; Zareban, Iraj; Sharifi-Rad, Javad

    2015-01-01

    Introduction: Tuberculosis is a single-agent infectious disease, which is the major cause of death around the world. Approximately one third of the world’s population is infected with tuberculosis (TB) bacilli and at risk of developing active TB. The purpose of this study was determined the impact of education based on health belief model in promoting behavior of smear-positive pulmonary TB among patients in Chabahar city, Iran. Material and methods: Of the 80 smear-positive pulmonary TB who referred to health centers in Chabahar voluntarily participated in this interventional study. The data collected using questionnaire based on health belief model. The data were analyzed by using paired t-test, independent t-test, pearson correlation and chi-square test with SPSS 16. Results: The cognitive skills were increased significantly from 6.10 to 6.88 after intervention. All behavioral skills were increased significantly from 2.08 to 2.88 after implementing the intervention. Perceived severity was increased from11.08to12.19 significantly. Percepted benefits were enhanced significantly from 11.48 to 12.23. Mean percepted barrier was decreased significantly from 17.52 to 16.68. Conclusion: Findings demonstrated that implementing educational intervention programs can increase the level of knowledge and behavior of patients regarding smear- positive pulmonary TB initiatives. PMID:26543411

  15. Pulmonary Infection with Hypervirulent Mycobacteria Reveals a Crucial Role for the P2X7 Receptor in Aggressive Forms of Tuberculosis

    PubMed Central

    Amaral, Eduardo P.; Ribeiro, Simone C. M.; Lanes, Verônica R.; Almeida, Fabrício M.; de Andrade, Marcelle R. M.; Bomfim, Caio Cesar Barbosa; Salles, Érika M.; Bortoluci, Karina R.; Coutinho-Silva, Robson; Hirata, Mario H.; Alvarez, José M.; Lasunskaia, Elena B.; D'Império-Lima, Maria Regina

    2014-01-01

    The purinergic P2X7 receptor (P2X7R) is a sensor of extracellular ATP, a damage-associated molecule that is released from necrotic cells and that induces pro-inflammatory cytokine production and cell death. To investigate whether the innate immune response to damage signals could contribute to the development of pulmonary necrotic lesions in severe forms of tuberculosis, disease progression was examined in C57BL/6 and P2X7R−/− mice that were intratracheally infected with highly virulent mycobacterial strains (Mycobacterium tuberculosis strain 1471 of the Beijing genotype family and Mycobacterium bovis strain MP287/03). The low-dose infection of C57BL/6 mice with bacteria of these strains caused the rapid development of extensive granulomatous pneumonia with necrotic areas, intense bacillus dissemination and anticipated animal death. In contrast, in P2X7R−/− mice, the lung pathology presented with moderate infiltrates of mononuclear leukocytes without visible signs of necrosis; the disease attenuation was accompanied by a delay in mortality. In vitro, the hypervirulent mycobacteria grew rapidly inside macrophages and induced death by a P2X7R-dependent mechanism that facilitated the release of bacilli. Furthermore, these bacteria were resistant to the protective mechanisms elicited in macrophages following extracellular ATP stimulation. Based on this study, we propose that the rapid intracellular growth of hypervirulent mycobacteria results in massive macrophage damage. The ATP released by damaged cells engages P2X7R and accelerates the necrotic death of infected macrophages and the release of bacilli. This vicious cycle exacerbates pneumonia and lung necrosis by promoting widespread cell destruction and bacillus dissemination. These findings suggest the use of drugs that have been designed to inhibit the P2X7R as a new therapeutic approach to treat the aggressive forms of tuberculosis. PMID:24991816

  16. Non-Pulmonary Tuberculosis--A Case Report: Importance and Pitfalls of Diagnosis.

    PubMed

    Pepper, Hannah; Davies, Rebecca; Hughes, Ceri; Thomas, Steve; Pring, Miranda; Hetzel, Martin

    2016-06-01

    A case of tuberculosis presenting as a neck lump is highlighted. Tuberculosis is on the increase. There are national and international strategies to improve the management of tuberculosis in the United Kingdom, and raising clinical awareness of tuberculosis is an important part of that strategy. Neck lumps can present in the dental setting and the differential diagnosis should include tuberculosis, with referral to an appropriate multidisciplinary team. Special tests to aid diagnosis are helpful but not completely discriminating. Tuberculosis is a notifiable disease and it must be treated by a designated specialist medical team. CPD/Clinical Relevance: Tuberculosis is a differential diagnosis for a persistent neck lump and clinicians should understand the problems of diagnosis and the importance of appropriate referral for treatment in the national and international strategy to reduce this disease. PMID:27529917

  17. Successful use of blood pleurodesis to resolve an iatrogenic persistent pneumothorax in a patient with pulmonary tuberculosis

    PubMed Central

    Shaukat, Masooma; Hyams, Catherine; Macavei, Vladimir M; O'Shaughnessy, Terence C

    2014-01-01

    A Somali patient with previous tuberculosis presented clinically unwell with features consistent with a right-sided pleural effusion. Subsequent investigations confirmed a community-acquired pneumonia and relapse of pulmonary tuberculosis, with a drug resistant strain isolated. The patient developed a large left-sided iatrogenic pneumothorax, which recurred and failed to resolve despite the successful insertion of both Seldinger and surgical chest drains, and the patient remained clinically unstable on the intensive care unit. A blood pleurodesis was successfully used to provide resolution of this patient's previously persistent pneumothorax, which has resulted in stabilisation of the patient and no further pneumothoraces have occurred subsequently. The authors therefore highlight the use of a blood pleurodesis as a little used technique that may provide a valuable tool to other clinicians in similar cases. PMID:25240008

  18. Granulocytic Myeloid Derived Suppressor Cells Expansion during Active Pulmonary Tuberculosis Is Associated with High Nitric Oxide Plasma Level

    PubMed Central

    El Daker, Sary; Sacchi, Alessandra; Tempestilli, Massimo; Carducci, Claudia; Goletti, Delia; Vanini, Valentina; Colizzi, Vittorio; Lauria, Francesco Nicola; Martini, Federico; Martino, Angelo

    2015-01-01

    Tuberculosis (TB) is still the principal cause of death caused by a single infectious agent, and the balance between the bacillus and host defense mechanisms reflects the different manifestations of the pathology. The aim of this work was to study the role of myeloid-derived suppressor cells (MDSCs) during active pulmonary tuberculosis at the site of infection. We observed an expansion of MDSCs in the lung and blood of patients with active TB, which are correlated with an enhanced amount of nitric oxide in the plasma. We also found that these cells have the remarkable ability to suppress T-cell response, suggesting an important role in the modulation of the immune response against TB. Interestingly, a trend in the diminution of MDSCs was found after an efficacious anti-TB therapy, suggesting that these cells may be used as a potential biomarker for monitoring anti-TB therapy efficacy. PMID:25879532

  19. Cost-effectiveness of chemotherapy for sputum smear-positive pulmonary tuberculosis in Malawi, Mozambique and Tanzania.

    PubMed

    de Jonghe, E; Murray, C J; Chum, H J; Nyangulu, D S; Salomao, A; Styblo, K

    1994-01-01

    The cost-effectiveness of chemotherapy for pulmonary sputum smear-positive tuberculosis was examined in the national tuberculosis control programmes of Malawi, Mozambique and Tanzania. In these three programmes, routine cure rates have exceeded 80 per cent. Average, average incremental and marginal unit costs for standard, short-course and retreatment regimens with and without hospitalization have been measured. The average incremental cost per year of life saved through chemotherapy ranged from US $0.90-3.10. In all conditions, short-course chemotherapy is preferable to standard 12-month chemotherapy. When hospitalization during the intensive phase of chemotherapy increases the cure rate by 10-15 percentage points, it can be relatively cost-effective. Analysing the cost-effectiveness of short-course and standard chemotherapy, where the depth of the margin of benefit is different, illustrates some of the dangers of simplistic use of cost-effectiveness ratios.

  20. LED fluorescence microscopy increases the detection of smear-positive pulmonary tuberculosis in medical colleges of India.

    PubMed

    Reza, L W; Satyanarayana, S; Pandey, A; Kumar, S; Devendrappa, N M; Anand, L; Singh, G; Kumar, A M V; Chadha, S S; Wilson, N; Sachdeva, K S; Nair, S A

    2013-09-21

    In July 2012, light-emitting diode fluorescence microscopy (LED-FM) replaced conventional light microscopy using Ziehl-Neelsen stain in the detection of sputum-positive pulmonary tuberculosis in 190 microscopy centres of medical colleges operating under India's Revised National Tuberculosis Control Programme. We compared the performance of LED-FM (July-December 2012) to that of conventional microscopy (July-December 2011) across 190 sites. Of 222 658 patients examined using conventional microscopy, 28 042 (12.6%) were smear-positive, while of 224 714 examined using LED-FM, 33 552 (14.9%) were smear-positive, an additional yield of 5251 cases after adjusting for the increase in patients examined. We recommend replacing conventional microscopy with LED-FM in high workload microscopy centres in India.

  1. The Role of Pulmonary Veins in Cancer Progression from a Computed Tomography Viewpoint

    PubMed Central

    Chang, Hung; Liao, Tzu-Yao; Wen, Ming-Sheng; Yu, Chih-Teng

    2016-01-01

    Background. We studied the role of pulmonary veins in cancer progression using computed tomography (CT) scans. Methods. We obtained data from 260 patients with pulmonary vein obstruction syndrome (PVOS). We used CT scans to investigate pulmonary lesions in relation to pulmonary veins. We divided the lesions into central and peripheral lesions by their anatomical location: in the lung parenchymal tissue or pulmonary vein; in the superior or inferior pulmonary vein; and by unilateral or bilateral presence in the lungs. Results. Of the 260 PVOS patients, 226 (87%) had central lesions, 231 (89%) had peripheral lesions, and 190 (75%) had mixed central and peripheral lesions. Among the 226 central lesions, 93% had lesions within the superior pulmonary vein, either bilaterally or unilaterally. Among the 231 peripheral lesions, 65% involved bilateral lungs, 70% involved lesions within the inferior pulmonary veins, and 23% had obvious metastatic extensions into the left atrium. All patients exhibited nodules within their pulmonary veins. The predeath status included respiratory failure (40%) and loss of consciousness (60%). Conclusion. CT scans play an important role in following tumor progression within pulmonary veins. Besides respiratory distress, PVOS cancer cells entering centrally can result in cardiac and cerebral events and loss of consciousness or can metastasize peripherally from the pulmonary veins to the lungs. PMID:27746816

  2. Systematic review: Comparison of Xpert MTB/RIF, LAMP and SAT methods for the diagnosis of pulmonary tuberculosis.

    PubMed

    Yan, Liping; Xiao, Heping; Zhang, Qing

    2016-01-01

    Technological advances in nucleic acid amplification have led to breakthroughs in the early detection of PTB compared to traditional sputum smear tests. The sensitivity and specificity of loop-mediated isothermal amplification (LAMP), simultaneous amplification testing (SAT), and Xpert MTB/RIF for the diagnosis of pulmonary tuberculosis were evaluated. A critical review of previous studies of LAMP, SAT, and Xpert MTB/RIF for the diagnosis of pulmonary tuberculosis that used laboratory culturing as the reference method was carried out together with a meta-analysis. In 25 previous studies, the pooled sensitivity and specificity of the diagnosis of tuberculosis were 93% and 94% for LAMP, 96% and 88% for SAT, and 89% and 98% for Xpert MTB/RIF. The I(2) values for the pooled data were >80%, indicating significant heterogeneity. In the smear-positive subgroup analysis of LAMP, the sensitivity increased from 93% to 98% (I(2) = 2.6%), and specificity was 68% (I(2) = 38.4%). In the HIV-infected subgroup analysis of Xpert MTB/RIF, the pooled sensitivity and specificity were 79% (I(2) = 72.9%) and 99% (I(2) = 64.4%). In the HIV-negative subgroup analysis for Xpert MTB/RIF, the pooled sensitivity and specificity were 72% (I(2) = 49.6%) and 99% (I(2) = 64.5%). LAMP, SAT and Xpert MTB/RIF had comparably high levels of sensitivity and specificity for the diagnosis of tuberculosis. The diagnostic sensitivity and specificity of three methods were similar, with LAMP being highly sensitive for the diagnosis of smear-positive PTB. The cost effectiveness of LAMP and SAT make them particularly suitable tests for diagnosing PTB in developing countries. PMID:26786658

  3. Tuberculosis in the lung (image)

    MedlinePlus

    Tuberculosis is caused by a group of organisms: Mycobacterium tuberculosis, M bovis , M africanum and a few other rarer subtypes. Tuberculosis usually appears as a lung (pulmonary) infection. However, ...

  4. Towards local progression estimation of pulmonary emphysema using CT

    SciTech Connect

    Staring, M. Bakker, M. E.; Shamonin, D. P.; Reiber, J. H. C.; Stoel, B. C.; Stolk, J.

    2014-02-15

    Purpose: Whole lung densitometry on chest CT images is an accepted method for measuring tissue destruction in patients with pulmonary emphysema in clinical trials. Progression measurement is required for evaluation of change in health condition and the effect of drug treatment. Information about the location of emphysema progression within the lung may be important for the correct interpretation of drug efficacy, or for determining a treatment plan. The purpose of this study is therefore to develop and validate methods that enable the local measurement of lung density changes, which requires proper modeling of the effect of respiration on density. Methods: Four methods, all based on registration of baseline and follow-up chest CT scans, are compared. The first naïve method subtracts registered images. The second employs the so-called dry sponge model, where volume correction is performed using the determinant of the Jacobian of the transformation. The third and the fourth introduce a novel adaptation of the dry sponge model that circumvents its constant-mass assumption, which is shown to be invalid. The latter two methods require a third CT scan at a different inspiration level to estimate the patient-specific density-volume slope, where one method employs a global and the other a local slope. The methods were validated on CT scans of a phantom mimicking the lung, where mass and volume could be controlled. In addition, validation was performed on data of 21 patients with pulmonary emphysema. Results: The image registration method was optimized leaving a registration error below half the slice increment (median 1.0 mm). The phantom study showed that the locally adapted slope model most accurately measured local progression. The systematic error in estimating progression, as measured on the phantom data, was below 2 gr/l for a 70 ml (6%) volume difference, and 5 gr/l for a 210 ml (19%) difference, if volume correction was applied. On the patient data an underlying

  5. Safety and effectiveness of CT-guided percutaneous pulmonary paracentesis and tuberculoma perfusing chemotherapy for the treatment of pleural tuberculosis

    PubMed Central

    Geng, Shujun; Li, Lijuan; Liu, Jianling; Song, Tao

    2016-01-01

    The aim of the study was to compare the mid- and long-term effects of different treatments such as CT-guided percutaneous pulmonary paracentesis, tuberculoma perfusing chemotherapy and whole-body standard chemotherapy or extended chemotherapy on safety and effectiveness for pleural chemotherapy. A total of 60 subjects diagnosed to have pleural tuberculosis between February 2010 and February 2014 were prospectively selected for this study and were considered as the experimental group. Seventy pleural tuberculosis patients who underwent treatment between February 2006 and February 2010 were considered as the control group. The patients in the experimental group were treated with CT-guided percutaneous pulmonary paracentesis and tuberculoma perfusing chemotherapy of not more than three courses with each course consisting of administration of 0.1 g isoniazid, n 0.5 gkanamyci, 0.2 g levofloxacin, and 1 ml lidocaine once a week for four times. The patients in the control group were treated with whole-body standard or extended chemotherapy regimen 3~6HRZE(S)/6~12HR. The patients were followed up for 18 months and the treatment effects were compared. The diameter of tuberculoma in patients of the experimental group during 6, 12 and 18 months was shorter than that of the control group (P<0.05). The total effective rate of treatment and the duration of treatment in experimental group during 18 months were higher than that of control group (P<0.05). The frequency of drug-related complications were lower in comparison with the control group (P<0.05). No surgically acquired complications were observed in the experimental group. Thus, treatments such as CT-guided percutaneous pulmonary paracentesis and tuberculoma perfusing chemotherapy for pleural tuberculosis are safe and effective, which has greater value and can be promoted for use in the clinical setting. PMID:27446302

  6. Tuberculosis

    MedlinePlus

    ... to address TB and HIV coinfection around the world? The President’s U.S. President's Emergency Plan for AIDS ... of those suffering from HIV/AIDS around the world. PEPFAR’s Global Fund to Fight AIDS, Tuberculosis and ...

  7. Prospective cross-sectional evaluation of the small membrane filtration method for diagnosis of pulmonary tuberculosis.

    PubMed

    Jones-López, Edward; Manabe, Yukari C; Palaci, Moises; Kayiza, Carol; Armstrong, Derek; Nakiyingi, Lydia; Ssengooba, Willy; Gaeddert, Mary; Kubiak, Rachel; Almeida Júnior, Pedro; Alland, David; Dietze, Reynaldo; Joloba, Moses; Ellner, Jerrold J; Dorman, Susan E

    2014-07-01

    Smear microscopy has suboptimal sensitivity, and there is a need to improve its performance since it is commonly used to diagnose tuberculosis (TB). We prospectively evaluated the diagnostic accuracy of the small membrane filtration (SMF) method, an approach that uses a vacuum manifold and is designed to concentrate bacilli onto a filter that can be examined microscopically. We enrolled hospitalized adults suspected to have pulmonary TB in Kampala, Uganda. We obtained a clinical history and three spontaneously expectorated sputum specimens for smear microscopy (direct, concentrated, and SMF), MGIT (mycobacterial growth indicator tube) 960 and Lowenstein-Jensen (LJ) cultures, and Xpert MTB/RIF testing. We performed per-specimen (primary) and per-patient analyses. From October 2012 to June 2013, we enrolled 212 patients (579 sputum specimens). The participants were mostly female (63.2%), and 81.6% were HIV infected; their median CD4 cell count was 47 cells/μl. Overall, 19.0%, 20.4%, 27.1%, 25.2%, and 25.9% of specimens tested positive by direct smear, concentrated smear, MGIT culture, LJ culture, and Xpert test, respectively. In the per-specimen analysis, the sensitivity of the SMF method (48.5%; 95% confidence interval [CI], 37.4 to 59.6) was lower than those of direct smear (60.9%; 51.4 to 70.5 [P = 0.0001]) and concentrated smear (63.3%; 53.6 to 73.1 [P < 0.0001]). Subgroup analyses showed that SMF performed poorly in specimens having a low volume or low bacterial load. The SMF method performed poorly compared to standard smear techniques and was sensitive to sample preparation techniques. The optimal laboratory SMF protocol may require striking a fine balance between sample dilution and filtration failure rate.

  8. Accuracy of the Bronchoalveolar Lavage Enzyme-Linked Immunospot Assay for the Diagnosis of Pulmonary Tuberculosis

    PubMed Central

    Pang, Caishuang; Wu, Yanqiu; Wan, Chun; Shen, Konglong; Hu, Yuzhu; Yang, Ting; Shen, Yongchun; Wen, Fuqiang

    2016-01-01

    Abstract Assessing of local immune response may improve the accuracy of pulmonary tuberculosis (PTB) diagnosis. Many studies have investigated diagnosing PTB based on enzyme-linked immunospot (ELISPOT) assay of bronchoalveolar lavage (BAL) fluid, but the results have been inconclusive. We meta-analyzed the available evidences on overall diagnostic performance of ELISPOT assay of BAL fluid for diagnosing PTB. A systematic literature search was performed using PubMed, Embase, Wangfang, Weipu, and CNKI. Data were pooled on sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Overall test performance was summarized using summary receiver operating characteristic curves and the area under the curve (AUC). Deeks test was used to test for potential publication bias. Seven publications with 814 subjects met our inclusion criteria and were included in this meta-analysis. The following pooled estimates for diagnostic parameters were obtained: sensitivity, 0.90 (95% CI: 0.85–0.94); specificity, 0.80 (95% CI: 0.77–0.84); PLR, 5.08 (95% CI: 2.70–9.57); NLR, 0.13 (95% CI: 0.06–0.28); DOR, 49.12 (95% CI: 12.97–186.00); and AUC, 0.96. No publication bias was identified. The available evidence suggests that ELISPOT assay of BAL fluid is a useful rapid diagnostic test for PTB. The results of this assay should be interpreted in parallel with clinical findings and the results of conventional tests. PMID:27015211

  9. Co-endemicity of Pulmonary Tuberculosis and Intestinal Helminth Infection in the People's Republic of China.

    PubMed

    Li, Xin-Xu; Ren, Zhou-Peng; Wang, Li-Xia; Zhang, Hui; Jiang, Shi-Wen; Chen, Jia-Xu; Wang, Jin-Feng; Zhou, Xiao-Nong

    2016-03-01

    Both pulmonary tuberculosis (PTB) and intestinal helminth infection (IHI) affect millions of individuals every year in China. However, the national-scale estimation of prevalence predictors and prevalence maps for these diseases, as well as co-endemic relative risk (RR) maps of both diseases' prevalence are not well developed. There are co-endemic, high prevalence areas of both diseases, whose delimitation is essential for devising effective control strategies. Bayesian geostatistical logistic regression models including socio-economic, climatic, geographical and environmental predictors were fitted separately for active PTB and IHI based on data from the national surveys for PTB and major human parasitic diseases that were completed in 2010 and 2004, respectively. Prevalence maps and co-endemic RR maps were constructed for both diseases by means of Bayesian Kriging model and Bayesian shared component model capable of appraising the fraction of variance of spatial RRs shared by both diseases, and those specific for each one, under an assumption that there are unobserved covariates common to both diseases. Our results indicate that gross domestic product (GDP) per capita had a negative association, while rural regions, the arid and polar zones and elevation had positive association with active PTB prevalence; for the IHI prevalence, GDP per capita and distance to water bodies had a negative association, the equatorial and warm zones and the normalized difference vegetation index had a positive association. Moderate to high prevalence of active PTB and low prevalence of IHI were predicted in western regions, low to moderate prevalence of active PTB and low prevalence of IHI were predicted in north-central regions and the southeast coastal regions, and moderate to high prevalence of active PTB and high prevalence of IHI were predicted in the south-western regions. Thus, co-endemic areas of active PTB and IHI were located in the south-western regions of China, which

  10. Retrospective cohort evaluation on risk of pneumonia in patients with pulmonary tuberculosis.

    PubMed

    Chang, Tsui-Ming; Mou, Chih-Hsin; Shen, Te-Chun; Yang, Chien-Lung; Yang, Min-Hui; Wu, Fang-Yang; Sung, Fung-Chang

    2016-06-01

    Pulmonary tuberculosis (PTb) and pneumonia are diseases that may exist concomitantly. Population study investigating the subsequent pneumonia development in PTb patients is limited. This study compares the risk of pneumonia between cohorts with and without PTb.We used the claims data of the Taiwan National Health Insurance to identify a cohort with PTb (N = 3417) newly diagnosed in 2000-2006 without pneumonia history, and a randomly selected comparison cohort (N = 6834) free of PTb and pneumonia, frequency matched by propensity score. Incidence rates and hazard ratios of pneumonia were calculated by sex, age, and comorbidity starting in the 7th month after the cohorts being established until the end of 2011.We found the incidence of pneumonia to be 1.9-fold higher in the PTb cohort than in the PTb free cohort (51.6 vs 27.0 per 1000 person-years). The PTb cohort had a Cox method estimated adjusted hazard ratio of 2.14 (95% confidence interval = 1.96-2.32). We also found that the risk was greater for men than for women, but lower for young adults aged 20-39 years. Comorbidity interacted with PTb by aggravating the pneumonia risk, particularly for those with asthma. For PTb patients comorbid with asthma, the pneumonia incidence was 2.5-fold higher than for PTb patients free of comorbidities (75.9 vs 29.3 per 1000 person-years).Our results display that PTb patients have an elevated risk of developing pneumonia. Adequate follow-up should be provided to the PTb patients, especially those with comorbidity. PMID:27368009

  11. Cytokine and Antibody Based Diagnostic Algorithms for Sputum Culture-Positive Pulmonary Tuberculosis

    PubMed Central

    Fleming, Joy; Chen, Liang; Wang, Yunxia; Li, Haicheng; Guo, Huixin; Zhou, Jie; Chen, Xunxun; Chen, Yuhui; Liao, Qinghua; Shu, Yang; Tan, Yaoju; Yu, Meiling; Li, Guozhou; Zhou, Lin; Zhong, Qiu; Bi, Lijun; Guo, Lina; Zhao, Meigui

    2015-01-01

    Background Tuberculosis (TB) is one of the most serious infectious diseases globally and has high mortality rates. A variety of diagnostic tests are available, yet none are wholly reliable. Serum cytokines, although significantly and frequently induced by different diseases and thus good biomarkers for disease diagnosis and prognosis, are not sufficiently disease-specific. TB-specific antibody detection, on the other hand, has been reported to be highly specific but not sufficiently sensitive. In this study, our aim was to improve the sensitivity and specificity of TB diagnosis by combining detection of TB-related cytokines and TB-specific antibodies in peripheral blood samples. Methods TB-related serum cytokines were screened using a human cytokine array. TB-related cytokines and TB-specific antibodies were detected in parallel with microarray technology. The diagnostic performance of the new protocol for active TB was systematically compared with other traditional methods. Results Here, we show that cytokines I-309, IL-8 and MIG are capable of distinguishing patients with active TB from healthy controls, patients with latent TB infection, and those with a range of other pulmonary diseases, and that these cytokines, and their presence alongside antibodies for TB-specific antigens Ag14-16kDa, Ag32kDa, Ag38kDa and Ag85B, are specific markers for active TB. The diagnostic protocol for active TB developed here, which combines the detection of three TB-related cytokines and TB-specific antibodies, is highly sensitive (91.03%), specific (90.77%) and accurate (90.87%). Conclusions Our results show that combining detection of TB-related cytokines and TB-specific antibodies significantly enhances diagnostic accuracy for active TB, providing greater accuracy than conventional diagnostic methods such as interferon gamma release assays (IGRAs), TB antibody Colloidal Gold Assays and microbiological culture, and suggest that this diagnostic protocol has potential for clinical

  12. Co-endemicity of Pulmonary Tuberculosis and Intestinal Helminth Infection in the People's Republic of China.

    PubMed

    Li, Xin-Xu; Ren, Zhou-Peng; Wang, Li-Xia; Zhang, Hui; Jiang, Shi-Wen; Chen, Jia-Xu; Wang, Jin-Feng; Zhou, Xiao-Nong

    2016-03-01

    Both pulmonary tuberculosis (PTB) and intestinal helminth infection (IHI) affect millions of individuals every year in China. However, the national-scale estimation of prevalence predictors and prevalence maps for these diseases, as well as co-endemic relative risk (RR) maps of both diseases' prevalence are not well developed. There are co-endemic, high prevalence areas of both diseases, whose delimitation is essential for devising effective control strategies. Bayesian geostatistical logistic regression models including socio-economic, climatic, geographical and environmental predictors were fitted separately for active PTB and IHI based on data from the national surveys for PTB and major human parasitic diseases that were completed in 2010 and 2004, respectively. Prevalence maps and co-endemic RR maps were constructed for both diseases by means of Bayesian Kriging model and Bayesian shared component model capable of appraising the fraction of variance of spatial RRs shared by both diseases, and those specific for each one, under an assumption that there are unobserved covariates common to both diseases. Our results indicate that gross domestic product (GDP) per capita had a negative association, while rural regions, the arid and polar zones and elevation had positive association with active PTB prevalence; for the IHI prevalence, GDP per capita and distance to water bodies had a negative association, the equatorial and warm zones and the normalized difference vegetation index had a positive association. Moderate to high prevalence of active PTB and low prevalence of IHI were predicted in western regions, low to moderate prevalence of active PTB and low prevalence of IHI were predicted in north-central regions and the southeast coastal regions, and moderate to high prevalence of active PTB and high prevalence of IHI were predicted in the south-western regions. Thus, co-endemic areas of active PTB and IHI were located in the south-western regions of China, which

  13. Mean platelet volume as an inflammation marker in active pulmonary tuberculosis

    PubMed Central

    2014-01-01

    Background The mean platelet volume (MPV) reflects the size of platelets. It has been shown to be inversely correlated with level of the inflammation in some chronic inflammatory diseases. This prospective study aims to show the usability of MPV as an inflammation marker in patients with active pulmonary tuberculosis (PTB) by comparison with healthy controls. In addition, its relationships with other inflammatory markers such as C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) as well as with the radiological extent of disease were examined. Methods This study included 82 patients with active PTB and 95 healthy subjects (control group). Whole blood counts, CRP level, and ESR were compared between the two groups. In the PTB group, the relationships between the radiological extent of disease and the MPV and other inflammation markers were investigated. Results The MPV was 7.74 ± 1.33/μL in the PTB group and 8.20 ± 1.13/μL in the control group (p = 0.005). The blood platelet count, CRP level, and ESR were significantly higher in the active PTB group than in the control group (p < 0.0001). In the PTB group, CRP levels (r = 0.26, p = 0.003) and ESR (r = 0.39, p = 0.003), but not MPV (p = 0.80), were significantly correlated with the radiologic extent of the disease. Conclusions The MPV was lower in patients with PTB than in healthy controls, however, the difference was limited. The MPV does not reflect the severity of the disease. The use of MPV as an inflammation marker and a negative acute-phase reactant in PTB does not seem to be reliable. PMID:24581084

  14. Diabetes Is a Risk Factor for Pulmonary Tuberculosis: A Case-Control Study from Mwanza, Tanzania

    PubMed Central

    Faurholt-Jepsen, Daniel; Range, Nyagosya; PrayGod, George; Jeremiah, Kidola; Faurholt-Jepsen, Maria; Aabye, Martine Grosos; Changalucha, John; Christensen, Dirk Lund; Pipper, Christian Bressen; Krarup, Henrik; Witte, Daniel Rinse; Andersen, Aase Bengaard; Friis, Henrik

    2011-01-01

    Background Diabetes and TB are associated, and diabetes is increasingly common in low-income countries where tuberculosis (TB) is highly endemic. However, the role of diabetes for TB has not been assessed in populations where HIV is prevalent. Methods A case-control study was conducted in an urban population in Tanzania among culture-confirmed pulmonary TB patients and non-TB neighbourhood controls. Participants were tested for diabetes according to WHO guidelines and serum concentrations of acute phase reactants were measured. The association between diabetes and TB, and the role of HIV as an effect modifier, were examined using logistic regression. Since blood glucose levels increase during the acute phase response, we adjusted for elevated serum acute phase reactants. Results Among 803 cases and 350 controls the mean (SD) age was 34.8 (11.9) and 33.8 (12.0) years, and the prevalence of diabetes was 16.7% (95% CI: 14.2; 19.4) and 9.4% (6.6; 13.0), respectively. Diabetes was associated with TB (OR 2.2, 95% CI: 1.5; 3.4, p<0.001). However, the association depended on HIV status (interaction, p = 0.01) due to a stronger association among HIV uninfected (OR 4.2, 95% CI: 1.5; 11.6, p = 0.01) compared to HIV infected (OR 0.1, 95% CI: 0.01; 1.8, p = 0.13) after adjusting for age, sex, demographic factors and elevated serum acute phase reactants. Conclusion Diabetes is a risk factor for TB in HIV uninfected, whereas the association in HIV infected patients needs further study. The increasing diabetes prevalence may be a threat to TB control. PMID:21912626

  15. Retrospective cohort evaluation on risk of pneumonia in patients with pulmonary tuberculosis

    PubMed Central

    Chang, Tsui-Ming; Mou, Chih-Hsin; Shen, Te-Chun; Yang, Chien-Lung; Yang, Min-Hui; Wu, Fang-Yang; Sung, Fung-Chang

    2016-01-01

    Abstract Pulmonary tuberculosis (PTb) and pneumonia are diseases that may exist concomitantly. Population study investigating the subsequent pneumonia development in PTb patients is limited. This study compares the risk of pneumonia between cohorts with and without PTb. We used the claims data of the Taiwan National Health Insurance to identify a cohort with PTb (N = 3417) newly diagnosed in 2000–2006 without pneumonia history, and a randomly selected comparison cohort (N = 6834) free of PTb and pneumonia, frequency matched by propensity score. Incidence rates and hazard ratios of pneumonia were calculated by sex, age, and comorbidity starting in the 7th month after the cohorts being established until the end of 2011. We found the incidence of pneumonia to be 1.9-fold higher in the PTb cohort than in the PTb free cohort (51.6 vs 27.0 per 1000 person-years). The PTb cohort had a Cox method estimated adjusted hazard ratio of 2.14 (95% confidence interval = 1.96–2.32). We also found that the risk was greater for men than for women, but lower for young adults aged 20–39 years. Comorbidity interacted with PTb by aggravating the pneumonia risk, particularly for those with asthma. For PTb patients comorbid with asthma, the pneumonia incidence was 2.5-fold higher than for PTb patients free of comorbidities (75.9 vs 29.3 per 1000 person-years). Our results display that PTb patients have an elevated risk of developing pneumonia. Adequate follow-up should be provided to the PTb patients, especially those with comorbidity. PMID:27368009

  16. Intermittent Versus Daily Pulmonary Tuberculosis Treatment Regimens: A Meta-Analysis

    PubMed Central

    Kasozi, Samuel; Clark, Justin; Doi, Suhail A. R.

    2015-01-01

    Background Several systematic reviews suggest that intermittent pulmonary tuberculosis (TB) chemotherapy is effective, but intensity (daily versus intermittent) and duration of rifampicin use (intensive phase only versus both phases) have not been distinguished. In addition, the various outcomes (success, failure, relapse, and default) have only selectively been evaluated. Methods We conducted a meta-analysis of proportions using all four outcomes as multi-category proportions to examine the effectiveness of WHO category 1 TB treatment regimens. Database searches of studies reporting treatment outcomes of HIV negative subjects were included and stratified by intensity of therapy and duration of rifampicin therapy. Using a bias-adjusted statistical model, we pooled proportions of the four treatment outcome categories using a method that handles multi-category proportions. Results A total of 27 studies comprising of 48 data sets with 10,624 participants were studied. Overall, treatment success was similar among patients treated with intermittent (I/I) (88%) (95% CI, 81–92) and daily (D/D) (90%) (95% CI, 84–95) regimens. Default was significantly less with I/I (0%) (95% CI, 0–2) compared to D/D regimens (5%) (95% CI, 1–9). Nevertheless, I/I relapse rates (7%) (95% CI, 3–11) were higher than D/D relapse rates (1%) (95% CI, 0–3). Conclusion Treatment regimens that are offered completely intermittently versus completely daily are associated with a trade-off between treatment relapse and treatment default. There is a possibility that I/I regimens can be improved by increasing treatment duration, and this needs to be urgently addressed by future studies. PMID:26056374

  17. Prevalence of and risk factors for pulmonary tuberculosis among newly diagnosed HIV-1 infected Nigerian children

    PubMed Central

    Ebonyi, Augustine O.; Oguche, Stephen; Ejeliogu, Emeka U.; Agbaji, Oche O.; Shehu, Nathan Y.; Abah, Isaac O.; Sagay, Atiene S.; Ugoagwu, Placid O.; Okonkwo, Prosper I.; Idoko, John A.; Kanki, Phyllis J.

    2016-01-01

    Introduction Studies on the prevalence of and risk factors for tuberculosis (TB) among newly diagnosed human immunodeficiency virus (HIV)-infected children in sub-Saharan Africa are scarce and in Nigeria there is paucity of reported data. We determined the prevalence of and risk factors for pulmonary TB (PTB) in newly diagnosed (treatment-naïve) HIV-1 infected children at the pediatric HIV clinic of the Jos University Teaching Hospital (JUTH) in Nigeria. Methods We performed a retrospective analysis of 876 children, aged 2 months – 13 years, diagnosed with HIV-1 infection between July 2005 and December 2012, of which 286 were diagnosed with PTB at presentation after TB screening. The study site was the AIDS Prevention Initiative in Nigeria (APIN)-supported Pediatric HIV clinic at JUTH, Jos. A multivariate forward logistic regression modelling was used to identify risk factors for PTB-HIV co-infection. Results The prevalence of PTB-HIV co-infection was 32% (286/876). Severe immunosuppression (SI) and World Health Organization (WHO) HIV clinical stage 3/4 were identified as independent risk factors for PTB-HIV co-infection in HIV infected children. The odds of PTB-HIV co-infection was increased two-fold in HIV-infected children with WHO clinical stage 3/4 compared to those with stage 1/2 (adjusted odds ratio (AOR) 1.76 [1.31-2.37], p<0.001) and 1.5-fold in children with SI compared to those without SI (AOR 1.52 [1.12-2.06], p=0.007). Conclusion In our setting, the burden of PTB was high among newly diagnosed HIV-infected children, and late WHO HIV clinical stage and severe immunosuppression were associated with PTB-HIV co-infection. Therefore there is a clear need to improve strategies for early diagnosis of both HIV and PTB to optimize clinical outcomes. PMID:27019829

  18. Special computer-aided computed tomography (CT) volume measurement and comparison method for pulmonary tuberculosis (TB)

    PubMed Central

    Liu, Jingming; Sun, Zhaogang; Xie, Ruming; Gao, Mengqiu; Li, Chuanyou

    2015-01-01

    The computed tomography (CT) manifestations in pulmonary tuberculosis (PTB) patients are complex and could not be quantitatively evaluated. We aimed to establish a new method to objectively measure the lung injury level in PTB by thoracic CT and make quantitative comparisons. In the retrospective study, a total of 360 adults were selected and divided into four groups according to their CT manifestations and medical history: Normal group, PTB group, PTB with diabetes mellitus (DM) group and Death caused by PTB group. Five additional patients who had continuous CT scans were chosen for preliminary longitudinal analysis. We established a new computer-aided CT volume measurement and comparison method for PTB patients (CACTV-PTB) which measured lung volume (LV) and thoracic volume (TV). RLT was calculated as the ratio of LV to TV and comparisons were performed among different groups. Standardized RLT (SRLT) was used in the longitudinal analysis among different patients. In the Normal group, LV and TV were positively correlated in linear regression (Ŷ=-0.5+0.46X, R2=0.796, P<0.01). RLT values were significantly different among four groups (Normal: 0.40±0.05, PTB: 0.37±0.08, PTB+DM: 0.34±0.06, Death: 0.23±0.04). The curves of SRLT value from different patients shared a same start point and could be compared directly. Utilizing the novel objective method CACTV-PTB makes it possible to compare the severity and dynamic change among different PTB patients. Our early experience also suggested that the lung injury is severer in the PTB+DM group than in the PTB group. PMID:26628995

  19. Adjunct therapy of Ayurvedic medicine with anti tubercular drugs on the therapeutic management of pulmonary tuberculosis

    PubMed Central

    Debnath, P. K.; Chattopadhyay, Jaydeb; Mitra, Achintya; Adhikari, Anjan; Alam, Mirza Samsur; Bandopadhyay, S. K.; Hazra, Jayram

    2012-01-01

    Background: Pulmonary tuberculosis (PTB) is an age old disease described in Vedic Medicine as ‘Yakshma’. Later on, in Ayurveda it earned a prefix and found way into mythology as ‘Rajayakshma’. After the discovery of streptomycin, the therapeutic management of PTB received a major breakthrough. The treatment module changed remarkably with the formulation of newer anti-tubercular drugs (ATD) with appreciable success. Recent resurgence of PTB in developed countries like United States posed a threat to the medical community due to resistant strains. Consequently, WHO looked toward traditional medicine. Literature reveals that Ayurvedic treatment of PTB was in vogue in India before the introduction of ATD with limited success. Records show that 2766 patients of PTB were treated with Ayurvedic drugs in a tertiary care hospital in Kolkata in the year 1933-1947. Objectives: To evaluate the toxicity reduction and early restoration by adjunct therapy of Ayurvedic drugs by increasing the bio-availability of ATDs. Materials and Methods: In the present study, treatment response of 99 patients treated with ATD as an adjunct with Aswagandha (Withania somnifera) and a multi-herbal formulation described in Chikitsa-sthana of Charaka samhita i.e. Chyawanprash were investigated. Hematological profile, sputum bacterial load count, immunoglobulin IgA and IgM, blood sugar, liver function test, serum creatinine were the assessed parameters besides blood isoniazid and pyrazinamide, repeated after 28 days of treatment. Results: The symptoms abated, body weight showed improvement, ESR values were normal, there was appreciable change in IgA and IgM patterns and significantly increased bioavailability of isoniazid and pyrazinamide were recorded. Conclusion: This innovative clinical study coupled with empowered research may turn out to be promising in finding a solution for the treatment of PTB. PMID:23125511

  20. Follow up of an immunocompromised contact group of a case of open pulmonary tuberculosis on a renal unit.

    PubMed Central

    Drobniewski, F. A.; Ferguson, J.; Barritt, K.; Higgins, R. M.; Higgon, M.; Neave, D.; Uttley, A. H.; O'Sullivan, D.; Hay, A.

    1995-01-01

    BACKGROUND--The organisation, management, outcome and cost of follow up of a large group of mainly immunocompromised patients and healthcare workers who were exposed to a staff member of a London renal unit with smear positive pulmonary tuberculosis are described. METHODS--Following British Thoracic Society (BTS) guidelines, 576 close contacts were identified and divided into three groups: (1) 303 renal patients including 61 with renal transplants; (2) 90 surgical patients; and (3) 183 staff members. Screened contacts were interviewed, completed a symptoms questionnaire, and were offered a chest radiograph and Heaf or Mantoux test if appropriate with referral to a chest physician if required. RESULTS--Overall, 524 (85%) living contacts have been screened: 243 (97%) renal (first screening), 63 (70%) surgical, and 135 (74%) staff contacts. Thirty one transplant patients were prescribed isoniazid chemoprophylaxis. Fifty two renal patients had died before screening and 11 deaths occurred after first interview. One case of tuberculosis epidemiologically related to the index case was diagnosed on clinical criteria. A review of the case records and/or death certificates and entries on to tuberculosis registers indicated no further cases. The cost of the investigation was estimated to be approximately franc25 000, or franc44 per contact screened, with staff costs comprising 79% of the total. CONCLUSIONS--Undiagnosed tuberculosis in healthcare workers working with immunosuppressed patients can lead to large and expensive follow up studies. The applicability of the 1990 and 1994 BTS guidelines to the investigation of tuberculosis in an immunocompromised nosocomial group, and the role of the infection control doctor and the consultant in Communicable Disease Control in overlapping nosocomial and community incidents, are discussed. PMID:7570438

  1. Xpert(®) MTB/RIF under routine conditions in diagnosing pulmonary tuberculosis: a study in two hospitals in Pakistan.

    PubMed

    Shah, S K; Kumar, A M V; Dogar, O F; Khan, M A; Qadeer, E; Tahseen, S; Masood, F; Chandio, A K; Edginton, M E

    2013-03-21

    Xpert(®) MTB/RIF testing was offered to consecutive patients with presumptive tuberculosis (TB) attending two hospitals in Pakistan during April-May 2012, in addition to routine diagnostic protocol (smear microscopy, chest radiography and clinical judgement). We assessed the relative contribution of each tool in detecting pulmonary TB under routine conditions. Of 606 participants, 121 (20%) were detected as pulmonary TB: 46 (38%) by microscopy, 38 (31%) by Xpert alone and 37 (31%) on clinical and radiological grounds; 41 (65%) were detected by both Xpert and microscopy. One patient had rifampicin resistance. Although Xpert detected approximately twice as many TB cases as microscopy (n = 79, 65%), clinical judgement remained favoured by clinicians even when smear and Xpert were negative.

  2. Progress in the development of tuberculosis vaccines for cattle and wildlife.

    PubMed

    Buddle, B M; Wedlock, D N; Denis, M

    2006-02-25

    Vaccination against bovine tuberculosis is likely to become an important disease control strategy in developing countries, which cannot afford a test and slaughter control programme, or in countries which have a wildlife reservoir of Mycobacterium bovis infection. In the past decade, considerable progress has been made in the development and evaluation of tuberculosis vaccines for cattle and for a range of wildlife maintenance hosts including possums, badgers, deer and African buffaloes. Experimental challenge systems have been established for the different target species and the resulting disease process has mimicked that seen in the field. In cattle, neonatal vaccination with BCG appeared to be more effective than vaccination of 6-month-old calves and in most situations no other vaccine has been shown to be better than BCG. However, prime-boost strategies involving combinations of BCG with a protein or DNA vaccine, to improve on BCG vaccination alone, have produced very encouraging results. Differential diagnostic tests have been developed using mycobacterial antigens that are only present in virulent M. bovis to differentiate between BCG-vaccinated and M. bovis-infected cattle. BCG vaccine has been shown to reduce the spread of tuberculous lesions in a range of wildlife species and a prototype oral bait delivery system has been developed. Prospects for the development of improved vaccines against bovine tuberculosis are promising and vaccination approaches could become very valuable in the control and eradication of bovine tuberculosis. PMID:16326043

  3. Application of cetylpyridinium chloride and sodium chloride decontamination method for recovery of Mycobacterium tuberculosis from clinically suspected cases of pulmonary tuberculosis.

    PubMed

    Shinu, Pottathil; Singh, Varsha; Nair, Anroop; Mehrishi, Priya; Mehta, Sonia; Joshi, Ekta

    2013-10-01

    The study was designed to compare the efficacy of cetylpyridinium chloride (CPC) and sodium chloride (NaCl) decontamination method with N-acetyl L-Cystine (NALC) and sodium hydroxide (NaOH) decontamination (the reference method) method for the recovery of Mycobacterium tuberculosis (MTB) from clinically suspected cases of pulmonary tuberculosis. To evaluate CPC-NaCl and NALC-NaOH decontamination methods, sputum specimens (n = 796) were studied (culturing on Löwenstein-Jensen medium), and the performances were compared. The CPC-NaCl decontamination method demonstrated a sensitivity, specificity, negative predictive value, and positive predictive value of 97.99%, 87.53%, 70.19%, and 99.32%, respectively, when compared to NALC-NaOH decontamination method. In summary, CPC-NaCl decontamination method effectively detected significantly higher number of MTB cases (n = 208) than NALC-NaOH decontamination method (n = 149) particularly in sputum with scanty bacilli and smear-negative cases, indicating the potential of CPC-NaCl decontamination method to preserve paucibacillary cases more efficient than NALC-NaOH decontamination method.

  4. Resolution of hypercalcemia and acute kidney injury after treatment for pulmonary tuberculosis without the use of corticosteroids.

    PubMed

    Araujo, Constance A A; Araujo, Nicole A A; Daher, Elizabeth F; Oliveira, José Daniel B; Kubrusly, Marcos; Duarte, Pastora M A; Silva, Sonia L; Araujo, Sonia M H A

    2013-03-01

    Abstract. Hypercalcemia caused by tuberculosis is rare and it is usually asymptomatic. Tuberculosis (TB) -related hypercalcemia associated with acute kidney injury (AKI) is rarely reported. We report a case of a 22-year-old immunocompetent man with 1-month history of daily fever, asthenia and weight loss. Laboratory findings on admission included serum calcium 14.9 mg/dL, urinary Ca(2+) 569.6 mg/24 hours, low level of parathyroid hormone, serum creatinine = 2.2 mg/dL and sodium fractional excretion (FeNa) 2.73%. The result of the tuberculin skin test was 17 mm. A chest X-ray revealed micronodular pulmonary infiltrate in the apex of the right lung, which was confirmed by computed tomography scan. The patient was diagnosed with hypercalcemia associated with pulmonary TB and AKI. A general improvement of the hypercalcemia and renal function was observed in the first 2 weeks after effective hydration and treatment of TB without corticosteroids. The patient was discharged with normal calcium levels and renal function.

  5. The Effect of Low CD4+ Lymphocyte Count on the Radiographic Patterns of HIV Patients with Pulmonary Tuberculosis among Nigerians.

    PubMed

    Affusim, Christopher; Abah, Vivien; Kesieme, Emeka B; Anyanwu, Kester; Salami, Taofik A T; Eifediyi, Reuben

    2013-01-01

    Objective. To assess the radiographic features in patients with Human Immunodeficiency Virus (HIV) complicated by pulmonary tuberculosis (PTB), and the association with CD4 lymphocyte count and sputum smear. Method. A prospective study was carried out on 89 HIV positive patients with PTB. The demographics, smoking history, sputum smear result, chest radiographic findings and CD4 lymphocyte count were documented. Results. Out of the 89 patients recruited in the study, 41 were males and 48 were females. Eighteen (18) patients had typical radiographic features, 60 patients had atypical radiographic features while only 11 of them had normal radiographic films. Sixty eight (68) patients had CD4 count <200 cells/mm(3), 19 patients had CD4 count between 200-499 cells/mm(3), while only 2 patients had CD4 count from 500 cells/mm(3) upwards. The association between low CD4 count and radiographic finding was statistically significant, (P value <0.05). Sixty (60) patients had negative sputum smear for Acid and Alcohol Fast Bacilli (AAFB), while the remaining 29 patients had positive smear. The association between low CD4 count and negative smear was statistically significant (P value <0.05). Conclusion. The radiographic pattern and the result of the sputum smear for AAFB has a significant relationship and association with the immune status of patients with Human Immunodeficiency Virus (HIV) complicated by pulmonary tuberculosis.

  6. Plasma Adenosine Deaminase Enzyme Reduces with Treatment of Pulmonary Tuberculosis in Nigerian Patients: Indication for Diagnosis and Treatment Monitoring.

    PubMed

    Ige, O; Edem, V F; Arinola, O G

    2016-01-01

    Tuberculosis(TB)-specific host biomarkers for diagnosis and monitoring of treatment response have been identified as priorities for TB research. Macrophage and T cell lymphocytes play vital roles in Mycobacterium tuberculosis immune response and their associated biomarkers could form good candidates for diagnosis and treatment monitoring. The enzyme adenosine deaminase (ADA) is produced mainly by monocytes and macrophages and increase in biological fluids in the course of infection with microorganisms infecting macrophages. This study comprised sixty-eight (68) participants; twenty-four (24) multi-drug-resistant TB(MDR-TB) patients, twenty-four (24) drug-sensitive TB patients(DS-TB) and twenty (20) non-TB apparently healthy individuals. Five (5) milliliters of blood was drawn before commencement of chemotherapy and 6 anti-TB therapy. In DSTB and MDR-TB patients before commencement of chemotherapy and 6 months of anti-TB treatment, the mean plasma levels of ADA were significantly increased compared with control. At 6 months of anti-TB chemotherapy of DSTB or MDR TB patients, ADA level was significantly decreased compared with before chemotherapy. Plasma ADA in DSTB patients before and 6 months of chemotherapy were not significantly different compared MDR TB patients. Plasma ADA level is a promising biomarker for the screening and treatment monitoring of pulmonary tuberculosis but not to differentiate MDR TB from DSTB patients. PMID:27574764

  7. A Phase 2 Randomized Trial of a Rifapentine plus Moxifloxacin-Based Regimen for Treatment of Pulmonary Tuberculosis

    PubMed Central

    Conde, Marcus B.; Mello, Fernanda C. Q.; Duarte, Rafael Silva; Cavalcante, Solange C.; Rolla, Valeria; Dalcolmo, Margareth; Loredo, Carla; Durovni, Betina; Armstrong, Derek T.; Efron, Anne; Barnes, Grace L.; Marzinke, Mark A.; Savic, Radojka M.; Dooley, Kelly E.; Cohn, Silvia; Moulton, Lawrence H.; Chaisson, Richard E.; Dorman, Susan E.

    2016-01-01

    Background The combination of rifapentine and moxifloxacin administered daily with other anti-tuberculosis drugs is highly active in mouse models of tuberculosis chemotherapy. The objective of this phase 2 clinical trial was to determine the bactericidal activity, safety, and tolerability of a regimen comprised of rifapentine, moxifloxacin, isoniazid, and pyrazinamide administered daily during the first 8 weeks of pulmonary tuberculosis treatment. Methods Adults with sputum smear-positive pulmonary tuberculosis were randomized to receive either rifapentine (approximately 7.5 mg/kg) plus moxifloxacin (investigational arm), or rifampin (approximately 10 mg/kg) plus ethambutol (control) daily for 8 weeks, along with isoniazid and pyrazinamide. The primary endpoint was sputum culture status at completion of 8 weeks of treatment. Results 121 participants (56% of accrual target) were enrolled. At completion of 8 weeks of treatment, negative cultures using Löwenstein-Jensen (LJ) medium occurred in 47/60 (78%) participants in the investigational arm vs. 43/51 (84%, p = 0.47) in the control arm; negative cultures using liquid medium occurred in 37/47 (79%) in the investigational arm vs. 27/41 (66%, p = 0.23) in the control arm. Time to stable culture conversion was shorter for the investigational arm vs. the control arm using liquid culture medium (p = 0.03), but there was no difference using LJ medium. Median rifapentine area under the concentration-time curve (AUC0-24) was 313 mcg*h/mL, similar to recent studies of rifapentine dosed at 450–600 mg daily. Median moxifloxacin AUC0-24 was 28.0 mcg*h/mL, much lower than in trials where rifapentine was given only intermittently with moxifloxacin. The proportion of participants discontinuing assigned treatment for reasons other than microbiological ineligibility was higher in the investigational arm vs. the control arm (11/62 [18%] vs. 3/59 [5%], p = 0.04) although the proportions of grade 3 or higher adverse events were

  8. The effectiveness of sputum pH analysis in the prediction of response to therapy in patients with pulmonary tuberculosis.

    PubMed

    Masuda, Makoto; Sato, Takashi; Sakamaki, Kentaro; Kudo, Makoto; Kaneko, Takeshi; Ishigatsubo, Yoshiaki

    2015-01-01

    Purpose. The predictive factor of response to antituberculous therapy has not been fully elucidated. Airway acidity has been thought to be a potential indicator of the bactericidal activity. Therefore, we hypothesized that monitoring airway acidity by measuring sputum pH could predict response to therapy. Methods. A total of 47 patients having newly diagnosed, smear-positive, active pulmonary tuberculosis were enrolled between October 2011 and March 2014. Sputum samples were serially analyzed before and after treatment. Eligible patients who initiated a standard 6-month treatment were monitored for the length of time to sputum smear and culture conversion. Results. There were 39 patients who completed a 2-month intensive phase of isoniazid, rifampicin, pyrazinamide, and ethambutol therapy followed by a 4-month continuation phase of isoniazid and rifampicin. Although factors including age, cavitation, sputum grade, and use of an acid-suppressant were associated with initial low sputum pH in univariate analysis, multivariate analysis revealed that only age ≥61 years was a statistically important factor predicting low pH value (p = 0.005). Further outcome analysis showed that initial low sputum pH before treatment was the only factor significantly associated with shorter length of time to both sputum smear and culture conversion (p = 0.034 and 0.019, respectively) independent of the effects of age, sputum bacterial load, extent of lung lesion, and cavitation. Thus, initial low sputum pH indicated favorable response to anti-tuberculosis therapy. Conclusions. Measuring sputum pH is an easy and inexpensive way of predicting response to standard combination therapy in patients with pulmonary tuberculosis. PMID:26644982

  9. Air Pollution and Pulmonary Tuberculosis: A Nested Case–Control Study among Members of a Northern California Health Plan

    PubMed Central

    Smith, Geneé S.; Van Den Eeden, Stephen K.; Garcia, Cynthia; Shan, Jun; Baxter, Roger; Herring, Amy H.; Richardson, David B.; Van Rie, Annelies; Emch, Michael; Gammon, Marilie D.

    2016-01-01

    Background: Ecologic analyses, case–case comparisons, and animal experiments suggest positive associations between air pollution and tuberculosis. Objectives: We evaluated this hypothesis in a large sample, which yielded results that are applicable to the general population. Methods: We conducted a case–control study nested within a cohort of Kaiser Permanente of Northern California members. All active pulmonary tuberculosis (TB) cases newly diagnosed between 1996 and 2010 (n = 2,309) were matched to two controls (n = 4,604) by age, sex, and race/ethnicity on the index date corresponding with the case diagnosis date. Average individual-level concentrations of carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5) and 10 μm (PM10) for 2 years before diagnosis/entry into the study were estimated using measurements from the California Air Resources Board monitor closest to the participant’s residence. Results: In single-pollutant adjusted conditional logistic regression models, the pulmonary TB odds ratios (95% confidence intervals) for the highest quintile (vs. lowest) were 1.50 (95% CI: 1.15, 1.95) for CO and 1.42 (95% CI: 1.10, 1.84) for NO2. Corresponding estimates were higher among never [1.68 (95% CI: 1.26, 2.24)] than ever [1.19 (95% CI: 0.74, 1.92)] smokers for CO. In contrast, for NO2, estimates were higher among ever [1.81 (95% CI: 1.13, 2.91)] than never [1.29 (95% CI: 0.97, 1.71)] smokers. O3 was inversely associated for smokers [0.66 (95% CI: 0.43, 1.02)] and never smokers [0.65 (95% CI: 0.52, 0.81)]. No other consistent patterns were observed. Conclusions: In this first, to our knowledge, U.S. nested case–control study on air pollution and pulmonary TB, we observed positive associations with ambient CO and NO2, which require confirmation. Citation: Smith GS, Van Den Eeden SK, Garcia C, Shan J, Baxter R, Herring AH, Richardson DB, Van Rie A, Emch M

  10. Differential influence of nutrient-starved Mycobacterium tuberculosis on adaptive immunity results in progressive tuberculosis disease and pathology.

    PubMed

    Dietrich, Jes; Roy, Sugata; Rosenkrands, Ida; Lindenstrøm, Thomas; Filskov, Jonathan; Rasmussen, Erik Michael; Cassidy, Joseph; Andersen, Peter

    2015-12-01

    When infected with Mycobacterium tuberculosis, most individuals will remain clinically healthy but latently infected. Latent infection has been proposed to partially involve M. tuberculosis in a nonreplicating stage, which therefore represents an M. tuberculosis phenotype that the immune system most likely will encounter during latency. It is therefore relevant to examine how this particular nonreplicating form of M. tuberculosis interacts with the host immune system. To study this, we first induced a state of nonreplication through prolonged nutrient starvation of M. tuberculosis in vitro. This resulted in nonreplicating persistence even after prolonged culture in phosphate-buffered saline. Infection with either exponentially growing M. tuberculosis or nutrient-starved M. tuberculosis resulted in similar lung CFU levels in the first phase of the infection. However, between week 3 and 6 postinfection, there was a very pronounced increase in bacterial levels and associated lung pathology in nutrient-starved-M. tuberculosis-infected mice. This was associated with a shift from CD4 T cells that coexpressed gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) or IFN-γ, TNF-α, and interleukin-2 to T cells that only expressed IFN-γ. Thus, nonreplicating M. tuberculosis induced through nutrient starvation promotes a bacterial form that is genetically identical to exponentially growing M. tuberculosis yet characterized by a differential impact on the immune system that may be involved in undermining host antimycobacterial immunity and facilitate increased pathology and transmission. PMID:26416911

  11. Assessing the progress of Mycobacterium tuberculosis H37Rv structural genomics.

    PubMed

    Fang, Zhuo; van der Merwe, Ruben Gerhard; Warren, Robin Mark; Schubert, Wolf-Dieter; Gey van Pittius, Nicolaas Claudius

    2015-03-01

    Tuberculosis threatens human health nowhere more than in developing countries with large malnourished and/or immune-compromised (e.g. HIV infected) populations. The etiological agent, Mycobacterium tuberculosis (Mtb), is highly infectious and current interventions demonstrate limited ability to control the epidemic in particular of drug resistant Mtb strains. New drugs and vaccines are thus urgently required. Structural biologists are critical to the TB research community. By identifying potential drug targets and solving their three dimensional structures they open new avenues of identifying potential inhibitors complementing the screening of novel compounds and the investigation of Mtb's molecular physiology by pharmaceutical companies and academic researchers. Much effort has gone into structurally elucidating the Mtb proteome though much remains to be done with progress primarily limited by technological constraints. We review the currently available data for Mtb H37Rv to extract the lessons they have taught us.

  12. Evaluation of Giant African Pouched Rats for Detection of Pulmonary Tuberculosis in Patients from a High-Endemic Setting

    PubMed Central

    Reither, Klaus; Jugheli, Levan; Glass, Tracy R.; Sasamalo, Mohamed; Mhimbira, Francis A.; Weetjens, Bart J.; Cox, Christophe; Edwards, Timothy L.; Mulder, Christiaan; Beyene, Negussie W.; Mahoney, Amanda

    2015-01-01

    Background This study established evidence about the diagnostic performance of trained giant African pouched rats for detecting Mycobacterium tuberculosis in sputum of well-characterised patients with presumptive tuberculosis (TB) in a high-burden setting. Methods The TB detection rats were evaluated using sputum samples of patients with presumptive TB enrolled in two prospective cohort studies in Bagamoyo, Tanzania. The patients were characterised by sputum smear microscopy and culture, including subsequent antigen or molecular confirmation of Mycobacterium tuberculosis, and by clinical data at enrolment and for at least 5-months of follow-up to determine the reference standard. Seven trained giant African pouched rats were used for the detection of TB in the sputum samples after shipment to the APOPO project in Morogoro, Tanzania. Results Of 469 eligible patients, 109 (23.2%) were culture-positive for Mycobacterium tuberculosis and 128 (27.3%) were non-TB controls with sustained recovery after 5 months without anti-TB treatment. The HIV prevalence was 46%. The area under the receiver operating characteristic curve of the seven rats for the detection of culture-positive pulmonary tuberculosis was 0.72 (95% CI 0.66–0.78). An optimal threshold could be defined at ≥2 indications by rats in either sample with a corresponding sensitivity of 56.9% (95% CI 47.0–66.3), specificity of 80.5% (95% CI 72.5–86.9), positive and negative predictive value of 71.3% (95% CI 60.6–80.5) and 68.7% (95% CI 60.6–76.0), and an accuracy for TB diagnosis of 69.6%. The diagnostic performance was negatively influenced by low burden of bacilli, and independent of the HIV status. Conclusion Giant African pouched rats have potential for detection of tuberculosis in sputum samples. However, the diagnostic performance characteristics of TB detection rats do not currently meet the requirements for high-priority, rapid sputum-based TB diagnostics as defined by the World Health

  13. Prevalence of Pulmonary Tuberculosis among Adults in a Rural Sub-District of South India

    PubMed Central

    Chadha, Vineet K.; Kumar, Prahlad; Anjinappa, Sharada M.; Singh, Sanjay; Narasimhaiah, Somashekar; Joshi, Malathi V.; Gupta, Joydev; Lakshminarayana; Ramchandra, Jitendra; Velu, Magesh; Papkianathan, Suganthi; Babu, Suseendra; Krishna, Hemalatha

    2012-01-01

    Background We conducted a survey to estimate point prevalence of bacteriologically positive pulmonary TB (PTB) in a rural area in South India, implementing TB program DOTS strategy since 2002. Methods Survey was conducted among persons ≥15 years of age in fifteen clusters selected by simple random sampling; each consisting of 5–12 villages. Persons having symptoms suggestive of PTB or history of anti-TB treatment (ATT) were eligible for sputum examination by smear microscopy for Acid Fast Bacilli and culture for Mycobacterium tuberculosis; two sputum samples were collected from each eligible person. Persons with one or both sputum specimen positive on microscopy and/or culture were labeled suffering from PTB. Prevalence was estimated after imputing missing values to correct for bias introduced by incompleteness of data. In six clusters, registered persons were also screened by X-ray chest. Persons with any abnormal shadow on X-ray were eligible for sputum examination in addition to those with symptoms and ATT. Multiplication factor calculated as ratio of prevalence while using both screening tools to prevalence using symptoms screening alone was applied to entire study population to estimate prevalence corrected for non-screening by X-ray. Results Of 71,874 residents ≥15 years of age, 63,362 (88.2%) were screened for symptoms and ATT. Of them, 5120 (8.1%) - 4681 (7.4%) with symptoms and an additional 439 (0.7%) with ATT were eligible for sputum examination. Spot specimen were collected from 4850 (94.7%) and early morning sputum specimens from 4719 (92.2%). Using symptom screening alone, prevalence of smear, culture and bacteriologically positive PTB in persons ≥15 years of age was 83 (CI: 57–109), 152 (CI: 108–197) and 196 (CI :145–246) per 100,000 population respectively. Prevalence corrected for non-screening by X-ray was 108 (CI: 82–134), 198 (CI: 153–243) and 254 (CI: 204–301) respectively. Conclusion Observed prevalence suggests further

  14. Adjuvant Efficacy of Nutrition Support During Pulmonary Tuberculosis Treating Course: Systematic Review and Meta-analysis

    PubMed Central

    Si, Zhuang-Li; Kang, Ling-Ling; Shen, Xu-Bo; Zhou, Yuan-Zhong

    2015-01-01

    Background: Malnutrition and tuberculosis (TB) tend to interact with each other. TB may lead to nutrition deficiencies that will conversely delay recovery by depressing immune functions. Nutrition support can promote recovery in the subject being treated for TB. The aim of this study was to evaluate the effectiveness of nutrition support on promoting the recovery of adult pulmonary TB patients with anti-TB drug therapy. Methods: English database of the Cochrane Controlled Trials Register, PubMed, EMBASE, and Chinese database of CBM, CNKI, VIP, and WANFANG were searched. Randomized controlled trials comparing nutrition support (given for more than 2 weeks) with no nutrition intervention, nutrition advice only, or placebo-control for TB patients being anti-TB treated were included. Two reviewers conducted data extraction, assessed the quality of the studies independently, and any discrepancies were solved by the third reviewer. Data were entered and analyzed by RevMan 5.2 software, and meta-analysis was done using risk ratios (RRs) for dichotomous variables and mean differences (MDs) for continuous variables with 95% confidence intervals (CIs). Results: A total of 19 studies (3681 participants) were included. In nutritional support for TB patients, pooled RR and its 95% CI of sputum smears- or culture-negative conversion rate and chest X-ray (CXR) absorption rate were 1.10 (1.04, 1.17) and 1.22 (1.08, 1.39), respectively, the pooled MD and its 95% CI of body mass index (BMI) and time of sputum smears or culture negativity were 0.59 (0.16, 1.2) and − 5.42 (−7.93, −2.92), respectively, compared with the control group. The differences in outcomes of CXR zone affected, TB score, serum albumin, and hemoglobin were not statistically significant (P = 0.76, 0.24, 0.28, and 0.20, respectively) between the intervention group and the control group. No systemic adverse events were recorded. Conclusions: During anti-TB course, nutrition support may be helpful in treatment

  15. Evaluation of public awareness and attitude to pulmonary tuberculosis in a Nigerian rural community

    PubMed Central

    Anochie, Philip Ifesinachi; Onyeneke, Edwina Chinwe; Onyeozirila, Anthony Chidiebere; Igbolekwu, Leonard Chibuzo; Onyeneke, Bestman Chukwuemeka; Ogu, Angelina Chinyere

    2013-01-01

    Introduction Community based interventions have long been linked to tuberculosis control efforts. Effectively treated and cured patients living within their home communities are often the best advocates and may become the drivers of social mobilization to support control of tuberculosis. Methods A descriptive cross-sectional knowledge, attitude, behavioral and practice (KABP) survey on tuberculosis was carried out in a rural Nigerian community. We used the multi-stage sampling method for subject selection. We administered an interview schedule consisting of a pre-tested structured interviewer-administered questionnaire, together with in-depth interviews and focus group discussions. Results We applied the questionnaire to 1186 people in designated rural households. Most of the participants, (1154, 97.3%) had prior knowledge and awareness about tuberculosis as a disease, 612 (51.6%) considered tuberculosis a result of HIV/AIDS epidemics or malnutrition, and 451 (38%) believed that it can be cured by Western medicine. The unwillingness of respondents to relate with TB patients was generally high (97%, 1150), even where levels of awareness and knowledge were high. Conclusion These results should be used to orient tuberculosis control programs, especially those aimed at mobilizing people for tuberculosis control and eradication. PMID:24432287

  16. Mycobacterium genotypes in pulmonary tuberculosis infections and their detection by trained African giant pouched rats.

    PubMed

    Mgode, Georgies F; Cohen-Bacrie, Stéphan; Bedotto, Marielle; Weetjens, Bart J; Cox, Christophe; Jubitana, Maureen; Kuipers, Dian; Machang'u, Robert S; Kazwala, Rudovick; Mfinanga, Sayoki G; Kaufmann, Stefan H E; Drancourt, Michel

    2015-02-01

    Tuberculosis (TB) diagnosis in low-income countries is mainly done by microscopy. Hence, little is known about the diversity of Mycobacterium spp. in TB infections. Different genotypes or lineages of Mycobacterium tuberculosis vary in virulence and induce different inflammatory and immune responses. Trained Cricetomys rats show a potential for rapid diagnosis of TB. They detect over 28 % of smear-negative, culture-positive TB. However, it is unknown whether these rats can equally detect sputa from patients infected with different genotypes of M. tuberculosis. A 4-month prospective study on diversity of Mycobacterium spp. was conducted in Dar es Salaam, Tanzania. 252 sputa from 161 subjects were cultured on Lowenstein-Jensen medium and thereafter tested by rats. Mycobacterial isolates were subjected to molecular identification and multispacer sequence typing (MST) to determine species and genotypes. A total of 34 Mycobacterium spp. isolates consisting of 32 M. tuberculosis, 1 M. avium subsp. hominissuis and 1 M. intracellulare were obtained. MST analyses of 26 M. tuberculosis isolates yielded 10 distinct MST genotypes, including 3 new genotypes with two clusters of related patterns not grouped by geographic areas. Genotype MST-67, shared by one-third of M. tuberculosis isolates, was associated with the Mwananyamala clinic. This study shows that diverse M. tuberculosis genotypes (n = 10) occur in Dar es Salaam and trained rats detect 80 % of the genotypes. Sputa with two M. tuberculosis genotypes (20 %), M. avium hominissuis and M. intracellulare were not detected. Therefore, rats detect sputa with different M. tuberculosis genotypes and can be used to detect TB in resource-poor countries.

  17. Estimation of Ten-Year Survival of Patients with Pulmonary Tuberculosis Based on the Competing Risks Model in Iran

    PubMed Central

    Kazempour-Dizaji, Mehdi; Tabarsi, Payam; Zayeri, Farid

    2016-01-01

    Background: Tuberculosis (TB) is a chronic bacterial disease, which despite the presence of effective drug strategies, still remains a serious health problem worldwide. Estimation of survival rate is an appropriate indicator for prognosis in patients with pulmonary TB. Therefore, this research was designed with the aim of accurate estimation of the survival of patients by taking both the death event and relapse into consideration. Materials and Methods: Based on a retrospective cohort study, information of 2,299 patients with pulmonary TB that had been referred to and treated in Masih Daneshvari Hospital from 2005 to 2015 was reviewed. To estimate the survival of patients with pulmonary TB, the competing risks model, which considered death and relapse as competing events, was used. In addition, the effect of factors affecting the cumulative incidence function (CIF) of death event and relapse was also examined. Results: The effect of risk factors on the CIF of death events and relapse showed that patients’ age, marital status, contact with TB patients, adverse effect of drugs, imprisonment and HIV positivity were factors that affected the CIF of death. Meanwhile, sex, marital status, imprisonment and HIV positivity were factors affecting the CIF of relapse (P <0.05). Considering death and relapse as competing events, survival estimation in pulmonary TB patients showed that survival in this group of patients in the first, third, fifth and tenth year after treatment was 39%, 14%, 7% and 0%, respectively. Conclusion: The use of competing risks model in survival analysis of patients with pulmonary TB with consideration of competing events, enables more accurate estimation of survival. PMID:27403177

  18. Pulmonary tuberculosis in Asian elephants (Elephas maximus): histologic lesions with correlation to local immune responses.

    PubMed

    Landolfi, J A; Terio, K A; Miller, M; Junecko, B F; Reinhart, T

    2015-05-01

    Although Mycobacterium tuberculosis infection is an important health concern for Asian elephants (Elephas maximus), no studies have evaluated the associated local immune responses or histologic lesions. In primates including humans, latent tuberculosis is distinguished by well-organized granulomas with TH1 cytokine expression, whereas active disease is characterized by poorly organized inflammation and local imbalance in TH1/TH2 cytokines. This study examined archival, formalin-fixed, paraffin-embedded lung samples from 5 tuberculosis-negative and 9 tuberculosis-positive Asian elephants. Lesions were assessed by light microscopy, and lymphoid infiltrates were characterized by CD3 and CD20 immunolabeling. Expression of TH1 (interferon [IFN]-γ, tumor necrosis factor [TNF]-α) and TH2 (interleukin [IL]-4, IL-10, transforming growth factor [TGF]-β) cytokines was determined using in situ hybridization. In 6 of 9 samples, inflammation was similar to the pattern of primate active disease with low to moderate numbers of lymphocytes, most of which were CD20 positive. In 1 sample, inflammation was most similar to latent tuberculosis in primates with numerous CD3-positive lymphocytes. Expression of IFN-γ was detected in 3 of 8 tuberculosis-positive samples. Expression of TNF-α was detected in 3 of 8 positive samples, including the one with latent morphology. Low-level expression of IL-4 was present in 4 of 8 positive samples. Only single positive samples displayed expression of IL-10 and TGF-β. Tuberculosis-negative samples generally lacked cytokine expression. Results showed heterogeneity in lesions of elephant tuberculosis similar to those of latent and active disease in primates, with variable expression of both TH1 and TH2 cytokines.

  19. Pulmonary tuberculosis in Asian elephants (Elephas maximus): histologic lesions with correlation to local immune responses.

    PubMed

    Landolfi, J A; Terio, K A; Miller, M; Junecko, B F; Reinhart, T

    2015-05-01

    Although Mycobacterium tuberculosis infection is an important health concern for Asian elephants (Elephas maximus), no studies have evaluated the associated local immune responses or histologic lesions. In primates including humans, latent tuberculosis is distinguished by well-organized granulomas with TH1 cytokine expression, whereas active disease is characterized by poorly organized inflammation and local imbalance in TH1/TH2 cytokines. This study examined archival, formalin-fixed, paraffin-embedded lung samples from 5 tuberculosis-negative and 9 tuberculosis-positive Asian elephants. Lesions were assessed by light microscopy, and lymphoid infiltrates were characterized by CD3 and CD20 immunolabeling. Expression of TH1 (interferon [IFN]-γ, tumor necrosis factor [TNF]-α) and TH2 (interleukin [IL]-4, IL-10, transforming growth factor [TGF]-β) cytokines was determined using in situ hybridization. In 6 of 9 samples, inflammation was similar to the pattern of primate active disease with low to moderate numbers of lymphocytes, most of which were CD20 positive. In 1 sample, inflammation was most similar to latent tuberculosis in primates with numerous CD3-positive lymphocytes. Expression of IFN-γ was detected in 3 of 8 tuberculosis-positive samples. Expression of TNF-α was detected in 3 of 8 positive samples, including the one with latent morphology. Low-level expression of IL-4 was present in 4 of 8 positive samples. Only single positive samples displayed expression of IL-10 and TGF-β. Tuberculosis-negative samples generally lacked cytokine expression. Results showed heterogeneity in lesions of elephant tuberculosis similar to those of latent and active disease in primates, with variable expression of both TH1 and TH2 cytokines. PMID:25228055

  20. The role of Xpert MTB/RIF in diagnosing pulmonary tuberculosis in post-mortem tissues

    PubMed Central

    García-Basteiro, Alberto L.; Ismail, Mamudo R.; Carrilho, Carla; Ussene, Esperança; Castillo, Paola; Chitsungo, Dércio; Rodríguez, Cristina; Lovane, Lucília; Vergara, Andrea; López-Varela, Elisa; Mandomando, Inacio; Lorenzoni, Cesaltina; Ordi, Jaume; Menéndez, Clara; Bassat, Quique; Martínez, Miguel J.

    2016-01-01

    The extent to which the Xpert MTB/RIF (Gene Xpert) contributes to tuberculosis (TB) diagnosis in samples other than sputum and cerebrospinal fluid remains uncertain. We aimed to assess the role of Xpert MTB/RIF for detecting M. tuberculosis in post-mortem tissues. We conducted a study among 30 complete diagnostic autopsies (CDA) performed at the Maputo Central Hospital (Mozambique). Lung tissues were screened for TB in all cases. In addition other tissues were tested when compatible lesions were identified in the histological exam. We used in-house real time PCR and LAMP assays to confirm the presence of M. tuberculosis DNA. The diagnosis of tuberculosis at death was established based on microbiological and histopathological results. Eight out of 30 cases (26.7%) were diagnosed of tuberculosis. Xpert had a sensitivity to detect TB in lung tissue of 87.5% (95% CI 47.3–99.7) and a specificity of 95.7% (95% CI: 78.1–99.9). In-house DNA amplification methods and Xpert showed 93.6% concordance for lung tissue and 100% concordance for brain and liver tissues. The final cause of death was attributable to tuberculosis in four cases. Xpert MTB/RIF may represent a valuable, easy-to perform technique for post-mortem TB diagnosis. PMID:26860394

  1. Saudi guidelines for testing and treatment of latent tuberculosis infection

    PubMed Central

    Al Jahdali, Hamdan H.; Baharoon, Salim; Abba, Abdullah A.; Memish, Ziad A.; Alrajhi, Abdulrahman A.; AlBarrak, Ali; Haddad, Qais A.; Al Hajjaj, Mohammad; Pai, Madhukar; Menzies, Dick

    2010-01-01

    Pulmonary tuberculosis is a common disease in Saudi Arabia. As most cases of tuberculosis are due to reactivation of latent infection, identification of individuals with latent tuberculosis infection (LTBI) who are at increased risk of progression to active disease, is a key element of tuberculosis control programs. Whereas general screening of individuals for LTBI is not cost-effective, targeted testing of individuals at high risk of disease progression is the right approach. Treatment of those patients with LTBI can diminish the risk of progression to active tuberculosis disease in the majority of treated patients. This statement is the first Saudi guideline for testing and treatment of LTBI and is a result of the cooperative efforts of four local Saudi scientific societies. This Guideline is intended to provide physicians and allied health workers in Saudi Arabia with the standard of care for testing and treatment of LTBI. PMID:20103957

  2. Cytokine Profiles for Peripheral Blood Lymphocytes from Patients with Active Pulmonary Tuberculosis and Healthy Household Contacts in Response to the 30-Kilodalton Antigen of Mycobacterium tuberculosis

    PubMed Central

    Torres, Martha; Herrera, Teresa; Villareal, Hector; Rich, Elizabeth A.; Sada, Eduardo

    1998-01-01

    Patients with active tuberculosis (TB) have a stronger humoral but a poorer cellular immune response to the secreted 30-kDa antigen (Ag) of Mycobacterium tuberculosis than do healthy household contacts (HHC), who presumably are more protected against disease. The basis for this observation was studied by examining the Th1 (interleukin 2 [IL-2] and gamma interferon [IFN-γ])- and Th2 (IL-10 and IL-4)-type cytokines produced in response to the 30-kDa Ag by peripheral blood mononuclear cells (PBMC) from patients with active pulmonary TB (n = 7) and from HHC who were tuberculin (purified protein derivative) skin test positive (n = 12). Thirty-kilodalton-Ag-stimulated PBMC from TB patients produced significantly lower levels of IFN-γ (none detectable) than did those from HHC (212 ± 73 pg/ml, mean ± standard error) (P < 0.001). Likewise, 30-kDa-Ag-stimulated PBMC from TB patients failed to express IFN-γ mRNA by reverse transcription-PCR, whereas cells from HHC expressed the IFN-γ gene. In contrast, 30-kDa-Ag-stimulated PBMC from TB patients produced significantly higher levels of IL-10 (403 ± 80 pg/ml) than did those from HHC (187 ± 66 pg/ml) (P < 0.013), although cells from both groups expressed the IL-10 gene. IL-2 and IL-4 were not consistently produced, and their genes were not expressed by 30-kDa-Ag-stimulated cells from either TB patients or HHC. After treatment with antituberculous drugs, lymphocytes from four of the seven TB patients proliferated and three of them expressed IFN-γ mRNA in response to the 30-kDa Ag and produced decreased levels of IL-10. PMID:9423855

  3. A Multifaceted Analysis of Immune-Endocrine-Metabolic Alterations in Patients with Pulmonary Tuberculosis

    PubMed Central

    Santucci, Natalia; D'Attilio, Luciano; Kovalevski, Leandro; Bozza, Verónica; Besedovsky, Hugo; del Rey, Adriana; Bay, María Luisa; Bottasso, Oscar

    2011-01-01

    Our study investigated the circulating levels of factors involved in immune-inflammatory-endocrine-metabolic responses in patients with tuberculosis with the aim of uncovering a relation between certain immune and hormonal patterns, their clinical status and in vitro immune response. The concentration of leptin, adiponectin, IL-6, IL-1β, ghrelin, C-reactive protein (CRP), cortisol and dehydroepiandrosterone (DHEA), and the in vitro immune response (lymphoproliferation and IFN-γ production) was evaluated in 53 patients with active untreated tuberculosis, 27 household contacts and 25 healthy controls, without significant age- or sex-related differences. Patients had a lower body mass index (BMI), reduced levels of leptin and DHEA, and increased concentrations of CRP, IL-6, cortisol, IL-1β and nearly significant adiponectin values than household contacts and controls. Within tuberculosis patients the BMI and leptin levels were positively correlated and decreased with increasing disease severity, whereas higher concentrations of IL-6, CRP, IL-1β, cortisol, and ghrelin were seen in cases with moderate to severe tuberculosis. Household contacts had lower DHEA and higher IL-6 levels than controls. Group classification by means of discriminant analysis and the k-nearest neighbor method showed that tuberculosis patients were clearly different from the other groups, having higher levels of CRP and lower DHEA concentration and BMI. Furthermore, plasma leptin levels were positively associated with the basal in vitro IFN-γ production and the ConA-driven proliferation of cells from tuberculosis patients. Present alterations in the communication between the neuro-endocrine and immune systems in tuberculosis may contribute to disease worsening. PMID:22022605

  4. Infection Rate and Tissue Localization of Murine IL-12p40-Producing Monocyte-Derived CD103+ Lung Dendritic Cells during Pulmonary Tuberculosis

    PubMed Central

    Leepiyasakulchai, Chaniya; Taher, Chato; Chuquimia, Olga D.; Mazurek, Jolanta; Söderberg-Naucler, Cecilia; Fernández, Carmen; Sköld, Markus

    2013-01-01

    Non-hematopoietic cells, including lung epithelial cells, influence host immune responses. By co-culturing primary alveolar epithelial cells and monocytes from naïve donor mice, we show that alveolar epithelial cells support monocyte survival and differentiation in vitro, suggesting a role for non-hematopoietic cells in monocyte differentiation during the steady state in vivo. CD103+ dendritic cells (αE-DC) are present at mucosal surfaces. Using a murine primary monocyte adoptive transfer model, we demonstrate that αE-DC in the lungs and pulmonary lymph nodes are monocyte-derived during pulmonary tuberculosis. The tissue localization may influence the functional potential of αE-DC that accumulate in Mycobacterium tuberculosis-infected lungs. Here, we confirm the localization of αE-DC in uninfected mice beneath the bronchial epithelial cell layer and near the vascular wall, and show that αE-DC have a similar distribution in the lungs during pulmonary tuberculosis and are detected in the bronchoalveolar lavage fluid from infected mice. Lung DC can be targeted by M. tuberculosis in vivo and play a role in bacterial dissemination to the draining lymph node. In contrast to other DC subsets, only a fraction of lung αE-DC are infected with the bacterium. We also show that virulent M. tuberculosis does not significantly alter cell surface expression levels of MHC class II on infected cells in vivo and that αE-DC contain the highest frequency of IL-12p40+ cells among the myeloid cell subsets in infected lungs. Our results support a model in which inflammatory monocytes are recruited into the M. tuberculosis-infected lung tissue and, depending on which non-hematopoietic cells they interact with, differentiate along different paths to give rise to multiple monocyte-derived cells, including DC with a distinctive αE-DC phenotype. PMID:23861965

  5. Comparison of the safety and efficacy of a fixed-dose combination regimen and separate formulations for pulmonary tuberculosis treatment

    PubMed Central

    Wu, Jiun-Ting; Chiu, Chien-Tung; Wei, Yu-Feng; Lai, Yung-Fa

    2015-01-01

    OBJECTIVES: Fixed-dose combination formulations, which simplify the administration of drugs and prevent the development of drug resistance, have been recommended as a standard anti-tuberculosis treatment regimen. However, the composition and dosage recommendations for fixed-dose combination formulations differ from those for separate formulations. Thus, questions about the effectiveness and side effects of combination formulations remain. The aim of this study was to compare the safety and efficacy of these two types of anti-tuberculosis regimens for pulmonary tuberculosis treatment. METHOD: A prospective, randomized controlled study was conducted using the directly observed treatment short-course strategy. Patients were randomly allocated to one of two short-course regimens. One year after completing the treatment, these patients' outcomes were analyzed. ClinicalTrials.gov: NCT00979290. RESULTS: A total of 161 patients were enrolled, 142 of whom were evaluable for safety assessment. The two regimens had a similar incidence of adverse effects. In the per-protocol population, serum bilirubin concentrations at the peak level, at week 4, and at week 8 were significantly higher for the fixed-dose combination formulation than for the separate formulations. All patients had negative sputum cultures at the end of the treatment, and no relapse occurred after one year of follow-up. CONCLUSIONS: In this randomized study, transient higher serum bilirubin levels were noted for the fixed-dose combination regimen compared with the separate formulations during treatment. However, no significant difference in safety or efficacy was found between the groups when the directly observed treatment short-course strategy was used. PMID:26106962

  6. Association between Interleukin-1 Receptor Antagonist (IL1RN) Variable Number of Tandem Repeats (VNTR) Polymorphism and Pulmonary Tuberculosis.

    PubMed

    Hashemi, Mohammad; Naderi, Mohammad; Ebrahimi, Mahboubeh; Amininia, Shadi; Bahari, Gholamreza; Taheri, Mohsen; Eskandari-Nasab, Ebrahim; Ghavami, Saeid

    2015-02-01

    Macrophages and T-lymphocytes are involved in immune response to Mycobacterium tuberculosis. Macrophage produces interleukin (IL)-1 as an inflammatory mediator. IL-1 receptor antagonist (IL1-Ra) is a natural antagonist of IL-1 receptors. In this study we aimed to examine the possible association between the variable number of tandem repeats (VNTR) of the IL-1 receptor antagonist (IL1RN) gene and pulmonary tuberculosis (TB) in a sample of Iranian population. Our study is a case-control study and we examined the VNTR of the IL1RN gene in 265 PTB and 250 healthy subjects by PCR. Neither the overall chi-square comparison of PTB and control subjects nor the logistic regression analysis indicated any association between VNTR IL1RN polymorphism and PTB. Our data suggest that VNTR IL1RN polymorphism may not be associated with the risk of PTB in a sample of Iranian population. Larger studies with different ethnicities are needed to find out the impact of IL1RN VNTR polymorphism on risk of developing TB.

  7. Regulatory role of Cdx-2 and Taq I polymorphism of vitamin D receptor gene on chemokine expression in pulmonary tuberculosis.

    PubMed

    Harishankar, M; Selvaraj, P

    2016-06-01

    Vitamin D receptor (VDR) gene variants have been shown to be regulating the immune response in tuberculosis. We studied the regulatory role of VDR promoter Cdx-2 and 3'UTR TaqI gene variants on chemokine levels from culture filtrate antigen (CFA) stimulated with or without 1,25(OH)2D3 treated peripheral blood mononuclear cells of 50 pulmonary tuberculosis patients (PTB) and 51 normal healthy controls (HCs). In CFA with 1,25(OH)2D3 treated cultures, the MIP-1α, MIP-1β, RANTES levels were significantly decreased in Cdx-2 AA genotype compared to GG genotype, while a significantly increased MIG level was observed in Cdx-2 AA genotype (p<0.05). In TaqI polymorphism, tt genotype significantly decreased MIP-1β and RANTES levels compared to TT genotype. Moreover, a significantly increased level of IP-10 and MIG was observed in TaqI tt genotype compared with TT genotype (p<0.05). The results suggests that the 1,25(OH)2D3 may alter the chemokine response through the VDR polymorphic variants during infection. PMID:27067904

  8. High resolution computed tomography findings in smear-negative pulmonary tuberculosis patients according to their culture status

    PubMed Central

    Caliskan, Tayfun; Ozkisa, Tuncer; Aribal, Serkan; Kaya, Hatice; Incedayi, Mehmet; Ulcay, Asim; Ciftci, Faruk

    2014-01-01

    Objective The aim of this study was to assess the clinical features and high resolution computed tomography (HRCT) findings in smear-negative pulmonary tuberculosis (PTB) and to evaluate the correlation between these parameters and the culture results. Methods We retrospectively studied 78 active smear-negative PTB patients. They were divided into two groups according to their culture results. The HRCT findings and clinical features at the beginning of the antituberculosis treatment were reviewed. Results The mean age was 22.48±3.18 years. Micronodules (87%), large nodules (63%) and centrilobular nodules (62%) were the most common HRCT findings. HRCT findings were observed in the right upper (72%), left upper (56%), right lower (32%), and left lower lobes (29%). Cough (37%) and chest pain (32%) were the most frequent symptoms at presentation. Conclusions There were no significant differences in the HRCT findings and clinical features between the two groups. Thus, in cases of smear-negative and culture-negative PTB, the patient with compatible clinical and radiological features should be considered for tuberculosis treatment. PMID:24976993

  9. Trend of Smear-positive Pulmonary Tuberculosis in Iran during 1995–2012: A Segmented Regression Model

    PubMed Central

    Khazaei, Salman; Soheilyzad, Mokhtar; Molaeipoor, Leila; Khazaei, Zaher; Rezaeian, Shahab; Khazaei, Somayeh

    2016-01-01

    Background: Describing trend in tuberculosis (TB) over time can play an important role to assess the disease control strategies and predict the future morbidity and mortality. This study aimed to determine the incidence trend of smear-positive pulmonary tuberculosis (SPPT) in sub-age and sex groups during the years of 1995–2012. Methods: This retrospective cohort study was performed in 2015 by using the dataset regarding National Statistics of SPPT reported by World Health Organization during 1995–2012. Annual percent changes (APCs) and average annual percent changes (AAPCs) were estimated to determine the summery statistics of trend using segmented regression model. Results: During 1995–2012, there were 96,579 SPPT case notifications in Iran (male to female ratio: 0.99). There was only one change point in 1997 for SPPT incidence in subgroups of age and sex during 1995–2012. The AAPCs for both genders and also all three age groups had a significant descending trend during the time period (P < 0.05). Conclusions: Our results showed a downward trend in the SPPT incidence. It seems that to achieve the set goals and high successful in TB control program especially reduction in SPPT, pay more attention to old age and males should be considered. In addition, improvement of clinical and medical care services and notification processes would be imperative. PMID:27413517

  10. Correlates of Delayed Diagnosis among Human Immunodeficiency Virus-Infected Pulmonary Tuberculosis Suspects in a Rural HIV Clinic, South Africa.

    PubMed

    Boniface, Respicious; Moshabela, Mosa; Zulliger, Rose; Macpherson, Peter; Nyasulu, Peter

    2012-01-01

    Background. Delay in pulmonary tuberculosis (PTB) diagnosis is one of the major factors that affect outcome and threatens continued spread of tuberculosis. This study aimed at determining factors associated with delayed PTB diagnosis among human immunodeficiency virus (HIV) infected individuals. Methods. A retrospective observational study was done using clinic records of HIV-infected PTB suspects attending an HIV/AIDS clinic at Tintswalo rural hospital in South Africa (SA) between January 2006 and December 2007. Using routine clinic registers, 480 records were identified. Results. PTB diagnosis delay was found among 77/176 (43.8%) of the patients diagnosed with PTB. The mean delay of PTB diagnosis was 170.6 days; diagnosis delay ranged 1-30 days in 27 (35.1%) patients, 31-180 days in 24 (33.8%) patients; 24 (31.2%) patients remained undiagnosed for ≥180 days. Independent factors associated with delayed diagnosis were: older age >40 years (Odds Ratio (OR) 3.43, 95% CI 1.45-8.08) and virological failure (OR 2.72, 95% CI 1.09-6.74). Conclusion. There is a considerable delayed PTB diagnosis among HIV-infected patients in rural SA. Older patients as well as patients with high viral load are at a higher risk of PTB diagnosis delay. Therefore efforts to reduce PTB diagnosis delay need to emphasised.

  11. Prevalence of extended treatment in pulmonary tuberculosis patients receiving first-line therapy and its association with recurrent tuberculosis in Beijing, China

    PubMed Central

    Xia, YinYin; Goel, Sonu; Harries, Anthony D.; Zhang, ZhiGuo; Gao, TieJie; Wang, LiXia; Cheng, ShiMing; Lin, Yan; Du, Xin

    2014-01-01

    Background In China, it is known that extended treatment is given to patients with pulmonary TB after they have successfully completed 6 months of first-line treatment. This practice is not officially reported to the National Tuberculosis Control Programme, so there are no data on its prevalence, its possible benefits in terms of preventing recurrent disease or the costs. This study aimed to provide information, from a single TB dispensary in Beijing, China, on the prevalence of extended anti-TB treatment and its relationship with recurrent TB. Methods Retrospective cohort study using the electronic national TB information system and dispensary medical records. Results Of 935 patients with pulmonary TB who completed 6–7 months of first-line drug treatment, 399 (43%) were given extended treatment. This was more common in patients with smear-positive disease, and those with lung cavities and more extensive radiographic lobar involvement at the time of diagnosis. Over 3–4 years' follow-up, recurrent disease was not significantly different in patients who received extended treatment (2.8%, 11/399) as compared to those who received the standard 6-month treatment (3.7%, 20/534). The median length of extended treatment was 89 days at a median cost of US$111 for drugs and US$32 for laboratory examinations. Conclusions This study shows that extended treatment is common in one TB dispensary in Beijing. Further studies are needed to determine the countrywide prevalence of this practice and ascertain more conclusively the apparent lack of benefit. PMID:24864048

  12. First insight into the genetic population structure of Mycobacterium tuberculosis isolated from pulmonary tuberculosis patients in Egypt.

    PubMed

    Diab, Hassan Mahmoud; Nakajima, Chie; Kotb, Saber A; Mokhtar, Alaa; Khder, Nagwa F M; Abdelaal, Ahmed S A; Hegazy, Azza; Poudel, Ajay; Shah, Yogendra; Suzuki, Yasuhiko

    2016-01-01

    The present study aimed to assess the population structure of Mycobacterium tuberculosis (MTB) isolates from Egypt. A total of 230 MTB isolates were analysed using spoligotyping, large sequence polymorphism (LSPs), mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing and multi-locus sequence typing (MLST). The majority of isolates (93.0%) belonged to lineage 4, including 44.3, 13.4 and 10.8% of the ill-defined T clade, LAM and Haarlem families, respectively, and lineage 3 was identified in 7.0% of the isolates. MIRU-VNTRs typing allowed efficient discrimination of the spoligotype-defined clusters, including spoligo-international types (SIT) 53, 34, and 4, into 56 patterns, including 13 clusters and 43 unique patterns. A new SNP at position 311614 was identified in all six isolates to form the biggest MIRU-VNTR cluster, which suggested a recent clonal expansion. This SNP could possibly be used as a genetic marker for robust discriminations of Egyptian MTB isolates belonging to SIT53. The combination of spoligotyping, 12 MIRU-VNTRs loci and MLST provided insight into the genetic diversity and transmission dynamics of the Egyptian MTB genotypes and could be a key to implementation of effective control measures by public health authorities.

  13. Global Progress and Challenges in Implementing New Medications for Treating Multidrug-Resistant Tuberculosis

    PubMed Central

    Brigden, Grania; Lessem, Erica; Rich, Michael; Vaughan, Laura; Lynch, Sharonann

    2016-01-01

    Two new drugs—bedaquiline and delamanid—have recently been approved by stringent regulatory authorities to treat multidrug-resistant tuberculosis (TB) and recommended by the World Health Organization for use under defined programmatic conditions. Introducing the medications in TB programs worldwide has not kept pace with the need for these drugs. In response, the DR-TB STAT (Drug-Resistant TB Scale-up Treatment Action Team) task force was formed in April 2015 to monitor progress and help overcome challenges. Information was collected from multiple sources and assessed monthly. Some progress has been made in introducing bedaquiline: as of October 2015, a total of 1,258 persons were on the medication under programmatic conditions. For delamanid, >100 patients, but few under programmatic conditions, have received the medication. Coordinated global action might help assist making these medications accessible for persons who need them most. PMID:26885674

  14. [Pulmonary tuberculosis among residents of municipalities in Mato Grosso do Sul State, Brazil, bordering on Paraguay and Bolivia].

    PubMed

    Marques, Marli; Ruffino-Netto, Antonio; Marques, Ana Maria Campos; Andrade, Sonia Maria Oliveira de; Silva, Baldomero Antonio Kato da; Pontes, Elenir Rose Jardim Cury

    2014-12-01

    This study analyzed the epidemiological profile of pulmonary tuberculosis from 2007 to 2010 in municipalities (counties) in Mato Grosso do Sul State, Brazil, that border on Paraguay and Bolivia. In the border region, the incidence rate (49.1/100,000 inhabitants), mortality rate (4.0/100,000 inhabitants), and treatment dropout rate (11.3%) were 1.6, 1.8, and 1.5 times higher than in the non-border region. Among indigenous individuals in the border region, the rates for incidence (253.4/100,000 inhabitants), mortality (11.6/100,000 inhabitants), and HIV/TB co-infection (1.9/100,000 inhabitants) were 6.4, 3.2, and 1.9 times higher than in non-indigenous individuals in this region. Living in the border regions was inversely associated with HIV/TB co-infection. Indigenous ethnicity was associated statistically with not abandoning TB treatment. The study concludes that the population residing in these municipalities along the border is exposed to high risk of pulmonary TB and TB mortality and treatment dropout, thus requiring special health surveillance interventions.

  15. Genitourinary and pulmonary multidrug resistant Mycobacterium tuberculosis infection in an Asian elephant (Elephas maximus).

    PubMed

    Dumonceaux, Genevieve A; St Leger, Judy; Olsen, John H; Burton, Michael S; Ashkin, David; Maslow, Joel N

    2011-12-01

    A female Asian elephant (Elephas maximus) developed vaginal and trunk discharge. Cultures were positive for pan-susceptible Mycobacterium tuberculosis. Isoniazid and pyrazinamide were given rectally and monitored by serum levels. After being trained at 10 mo to accept oral dosing, treatment was changed and rifampin was added. Oral medications were administered for another 10 mo. A year after completion of therapy, the vaginal discharge increased and cultures yielded M. tuberculosis, resistant to isoniazid and rifampin. Treatment with oral ethambutol, pyrazinamide, and enrofloxacin and intramuscular amikacin was initiated. Although followup cultures became negative, adverse reactions to medications precluded treatment completion. Due to public health concerns related to multidrug resistant M. tuberculosis (MDR-TB), the elephant was euthanized. Postmortem smears from the lung, peribronchial, and abdominal lymph nodes yielded acid-fast bacteria, although cultures were negative. This case highlights important considerations in the treatment of M. tuberculosis in animals and the need for a consistent approach to diagnosis, treatment, and follow-up. PMID:22204067

  16. Psychiatric Morbidity and Other Factors Affecting Treatment Adherence in Pulmonary Tuberculosis Patients

    PubMed Central

    Pachi, Argiro; Bratis, Dionisios; Moussas, Georgios; Tselebis, Athanasios

    2013-01-01

    As the overall prevalence of TB remains high among certain population groups, there is growing awareness of psychiatric comorbidity, especially depression and its role in the outcome of the disease. The paper attempts a holistic approach to the effects of psychiatric comorbidity to the natural history of tuberculosis. In order to investigate factors associated with medication nonadherence among patients suffering from tuberculosis, with emphasis on psychopathology as a major barrier to treatment adherence, we performed a systematic review of the literature on epidemiological data and past medical reviews from an historical perspective, followed by theoretical considerations upon the relationship between psychiatric disorders and tuberculosis. Studies reporting high prevalence rates of psychiatric comorbidity, especially depression, as well as specific psychological reactions and disease perceptions and reviews indicating psychiatric complications as adverse effects of anti-TB medication were included. In sum, data concerning factors affecting medication nonadherence among TB patients suggested that better management of comorbid conditions, especially depression, could improve the adherence rates, serving as a framework for the effective control of tuberculosis, but further studies are necessary to identify the optimal way to address such issues among these patients. PMID:23691305

  17. Half of Pulmonary Tuberculosis Cases Were Left Undiagnosed in Prisons of the Tigray Region of Ethiopia: Implications for Tuberculosis Control

    PubMed Central

    Adane, Kelemework; Spigt, Mark; Ferede, Semaw; Asmelash, Tsehaye; Abebe, Markos; Dinant, Geert-Jan

    2016-01-01

    Introduction Prison settings have been often identified as important but neglected reservoirs for TB. This study was designed to determine the prevalence of undiagnosed pulmonary TB and assess the potential risk factors for such TB cases in prisons of the Tigray region. Method A cross-sectional study was conducted between August 2013 and February 2014 in nine prisons. A standardized symptom-based questionnaire was initially used to identify presumptive TB cases. From each, three consecutive sputum samples were collected for acid-fast bacilli (AFB) microscopy and culture. Blood samples were collected from consented participants for HIV testing. Result Out of 809 presumptive TB cases with culture result, 4.0% (95% CI: 2.65–5.35) were confirmed to have undiagnosed TB. The overall estimated point prevalence of undiagnosed TB was found to be 505/100,000 prisoners (95% CI: 360–640). Together with the 27 patients who were already on treatment, the overall estimated point prevalence of TB would be 793/100,000 prisoners (95% CI: 610–970), about four times higher than in the general population. The ratio of active to passive case detection was 1.18:1. The prevalence of HIV was 4.4% (36/809) among presumptive TB cases and 6.3% (2/32) among undiagnosed TB cases. In a multivariate logistic regression analysis, chewing Khat (adjusted OR = 2.81; 95% CI: 1.02–7.75) and having had a close contact with a TB patient (adjusted OR = 2.18; 95% CI: 1.05–4.51) were found to be predictors of undiagnosed TB among presumptive TB cases. Conclusions This study revealed that at least half of symptomatic pulmonary TB cases in Northern Ethiopian prisons remain undiagnosed and hence untreated. The prevalence of undiagnosed TB in the study prisons was more than two folds higher than in the general population of Tigray. This may indicate the need for more investment and commitment to improving TB case detection in the study prisons. PMID:26914770

  18. [Tuberculosis].

    PubMed

    Iinuma, Y

    2000-11-01

    The incidence of tuberculosis in Japan is the highest among developed countries, with approximately 42,000 new cases reported in 1997, marking the first increase in 38 years. The growing incidence among the elderly and group infections among young adults may be responsible for this increase. Infection with tubercle bacilli(TB) occurs via airborne transmission, which involves dissemination of either airborne droplet nuclei on evaporated droplets that may remain suspended in the air for long periods of time. Microorganisms carried in this manner can be dispersed widely by air currents, therefore, special air handling and ventilation are required to prevent airborne transmission. Patients with infectious TB must be placed in a single room with negative pressure and a ventilation rate of 6 or more air changes per hour. Health care workers must wear an N95 mask when entering the room, and if an incident involving possible TB infection occurs in the hospital, the concerned people should be examined for Tuberculin reaction. Two to 12 weeks after the TB infection has occurred, the tuberculin reaction converts to positive. However, most Japanese people have been vaccinated with BCG, so assessment of the results is difficult. A comparison of the diameter of erythema before and after the potential infection may be the most confirmatory. If latent TB infection is suspected, preventive therapy with isoniazid must be considered. Special biohazard systems in the clinical laboratory and autopsy room have also been proposed to prevent TB dispersal. DOTS(Directly Observed Treatment, Short-course) is useful to prevent the emergence of multi-drug-resistant TB. In some areas of Japan that have low levels of compliance with TB therapy, trials of DOTS have been started. PMID:11132556

  19. Pulmonary tuberculosis diagnostic delays in Chad: a multicenter, hospital-based survey in Ndjamena and Moundou

    PubMed Central

    2012-01-01

    Background Tuberculosis remains one of the leading causes of morbidity and mortality in low-resource countries. One contagious patient can infect 10 to 20 contacts in these settings. Delays in diagnosing TB therefore contribute to the spread of the disease and sustain the epidemic. Objectives The aim of this study was to assess delays in diagnosing tuberculosis and the factors associated with these delays in the public hospitals in Moundou and Ndjamena, Chad. Methods A structured questionnaire was administered to 286 new tuberculosis patients to evaluate patient delay (time from the onset of symptoms to the first formal or informal care), health-care system delay (time from the first health care to tuberculosis treatment) and total delay (sum of the patient and system delays). Logistic regression was used to identify risk factors associated with long diagnostic delays (defined as greater than the median). Results and discussion The median [interquartile range] patient delay, system delay and total delay were 15 [7–30], 36 [19–65] and 57.5 [33–95] days, respectively. Low economic status (aOR [adjusted odds ratio] =2.38 [1.08-5.25]), not being referred to a health service (aOR = 1.75 [1.02- 3.02]) and a secondary level education (aOR = 0.33 [0.12-0.92]) were associated with a long patient delay. Risk factors for a long system delay were a low level of education (aOR = 4.71 [1.34-16.51]) and the belief that traditional medicine and informal care can cure TB (aOR = 5.46 [2.37-12.60]). Conclusion Targeted strengthening of the health-care system, including improving patient access, addressing deficiencies in health-related human resources, and improving laboratory networks and linkages as well as community mobilization will make for better outcomes in tuberculosis diagnosis. PMID:22776241

  20. [Efficiency of the use of peppermint (Mentha piperita L) essential oil inhalations in the combined multi-drug therapy for pulmonary tuberculosis].

    PubMed

    Shkurupiĭ, V A; Kazarinova, N V; Ogirenko, A P; Nikonov, S D; Tkachev, A V; Tkachenko, K G

    2002-01-01

    The essential oil of peppermint (Mentha piperita L.) has been found to have an in vitro pronounced and equal antimycobacterial effect in doses of 300 and 600 micrograms/ml, respectively. The use of its inhalations (upon 20-min heat evaporation into the room atmosphere for 2 months) as a supplement to combined multidrug therapy for pulmonary tuberculosis has indicated their significantly high positive effect in terms of abacillation (by 26.8 and 58.5% with doses of 0.01 and 0.005 ml/m3, respectively). This was followed by earlier positive X-ray changes in the lung and by attenuation of the intoxication syndrome. The findings suggest that peppermint essential oil may be used in combined multidrug therapy in patients with disseminated and infiltrative pulmonary tuberculosis.

  1. Type 2 diabetes mellitus is associated with altered CD8+ T and natural killer cell function in pulmonary tuberculosis

    PubMed Central

    Kumar, Nathella P; Sridhar, Rathinam; Nair, Dina; Banurekha, Vaithilingam V; Nutman, Thomas B; Babu, Subash

    2015-01-01

    Type 2 diabetes mellitus (DM) is associated with expanded frequencies of mycobacterial antigen-specific CD4+ T helper type 1 (Th1) and Th17 cells in individuals with active pulmonary tuberculosis (TB). No data are available on the role of CD8+ T and natural killer (NK) cells in TB with coincident DM. To identify the role of CD8+ T and NK cells in pulmonary TB with diabetes, we examined mycobacteria-specific immune responses in the whole blood of individuals with TB and DM (TB-DM) and compared them with those without DM (TB-NDM). We found that TB-DM is characterized by elevated frequencies of mycobacterial antigen-stimulated CD8+ T cells expressing type 1 [interferon-γ and interleukin-2 (IL-2)] and type 17 (IL-17F) cytokines. We also found that TB-DM is characterized by expanded frequencies of TB antigen-stimulated NK cells expressing type 1 (tumour necrosis factor-α) and type 17 (IL-17A and IL-17F) cytokines. In contrast, CD8+ T cells were associated with significantly diminished expression of the cytotoxic markers perforin, granzyme B and CD107a both at baseline and following antigen or anti-CD3 stimulation, while NK cells were associated with significantly decreased antigen-stimulated expression of CD107a only. This was not associated with alterations in CD8+ T-cell or NK cell numbers or subset distribution. Therefore, our data suggest that pulmonary TB complicated with type 2 DM is associated with an altered repertoire of cytokine-producing and cytotoxic molecule-expressing CD8+ T and NK cells, possibly contributing to increased pathology. PMID:25363329

  2. Type 2 diabetes mellitus is associated with altered CD8(+) T and natural killer cell function in pulmonary tuberculosis.

    PubMed

    Kumar, Nathella P; Sridhar, Rathinam; Nair, Dina; Banurekha, Vaithilingam V; Nutman, Thomas B; Babu, Subash

    2015-04-01

    Type 2 diabetes mellitus (DM) is associated with expanded frequencies of mycobacterial antigen-specific CD4(+) T helper type 1 (Th1) and Th17 cells in individuals with active pulmonary tuberculosis (TB). No data are available on the role of CD8(+) T and natural killer (NK) cells in TB with coincident DM. To identify the role of CD8(+) T and NK cells in pulmonary TB with diabetes, we examined mycobacteria-specific immune responses in the whole blood of individuals with TB and DM (TB-DM) and compared them with those without DM (TB-NDM). We found that TB-DM is characterized by elevated frequencies of mycobacterial antigen-stimulated CD8(+) T cells expressing type 1 [interferon-γ and interleukin-2 (IL-2)] and type 17 (IL-17F) cytokines. We also found that TB-DM is characterized by expanded frequencies of TB antigen-stimulated NK cells expressing type 1 (tumour necrosis factor-α) and type 17 (IL-17A and IL-17F) cytokines. In contrast, CD8(+) T cells were associated with significantly diminished expression of the cytotoxic markers perforin, granzyme B and CD107a both at baseline and following antigen or anti-CD3 stimulation, while NK cells were associated with significantly decreased antigen-stimulated expression of CD107a only. This was not associated with alterations in CD8(+) T-cell or NK cell numbers or subset distribution. Therefore, our data suggest that pulmonary TB complicated with type 2 DM is associated with an altered repertoire of cytokine-producing and cytotoxic molecule-expressing CD8(+) T and NK cells, possibly contributing to increased pathology.

  3. The effect of HIV and antiretroviral therapy on characteristics of pulmonary tuberculosis in northern Malawi: a cross-sectional study

    PubMed Central

    2014-01-01

    Background HIV infection reduces the likelihood that individuals with pulmonary tuberculosis are smear positive and that they have cavitatory disease. Antiretroviral therapy (ART) may shift the pattern of disease to be more similar to that of HIV negative patients. This would aid diagnosis- which often depends on sputum smears – but would also increase infectiousness. We assessed the effect of HIV and ART on smear positivity and cavitatory disease in laboratory-confirmed pulmonary TB patients. Methods Three sputum samples were collected per pulmonary TB suspect and were examined using microscopy and culture. Chest radiographs were available for a subset of patients as part of another study. The effect of HIV and ART status on sputum smear positivity and lung cavitation were evaluated using multivariable logistic regression. Results Of 1024 laboratory-confirmed pulmonary TB patients who were identified between January 2005 and December 2011, 766 had HIV and ART status available. Positive sputum smears were significantly more common among HIV negative individuals than HIV positive individuals (adjusted OR = 2.91, 95% CI 1.53 – 5.55). Compared to those HIV positive but not on ART, patients on ART were more likely to be smear positive (adjusted OR = 2.33, 95% CI 1.01 – 5.39) if they had been on ART ≤ 6 months, but only slightly more likely to be smear positive (adjusted OR = 1.43, 95% CI 0.68 – 2.99) if they were on ART > 6 months. HIV negative patients were more likely than HIV positive patients to have cavitatory disease (adjusted OR = 1.97, 95% CI 1.20 – 3.23). Patients on ART > 6 months had a slight increase in cavitatory disease compared to HIV positive patients not on ART (adjusted OR = 1.68, CI 0.78 – 3.63). Conclusions HIV infection is associated with less smear positivity and cavitation in pulmonary TB patients. Among HIV positive patients, the use of ART shifts the presentation of disease towards that seen in HIV

  4. The mechanism by which the phenothiazine thioridazine contributes to cure problematic drug-resistant forms of pulmonary tuberculosis: recent patents for "new use".

    PubMed

    Amaral, Leonard; Martins, Ana; Spengler, Gabriella; Hunyadi, Attila; Molnar, Joseph

    2013-12-01

    At this moment, over half million patients suffer from multi-drug resistant tuberculosis (MDR-TB) according to the data from the WHO. A large majority is terminally ill with essentially incurable pulmonary tuberculosis. This herein mini-review provides the experimental and observational evidence that a specific phenothiazine, thioridazine, will contribute to cure any form of drug-resistant tuberculosis. This antipsychotic agent is no longer under patent protection for its initial use. The reader is informed on the recent developments in patenting this compound for "new use" with a special emphasis on the aspects of drug-resistance. Given that economic motivation can stimulate the use of this drug as an antitubercular agent, future prospects are also discussed. PMID:24320229

  5. Dietary Vitamin D3 Suppresses Pulmonary Immunopathology Associated with Late-Stage Tuberculosis in C3HeB/FeJ Mice.

    PubMed

    Reeme, Allison E; Robinson, Richard T

    2016-02-01

    Tuberculosis (TB) is a significant human disease caused by inhalation of Mycobacterium tuberculosis. Left untreated, TB mortality is associated with a failure to resolve pulmonary immunopathology. There is currently widespread interest in using vitamin D3 (VitD3) as an adjunct therapy for TB because numerous in vitro studies have shown that VitD3 has direct and indirect mycobactericidal activities. However, to date, there have been no in vivo studies addressing whether VitD3 affects experimental TB outcome. In this study, we used C3HeB/FeJ mice to determine whether dietary VitD3 influences the outcome of experimental TB. We observed that although M. tuberculosis burdens did not differ between mice on a VitD3-replete diet (VitD(HI) mice) and mice on a VitD3-deficient diet (VitD(LO) mice), the inflammatory response in VitD(HI) mice was significantly attenuated relative to VitD(LO) controls. Specifically, the expression of multiple inflammatory pathways was reduced in the lungs at later disease stages as were splenocyte IL12/23p40 and IFN-γ levels following ex vivo restimulation. Dietary VitD3 also suppressed the accumulation of T cells in the mediastinal lymph nodes and lung granulomatous regions while concomitantly accelerating the accumulation of F4/80(+) and Ly6C/Ly6G(+) lineages. The altered inflammatory profile of VitD(HI) mice also associated with reductions in pulmonary immunopathology. VitD receptor-deficient (vdr(-/-)) radiation bone marrow chimeras demonstrate that reductions in pulmonary TB immunopathology are dependent on hematopoietic VitD responsiveness. Collectively, our data support a model wherein the in vivo role of VitD3 during TB is not to promote M. tuberculosis killing but rather to function through hematopoietic cells to reduce M. tuberculosis-elicited immunopathology. PMID:26729807

  6. Transmission and Progression to Disease of Mycobacterium tuberculosis Phylogenetic Lineages in The Netherlands.

    PubMed

    Nebenzahl-Guimaraes, Hanna; Verhagen, Lilly M; Borgdorff, Martien W; van Soolingen, Dick

    2015-10-01

    The aim of this study was to determine if mycobacterial lineages affect infection risk, clustering, and disease progression among Mycobacterium tuberculosis cases in The Netherlands. Multivariate negative binomial regression models adjusted for patient-related factors and stratified by patient ethnicity were used to determine the association between phylogenetic lineages and infectivity (mean number of positive contacts around each patient) and clustering (as defined by number of secondary cases within 2 years after diagnosis of an index case sharing the same fingerprint) indices. An estimate of progression to disease by each risk factor was calculated as a bootstrapped risk ratio of the clustering index by the infectivity index. Compared to the Euro-American reference, Mycobacterium africanum showed significantly lower infectivity and clustering indices in the foreign-born population, while Mycobacterium bovis showed significantly lower infectivity and clustering indices in the native population. Significantly lower infectivity was also observed for the East African Indian lineage in the foreign-born population. Smear positivity was a significant risk factor for increased infectivity and increased clustering. Estimates of progression to disease were significantly associated with age, sputum-smear status, and behavioral risk factors, such as alcohol and intravenous drug abuse, but not with phylogenetic lineages. In conclusion, we found evidence of a bacteriological factor influencing indicators of a strain's transmissibility, namely, a decreased ability to infect and a lower clustering index in ancient phylogenetic lineages compared to their modern counterparts. Confirmation of these findings via follow-up studies using tuberculin skin test conversion data should have important implications on M. tuberculosis control efforts.

  7. The Effectiveness and Safety of Fluoroquinolone-Containing Regimen as a First-Line Treatment for Drug-Sensitive Pulmonary Tuberculosis: A Systematic Review and Meta-Analysis

    PubMed Central

    Lee, Hyun Woo; Lee, Jung Kyu; Kim, Eunyoung; Yim, Jae-Joon; Lee, Chang-Hoon

    2016-01-01

    Background Fluoroquinolone is recommended as a pivotal antituberculous agent for treating multi-drug-resistant pulmonary tuberculosis. However, its effectiveness as first-line treatment remains controversial. The present study was conducted to validate the fluoroquinolone-containing regimen for drug-sensitive pulmonary tuberculosis. Methods We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials until June 5, 2015. Randomized controlled trials (RCTs) that compared antituberculous regimens containing fluoroquinolone with the standard regimen were included. Results Eleven RCTs that included 6,334 patients were selected. Fluoroquinolone-containing regimens had a higher rate of sputum culture conversion at 2 months of treatment (M-H fixed odds ratio [OR], 1.36; 95% confidence interval [CI], 1.20–1.54). However, the outcomes were less favorable (M-H fixed OR, 0.69; 95% CI, 0.59–0.82) and the associated total adverse events were more frequent (M-H fixed OR, 1.84; 95% CI, 1.46–2.31) in the fluoroquinolone-containing regimen group, without a significant heterogeneity according to treatment duration. Treatment with the fluoroquinolone-containing regimen for 4 months showed a higher relapse rate. Conclusions Despite a higher culture conversion rate at 2 months of treatment, the fluoroquinolone-containing regimen had limitations, including less favorable outcomes and more adverse events, as the first-line therapy for drug-sensitive pulmonary tuberculosis. PMID:27455053

  8. Characteristics of the Vδ2 CDR3 Sequence of Peripheral γδ T Cells in Patients with Pulmonary Tuberculosis and Identification of a New Tuberculosis-Related Antigen Peptide

    PubMed Central

    Ding, Yan; Ma, Fei; Wang, Zhaohua

    2015-01-01

    Antigen-specific γδ T cells may play an important role in the immune response to Mycobacterium tuberculosis. However, little is known about the characteristics of the length distribution of the δ2-chain complementarity determining region 3 (δ2 CDR3) of the γδ T-cell receptor (TCR) in patients with active pulmonary tuberculosis (TB) on a large scale. In addition, M. tuberculosis-activated γδ T cells potentially inhibit intracellular mycobacterial growth, but phosphoantigen-activated γδ T cells do not. Only a few M. tuberculosis-related antigen peptides or proteins that are recognized by γδ TCR have been identified. Twenty-four healthy donors (HDs) and 27 TB patients were included in the present study. The gene-scanning technique found that the δ2 CDR3 length distribution patterns of γδ TCR in TB patients were perturbed, and each pattern included different predominant CDR3 sequences. The predominant δ2 CDR3 sequences of γδ TCRs, which originated from TB patients and HD γδ T cells that were stimulated by M. tuberculosis heat resistance antigen (Mtb-HAg), were used as probes to screen peptides recognized by γδ TCR using a phage display library. We identified four peptides that bound to the predominant δ2 CDR3 fragments and showed homology to M. tuberculosis genes in a BLAST search. Notably, one peptide was related to M. tuberculosis H37Rv (QHIPKPP), and this fragment was confirmed as a ligand for the γδ TCR. Two fragments, Ag1 and Ag2, activated γδ T cells from HD or TB patients. In summary, the δ2 CDR3 lineage of TB patients apparently drifts, and the predominant δ2 CDR3 sequence that recognizes M. tuberculosis may exhibit specificity. The identified M. tuberculosis-related antigen peptides may be used as vaccines or adjuvants for protective immunity against M. tuberculosis. PMID:25947144

  9. [Effects of different factors on work capacity status of patients with newly diagnosed pulmonary tuberculosis].

    PubMed

    Khudushina, T A; Maslakova, M G

    1994-01-01

    As shown by medical disability expert commission which followed up 142 tuberculous patients throughout chemotherapy, the disability in new-onset tuberculosis cases is related both to medical and social factors. The jobs of 1/2 of the examinees were not fit for such patients. More than half of them had concomitant visceral lesions. The duration of temporary disability was consequent to many factors, the principal of which were dissemination and destruction: subjects with local infection without destruction were incapable 192 days, on the average, while those with tuberculosis dissemination and destruction 266 days. 14.1% became invalids. Only a small group of the patients were not in need of social support. PMID:7870714

  10. Survival in progressive systemic sclerosis with pulmonary involvement: a single-center experience in Istanbul, Turkey.

    PubMed

    Zuhur, Ferit; Zuhur, Sayid Shafi; Zuhur, Cigdem; Musellim, Benan; Ongen, Gul

    2012-06-01

    The objective of the current study was to determine survival and factors that affect survival in progressive systemic sclerosis (SSc) with pulmonary involvement. A total of 102 SSc patients with pulmonary involvement, diagnosed between 1994 and 2008, enrolled into the study. Pulmonary involvement was defined based on the presence of interstitial changes on high-resolution CT (HRCT). Demographical, clinical, radiological, and laboratory data of the patients were found from patient records and were used for the evaluation of survival. The mean age of the patients at diagnosis was 50 ± 12 years. In follow-up, 22 (21.5%) patients were deceased. The mean age of the patients at death was 55 ± 12 years. Seventy-eight percent of known causes of mortality were related to pulmonary complications. After any initial systemic manifestation of disease, the mean survival was 447 ± 27 months and 5, 10, 15, and 20 year survival rates were 99, 92, 83, and 72%, respectively. The mean survival after initial pulmonary manifestation was 269 ± 23 months and 5, 10 and 15 year survival rates were 91, 73 and 57%, respectively. Mean survival was 113 ± 5 months, and 5- and 10-year survival rates after the lung involvement detected with HRCT were 85 and 66%, respectively. Pulmonary artery hypertension, disease onset after the age of 40, and honeycombing on HRCT were associated with poor survival. Our data suggest that pulmonary involvement is the most important determinant factor for poor prognosis in patients with SSc. Therefore, echocardiography, pulmonary function tests, and HRCT should be performed in early stages of the disease for early diagnosis of pulmonary artery hypertension and lung involvement before irreversible vascular and interstitial changes exist.

  11. Isoniazid Induced Cutaneous Leukocytoclastic Vasculitis in Extra Pulmonary Tuberculosis (Pott’s Spine): A Case Report

    PubMed Central

    V, Dharma Rao; Rampure, Dilip; S, Rama Rao

    2014-01-01

    Anti-tuberculosis drugs frequently result in cutaneous adverse reactions but Isoniazid is known to have least toxic potential for cutaneous reactions. We report a rare case of Isoniazid induced cutaneous leucocytoclastic vasculitis. A 64-year-old male was diagnosed to have Pott’s spine with multiple vertebral body involvement (D8-12 vertebrae). Subsequently, he was treated with first line anti-TB drugs i.e., Isoniazid, Rifampicin, Pyrazinamide and Ethambutol. On the fourth day of treatment with Anti Tuberculosis Treatment (ATT), the patient developed an erythematosus rash over right upper limb not associated with itching or pain, non-blanchable macules and papules over bilateral shins on lower limbs, petechiae on both forearms and hyper pigmented, scaly rash over right axilla and buttocks. The skin biopsy report was consistent with cutaneous leukocytoclastic vasculitis. Although rare, Isoniazid among anti-tuberculosis drugs should be considered as potential cause of drug-induced cutaneous leukocytoclastic vasculitis in the differential diagnosis of erythematosus rash with petechiae. PMID:25302231

  12. Neutrophils from pulmonary tuberculosis patients show augmented levels of chemokines MIP-1α, IL-8 and MCP-1 which further increase upon in vitro infection with mycobacterial strains.

    PubMed

    Hilda, J Nancy; Narasimhan, Meenakshi; Das, Sulochana D

    2014-08-01

    Neutrophils being innate cells initiate the immune defence against mycobacteria by sending signals to other immune cells. Chemokines being the vital link in signaling processes, it is of interest to study their secretion by neutrophils as a response to tuberculosis infection. The levels of various chemokines (MIP-1α, MCP-1, IL-8 and IP-10) and chemokine receptors (CXCR1, CXCR2 and CCR1) in neutrophils from healthy individuals and pulmonary tuberculosis patients were studied following infection with Mycobacterium tuberculosis strains (clinical--S7 and S10 and laboratory--H37Rv). The release of MIP-1α, IL-8 and MCP-1 is found to be greatly increased in patient neutrophils. Mycobacterial strains differentially influenced neutrophils affecting the release of chemokines to different extent. H37Rv significantly increased the release of MIP-1α and IL-8 in both normals and tuberculosis patients, while S10 up regulated only the release of MIP-1α in patients. Thus, during tuberculosis, neutrophils undergo functional alteration to combat infection. While H37Rv is greatly recognized by neutrophils and triggers the release of chemokines, clinical strains by some means try to suppress immune activation of neutrophils in their favor.

  13. Serum complement C4b, fibronectin, and prolidase are associated with the pathological changes of pulmonary tuberculosis

    PubMed Central

    2014-01-01

    Background Mycobacterium tuberculosis infection can activate the immune system, leading to characteristic pathological changes such as inflammatory granuloma, caseous necrosis, and cavity formation. Methods Clinical data of 187 cases of pulmonary tuberculosis (PTB) were analyzed using statistical methods, while serum levels of complement C4b (C4b), fibronectin (FN), and prolidase (PEPD) were detected using the ELISA method among the control, minimal PTB, moderate PTB, and advanced PTB groups. Results We found significantly higher levels of serum C4b and PEPD (P = 0.018, P = 0.003), and significantly lower levels of serum FN (P < 0.001) in PTB patients. Furthermore, the serum levels of 3 proteins were significantly different among 3 PTB groups. FN level was significantly higher in the moderate PTB group, compared with patients in the minimal and advanced PTB groups (P < 0.05, P < 0.01). PEPD level was significantly higher in the moderate PTB group, compared with the minimal PTB group (P < 0.05). Analysis of clinical data showed that serum albumin, C-reactive protein (CRP), prealbumin, and C4 were significantly higher (P < 0.05), while serum globulin was significantly lower in patients with PTB (P < 0.001). A significant negative correlation was found between C4b and albumin, prealbumin. On the other hand, a significant positive correlation was found between C4b and globulin, CRP, PEPD, as well as between PEPD and CRP (P < 0.05). Conclusions Our study showed that C4b, FN, and PEPD are associated with tissue damage, granuloma formation, and cavity formation, respectively, in patients with PTB. The present study provides a new experimental basis to understand the pathogenesis and pathological changes of PTB. PMID:24484408

  14. Factors influencing development and mortality of acute respiratory failure in hospitalized patient with active pulmonary tuberculosis: a 10-year retrospective review

    PubMed Central

    Maneenil, Kunlatida

    2016-01-01

    Background Pulmonary tuberculosis with acute respiratory failure is fatal and is a burden in the intensive care units and leads to mortality. This retrospective study identifies the factors influencing the development of pulmonary tuberculosis requiring mechanical ventilation (TBMV) and mortality in the hospitalized patients with pulmonary tuberculosis. Methods The medical records of hospitalized adult patients with pulmonary tuberculosis were retrospectively reviewed. Demographic data, clinical presentations, radiographic findings, biochemical tests, and clinical outcomes were collected. Data were compared by Student’s t-test and Chi-square test between groups. Select variables that were statistically significant with P values <0.1 were introduced into a forward, stepwise, logistic regression model. Odds ratios (ORs) and their 95% confidence intervals (CIs) identified the independent influencing factors in the development of TBMV and mortality. Results Of 268 enrolled patients, 185 (69.0%) were male. The patients were equally divided between the TBMV and non-TBMV groups. The shorter duration of illness (OR, 0.99; 95% CI, 0.98–0.99), underlying disease of AIDS (OR, 14.55; 95% CI, 1.71–123.91), presentation of fever (OR, 2.11; 95% CI, 1.20–3.71) and dyspnea (OR, 3.51; 95% CI, 2.02–6.11), large amount of acid fast bacilli on sputum smear (OR, 3.76; 95% CI, 1.90–7.47), lower serum albumin level (OR, 0.39; 95% CI, 0.26–0.59), and delayed initiation of anti-tuberculosis agents (OR, 1.06; 95% CI, 1.00–1.12) were independent factors to develop TBMV. Male gender (OR, 2.16; 95% CI, 1.01–4.61), consolidation pattern on chest X-ray (OR, 2.41; 95% CI, 1.17–4.98), and lower serum albumin (OR, 0.39; 95% CI, 0.21–0.71) were correlated to mortality. Conclusions The incidence and mortality rate of TBMV patients were high. Acute tuberculous pneumonia, underlying disease of AIDS, amount of acid fast bacilli, and delayed administration of anti-tuberculosis agents

  15. Pulmonary aspergilloma

    MedlinePlus

    ... Coccidioidomycosis Cystic fibrosis Histoplasmosis Lung abscess Lung cancer Sarcoidosis See also: Aspergillosis Symptoms You may not have ... fibrosis Histoplasmosis Lung cancer - small cell Pulmonary tuberculosis Sarcoidosis Update Date 8/31/2014 Updated by: Jatin ...

  16. [Progress report on a World Bank loan to China for a tuberculosis control project].

    PubMed

    Zhao, F; Chi, Y; Wang, K

    1995-02-01

    The progress of the World Bank loaned TB control project implemented from the second quarter of 1991 to the fourth quarter of 1993 was described in this paper. In the past three years, 737 counties of the 12 provinces with the population of 360 million has been covered by the project. Among 95176 new smear positive cases discovered, 93909 patients received free treatment of TB. The treatment coverage is 98.7%, of which 95% were treated under full course supervision. The smear conversion rate at two, three months of new smear positive TB patients are 83.4% and 90.6% respectively. The cohort analysis showed that the cure rate is 89.8%, which has reached the advanced level of the modern national tuberculosis control programme in the world.

  17. Bacillus Calmette-Guérin vaccination reduces the severity and progression of tuberculosis in badgers.

    PubMed

    Chambers, Mark A; Rogers, Fiona; Delahay, Richard J; Lesellier, Sandrine; Ashford, Roland; Dalley, Deanna; Gowtage, Sonya; Davé, Dipesh; Palmer, Si; Brewer, Jacky; Crawshaw, Timothy; Clifton-Hadley, Richard; Carter, Steve; Cheeseman, Chris; Hanks, Chris; Murray, Alistair; Palphramand, Kate; Pietravalle, Stéphane; Smith, Graham C; Tomlinson, Alexandra; Walker, Neil J; Wilson, Gavin J; Corner, Leigh A L; Rushton, Stephen P; Shirley, Mark D F; Gettinby, George; McDonald, Robbie A; Hewinson, R Glyn

    2011-06-22

    Control of bovine tuberculosis (TB) in cattle has proven particularly challenging where reservoirs of infection exist in wildlife populations. In Britain and Ireland, control is hampered by a reservoir of infection in Eurasian badgers (Meles meles). Badger culling has positive and negative effects on bovine TB in cattle and is difficult, costly and controversial. Here we show that Bacillus Calmette-Guérin (BCG) vaccination of captive badgers reduced the progression, severity and excretion of Mycobacterium bovis infection after experimental challenge. In a clinical field study, BCG vaccination of free-living badgers reduced the incidence of positive serological test results by 73.8 per cent. In common with other species, BCG did not appear to prevent infection of badgers subjected to experimental challenge, but did significantly reduce the overall disease burden. BCG vaccination of badgers could comprise an important component of a comprehensive programme of measures to control bovine TB in cattle.

  18. Changes in respiratory function impairment following the treatment of severe pulmonary tuberculosis – limitations for the underlying COPD detection

    PubMed Central

    Radovic, Milan; Ristic, Lidija; Ciric, Zorica; Dinic-Radovic, Violeta; Stankovic, Ivana; Pejcic, Tatjana; Rancic, Milan; Bogdanovic, Dragan

    2016-01-01

    Background During the treatment phase of active pulmonary tuberculosis (PTB), respiratory function impairment is usually restrictive. This may become obstructive, as a PTB-associated airflow obstruction (AFO) or as a later manifestation of underlying COPD. Purpose The aim of the study was to examine the potential causes and risks for AFO development in PTB by exploring the aspects of spirometry limitations and clinical implications for the underlying COPD detection, taking into account various confounding factors. Patients and methods Prospective, nest case–control study on 40 new cases of PTB with initial restrictive respiratory function impairment, diagnosed and treated according to the directly observed treatment short course (DOTS) strategy. Results From all observed patients, 37.5% of them developed AFO upon the completion of PTB treatment, with significantly increased average of forced vital capacity (%) (P<0.01). Their changes in forced expiratory volume in the first second (%) during the PTB treatment were strongly associated with the air pollution exposure in living (0.474%–20.971% for 95% confidence interval [CI]; P=0.041) and working environments (3.928%–20.379% for 95% CI; P=0.005), initial radiological extent of PTB lesions (0.018%–0.700% for 95% CI; P=0.047), leukocyte count (0.020%–1.328% for 95% CI; P=0.043), and C-reactive protein serum level (0.046%–0.205% for 95% CI; P=0.003) compared to the other patients. The multivariate logistic regression analysis model shows initial radiological extent of pulmonary tuberculosis lesions (OR 1.01–1.05 for 95% CI; P=0.02) and sputum conversion rate on culture (OR 1.02–1.68 for 95% CI; P=0.04) as the most significant predictors for the risk of AFO development. Conclusion AFO upon PTB treatment is a common manifestation of underlying COPD, which mostly occurs later, during the reparative processes in active PTB, even in the absence of major risk factors, such as cigarette smoking and biomass fuel

  19. Intestinal parasite co-infection among pulmonary tuberculosis cases without human immunodeficiency virus infection in a rural county in China.

    PubMed

    Li, Xin-Xu; Chen, Jia-Xu; Wang, Li-Xia; Tian, Li-Guang; Zhang, Yu-Ping; Dong, Shuang-Pin; Hu, Xue-Guang; Liu, Jian; Wang, Feng-Feng; Wang, Yue; Yin, Xiao-Mei; He, Li-Jun; Yan, Qiu-Ye; Zhang, Hong-Wei; Xu, Bian-Li; Zhou, Xiao-Nong

    2014-01-01

    Epidemiologic studies of co-infection with tuberculosis (TB) and intestinal parasites in humans have not been extensively investigated in China. A cross-section study was conducted in a rural county of Henan Province, China. Pulmonary TB (PTB) case-patients receiving treatment for infection with Mycobacterium tuberculosis and healthy controls matched for geographic area, age, and sex were surveyed by using questionnaires. Fecal and blood specimens were collected for detection of intestinal parasites, routine blood examination, and infection with human immunodeficiency virus. The chi-square test was used for univariate analysis and multivariate logistic regression models were used to adjust for potential confounding factors. A total of 369 persons with PTB and 366 healthy controls were included; all participants were negative for human immunodeficiency virus. The overall prevalence of intestinal parasites in persons with PTB was 14.9%, including intestinal protozoa (7.9%) and helminthes (7.6%). The infection spectrum of intestinal parasites was Entamoeba spp. (1.4%), Blastocystis hominis (6.2%), Trichomonas hominis (0.3%), Clonorchis sinensis (0.3%), Ascaris lumbricoides (0.5%), Trichuris trichiura (2.2%), and hookworm (4.6%). The prevalence of intestinal parasites showed no significant difference between persons with PTB and healthy controls after adjusting for potential confounding factors. There was no factor that affected infection rates for intestinal parasites between the two groups. Infection with intestinal parasites of persons with PTB was associated with female sex (adjusted odds ratio [AOR] = 2.05, 95% confidence interval [CI] = 1.01-4.17), body mass index ≤ 19 (AOR = 3.02, 95% CI = 1.47-6.20), and anemia (AOR = 2.43, 95% CI = 1.17-5.03). Infection of healthy controls was only associated with an annual labor time in farmlands > 2 months (AOR = 4.50, 95% CI = 2.03-10.00). In addition, there was no significant trend between rates of infection with

  20. Management of pulmonary tuberculosis in health clinics in the Gombak district: How are we doing so far?

    PubMed

    Ariffin, F; Ahmad Zubaidi, A Z; Md Yasin, M; Ishak, R

    2015-01-01

    This audit report assessed the structure, processes and outcome of the pulmonary tuberculosis (PTB) management in adults conducted at eight government health clinics within the high TB burden Gombak district. All newly diagnosed PTB patients from November 2012 to November 2013 were identified from the tuberculosis registry. Patients less than 18 years old, were transferred out or extrapulmonary tuberculosis was excluded from the study. The assessment criteria for PTB were defined according to the latest Malaysian TB clinical practice guidelines (TB CPG) 2012. A total of 117 patients were included in this report and data were extracted and analysed using SPSS version 20.0. The mean age of patients was 40.4 ± 14.4 SD. Majority was men (63.2%). Out of 117 patients, 82.1% were Malaysian citizens and 17.9% were foreigners. Malays were the majority (65%) followed by 7.7% Chinese, 10.3% Indian and 17.1% others. The most common clinical feature was cough (88.0%) followed by loss of weight (58.1%), loss of appetite (57.3%), fever (56.4%), night sweat (30.8%) and haemoptysis (32.5%). Acid-fast bacilli (AFB) smear was positive in 94% of cases. Chest X-ray and human immunodeficiency virus (HIV) screening results were available for 89.1 and 82.1% cases respectively. The results for the sputum culture were available in 27.4% of patients and 54.7% were documented as done but pending results. The clinics have a successful directly observed therapy (DOT) program with 94.0% patients documented under DOT. Out of 53 patients on maintenance phase, 47.2% were identified as cured. Cure rate for those completed treatment was 100%. The defaulter rate was 17.1%. This audit demonstrated the attempt made by the clinics to adhere to the recommended guidelines. However, improvements are to be made in the documentation of medical records, tracing of investigation results and reduction of the number of defaulters. PMID:26425292

  1. Intestinal Parasite Co-infection among Pulmonary Tuberculosis Cases without Human Immunodeficiency Virus Infection in a Rural County in China

    PubMed Central

    Li, Xin-Xu; Chen, Jia-Xu; Wang, Li-Xia; Tian, Li-Guang; Zhang, Yu-Ping; Dong, Shuang-Pin; Hu, Xue-Guang; Liu, Jian; Wang, Feng-Feng; Wang, Yue; Yin, Xiao-Mei; He, Li-Jun; Yan, Qiu-Ye; Zhang, Hong-Wei; Xu, Bian-Li; Zhou, Xiao-Nong

    2014-01-01

    Epidemiologic studies of co-infection with tuberculosis (TB) and intestinal parasites in humans have not been extensively investigated in China. A cross-section study was conducted in a rural county of Henan Province, China. Pulmonary TB (PTB) case-patients receiving treatment for infection with Mycobacterium tuberculosis and healthy controls matched for geographic area, age, and sex were surveyed by using questionnaires. Fecal and blood specimens were collected for detection of intestinal parasites, routine blood examination, and infection with human immunodeficiency virus. The chi-square test was used for univariate analysis and multivariate logistic regression models were used to adjust for potential confounding factors. A total of 369 persons with PTB and 366 healthy controls were included; all participants were negative for human immunodeficiency virus. The overall prevalence of intestinal parasites in persons with PTB was 14.9%, including intestinal protozoa (7.9%) and helminthes (7.6%). The infection spectrum of intestinal parasites was Entamoeba spp. (1.4%), Blastocystis hominis (6.2%), Trichomonas hominis (0.3%), Clonorchis sinensis (0.3%), Ascaris lumbricoides (0.5%), Trichuris trichiura (2.2%), and hookworm (4.6%). The prevalence of intestinal parasites showed no significant difference between persons with PTB and healthy controls after adjusting for potential confounding factors. There was no factor that affected infection rates for intestinal parasites between the two groups. Infection with intestinal parasites of persons with PTB was associated with female sex (adjusted odds ratio [AOR] = 2.05, 95% confidence interval [CI] = 1.01–4.17), body mass index ≤ 19 (AOR = 3.02, 95% CI = 1.47–6.20), and anemia (AOR = 2.43, 95% CI = 1.17–5.03). Infection of healthy controls was only associated with an annual labor time in farmlands > 2 months (AOR = 4.50, 95% CI = 2.03–10.00). In addition, there was no significant trend between rates of infection with

  2. Schistosoma mansoni, nematode infections, and progression to active tuberculosis among HIV-1-infected Ugandans.

    PubMed

    Brown, Michael; Miiro, George; Nkurunziza, Peter; Watera, Christine; Quigley, Maria A; Dunne, David W; Whitworth, James A G; Elliott, Alison M

    2006-05-01

    Rates of tuberculosis (TB) in Africa are highest among people infected with HIV. Searching for additional risk factors in a cohort of HIV-infected Ugandan adults, we previously found that a type 2 cytokine bias and eosinophilia were associated with progression to active TB. A possible role for helminth infection was assessed in this study. We analyzed TB incidence in 462 members of this cohort who were screened for filarial infections, gastrointestinal nematodes, and schistosomiasis. Progression to TB was not associated with gastrointestinal nematodes (rate ratio [RR], 1.18; confidence intervals [CIs], 0.66-2.10) or Mansonella perstans (RR, 0.42; CI, 0.13-1.34). A weak association between Schistosoma mansoni infection and TB was found (RR, 1.42; CI, 0.86-2.34); after adjusting for potential explanatory variables and using more stringent diagnostic criteria, the association was strengthened (RR, 2.31; 1.00-5.33). This analysis suggests an effect of S. mansoni infection on progression to active TB among HIV-1-infected Ugandans. PMID:16687687

  3. Mycobacterium tuberculosis modulates the gene interactions to activate the HIV replication and faster disease progression in a co-infected host.

    PubMed

    Toor, Jaideep S; Singh, Sukhvinder; Sharma, Aman; Arora, Sunil K

    2014-01-01

    Understanding of the chronic immune activation, breakdown of immune defense and synergistic effect between HIV and Mycobacterium tuberculosis (Mtb) may provide essential information regarding key factors involved in the pathogenesis of HIV disease. In this study, we aimed to highlight a few of the immunological events that may influence and accelerate the progression of HIV disease in the presence of co-infecting Mtb. A cross-sectional study was performed on cohorts, including anti-tubercular therapy (ATT) naïve active pulmonary tuberculosis (PTB) patients, antiretroviral therapy (ART) naïve HIV-1 infected individuals at different stages of disease, ATT and ART naïve HIV-PTB co-infected individuals and healthy controls. A significantly higher T-regulatory cell (Treg) frequency coupled with the high FoxP3 expression in the CD4 T-cells indicated an immunosuppressive environment in the advance stage of HIV-1 infection. This is further substantiated by high HO-1 expression favoring TB co-infection. Functionally, this change in Treg frequency in HIV-1 infected individuals correlated well with suppression of T-cell proliferation. Mtb infection seems to facilitate the expansion of the Treg pool along with increased expression of FoxP3, specifically the variant-1, as evident from the data in HIV-1 co-infected as well as in patients with only PTB. A significantly lower expression of HO-1 in co-infected individuals compared to patients with only HIV-infection having comparable CD4 count correlated well with increased expression of CCR5 and CxCR4 as well as NF-κB and inflammatory cytokines IL-6 and TNF-α, which collectively may contribute to enhanced viral replication and increased cell death, hence faster disease progression in co-infected individuals.

  4. Extra pulmonary tuberculosis presenting as fever with massive splenomegaly and pancytopenia.

    PubMed

    Chandni R; Rajan G; Udayabhaskaran V

    2016-01-01

    Disseminated tuberculosis is an important differential diagnosis for fever of unknown origin (FUO) and it can present with hepatosplenomegaly and lymphadenopathy and may have meningitis and with hematological abnormalities including pancytopenia or a leukemoid reaction. We report the case of a 13-year old male who presented with fever, weight loss, pallor and massive splenomegaly with pancytopenia, in whom a bone marrow trephine biopsy showed caseating granulomata, who responded well to antituberculous treatment and has remained healthy on follow up after nine years. PMID:27051579

  5. Diagnostic Accuracy of the Small Membrane Filtration Method for Diagnosis of Pulmonary Tuberculosis in a High-HIV-Prevalence Setting.

    PubMed

    Boum, Yap; Kim, Soyeon; Orikiriza, Patrick; Acuña-Villaorduña, Carlos; Vinhas, Solange; Bonnet, Maryline; Nyehangane, Dan; Mwanga-Amumpaire, Juliet; Fennelly, Kevin P; Jones-López, Edward C

    2016-06-01

    Sputum acid-fast bacilli (AFB) smear microscopy has suboptimal sensitivity but remains the most commonly used laboratory test to diagnose pulmonary tuberculosis (TB). We prospectively evaluated the small membrane filtration (SMF) method that concentrates AFB in a smaller area to facilitate detection to improve the diagnostic performance of microscopy. We enrolled adults with suspicion of pulmonary TB from health facilities in southwestern Uganda. Clinical history, physical examination, and 3 sputum samples were obtained for direct fluorescent AFB smear, SMF, Xpert MTB/RIF, and MGIT culture media. Sensitivity and specificity were estimated for SMF, AFB smear, and Xpert MTB/RIF, using MGIT as the reference standard. The analysis was stratified according to HIV status. From September 2012 to April 2014, 737 participants were included in the HIV-infected stratum (146 [20.5%] were culture positive) and 313 were in the HIV-uninfected stratum (85 [28%] were culture positive). In HIV-infected patients, the sensitivity of a single SMF was 67.4% (95% confidence interval [CI], 59.9% to 74.1%); for AFB, 68.0% (95% CI, 60.6% to 74.6%); and for Xpert MTB/RIF, 91.0% (95% CI, 85.0% to 94.8%). In HIV-uninfected patients, the corresponding sensitivities were 72.5% (95% CI, 62.1% to 80.9%), 80.3% (95% CI, 70.8% to 87.2%), and 93.5% (95% CI, 85.7% to 97.2%). The specificity for all 3 tests in both HIV groups was ≥96%. In this setting, the SMF method did not improve the diagnostic accuracy of sputum AFB. The Xpert MTB/RIF assay performed well in both HIV-infected and -uninfected groups.

  6. Nutritional status of adult patients with pulmonary tuberculosis in rural central India and its association with mortality.

    PubMed

    Bhargava, Anurag; Chatterjee, Madhuri; Jain, Yogesh; Chatterjee, Biswaroop; Kataria, Anju; Bhargava, Madhavi; Kataria, Raman; D'Souza, Ravi; Jain, Rachna; Benedetti, Andrea; Pai, Madhukar; Menzies, Dick

    2013-01-01

    Under-nutrition is a known risk factor for TB and can adversely affect treatment outcomes. However, data from India are sparse, despite the high burden of TB as well as malnutrition in India. We assessed the nutritional status at the time of diagnosis and completion of therapy, and its association with deaths during TB treatment, in a consecutive cohort of 1695 adult patients with pulmonary tuberculosis in rural India during 2004 - 2009.Multivariable logistic regression was used to obtain adjusted estimates of the association of nutritional status with deaths during treatment. At the time of diagnosis, median BMI and body weights were 16.0 kg/m(2)and 42.1 kg in men, and 15.0 kg/m(2)and 34.1 kg in women, indicating that 80% of women and 67% of men had moderate to severe under-nutrition (BMI<17.0 kg/m(2)). Fifty two percent of the patients (57% of men and 48% of women) had stunting indicating chronic under-nutrition. Half of women and one third of men remained moderately to severely underweight at the end of treatment. 60 deaths occurred in 1179 patients (5%) in whom treatment was initiated. Severe under-nutrition at diagnosis was associated with a 2 fold higher risk of death. Overall, a majority of patients had evidence of chronic severe under-nutrition at diagnosis, which persisted even after successful treatment in a significant proportion of them. These findings suggest the need for nutritional support during treatment of pulmonary TB in this rural population.

  7. Value of Urine Lipoarabinomannan Grade and Second Test for Optimizing Clinic-based Screening for HIV-associated Pulmonary Tuberculosis

    PubMed Central

    Drain, Paul K.; Losina, Elena; Coleman, Sharon M.; Giddy, Janet; Ross, Douglas; Katz, Jeffrey N.; Bassett, Ingrid V.

    2014-01-01

    Background We assessed the role of urine LAM (lipoarabinomannan) grade and a second LAM test for HIV-associated pulmonary tuberculosis (TB) screening in outpatient clinics in South Africa. Methods We enrolled newly-diagnosed HIV-infected adults (≥18 years) at 4 clinics, excluding those on TB therapy. Participants provided sputum for AFB microscopy and culture. Nurses conducted two rapid urine LAM tests at the point-of-care, and graded positive results from low (“faint”) to high (5+). Culture-confirmed pulmonary TB was the gold standard. We used area under receiver operating curves (AUROC) to compare screening strategies. Results Among 320 HIV-infected adults, median CD4 was 248/mm3 (IQR 107–379/mm3); 54 (17%) were TB culture-positive. 52 (16%) of all participants were LAM-positive by either test; correlation between LAM tests was high. Among 10 “faint” positive results, 2 (20%) had culture-positive TB. Using ≥1+ LAM grade as positive, one LAM test had sensitivity of 41% (95% CI 28–55%) and specificity of 92% (95% CI 88–95%). A 2 LAM test strategy had a sensitivity of 43% (95% CI 29–57%). One LAM test ≥1+ grade (AUROC=0.66; 95% CI 0.60–0.73) was significantly better than sputum AFB alone. The optimal strategy was sequentially performing one LAM test followed by sputum AFB if LAM grade <1+ (AUROC=0.70; 95% CI 0.63–0.77), which had sensitivity of 48% (95% CI 34–62%) and specificity of 91% (95% CI 87–94%). Conclusions In this clinic-based study, “faint” line was a false-positive, second urine LAM test added no value, and an optimal screening strategy was one LAM test followed by sputum AFB microscopy for urine LAM-negative people. PMID:25415288

  8. Clinical Correlates and Drug Resistance in HIV-Infected and -Uninfected Pulmonary Tuberculosis Patients in South India

    PubMed Central

    Sara, Chandy; Elsa, Heylen; Baijayanti, Mishra; Lennartsdotter, Ekstrand Maria

    2016-01-01

    Objectives To examine demographics, clinical correlates, sputum AFB (acid fast bacilli) smear grading DOTS (Directly Observed Therapy Short Course) uptake, and drug resistance in a cohort of newly-diagnosed, smear positive pulmonary tuberculosis (TB) patients with respect to HIV status at baseline, and compare smear conversion rates, side effects and mortality after two months. Design A prospective study among 54 HIV positive and 41 HIV negative pulmonary TB patients. Data were collected via face-to-face interviews, review of medical records, and lab tests. Results HIVTB co-infected patients, though more symptomatic at baseline, showed more improvement in their symptoms compared to HIV-uninfected TB patients at follow-up. The HIV co-infected group had more prevalent perceived side effects, and sputum smear positivity was marginally higher compared to the HIV negative group at follow-up. Mortality was higher among the HIV-infected group. Both groups had high rates of resistance to first-line anti-tubercular drugs, particularly isoniazid. There was no significant difference in the drug resistance patterns between the groups. Conclusions Prompt initiation and provision of daily regimens of ATT (Anti-Tubercular treatment) along with ART (Anti-Retroviral treatment) via ART centers is urgently needed in India. As resistance to ART and/or ATT is directly linked to medication non-adherence, the use of counseling, regular reinforcement, early detection and appropriate intervention strategies to tackle this complex issue could help prevent premature mortality and development of resistance in HIV-TB co-infected patients. The high rate of isoniazid resistance might preclude its use in India as prophylaxis for latent TB in HIV infected persons as per the World Health Organization (WHO) guideline.

  9. Diagnostic Accuracy of the Small Membrane Filtration Method for Diagnosis of Pulmonary Tuberculosis in a High-HIV-Prevalence Setting.

    PubMed

    Boum, Yap; Kim, Soyeon; Orikiriza, Patrick; Acuña-Villaorduña, Carlos; Vinhas, Solange; Bonnet, Maryline; Nyehangane, Dan; Mwanga-Amumpaire, Juliet; Fennelly, Kevin P; Jones-López, Edward C

    2016-06-01

    Sputum acid-fast bacilli (AFB) smear microscopy has suboptimal sensitivity but remains the most commonly used laboratory test to diagnose pulmonary tuberculosis (TB). We prospectively evaluated the small membrane filtration (SMF) method that concentrates AFB in a smaller area to facilitate detection to improve the diagnostic performance of microscopy. We enrolled adults with suspicion of pulmonary TB from health facilities in southwestern Uganda. Clinical history, physical examination, and 3 sputum samples were obtained for direct fluorescent AFB smear, SMF, Xpert MTB/RIF, and MGIT culture media. Sensitivity and specificity were estimated for SMF, AFB smear, and Xpert MTB/RIF, using MGIT as the reference standard. The analysis was stratified according to HIV status. From September 2012 to April 2014, 737 participants were included in the HIV-infected stratum (146 [20.5%] were culture positive) and 313 were in the HIV-uninfected stratum (85 [28%] were culture positive). In HIV-infected patients, the sensitivity of a single SMF was 67.4% (95% confidence interval [CI], 59.9% to 74.1%); for AFB, 68.0% (95% CI, 60.6% to 74.6%); and for Xpert MTB/RIF, 91.0% (95% CI, 85.0% to 94.8%). In HIV-uninfected patients, the corresponding sensitivities were 72.5% (95% CI, 62.1% to 80.9%), 80.3% (95% CI, 70.8% to 87.2%), and 93.5% (95% CI, 85.7% to 97.2%). The specificity for all 3 tests in both HIV groups was ≥96%. In this setting, the SMF method did not improve the diagnostic accuracy of sputum AFB. The Xpert MTB/RIF assay performed well in both HIV-infected and -uninfected groups. PMID:27030493

  10. Comparative study of clinico-bacterio-radiological profile and treatment outcome of smokers and nonsmokers suffering from pulmonary tuberculosis

    PubMed Central

    Rathee, Deepti; Arora, Piyush; Meena, Manoj; Sarin, Rohit; Chakraborty, Pitambar; Jaiswal, Anand; Goyal, Mukesh

    2016-01-01

    Introduction: Tuberculosis (TB) is one of the leading causes of death and disease worldwide. Tobacco smoking has been linked as a risk factor for TB. This study was aimed to affirm the strength of association between smoking and pulmonary TB. Materials and Methods: Pulmonary TB patients aged between 18 and 65 years were enrolled and followed-up until treatment completion. Two consecutive sputum smears were examined from each patient for the presence of acid-fast bacilli (AFB) using Ziehl–Neelsen technique. Radiological severity of disease was assessed using guidelines of National TB Association of USA. Sputum smears for AFB were graded for positivity as per WHO Revised National TB Control Programme criteria. Response was determined in terms of sputum conversion at the end of intensive phase and final treatment outcomes. Results: Sputum smear grading of 3+ increased from 12.5% to 68.18% and 66.66% as smoking index increased from <100 to 100–299 and >300 (P < 0.05). In nonsmokers, 79.2% patients had minimal disease while only 4.2% had advanced disease as compared to smokers where 52.4% had moderate disease, 26.2% advanced disease, and 21.4% minimal disease (P < 0.01). Smokers had significantly lower treatment success rate (69%) as against nonsmokers and former smokers (93.8% and 90.9%, respectively, P = 0.001) owing to a higher default rate among smokers (28.5%) than nonsmokers (6.3%) and former smokers (9.1%). Conclusion: Smokers during initial presentation, as well as at end of the treatment demonstrate more radiological findings, cavitary disease, and worse sputum AFB smear grading. Smokers also have a poorer treatment success rate largely due to high percentage of default rate thus suggesting noncompliance as a main confounder to treatment success. Focus needs to be made to reduce defaulters which are more common among smokers.

  11. Comparative study of clinico-bacterio-radiological profile and treatment outcome of smokers and nonsmokers suffering from pulmonary tuberculosis

    PubMed Central

    Rathee, Deepti; Arora, Piyush; Meena, Manoj; Sarin, Rohit; Chakraborty, Pitambar; Jaiswal, Anand; Goyal, Mukesh

    2016-01-01

    Introduction: Tuberculosis (TB) is one of the leading causes of death and disease worldwide. Tobacco smoking has been linked as a risk factor for TB. This study was aimed to affirm the strength of association between smoking and pulmonary TB. Materials and Methods: Pulmonary TB patients aged between 18 and 65 years were enrolled and followed-up until treatment completion. Two consecutive sputum smears were examined from each patient for the presence of acid-fast bacilli (AFB) using Ziehl–Neelsen technique. Radiological severity of disease was assessed using guidelines of National TB Association of USA. Sputum smears for AFB were graded for positivity as per WHO Revised National TB Control Programme criteria. Response was determined in terms of sputum conversion at the end of intensive phase and final treatment outcomes. Results: Sputum smear grading of 3+ increased from 12.5% to 68.18% and 66.66% as smoking index increased from <100 to 100–299 and >300 (P < 0.05). In nonsmokers, 79.2% patients had minimal disease while only 4.2% had advanced disease as compared to smokers where 52.4% had moderate disease, 26.2% advanced disease, and 21.4% minimal disease (P < 0.01). Smokers had significantly lower treatment success rate (69%) as against nonsmokers and former smokers (93.8% and 90.9%, respectively, P = 0.001) owing to a higher default rate among smokers (28.5%) than nonsmokers (6.3%) and former smokers (9.1%). Conclusion: Smokers during initial presentation, as well as at end of the treatment demonstrate more radiological findings, cavitary disease, and worse sputum AFB smear grading. Smokers also have a poorer treatment success rate largely due to high percentage of default rate thus suggesting noncompliance as a main confounder to treatment success. Focus needs to be made to reduce defaulters which are more common among smokers. PMID:27625444

  12. Clinical Correlates and Drug Resistance in HIV-Infected and -Uninfected Pulmonary Tuberculosis Patients in South India

    PubMed Central

    Sara, Chandy; Elsa, Heylen; Baijayanti, Mishra; Lennartsdotter, Ekstrand Maria

    2016-01-01

    Objectives To examine demographics, clinical correlates, sputum AFB (acid fast bacilli) smear grading DOTS (Directly Observed Therapy Short Course) uptake, and drug resistance in a cohort of newly-diagnosed, smear positive pulmonary tuberculosis (TB) patients with respect to HIV status at baseline, and compare smear conversion rates, side effects and mortality after two months. Design A prospective study among 54 HIV positive and 41 HIV negative pulmonary TB patients. Data were collected via face-to-face interviews, review of medical records, and lab tests. Results HIVTB co-infected patients, though more symptomatic at baseline, showed more improvement in their symptoms compared to HIV-uninfected TB patients at follow-up. The HIV co-infected group had more prevalent perceived side effects, and sputum smear positivity was marginally higher compared to the HIV negative group at follow-up. Mortality was higher among the HIV-infected group. Both groups had high rates of resistance to first-line anti-tubercular drugs, particularly isoniazid. There was no significant difference in the drug resistance patterns between the groups. Conclusions Prompt initiation and provision of daily regimens of ATT (Anti-Tubercular treatment) along with ART (Anti-Retroviral treatment) via ART centers is urgently needed in India. As resistance to ART and/or ATT is directly linked to medication non-adherence, the use of counseling, regular reinforcement, early detection and appropriate intervention strategies to tackle this complex issue could help prevent premature mortality and development of resistance in HIV-TB co-infected patients. The high rate of isoniazid resistance might preclude its use in India as prophylaxis for latent TB in HIV infected persons as per the World Health Organization (WHO) guideline. PMID:27708985

  13. Prevalence of Pulmonary Tuberculosis among Prison Inmates in Ethiopia, a Cross-Sectional Study

    PubMed Central

    Ali, Solomon; Haileamlak, Abraham; Wieser, Andreas; Pritsch, Michael; Heinrich, Norbert; Loscher, Thomas; Hoelscher, Michael; Rachow, Andrea

    2015-01-01

    Setting Tuberculosis (TB) is one of the major health problems in prisons. Objective This study was done to assess the prevalence and determinants of active tuberculosis in Ethiopian prisons. Design A cross-sectional study was conducted from January 2013 to December 2013 in 13 zonal prisons. All incarcerated inmates underwent TB symptom screening according to WHO criteria. From identified TB-suspects two sputum samples were analyzed using smear microscopy and solid culture. A standardized questionnaire assessing TB risk factors was completed for each TB suspect. Results 765 (4.9%) TB suspects were identified among 15,495 inmates. 51 suspects were already on anti-TB treatment (6.67%) and 20 (2.8%) new culture-confirmed TB cases were identified in the study, resulting in an overall TB prevalence of 458.1/100,000 (95%CI: 350-560/100,000). Risk factors for active TB were alcohol consumption, contact with a TB case before incarceration and no window in prison cell. HIV prevalence was not different between TB suspects and active TB cases. Further, the TB burden in prisons increased with advancing distance from the capital Addis Ababa. Conclusions The overall TB prevalence in Ethiopian prisons was high and extremely variable among different prisons. TB risk factors related to conditions of prison facilities and the impact of implemented TB control measures need to be further studied in order to improve TB control among inmates. PMID:26641654

  14. Cerebral aspergillosis and pulmonary tuberculosis in a child with chronic granulomatous disease

    PubMed Central

    Waqas, Muhammed; Zafar, Sidra; Rehman, Tooba; Riyaz, Muhammed; Bari, Muhammed E.; Idrees, Romana

    2016-01-01

    Background: Chronic granulomatous disease (CGD) is an immune disorder that affects phagocytes. It is characterized by recurrent or persistent bacterial and fungal infections. Reports of tuberculosis (TB) in patients with CGD are rare. In developing countries, where TB is endemic, possibility of other chronic infections is often overlooked by physicians. Case Description: We report the case of a 4-year-old boy who had recurrent respiratory infections and episodes of headache. He was put on antituberculosis (ATT) drugs without microbiological or pathological evidence 2 months prior to presentation. The child did not improve and was brought to our hospital where a computed tomography scan revealed multiple cerebral abscesses. These abscesses were excised. The microbiological specimen was determined to be positive for Aspergillus fumigatus. His tracheal aspirate was positive for Mycobacterium tuberculosis polymerase chain reaction assay. Further work-up confirmed the diagnosis of CGD in the child. Conclusion: This report describes the course of the patient's illness in order to highlight the challenges associated with the management of these infections. We also aim to stress on the importance of pathological diagnosis before starting a therapy. PMID:27308089

  15. Microscopical and immunological features of tuberculoid granulomata and cavitary pulmonary tuberculosis in naturally infected goats.

    PubMed

    Sanchez, J; Tomás, L; Ortega, N; Buendía, A J; del Rio, L; Salinas, J; Bezos, J; Caro, M R; Navarro, J A

    2011-01-01

    Caprine tuberculosis is caused by bacteria of the Mycobacterium tuberculosis complex (Mycobacterium bovis and Mycobacterium caprae). Although typical tuberculoid granulomata are usually observed in the lungs and lymph nodes of infected goats, the presence of cavitary lesions with exuberant mycobacterial growth is also a common feature in this species. The aim of this study was to characterize the immunological mechanisms that lead to liquefaction and cavity formation by comparing granulomata and cavitary lesions. Samples from animals positive by skin testing were collected for microscopical and immunohistochemical examination. Samples were also collected for analysis of cytokine gene expression in the lesions by real time polymerase chain reaction. There were marked differences between granulomata and cavitary lesions. In cavitary lesions there was a substantial population of neutrophils and a significant decrease in the number of CD4(+) T cells, with concomitant increases in other T-cell populations (CD8(+) and cells expressing the γδ form of the T-cell receptor). The enzyme iNOS was strongly expressed by macrophages in the cavitary lesions. There was no difference in the balance of pro- and anti-inflammatory cytokine gene expression in the lesions. These findings suggest that cavitary lesions are reactivation sites, where conditions are optimal for Mycobacterium proliferation and that immunological mechanisms may underlie the severe destruction of lung tissue that characterizes the cavitary pathology.

  16. Lesion-Specific Immune Response in Granulomas of Patients with Pulmonary Tuberculosis: A Pilot Study

    PubMed Central

    Subbian, Selvakumar; Tsenova, Liana; Kim, Mi-Jeong; Wainwright, Helen C.; Visser, Annalie; Bandyopadhyay, Nirmalya; Bader, Joel S.; Karakousis, Petros C.; Murrmann, Gabriele B.; Bekker, Linda-Gail; Russell, David G.; Kaplan, Gilla

    2015-01-01

    The formation and maintenance of granulomas is central to the host response to Mycobacterium tuberculosis (Mtb) infection. It is widely accepted that the lungs of patients with tuberculosis (TB) usually contain multiple infection foci, and that the granulomas evolve and differentiate independently, resulting in considerable heterogeneity. Although gene expression profiles of human blood cells have been proposed as biomarkers of Mtb infection and/or active disease, the immune profiles of discrete lesion types has not been studied extensively. Using histology, immunopathology and genome-wide transcriptome analysis, we explored the immunological profile of human lung TB granulomas. We show that although the different granulomas share core similarities in their immunological/inflammatory characteristics, they also exhibit significant divergence. Despite similar numbers of CD68+ macrophages in the different lesions, the extent of immune reactivity, as determined by the density of CD3+ T cells in the macrophage rich areas, and the extent of fibrosis, shows considerable variation. Both quantitative and qualitative differences among significantly differentially expressed genes (SDEG) were noted in each of the lesion types studied. Further, network/pathway analysis of SDEG revealed differential regulation of inflammatory response, immune cell trafficking, and cell mediated immune response in the different lesions. Our data highlight the formidable challenges facing ongoing efforts to identify peripheral blood biomarkers due to the diversity of lesion types and complexity of local immune responses in the lung. PMID:26133981

  17. Evaluation of a whole-blood chemiluminescent immunoassay of IFN-γ, IP-10, and MCP-1 for diagnosis of active pulmonary tuberculosis and tuberculous pleurisy patients.

    PubMed

    Liang, Yan; Wang, Ying; Li, Hang; Yang, Yourong; Liu, Jianyang; Yu, Ting; Wu, Xueqiong

    2016-10-01

    The study explored the use of IP-10, MCP-1, and IFN-γ as biomarkers to improve the diagnoses of active pulmonary tuberculosis and tuberculous pleurisy. We enrolled 267 individuals, including 134 TB patients, 93 patients with non-tuberculous pulmonary diseases, and 40 healthy controls. Whole bloods were stimulated in vitro with rCFP-10/ESAT-6 protein antigen of Mycobacterium tuberculosis. The levels of IFN-γ, IP-10, and MCP-1 in cultured supernatants of whole bloods were detected by a chemiluminescence immunoassay. A receiver operating characteristic (ROC) curve was drawn to determine the cutoff value for diagnosing TB and to evaluate the diagnostic efficacies of the IFN-γ, IP-10, and MCP-1 for TB. The antigen-specific release of each cytokine, IFN-γ, IP-10, and MCP-1, was significantly higher in the TB groups than in either the non-tuberculous pulmonary disease group (p < 0.001) or the healthy control group (p < 0.001). The ROC curves indicated cutoff values for IFN-γ, IP-10, and MCP-1 at 147.8, 160.4, and 496.4 pg/mL, respectively. The sensitivity, specificity, PPV, NPV, and diagnostic efficiency for IFN-γ were 85.8%, 70.7%, 74.7%, 83.2%, and 78.3%, respectively; for IP-10 were 72.4%, 75.9%, 75.2%, 73.2%, and 74.2%, respectively; and for MCP-1 were 90.3%, 97.0%, 96.8%, 90.8%, and 93.6%, respectively. IFN-γ combined MCP-1 improved the sensitivity to 97.8% compared with IFN-γ (p < 0.001). Our findings indicate high sensitivity and specificity of MCP-1 as novel biomarkers for the diagnosis of active pulmonary tuberculosis and tuberculous pleurisy.

  18. The relationship between perceived discrimination and psychological distress among Chinese pulmonary tuberculosis patients: the moderating role of self-esteem.

    PubMed

    Feng, Danjun; Xu, Lingzhong

    2015-01-01

    This study described the prevalence of psychological distress and examined the moderating effect of self-esteem in the relationship between perceived discrimination and psychological distress among Chinese pulmonary tuberculosis (TB) patients. Seven hundred and twenty patients with TB from three cities of Shandong Province in eastern China participated in a cross-sectional survey. Patients were measured with the Kessler 10 (K10), the Rosenberg self-esteem scale, and a self-developed perceived discrimination questionnaire. A total of 58.6% of patients with TB scored above 16 on the K10, indicating moderate and serious psychological distress. Chi-square test revealed that female patients reported higher psychological distress than male patients. The structural equation modeling (SEM) analysis among the whole sample indicated that perceived discrimination was significantly related with psychological distress (β = .28, p ≤ .01). The multiple group analysis of SEM showed that perceived discrimination had a significantly substantial (β = .50, p ≤ .001), significantly moderate (β = .15, p ≤ .01), and insignificant effect (β = .05, p ≥ .05) on psychological distress among low self-esteem, moderate self-esteem, and high self-esteem patients with TB, respectively, which verified the moderating effect of self-esteem in the relationship between perceived discrimination and psychological distress.

  19. Performance of LED Fluorescence Microscopy for the Diagnosis of Pulmonary Tuberculosis in HIV Positive Individuals in Addis Ababa, Ethiopia

    PubMed Central

    Getachew, Konjit; Abebe, Tamrat; Kebede, Abebaw; Mihret, Adane; Melkamu, Getachew

    2015-01-01

    Background. Despite its lower sensitivity, smear microscopy remains the main diagnostic method for pulmonary tuberculosis (PTB) in resource-limited countries as TB culturing methods like LJ (Lowenstein-Jensen) are expensive to use as a routine base. This study aimed to evaluate the performance of LED-FM for the diagnosis of PTB in HIV positive individuals. Methods. Cross-sectional study was conducted in Zewditu Memorial Hospital and Teklehaimanot Health Center HIV/ART clinics in Addis Ababa, Ethiopia. Each sample was stained with ZN and Auramine O staining and examined with bright-field microscope and LED-FM microscope, respectively. LJ culture was used as a reference. Results. Out of 178 study participants, twenty-four (13.5%) patients were confirmed as positive for MTB with LJ culture. The yield of ZN microscopy and LED-FM in direct and concentrated sample was 3.9%, 8.4%, 6.2%, and 8.4%, respectively. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of direct ZN microscopy were 29.2%, 100%, 100%, and 90.1%, respectively, and of LED-FM microscopy in direct sputum sample were 62.5%, 100%, 100%, and 94.5%, respectively. Conclusion. LED-FM has better sensitivity for the diagnosis of PTB in HIV positive individuals as compared to conventional ZN microscopy. LED-FM can be used as an alternative to conventional ZN microscopy. PMID:26688753

  20. Performance of LED Fluorescence Microscopy for the Diagnosis of Pulmonary Tuberculosis in HIV Positive Individuals in Addis Ababa, Ethiopia.

    PubMed

    Getachew, Konjit; Abebe, Tamrat; Kebede, Abebaw; Mihret, Adane; Melkamu, Getachew

    2015-01-01

    Background. Despite its lower sensitivity, smear microscopy remains the main diagnostic method for pulmonary tuberculosis (PTB) in resource-limited countries as TB culturing methods like LJ (Lowenstein-Jensen) are expensive to use as a routine base. This study aimed to evaluate the performance of LED-FM for the diagnosis of PTB in HIV positive individuals. Methods. Cross-sectional study was conducted in Zewditu Memorial Hospital and Teklehaimanot Health Center HIV/ART clinics in Addis Ababa, Ethiopia. Each sample was stained with ZN and Auramine O staining and examined with bright-field microscope and LED-FM microscope, respectively. LJ culture was used as a reference. Results. Out of 178 study participants, twenty-four (13.5%) patients were confirmed as positive for MTB with LJ culture. The yield of ZN microscopy and LED-FM in direct and concentrated sample was 3.9%, 8.4%, 6.2%, and 8.4%, respectively. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of direct ZN microscopy were 29.2%, 100%, 100%, and 90.1%, respectively, and of LED-FM microscopy in direct sputum sample were 62.5%, 100%, 100%, and 94.5%, respectively. Conclusion. LED-FM has better sensitivity for the diagnosis of PTB in HIV positive individuals as compared to conventional ZN microscopy. LED-FM can be used as an alternative to conventional ZN microscopy. PMID:26688753

  1. The antifibrotic drug pirfenidone promotes pulmonary cavitation and drug resistance in a mouse model of chronic tuberculosis

    PubMed Central

    Ahidjo, Bintou A.; Maiga, Mariama C.; Ihms, Elizabeth A.; Maiga, Mamoudou; Ordonez, Alvaro A.; Cheung, Laurene S.; Beck, Sarah; Andrade, Bruno B.; Jain, Sanjay

    2016-01-01

    Pirfenidone is a recently approved antifibrotic drug for the treatment of idiopathic pulmonary fibrosis (IPF). Because tuberculosis (TB) is characterized by granulomatous inflammation in conjunction with parenchymal destruction and replacement fibrosis, we sought to determine whether the addition of pirfenidone as an adjunctive, host-directed therapy provides a beneficial effect during antimicrobial treatment of TB. We hypothesized that pirfenidone’s antiinflammatory and antifibrotic properties would reduce inflammatory lung damage and increase antimicrobial drug penetration in granulomas to accelerate treatment response. The effectiveness of adjunctive pirfenidone during TB drug therapy was evaluated using a murine model of chronic TB. Mice treated with standard therapy 2HRZ/4HR (H, isoniazid; R, rifampin; and Z, pyrazinamide) were compared with 2 alternative regimens containing pirfenidone (Pf) (2HRZPf/4HRPf and 2HRZPf/4HR). Contrary to our hypothesis, adjunctive pirfenidone use leads to reduced bacterial clearance and increased relapse rates. This treatment failure is closely associated with the emergence of isoniazid monoresistant bacilli, increased cavitation, and significant lung pathology. While antifibrotic agents may eventually be used as part of adjunctive host-directed therapy of TB, this study clearly demonstrates that caution must be exercised. Moreover, as pirfenidone becomes more widely used in clinical practice, increased patient monitoring would be required in endemic TB settings. PMID:27699232

  2. Did FIDELIS projects contribute to the detection of new smear-positive pulmonary tuberculosis cases in China?

    PubMed Central

    Rusen, I. D.; Hinderaker, S. G.; Roldan, A.; Heldal, E.; Enarson, D. A.; Zhang, L-X.

    2016-01-01

    Setting: The first phase of the Fund for Innovative DOTS Expansion through Local Initiatives to Stop TB (FIDELIS) projects in China started in 2003. Objective: To determine whether the FIDELIS projects contributed to the increased case detection rate for new smear-positive pulmonary tuberculosis (PTB) in China. Methods: We compared the case notification rates (CNRs) in the intervention year with those of the previous year in the FIDELIS areas, then compared the difference between the CNRs of the intervention year and the previous year in the FIDELIS areas with those in the non-FI-DELIS areas within the province. Results: There was an increase in the CNR in the intervention year compared with the previous year for all the project sites. The differences between the CNR in the intervention year and the previous year ranged from 6.4 to 31.1 per 100 000 population in the FIDELIS areas and from 2.9 to 20.4/100 000 in the non-FIDELIS areas. Differences-in-differences analysis shows that the differences in the CNRs in the FIDELIS areas were not statistically significantly different from those in the non-FIDELIS areas (P = 0.393). Conclusion: The FIDELIS projects may have contributed to the increase in case detection of new smear-positive PTB in China, but the level of evidence is low. PMID:27695680

  3. Correlation between Either Cupriavidus or Porphyromonas and Primary Pulmonary Tuberculosis Found by Analysing the Microbiota in Patients’ Bronchoalveolar Lavage Fluid

    PubMed Central

    Zhou, Yuhua; Lin, Feishen; Cui, Zelin; Zhang, Xiangrong; Hu, Chunmei; Shen, Tian; Chen, Chunyan; Zhang, Xia; Guo, Xiaokui

    2015-01-01

    Pulmonary tuberculosis (TB) has gained attention in recent decades because of its rising incidence trend; simultaneously, increasing numbers of studies have identified the relationship between microbiota and chronic infectious diseases. In our work, we enrolled 32 patients with primary TB characterised by unilateral TB lesion formation diagnosed by chest radiographic exam. Bronchoalveolar lavage fluid was taken from both lungs. Twenty-four healthy people were chosen as controls. Pyrosequencing was performed on the V3 hypervariable region of 16S rDNA in all bacterial samples and used as a culture-independent method to describe the phylogenetic composition of the microbiota. Through pyrosequencing, 271,764 amplicons were detected in samples and analysed using tools in the Ribosomal Database Project (RDP) and bioinformatics. These analyses revealed significant differences in the microbiota in the lower respiratory tract (LRT) of TB patients compared with healthy controls; in contrast, the microbiota of intra/extra-TB lesions were similar. These results showed that the dominant bacterial genus in the LRT of TB patients was Cupriavidus and not Streptococcus, which resulted in a significant change in the microbiota in TB patients. The abundance of Mycobacteria and Porphyromonas significantly increased inside TB lesions when compared with non-lesion-containing contralateral lungs. From these data, it can be concluded that Cupriavidus plays an important role in TB’s secondary infection and that in addition to Mycobacteria, Porphyromonas may also be a co-factor in lesion formation. The mechanisms underlying this connection warrant further research. PMID:26000957

  4. A review of Vitamin D effects on common respiratory diseases: Asthma, chronic obstructive pulmonary disease, and tuberculosis.

    PubMed

    Hejazi, Mohammad Esmaeil; Modarresi-Ghazani, Faezeh; Entezari-Maleki, Taher

    2016-01-01

    Despite the classic role of Vitamin D in skeletal health, new aspects of Vitamin D have been discovered in tissues and organs other than bones. Epidemiological and observational studies demonstrate a link between Vitamin D deficiency and risk of developing respiratory diseases including asthma, chronic obstructive pulmonary disease (COPD), and tuberculosis (TB). To review the literature, we searched the terms "Vitamin D" (using the set operator) and "asthma," "COPD" and "TB" in electronic databases, including PubMed/MEDLINE, Scopus, and Google Scholar until July 2015. Non-English articles or articles with unavailable full text were excluded. Both in vivo and in vitro studies were included. All the reviewed articles state that Vitamin D deficiency is very common among patients with respiratory diseases. The present data regarding Vitamin D and asthma is still controversial, but data about COPD and TB are more encouraging. The relevant studies have been conducted in different populations therefore it is not particularly possible to compare the data due to genetic variations. In order to point out a role for Vitamin D, large clinical trials with Vitamin D deficient subjects and sufficient Vitamin D supplementation are needed.

  5. Sociodemographic, Epidemiological, and Clinical Risk Factors for Childhood Pulmonary Tuberculosis in Severely Malnourished Children Presenting With Pneumonia

    PubMed Central

    Ahmed, Tahmeed; Shahid, Abu S. M. S. B.; Shahunja, K. M.; Bardhan, Pradip Kumar; Faruque, Abu Syeed Golam; Das, Sumon Kumar; Salam, Mohammed Abdus

    2015-01-01

    We aimed to evaluate sociodemographic, epidemiological, and clinical risk factors for pulmonary tuberculosis (PTB) in children presenting with severe acute malnutrition (SAM) and pneumonia. Children aged 0 to 59 months with SAM and radiologic pneumonia from April 2011 to July 2012 were studied in Bangladesh. Children with confirmed PTB (by culture and/or X-pert MTB/RIF) (cases = 27) and without PTB (controls = 81; randomly selected from 378 children) were compared. The cases more often had the history of contact with active PTB patient (P < .01) and exposure to cigarette smoke (P = .04) compared with the controls. In logistic regression analysis, after adjusting for potential confounders, the cases were independently associated with working mother (P = .05) and positive tuberculin skin test (TST; P = .02). Thus, pneumonia in SAM children is a common presentation of PTB and further highlights the importance of the use of simple TST and/or history of contact with active TB patients in diagnosing PTB in such children, especially in resource-limited settings. PMID:27335971

  6. The antifibrotic drug pirfenidone promotes pulmonary cavitation and drug resistance in a mouse model of chronic tuberculosis

    PubMed Central

    Ahidjo, Bintou A.; Maiga, Mariama C.; Ihms, Elizabeth A.; Maiga, Mamoudou; Ordonez, Alvaro A.; Cheung, Laurene S.; Beck, Sarah; Andrade, Bruno B.; Jain, Sanjay

    2016-01-01

    Pirfenidone is a recently approved antifibrotic drug for the treatment of idiopathic pulmonary fibrosis (IPF). Because tuberculosis (TB) is characterized by granulomatous inflammation in conjunction with parenchymal destruction and replacement fibrosis, we sought to determine whether the addition of pirfenidone as an adjunctive, host-directed therapy provides a beneficial effect during antimicrobial treatment of TB. We hypothesized that pirfenidone’s antiinflammatory and antifibrotic properties would reduce inflammatory lung damage and increase antimicrobial drug penetration in granulomas to accelerate treatment response. The effectiveness of adjunctive pirfenidone during TB drug therapy was evaluated using a murine model of chronic TB. Mice treated with standard therapy 2HRZ/4HR (H, isoniazid; R, rifampin; and Z, pyrazinamide) were compared with 2 alternative regimens containing pirfenidone (Pf) (2HRZPf/4HRPf and 2HRZPf/4HR). Contrary to our hypothesis, adjunctive pirfenidone use leads to reduced bacterial clearance and increased relapse rates. This treatment failure is closely associated with the emergence of isoniazid monoresistant bacilli, increased cavitation, and significant lung pathology. While antifibrotic agents may eventually be used as part of adjunctive host-directed therapy of TB, this study clearly demonstrates that caution must be exercised. Moreover, as pirfenidone becomes more widely used in clinical practice, increased patient monitoring would be required in endemic TB settings.

  7. Did FIDELIS projects contribute to the detection of new smear-positive pulmonary tuberculosis cases in China?

    PubMed Central

    Rusen, I. D.; Hinderaker, S. G.; Roldan, A.; Heldal, E.; Enarson, D. A.; Zhang, L-X.

    2016-01-01

    Setting: The first phase of the Fund for Innovative DOTS Expansion through Local Initiatives to Stop TB (FIDELIS) projects in China started in 2003. Objective: To determine whether the FIDELIS projects contributed to the increased case detection rate for new smear-positive pulmonary tuberculosis (PTB) in China. Methods: We compared the case notification rates (CNRs) in the intervention year with those of the previous year in the FIDELIS areas, then compared the difference between the CNRs of the intervention year and the previous year in the FIDELIS areas with those in the non-FI-DELIS areas within the province. Results: There was an increase in the CNR in the intervention year compared with the previous year for all the project sites. The differences between the CNR in the intervention year and the previous year ranged from 6.4 to 31.1 per 100 000 population in the FIDELIS areas and from 2.9 to 20.4/100 000 in the non-FIDELIS areas. Differences-in-differences analysis shows that the differences in the CNRs in the FIDELIS areas were not statistically significantly different from those in the non-FIDELIS areas (P = 0.393). Conclusion: The FIDELIS projects may have contributed to the increase in case detection of new smear-positive PTB in China, but the level of evidence is low.

  8. Association of DC-SIGN and DC-SIGNR Repeat Regions with Susceptibility to Pulmonary Tuberculosis in Zahedan, Southeastern Iran.

    PubMed

    Naderi, Mohammad; Hashemi, Mohammad; Soroush, Navid; Amininia, Shadi; Taheri, Mohsen

    2016-05-01

    There are conflicting results concerning DC-SIGN and DC-SIGNR VNTR polymorphisms. The present study aimed to evaluate the possible association between DC-SIGN as well as DC-SIGNR VNTR polymorphisms and pulmonary tuberculosis (PTB) in a sample of Iranian population. This case-control study was done on 171 PTB and 161 healthy subjects. The variants were detected by polymerase chain reaction (PCR). DC-SIGNR VNTR genotypes in cases were 12.7% for 5/5, 2.4% for 6/5, 32.7% for 7/7, 38.2% for 7/5, 5.5% for 7/6, 1.2% for /5, 0.6% for 9/6, 6.7% for 9/7 in PTB patients and 19.7% for 5/5, 2.0% for 6/5, 31.6% for 7/7, 37.5% for 7/5, 5.7% for 7/6, 0.0% for 9/5, 0.7% for 9/6, 2.6% for 9/7 in controls. The findings showed no significant association between DC-SIGNR VNTR polymorphism and PTB. All subjects in cases and controls were 7/7 genotype regarding DC-SIGN VNTR polymorphism. Our data propose that DC-SIGNR VNTR, as well as DC-SIGN VNTR, were not associated with the risk of PTB in a sample of Iranian population. PMID:27309478

  9. [Recent progress in genetic background of chronic obstructive pulmonary disease (COPD)].

    PubMed

    Teramoto, Shinji

    2016-05-01

    A genetic contribution to develop chronic obstructive pulmonary disease(COPD) is estimated. However, candidate gene studies on COPD and related phenotypes have not been well replicated. Research on the genetic pathologic background of COPD using genome-wide association studies (GWASs) has progressed in recent years. The novel candidate genes including CHRNA3/5 (cholinergic nicotine receptor alpha 3/5), IREB2 (iron regulatory binding protein 2), HHIP (hedgehog-interacting protein), and FAM13A (family with sequence similarity 13, member A) are identified in multiple populations. However, their pathological roles remain poorly understood. The nicotine dependency, pulmonary development, and pulmonary/systemic inflammatory diathesis may be involved in genetic background of COPD.

  10. [Recent progress in genetic background of chronic obstructive pulmonary disease (COPD)].

    PubMed

    Teramoto, Shinji

    2016-05-01

    A genetic contribution to develop chronic obstructive pulmonary disease(COPD) is estimated. However, candidate gene studies on COPD and related phenotypes have not been well replicated. Research on the genetic pathologic background of COPD using genome-wide association studies (GWASs) has progressed in recent years. The novel candidate genes including CHRNA3/5 (cholinergic nicotine receptor alpha 3/5), IREB2 (iron regulatory binding protein 2), HHIP (hedgehog-interacting protein), and FAM13A (family with sequence similarity 13, member A) are identified in multiple populations. However, their pathological roles remain poorly understood. The nicotine dependency, pulmonary development, and pulmonary/systemic inflammatory diathesis may be involved in genetic background of COPD. PMID:27254938

  11. Molecular insights into the progression of crystalline silica-induced pulmonary toxicity in rats

    PubMed Central

    Sellamuthu, Rajendran; Umbright, Christina; Roberts, Jenny R.; Cumpston, Amy; McKinney, Walter; Chen, Bean T.; Frazer, David; Li, Shengqiao; Kashon, Michael; Joseph, Pius

    2015-01-01

    Identification of molecular target(s) and mechanism(s) of silica-induced pulmonary toxicity is important for the intervention and/or prevention of diseases associated with exposure to silica. Rats were exposed to crystalline silica by inhalation (15 mg m−3, 6 h per day, 5 days) and global gene expression profile was determined in the lungs by microarray analysis at 1, 2, 4, 8 and 16 weeks following termination of silica exposure. The number of significantly differentially expressed genes (>1.5-fold change and <0.01 false discovery rate P-value) detected in the lungs during the post-exposure time intervals analyzed exhibited a steady increase in parallel with the progression of silica-induced pulmonary toxicity noticed in the rats. Quantitative real-time PCR analysis of a representative set of 10 genes confirmed the microarray findings. The number of biological functions, canonical pathways and molecular networks significantly affected by silica exposure, as identified by the bioinformatics analysis of the significantly differentially expressed genes detected during the post-exposure time intervals, also exhibited a steady increase similar to the silica-induced pulmonary toxicity. Genes involved in oxidative stress, inflammation, respiratory diseases, cancer, and tissue remodeling and fibrosis were significantly differentially expressed in the rat lungs; however, unresolved inflammation was the single most significant biological response to pulmonary exposure to silica. Excessive mucus production, as implicated by significant overexpression of the pendrin coding gene, SLC26A4, was identified as a potential novel mechanism for silica-induced pulmonary toxicity. Collectively, the findings of our study provided insights into the molecular mechanisms underlying the progression of crystalline silica-induced pulmonary toxicity in the rat. Published 2012. This article is a US Government work and is in the public domain in the USA. PMID:22431001

  12. Association between Toll-Like Receptor 4 and Occurrence of Type 2 Diabetes Mellitus Susceptible to Pulmonary Tuberculosis in Northeast China.

    PubMed

    Li, Yuze; Li, Dianzhong; Zhang, Jinfeng; Liu, Shurui; Chen, Haijun; Wu, Kun

    2016-01-01

    The purpose of this study is to explore why type 2 diabetes mellitus (T2DM) patients are susceptible to pulmonary tuberculosis through detection of serum Toll-like receptor 4 (TLR4), an important immune-related receptor, especially in terms of content and TLR4 gene polymorphism. Patients with T2DM complicated by pulmonary tuberculosis (T2DMTB) were selected as the case group and T2DM patients without tuberculosis were selected as the control group. Forty patients in each group were randomly selected and their serum TLR4 levels were detected and compared. Determination of six sites of TLR4 gene polymorphism was carried out in 238 T2DMTB patients and 310 patients with T2DM, and results showed that the serum TLR4 content of the T2DMTB group was significantly lower than that of the T2DM group (p < 0.05). The six sites of TLR4 gene polymorphism did not show significant associations with T2DMTB risk. No statistically significant differences in genotype distributions were observed between T2DMTB patients and patients with T2DM when studied using the recessive and dominant genetic models. How two diseases with contradictory nutritional statuses can occur in the same person is difficult to explain from environmental factors perspective alone. Future research should study the causes of T2DMTB from the perspective of genetics. PMID:27123010

  13. Evaluation of serum levels of essential trace elements in patients with pulmonary tuberculosis before and after treatment by age and gender.

    PubMed

    Pourfallah, F; Javadian, S; Zamani, Z; Saghiri, R; Sadeghi, S; Zarea, B; Mirkhani, F; Fatemi, N; Kordi, T

    2011-05-15

    The purpose of this study was to evaluate the levels of Zinc, Copper, Iron and Copper/Zinc ratio in the serum of adult patients with pulmonary tuberculosis in Iran. Serum levels of Zinc and Copper were determined by flame atomic absorption spectrophotometer and scrum iron concentration was measured by using an Auto Analyzer. The study group consisted of 50 pulmonary tuberculosis patients before treatment and after 6 months of anti-tubercular therapy. Levels of scrum Zn (p < 0.001) and Fe (p < 0.001) in TB patients were significantly increased after 6 months of anti-tubercular therapy. However, serum Cu concentration (p < 0.01) and Cu/Zn ratio (p < 0.05) were decreased after 6 months of anti-tubercular therapy. Some studies indicated a strong association of Zn, Cu, Fe and the Cu/Zn ratio with TB. In this study, we found remarkable change in Cu/Zn ratio. Some researchers mentioned that serum Cu/Zn ratio could be used as an important laboratory marker for diagnosis and treatment of tuberculosis. They also mentioned that trace element levels must be closely monitored during the process of disease. PMID:22097095

  14. Association between Toll-Like Receptor 4 and Occurrence of Type 2 Diabetes Mellitus Susceptible to Pulmonary Tuberculosis in Northeast China

    PubMed Central

    2016-01-01

    The purpose of this study is to explore why type 2 diabetes mellitus (T2DM) patients are susceptible to pulmonary tuberculosis through detection of serum Toll-like receptor 4 (TLR4), an important immune-related receptor, especially in terms of content and TLR4 gene polymorphism. Patients with T2DM complicated by pulmonary tuberculosis (T2DMTB) were selected as the case group and T2DM patients without tuberculosis were selected as the control group. Forty patients in each group were randomly selected and their serum TLR4 levels were detected and compared. Determination of six sites of TLR4 gene polymorphism was carried out in 238 T2DMTB patients and 310 patients with T2DM, and results showed that the serum TLR4 content of the T2DMTB group was significantly lower than that of the T2DM group (p < 0.05). The six sites of TLR4 gene polymorphism did not show significant associations with T2DMTB risk. No statistically significant differences in genotype distributions were observed between T2DMTB patients and patients with T2DM when studied using the recessive and dominant genetic models. How two diseases with contradictory nutritional statuses can occur in the same person is difficult to explain from environmental factors perspective alone. Future research should study the causes of T2DMTB from the perspective of genetics. PMID:27123010

  15. Genetic polymorphisms of CCL1 rs2072069 G/A and TLR2 rs3804099 T/C in pulmonary or meningeal tuberculosis patients

    PubMed Central

    Zhao, Yue; Bu, Hui; Hong, Kun; Yin, Hua; Zou, Yue-Li; Geng, Shu-Jun; Zheng, Ming-Ming; He, Jun-Ying

    2015-01-01

    CCL1, one of the members of the CC chemokine family, is an inflammatory mediator that stimulates the migration of human monocytes. CCL1 expression is induced by Mycobacterium tuberculosis and TLR ligands in macrophage. TLR2 plays critical role in host immune response against M. tuberculosis infection by regulating the macrophage activation and cytokine secretion. M. tuberculosis causes different clinical forms of tuberculosis (TB) disease. Single-nucleotide polymorphisms (SNPs) in the CCL1 gene and TLR2 gene may be associated with the development of different clinical forms of TB, depending on the different immune mechanisms. This study was to evaluate the possible association between CCL1 rs2072069 G/A or/and TLR2 rs3804099 T/C (T597C) polymorphisms and pulmonary tuberculosis (PTB) or/and tuberculous meningitis (TBM) in a sample of the Chinese adult population. A case-control study was designed to compare the allele frequency and genotype distribution between control (n=386) and TB (n=341) who had either PTB (n=230) or TBM (n=111). The genotype typing was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. TLR2 variant genotype 597CC was associated with susceptibility to PTB rather than to TBM. In the male PTB subgroup, 597CC genotype was identified in a higher rate, compared with male control subgroup. This study demonstrates that T597C polymorphism of TLR2 is a risk factor for susceptibility to PTB rather than to TBM in a sample of Chinese adult population. Patient gender may affect the outcome of M. tuberculosis infection. TLR2 gene may influence the development of PTB and TBM by different immune mechanisms. PMID:26722451

  16. Socio-Demographic Predictors and Distribution of Pulmonary Tuberculosis (TB) in Xinjiang, China: A Spatial Analysis

    PubMed Central

    Wubuli, Atikaimu; Xue, Feng; Jiang, Daobin; Yao, Xuemei; Upur, Halmurat; Wushouer, Qimanguli

    2015-01-01

    Objectives Xinjiang is one of the high TB burden provinces of China. A spatial analysis was conducted using geographical information system (GIS) technology to improve the understanding of geographic variation of the pulmonary TB occurrence in Xinjiang, its predictors, and to search for targeted interventions. Methods Numbers of reported pulmonary TB cases were collected at county/district level from TB surveillance system database. Population data were extracted from Xinjiang Statistical Yearbook (2006~2014). Spatial autocorrelation (or dependency) was assessed using global Moran’s I statistic. Anselin’s local Moran’s I and local Getis-Ord statistics were used to detect local spatial clusters. Ordinary least squares (OLS) regression, spatial lag model (SLM) and geographically-weighted regression (GWR) models were used to explore the socio-demographic predictors of pulmonary TB incidence from global and local perspectives. SPSS17.0, ArcGIS10.2.2, and GeoDA software were used for data analysis. Results Incidence of sputum smear positive (SS+) TB and new SS+TB showed a declining trend from 2005 to 2013. Pulmonary TB incidence showed a declining trend from 2005 to 2010 and a rising trend since 2011 mainly caused by the rising trend of sputum smear negative (SS-) TB incidence (p<0.0001). Spatial autocorrelation analysis showed the presence of positive spatial autocorrelation for pulmonary TB incidence, SS+TB incidence and SS-TB incidence from 2005 to 2013 (P <0.0001). The Anselin’s Local Moran’s I identified the “hotspots” which were consistently located in the southwest regions composed of 20 to 28 districts, and the “coldspots” which were consistently located in the north central regions consisting of 21 to 27 districts. Analysis with the Getis-Ord Gi* statistic expanded the scope of “hotspots” and “coldspots” with different intensity; 30 county/districts clustered as “hotspots”, while 47 county/districts clustered as

  17. TLR1 Variant H305L Associated with Protection from Pulmonary Tuberculosis

    PubMed Central

    Meyer, Christian G.; Reiling, Norbert; Ehmen, Christa; Ruge, Gerd; Owusu-Dabo, Ellis; Horstmann, Rolf D.; Thye, Thorsten

    2016-01-01

    Toll like receptors (TLR) are key elements of the innate immune response and involved in the recognition of pathogens. To test common and rare TLR variants involved in susceptibility or resistance to infection with Mycobacterium tuberculosis we screened the exons of the genes encoding TLR 1, 2, 4, and the adaptor molecule TIRAP in more than 4500 tuberculosis (TB) cases and controls from Ghana. The analysis yielded 109 variants with possible functional impact, including 101 non-synonymous variants, three stop-variants, and five indels. Association analyses yielded a significant result for the TLR1 variant rs3923647, conferring strong protection against TB (Odds ratio [OR] 0.21, CI confidence interval [CI] 0.05–0.6, Pnominal 1 x 10−3) when applying a recessive model of inheritance. Replication analyses with an additional 3370 Ghanaian cases and control samples, and with data from a recent TB study of 533 African-Americans confirmed the protective effect and resulted in a combined OR of 0.19, with a nominal P value of 2.2 x 10−5, and a corrected P value of 4.1 x 10−4. The SNP is located near the binding pocket of TLR1 and causes an amino acid exchange from histidine to leucine at position 305. The observed effect may, therefore, be attributable to structural changes in the recognition site of the TLR1 molecule, allowing to bind those mycobacterial ligands which preferentially may induce a protective immune response. This is supported by the analysis of BCG-stimulated peripheral blood mononuclear cells, showing increased induction of the proinflammatory cytokine IFN-γ in carriers of the mutant TLR1 rs3923647 TT genotype, compared to the IFN-γ levels of individuals with the AT and AA genotypes. PMID:27214039

  18. Formulation and Characterization of Pyrazinamide Polymeric Nanoparticles for Pulmonary Tuberculosis: Efficiency for Alveolar Macrophage Targeting

    PubMed Central

    Varma, J. N. Ravi; Kumar, T. Santosh; Prasanthi, B.; Ratna, J. Vijaya

    2015-01-01

    Pyrazinamide, a highly specific agent against Mycobacterium tuberculosis is used as first-line drug to treat tuberculosis. The current work aims to formulate polymeric nanoparticles based drug delivery system to sustain the release profile and reduce the dosing frequency of pyrazinamide. Further aim was to target the macrophages within body fluid. These polymeric nanoparticles were prepared by simultaneous double-emulsion (W/O/W) solvent evaporation/diffusion technique. The prepared dispersions were characterized for various biopharmaceutical parameters such as particle size, zeta potential, polydispersity index, drug loading capacity, entrapment efficiency and targeting to alveolar macrophages. The formulated polymeric nanoparticles were in the particle size range of 45.51 to 300.4 nm with a maximum drug entrapment efficiency of 80.9%. The stability study of optimized batch conducted at 40±2°/75±5% relative humidity showed no significant changes up to 90 days. X-Ray Diffraction spectrum exhibits the transformation of crystalline form of drug to amorphous in the formulation. Scanning Electron Microscope image showed nanoparticles spherical in shape with smooth surface. In vitro release profiles were biphasic in nature with burst release followed by controlled release over a period of 24 h obeying diffusion mechanism. In vivo and ex vivo studies results of the study show significant uptake of the nanoparticles by alveolar macrophages through fluorescent micrograph. Polymeric nanoparticles formulation of pyrazinamide could encompass significant uptake by alveolar macrophages, the high first-pass metabolism, sustain the release of drug leading to reduction in dose, toxicity and improvement of patient compliance. PMID:26180270

  19. Health Seeking Behaviour and Associated Factors among Pulmonary Tuberculosis Suspects in Lay Armachiho District, Northwest Ethiopia: A Community-Based Study

    PubMed Central

    Dachew, Berihun Assefa; Kassa Woreta, Hiwot; Mekonnen Kelkay, Mengistu; Ashenafie, Tesfaye Demeke

    2016-01-01

    Studies in the northern part of Ethiopia showed high prevalence of undiagnosed cluster of tuberculosis cases within the community which demanded an investigation of the health care seeking behaviour of tuberculosis suspects. A community-based cross-sectional study was conducted in Lay Armachiho district, Northwest Ethiopia. Individuals who had cough for at least two weeks and aged greater than or equal to 15 years were included in the study. Data were collected by interview using pretested and structured questionnaire. Logistic regression was computed and adjusted odds ratio with 95% confidence interval was calculated. Out of the total population surveyed (29, 735), 663 (2.2%) individuals were found to be pulmonary tuberculosis suspects. Majority of the suspects reported that they had visited a modern health care facility. Those aged 15 to 34 and aged 35–54 had secondary educational level and above; those who were civil servants, those who were farmers, those who had previous history of tuberculosis treatment, and those who perceived that they were sick were more likely to visit a modern health care facility. The proportion of respondents who had taken traditional measures was found to be higher than some other districts. Improving the socioeconomic status of the community is recommended. PMID:27022483

  20. Determinants of consultation, diagnosis and treatment delays among new smear-positive pulmonary tuberculosis patients in Morocco: a cross-sectional study.

    PubMed

    Akrim, M; Bennani, K; Essolbi, A; Sghiar, M; Likos, A; Benmamoun, A; Menzhi, O El; Maaroufi, A

    2014-12-17

    We conducted a cross-sectional survey in 2012 in 12 selected provinces and prefectures in Morocco to determine consultation delay (patient delay), diagnosis delay and treatment delay (health system delays), and factors relating to these delays. The sample included 250 eligible and consenting newly diagnosed smearpositive pulmonary tuberculosis patients who were interviewed at the time of their registration within Diagnosis of Tuberculosis and Respiratory Diseases Reference Centers (CDTMR) or Integrated Health Centers (CSI) using a pretested and structured questionnaire. The median total delay was 46 days [inter-quartile interval (IQI) = 29-84 days]. Patient delay (median = 20; IQI = 8-47 days) was higher than health system delay (median=15; IIQ = 7-35 days). Being illiterate, thinking symptoms will disappear by themselves; having financial constraints and feeling fear of diagnosis or social isolation were associated with patient delay. Consulting first in the private sector or having 3 or more consultations before diagnosis was associated with health system delay.

  1. Influence of pathological progression on the balance between cellular and humoral immune responses in bovine tuberculosis

    PubMed Central

    Welsh, Michael D; Cunningham, Rodat T; Corbett, David M; Girvin, R Martyn; McNair, James; Skuce, Robin A; Bryson, David G; Pollock, John M

    2005-01-01

    Studies of tuberculosis have suggested a shift in dominance from a T helper type 1 (Th1) towards a Th2 immune response that is associated with suppressed cell-mediated immune (CMI) responses and increased humoral responses as the disease progresses. In this study a natural host disease model was used to investigate the balance of the evolving immune response towards Mycobacterium bovis infection in cattle with respect to pathogenesis. Cytokine analysis of CD4 T-cell clones derived from M. bovis-infected animals gave some indication that there was a possible relationship between enhanced pathogenesis and an increased ratio of Th0 [interleukin-4-positive/interferon-γ-positive (IL-4+/IFN-γ+)] clones to Th1 (IFN-γ+) clones. All animals developed strong antimycobacterial CMI responses, but depressed cellular responses were evident as the disease progressed, with the IFN-γ test failing to give consistently positive results in the latter stages. Furthermore, a stronger Th0 immune bias, depressed in vitro CMI responses, elevated levels of IL-10 expression and enhanced humoral responses were also associated with increased pathology. In minimal disease, however, a strong Th1 immune bias was maintained and an anti-M. bovis humoral response failed to develop. It was also seen that the level of the anti-M. bovis immunoglobulin G1 (IgG1) isotype antibody responses correlated with the pathology scores, whereas CMI responses did not have as strong a relationship with the development of pathology. Therefore, the development and maintenance of a Th1 IFN-γ response is associated with a greater control of M. bovis infection. Animals progressing from a Th1-biased to a Th0-biased immune response developed more extensive pathology and performed less well in CMI-based diagnostic tests but developed strong IgG1 humoral responses. PMID:15606800

  2. Rapid and effective diagnosis of pulmonary tuberculosis with novel and sensitive loop-mediated isothermal amplification (LAMP) assay in clinical samples: a meta-analysis.

    PubMed

    Yuan, Le-yong; Li, Yan; Wang, Ming; Ke, Zun-qiong; Xu, Wan-zhou

    2014-02-01

    In recent years, Loop-mediated isothermal amplification (LAMP) assay has been introduced for the diagnosis of pulmonary tuberculosis (TB). We performed the meta-analysis to establish the overall accuracy of LAMP assay for diagnosing pulmonary TB. Based on comprehensive searches of the pubmed, embase and cochrane databases, we identified outcome datas from all articles estimating diagnostic accuracy with LAMP assay until 1 October 2012. A summary estimation for sensitivity, specificity, diagnostic odds ratios (DOR) and the area under the summary ROC curve (AUC) was calculated by using the bivariate random-effects approach. The meta-analysis included 10 studies (1920 suspected specimens). The summary estimate was 80.0% (95%CI, 78.0%-83.0%) for sensitivity, 96.0% (95%CI, 95.0%-97.0%) for specificity and 119.85/0.9633 for DOR/AUC in pulmonary TB. The findings in subgroup analysis were as follows: the accuracy of LAMP assay is higher in high quality level studies than moderate and low quality level studies. The pooled sensitivity for the diagnosis of pulmonary TB was 90.0% (95%CI, 86.0-93.0%) and 75.0% (95%CI, 71.0-78.0%) for high quality level studies and moderate combined low quality level studies, respectively, while the specificity was 99.0% (95%CI, 98.0-100.0%) and 91.0% (95%CI, 88.0-94.0%). Pulmonary TB can be rapidly and accurately diagnosed with LAMP assay.

  3. Multidrug-Resistant Tuberculosis in Patients with Chronic Obstructive Pulmonary Disease in China

    PubMed Central

    Zhao, Jiang-nan; Zhang, Xian-xin; He, Xiao-chun; Yang, Guo-ru; Zhang, Xiao-qi; Xin, Wen-gen; Li, Huai-chen

    2015-01-01

    Background Relatively little is known about the specific relationship and impact from chronic obstructive pulmonary disease (COPD) on multidrug-resistant tuberculsosis (MDR-TB). Methods We conducted a retrospective study included patients aged ≥40 years with a confirmed pulmonary TB at three tertiary hospitals (Shandong, China) between January 2011 and October 2014. Univariable and multivariable analyses were performed to identify the relationship of MDR-TB and COPD. Results A total of 2164 patients aged ≥ 40 years with available results of drug susceptibility test (DST) and medical records were screened for this study: 268 patients with discharge diagnosis of COPD and 1896 patients without COPD. Overall, 14.2% of patients with COPD and 8.5% patients without COPD were MDR-TB. The rate of MDR-TB were significantly higher in patients with COPD (P<0.05). Migrant (odds ratios (OR) 1.32, 95% confidence interval (CI) 1.02–1.72), previous anti-TB treatment (OR 4.58, 95% CI 1.69–12.42), cavity (OR 2.33, 95% CI 1.14–4.75), and GOLD stage (OR 1.86, 95% CI 1.01–2.93) were the independent predictors for MDR-TB among patients with COPD. Conclusions MDR-TB occurs more frequently in patients with underlying COPD, especially those with being migrant, previous anti-TB therapy, cavity and severe airway obstruction. PMID:26284920

  4. Perceptions of Research Bronchoscopy in Malawian Adults with Pulmonary Tuberculosis: A Cross-Sectional Study

    PubMed Central

    Lora, Wezzie; Khoo, Saye H.; Sloan, Derek J.; Mwandumba, Henry C.; Desmond, Nicola; Davies, Geraint R.

    2016-01-01

    Bronchoscopy is an established research tool in Malawi, enabling collection of pulmonary samples for immunological, pharmacological, and microbiological studies. It is, however, an invasive clinical procedure that offers no direct benefit to volunteering participants when used in a research capacity alone, and thus informed consent is essential. This study aimed to explore TB patients’ understanding of research bronchoscopy, what would motivate them to participate in research bronchoscopy, and their concerns, in order to inform consenting processes for future clinical studies. We used a qualitative research design. Two focus group discussions were conducted with community members and TB patients to understand their perceptions of bronchoscopy. Transcripts were coded by multiple co-authors and thematic content analysis was used to analyse main findings. We found that Malawian patients with pulmonary TB were willing to participate in a study using research bronchoscopy for health assessment and access to improved healthcare. We identified information of value to potential participants when consenting to that may lessen some of the anxieties expressed by participants. Patient and public involvement is essential to improve informed consent and institutional trust. PMID:27792765

  5. Virulence-Dependent Alterations in the Kinetics of Immune Cells during Pulmonary Infection by Mycobacterium tuberculosis

    PubMed Central

    Han, Seung Jung; Kim, HongMin; Kwon, Kee Woong; Kim, So Jeong; Eum, Seok-Yong; Cho, Sang-Nae; Shin, Sung Jae

    2015-01-01

    A better understanding of the kinetics of accumulated immune cells that are involved in pathophysiology during Mycobacterium tuberculosis (Mtb) infection may help to facilitate the development of vaccines and immunological interventions. However, the kinetics of innate and adaptive cells that are associated with pathogenesis during Mtb infection and their relationship to Mtb virulence are not clearly understood. In this study, we used a mouse model to compare the bacterial burden, inflammation and kinetics of immune cells during aerogenic infection in the lung between laboratory-adapted strains (Mtb H37Rv and H37Ra) and Mtb K strain, a hyper-virulent W-Beijing lineage strain. The Mtb K strain multiplied more than 10- and 3.54-fold more rapidly than H37Ra and H37Rv, respectively, during the early stage of infection (at 28 days post-infection) and resulted in exacerbated lung pathology at 56 to 112 days post-infection. Similar numbers of innate immune cells had infiltrated, regardless of the strain, by 14 days post-infection. High, time-dependent frequencies of F4/80-CD11c+CD11b-Siglec-H+PDCA-1+ plasmacytoid DCs and CD11c-CD11b+Gr-1int cells were observed in the lungs of mice that were infected with the Mtb K strain. Regarding adaptive immunity, Th1 and Th17 T cells that express T-bet and RORγt, respectively, significantly increased in the lungs that were infected with the laboratory-adapted strains, and the population of CD4+CD25+Foxp3+ regulatory T cells was remarkably increased at 112 days post-infection in the lungs of mice that were infected with the K strain. Collectively, our findings indicate that the highly virulent Mtb K strain may trigger the accumulation of pDCs and Gr1intCD11b+ cells with the concomitant down-regulation of the Th1 response and the maintenance of an up-regulated Th2 response without inducing a Th17 response during chronic infection. These results will help to determine which immune system components must be considered for the development

  6. Protective effect of Bacillus Calmette-Guerin (BCG) vaccination in children with extra-pulmonary tuberculosis, but not the pulmonary disease. A case-control study in Rosario, Argentina.

    PubMed

    Bonifachich, Elena; Chort, Monica; Astigarraga, Ana; Diaz, Nora; Brunet, Beatriz; Pezzotto, Stella Maris; Bottasso, Oscar

    2006-04-01

    A hospital-based case-control study was carried out at the Vilela Children's Hospital in Rosario, Argentina, to measure the protection conferred by BCG vaccination against tuberculosis (TB). The study included 148 newly diagnosed cases of TB (75 males and 73 females, mean age 3.34+/-2.97 years, S.D.), 134 of them with pulmonary TB and 14 cases with extra-pulmonary disease. Controls (425 males and 357 females, 3.39+/-2.98 years) were selected randomly among children who attended to the Hospital showing, neither respiratory diseases nor any other infectious illnesses. Information on BCG vaccination history was assessed from scars or immunisation records. All participants were negative to human immunodeficiency virus and belonged to the lower and upper-lower socioeconomic status, being similar in place of residence and ethnic characteristics. Rate of vaccinated children was 92.6% of cases and 94.5% of controls (3.4 and 3.9% of them without scars, respectively). Regarding the total cases, the protective association between BCG and TB was statistically insignificant, as was for the pulmonary form. Among cases with extra-pulmonary disease, vaccine effectiveness attained significance [79% (95% CI=26-94)], no matter their age, sex or nutritional status. BCG vaccination exerted a beneficial role in extra-pulmonary TB, even in children not seriously undernourished.

  7. Tuberculosis and Diabetes

    MedlinePlus

    TUBERCULOSIS www.who.int/tb & DIABETES THE DUAL EPIDEMIC OF TB AND DIABETES DEADLY LINKAGES  People with ... higher risk of progressing from latent to active tuberculosis.  Diabetes triples a person’s risk of developing TB. ...

  8. The microbiome at the pulmonary alveolar niche and its role in Mycobacterium tuberculosis infection.

    PubMed

    Adami, Alexander J; Cervantes, Jorge L

    2015-12-01

    Advances in next generation sequencing (NGS) technology have provided the tools to comprehensively and accurately characterize the microbial community in the respiratory tract in health and disease. The presence of commensal and pathogenic bacteria has been found to have important effects on the lung immune system. Until relatively recently, the lung has received less attention compared to other body sites in terms of microbiome characterization, and its study carries special technological difficulties related to obtaining reliable samples as compared to other body niches. Additionally, the complexity of the alveolar immune system, and its interactions with the lung microbiome, are only just beginning to be understood. Amidst this complexity sits Mycobacterium tuberculosis (Mtb), one of humanity's oldest nemeses and a significant public health concern, with millions of individuals infected with Mtb worldwide. The intricate interactions between Mtb, the lung microbiome, and the alveolar immune system are beginning to be understood, and it is increasingly apparent that improved treatment of Mtb will only come through deep understanding of the interplay between these three forces. In this review, we summarize our current understanding of the lung microbiome, alveolar immunity, and the interaction of each with Mtb.

  9. Determinants of Pulmonary Tuberculosis among Inmates at Mangaung Maximum Correctional Facility in Bloemfontein, South Africa

    PubMed Central

    Nyasulu, Peter; Mogoere, Serame; Umanah, Teye; Setswe, Geoffrey

    2015-01-01

    Introduction. Correctional facilities house large number of inmates who are at high risk of developing tuberculosis (TB); however factors associated with TB among inmates at Mangaung Correctional Centre have not been studied. Study Population and Methods. We undertook a case control study and reviewed a total of 1140 medical records of inmates treated for TB between 2009 and 2010. Cases were selected randomly from the medical records of inmates who were treated. Data collected were analysed using STATA version 12.0 and determinants of TB were evaluated using multiple logistic regression analyses. Factors with P < 0.05 were considered significant. Results. Prevalence of TB was 8.8% and 52% of inmates with TB were aged 31–40 years; 58% of the TB cases were HIV positive and 34% of them had CD4 cell count 350 cells/mm3. Factors associated with TB among inmates were HIV coinfection (OR: 4.2; 95% CI: 2.64–7.00); previous history of TB disease (OR: 3.58; 95% CI: 2.25–5.70); and smoking (OR: 2.1; 95% CI: 1.16–3.81). Conclusion. Interventions to improve TB detection such as regular screening of inmates with such factors need to be reinforced to control transmission of TB among inmates and the community. PMID:25866677

  10. Patient and health system delay among patients with pulmonary tuberculosis in Beira city, Mozambique

    PubMed Central

    2013-01-01

    Background TB control is based on the rapid identification of cases and their effective treatment. However, many studies have shown that there are important delays in diagnosis and treatment of patients with TB. The purpose of this study was to assess the prevalence of and identify risk factors associated with patient delay and health system delay among newly diagnosed patients with pulmonary TB. Methods A cross sectional study was carried out in Beira city, Mozambique between September 2009 and February 2010. Patients in the first month of treatment were consecutively selected to this study if they had a diagnosis of pulmonary TB, had no history of previous TB treatment, and were 18 years or older and provided informed consent. Data was obtained through a questionnaire administered to the patients and from patients’ files. Results Among the 622 patients included in the study the median age was 32 years (interquartile range, 26–40) and 272 (43.7%) were females. The median total delay, patient delay and health system delay was 150 days (interquartile range, 91–240), 61 days (28–113) and 62 days (37–120), respectively. The contribution of patient delay and health system delay to total delay was similar. Farming, visiting first a traditional healer, low TB knowledge and coexistence of a chronic disease were associated with increased patient delay. More than two visits to a health facility, farming and coexistence of a chronic disease were associated with increased health system delay. Conclusions This study revealed a long total delay with a similar contribution of patient delay and health system delay. To reduce the total delay in this setting we need a combination of interventions to encourage patients to seek appropriate health care earlier and to expedite TB diagnosis within the health care system. PMID:24499197

  11. Multidrug-resistant tuberculosis around the world: what progress has been made?

    PubMed

    Falzon, Dennis; Mirzayev, Fuad; Wares, Fraser; Baena, Inés Garcia; Zignol, Matteo; Linh, Nguyen; Weyer, Karin; Jaramillo, Ernesto; Floyd, Katherine; Raviglione, Mario

    2015-01-01

    Multidrug-resistant tuberculosis (MDR-TB) (resistance to at least isoniazid and rifampicin) will influence the future of global TB control. 88% of estimated MDR-TB cases occur in middle- or high-income countries, and 60% occur in Brazil, China, India, the Russian Federation and South Africa. The World Health Organization collects country data annually to monitor the response to MDR-TB. Notification, treatment enrolment and outcome data were summarised for 30 countries, accounting for >90% of the estimated MDR-TB cases among notified TB cases worldwide. In 2012, a median of 14% (interquartile range 6-50%) of estimated MDR-TB cases were notified in the 30 countries studied. In 15 of the 30 countries, the number of patients treated for MDR-TB in 2012 (71 681) was >50% higher than in 2011. Median treatment success was 53% (interquartile range 40-70%) in the 25 countries reporting data for 30 021 MDR-TB cases who started treatment in 2010. Although progress has been noted in the expansion of MDR-TB care, urgent efforts are required in order to provide wider access to diagnosis and treatment in most countries with the highest burden of MDR-TB.

  12. Multidrug-resistant tuberculosis around the world: what progress has been made?

    PubMed

    Falzon, Dennis; Mirzayev, Fuad; Wares, Fraser; Baena, Inés Garcia; Zignol, Matteo; Linh, Nguyen; Weyer, Karin; Jaramillo, Ernesto; Floyd, Katherine; Raviglione, Mario

    2015-01-01

    Multidrug-resistant tuberculosis (MDR-TB) (resistance to at least isoniazid and rifampicin) will influence the future of global TB control. 88% of estimated MDR-TB cases occur in middle- or high-income countries, and 60% occur in Brazil, China, India, the Russian Federation and South Africa. The World Health Organization collects country data annually to monitor the response to MDR-TB. Notification, treatment enrolment and outcome data were summarised for 30 countries, accounting for >90% of the estimated MDR-TB cases among notified TB cases worldwide. In 2012, a median of 14% (interquartile range 6-50%) of estimated MDR-TB cases were notified in the 30 countries studied. In 15 of the 30 countries, the number of patients treated for MDR-TB in 2012 (71 681) was >50% higher than in 2011. Median treatment success was 53% (interquartile range 40-70%) in the 25 countries reporting data for 30 021 MDR-TB cases who started treatment in 2010. Although progress has been noted in the expansion of MDR-TB care, urgent efforts are required in order to provide wider access to diagnosis and treatment in most countries with the highest burden of MDR-TB. PMID:25261327

  13. Effects of dust storm events on weekly clinic visits related to pulmonary tuberculosis disease in Minqin, China

    NASA Astrophysics Data System (ADS)

    Wang, Yun; Wang, Ruoyu; Ming, Jing; Liu, Guangxiu; Chen, Tuo; Liu, Xinfeng; Liu, Haixia; Zhen, Yunhe; Cheng, Guodong

    2016-02-01

    Pulmonary tuberculosis (PTB) is a major public health problem in China. Minqin, a Northwest county of China, has a very high number of annual PTB clinic visits and it is also known for its severe dust storms. The epidemic usually begins in February and ends in July, while the dust storms mainly occur throughout spring and early summer, thereby suggesting that there might be a close link between the causative agent of PTB and dust storms. We investigated the general impact of dust storms on PTB over time by analyzing the variation in weekly clinic visits in Minqin during 2005-2012. We used the Mann-Whitney-Pettitt test and a regression model to determine the seasonal periodicity of PTB and dust storms in a time series, as well as assessing the relationships between meteorological variables and weekly PTB clinic visits. After comparing the number of weekly PTB cases in Gansu province with dust storm events, we detected a clear link between the population dynamics of PTB and climate events, i.e., the onset of epidemics and dust storms (defined by an atmospheric index) occurred in almost the same mean week. Thus, particulate matter might be the cause of PTB outbreaks on dust storm days. It is highly likely that the significant decline in annual clinic visits was closely associated with improvements in the local environment, which prevented desertification and decreased the frequency of dust storm events. To the best of our knowledge, this is the first population-based study to provide clear evidence that a PTB epidemic was affected by dust storms in China, which may give insights into the association between this environmental problem and the evolution of epidemic disease.

  14. Durations and Delays in Care Seeking, Diagnosis and Treatment Initiation in Uncomplicated Pulmonary Tuberculosis Patients in Mumbai, India

    PubMed Central

    Mistry, Nerges; Rangan, Sheela; Dholakia, Yatin; Lobo, Eunice; Shah, Shimoni; Patil, Akshaya

    2016-01-01

    Background Timely diagnosis and treatment initiation are critical to reduce the chain of transmission of Tuberculosis (TB) in places like Mumbai, where almost 60% of the inhabitants reside in overcrowded slums. This study documents the pathway from the onset of symptoms suggestive of TB to initiation of TB treatment and examines factors responsible for delay among uncomplicated pulmonary TB patients in Mumbai. Methods A population-based retrospective survey was conducted in the slums of 15 high TB burden administrative wards to identify 153 self-reported TB patients. Subsequently in-depth interviews of 76 consenting patients that fit the inclusion criteria were undertaken using an open-ended interview schedule. Mean total, first care seeking, diagnosis and treatment initiation duration and delays were computed for new and retreatment patients. Patients showing defined delays were divided into outliers and non-outliers for all three delays using the median values. Results The mean duration for the total pathway was 65 days with 29% of patients being outliers. Importantly the mean duration of first care seeking was similar in new (24 days) and retreatment patients (25 days). Diagnostic duration contributed to 55% of the total pathway largely in new patients. Treatment initiation was noted to be the least among the three durations with mean duration in retreatment patients twice that of new patients. Significantly more female patients experienced diagnostic delay. Major shift of patients from the private to public sector and non-allopaths to allopaths was observed, particularly for treatment initiation. Conclusion Achieving positive behavioural changes in providers (especially non-allopaths) and patients needs to be considered in TB control strategies. Specific attention is required in counselling of TB patients so that timely care seeking is effected at the time of relapse. Prioritizing improvement of environmental health in vulnerable locations and provision of

  15. Co-endemicity of Pulmonary Tuberculosis and Intestinal Helminth Infection in the People’s Republic of China

    PubMed Central

    Li, Xin-Xu; Ren, Zhou-Peng; Wang, Li-Xia; Zhang, Hui; Jiang, Shi-Wen; Chen, Jia-Xu; Wang, Jin-Feng; Zhou, Xiao-Nong

    2016-01-01

    Both pulmonary tuberculosis (PTB) and intestinal helminth infection (IHI) affect millions of individuals every year in China. However, the national-scale estimation of prevalence predictors and prevalence maps for these diseases, as well as co-endemic relative risk (RR) maps of both diseases’ prevalence are not well developed. There are co-endemic, high prevalence areas of both diseases, whose delimitation is essential for devising effective control strategies. Bayesian geostatistical logistic regression models including socio-economic, climatic, geographical and environmental predictors were fitted separately for active PTB and IHI based on data from the national surveys for PTB and major human parasitic diseases that were completed in 2010 and 2004, respectively. Prevalence maps and co-endemic RR maps were constructed for both diseases by means of Bayesian Kriging model and Bayesian shared component model capable of appraising the fraction of variance of spatial RRs shared by both diseases, and those specific for each one, under an assumption that there are unobserved covariates common to both diseases. Our results indicate that gross domestic product (GDP) per capita had a negative association, while rural regions, the arid and polar zones and elevation had positive association with active PTB prevalence; for the IHI prevalence, GDP per capita and distance to water bodies had a negative association, the equatorial and warm zones and the normalized difference vegetation index had a positive association. Moderate to high prevalence of active PTB and low prevalence of IHI were predicted in western regions, low to moderate prevalence of active PTB and low prevalence of IHI were predicted in north-central regions and the southeast coastal regions, and moderate to high prevalence of active PTB and high prevalence of IHI were predicted in the south-western regions. Thus, co-endemic areas of active PTB and IHI were located in the south-western regions of China, which

  16. Patient and Healthcare System Delays in the Start of Pulmonary Tuberculosis Treatment Among Tribal Patients Registered Under DOTS, Odisha

    PubMed Central

    Venkatesh, S.

    2016-01-01

    Introduction Tuberculosis (TB) is a highly infectious disease which continues to be an important public health problem worldwide. Aim This study puts an effort to determine patient and health system delay in diagnosis and treatment and association to specific types of delay among tribals in Mayurbhanj district, Odisha. Materials and Methods A total of 261 TB patients reporting to 4 TB Units of Mayurbhanj were interviewed using pre-tested structured questionnaire. Extra-pulmonary TB patients and death cases were excluded. Data entry and analysis was carried out in Epi-info 3.32 version. Chi-square test was used to test the association between dependant variable (patient and health system delays) with different independent variables (age, sex, reasons for delay etc.). Results Median patient, health system and total delay were 24, 3 and 24 days respectively. Risk factors that were significantly associated with patient delay were education (95% CI= 1.01-1.11, p=0.015), cost of treatment/transport (95% CI=0.87-1.01, p=0.020), distance (95% CI=1.00-1.29, p=0.002) and lack of awareness about TB (95% CI=1.01-1.34, p=0.001). Health system delay risk factors were distance (95% CI=0.32-0.96, p=0.043), delay due to administrative verification (95% CI=1.18-57.97, p= 0.005) and delay due to traditional healers/ private practitioners (95% CI=1.61-15.45, p=0.0008). Conclusion This study revealed longer patient delay compared to health system delay. Therefore, public awareness in tribal dialect about chest symptoms and availability of free diagnostics services should be increased along with involvement of traditional healers. PMID:27790474

  17. Asthma–Chronic Obstructive Pulmonary Diseases Overlap Syndrome Increases the Risk of Incident Tuberculosis: A National Cohort Study

    PubMed Central

    Yeh, Jun-Jun; Wang, Yu-Chiao; Kao, Chia-Hung

    2016-01-01

    Purpose The association between asthma–chronic obstructive pulmonary diseases (COPD) overlap syndrome (ACOS) and tuberculosis (TB) has yet to be studied. Methods The newly diagnosed TB patients (age > 20 y) treated from January 2000 to December 2008 were included (ACOS cohort, n = 10 751; non-ACOS cohort, n = 42 966). The non-ACOS cohort involved patients with confirmed absence of ACOS. We calculated incidence rate ratios (IRRs) for TB in the ACOS and non-ACOS cohorts by using poisson regression analysis. Cox proportional hazards regression models were used to determine the adjusted HR (aHR) for TB in the ACOS cohort compared with the non-ACOS cohort. Results The aHR for TB was 2.41 (95% confidence interval [CI], 2.19–2.66) in the ACOS cohort. The TB risk was significantly higher in the ACOS cohort than in the non-ACOS cohort when stratified by age, sex, comorbidities, and atopy. Within the ACOS cohort, the aHR was higher among patients receiving SABAs+SAMAs, LABAs+LAMAs, and ICSs (aHR [95% CI]: 3.06 [2.75–3.41], 3.68 [2.93–4.61], and 2.79 [1.25–6.22], respectively; all P < .05). Furthermore, patients with more than 15 outpatient visits and hospitalizations per year demonstrated the highest aHR (8.09; 95% CI, 6.85–9.56). Conclusions ACOS cohort potentially develop incident TB, regardless of the age,sex, comorbidities and atopy; even without receiving the inhalers.This risk is higher, especially in the ACOS cohort have a high frequency of medical services or receiving the inhalers such as SABAs+SAMAs, LABAs+LAMAs and ICSs. PMID:27448309

  18. The application of anti-ESAT-6 monoclonal antibody fluorescent probe in ex vivo near-infrared fluorescence imaging in mice with pulmonary tuberculosis.

    PubMed

    Feng, Feng; Zhang, Haoling; Zhu, Zhaoqin; Li, Cong; Shi, Yuxin; Zhang, Zhiyong

    2014-09-01

    Here, we aimed to assess the feasibility of anti-ESAT-6 monoclonal antibody (mAb) coupling with IR783 and rhodamine fluorescent probe in the detection of ESAT-6 expression in tuberculosis tissue of mice using near-infrared fluorescence imaging. IR783 and rhodamine were conjugated to the anti-ESAT-6 mAb or IgG. Mice in the experimental group were injected with fluorescence-labeled mAb probe, and mice in the control group were injected with fluorescence-labeled non-specific IgG antibody. Twenty-four hours later, the lung tissue of mice was examined using ex vivo near-infrared fluorescence imaging. In addition, the contrast-to-noise ratio (CNR) was calculated by measuring the signal intensities of the pulmonary lesions, normal lung tissue and background noise. The frozen lung tissue section was examined under fluorescence microscopy and compared with hemoxylin and eosin (HE) staining. The ex vivo near-infrared fluorescence imaging showed that the fluorescence signal in the lung tuberculosis lesions in the experimental group was significantly enhanced, whereas there was only a weak fluorescence signal or even no fluorescence signal in the control group. CNR values were 64.40 ± 7.02 (n = 6) and 8.75 ± 3.87 (n = 6), respectively (t = 17.01, p < 0.001). The fluorescence accumulation distribution detected under fluorescence microscopy was consistent with HE staining of the tuberculosis region. In conclusion, anti-ESAT-6 mAb fluorescent probe could target and be applied in specific ex vivo imaging of mice tuberculosis, and may be of further use in tuberculosis in living mice.

  19. Common types of tuberculosis and co-infection with HIV at private health institutions in Ethiopia: a cross sectional study

    PubMed Central

    2014-01-01

    Background Tuberculosis is a global emergency predominantly affecting developing countries. HIV has been the single most important reason for acquisition of tuberculosis for many patients. Conversely, tuberculosis can result in rapid progression of HIV disease. Ethiopia is a country affected seriously by HIV and tuberculosis. The main aim of this study is assessment of the types of tuberculosis and the extent of HIV infection among tuberculosis patients visiting private health institutions in Amhara region of Ethiopia. Methods The study used a cross sectional method with data collected using well structured pretested questionnaires containing socio-demographic and clinical variables including HIV serostatus. The setting is tuberculosis treatment sites situated at 15 private health institutions in Amhara region. Results A total of 1153 TB patients were included. The proportions of smear positive pulmonary TB, smear negative pulmonary TB, isolated extrapulmonary TB and disseminated TB cases were found to be 29.6%, 22.2%, 43.9% and 2.9%, respectively. TB lymphadenitis accounted for about 61% of the extrapulmonary cases followed by TB pleurisy (10.6%). Seventy percent of the patients had undergone HIV test, and 20% of them were HIV positive. Marital status, patient residence and type of TB are the major determinants of co-infection. Conclusion The occurrence of pulmonary tuberculosis is relatively low. Tuberculosis/HIV co-infection is also lower than other reports. PMID:24708793

  20. [Progress on pathogenesis and treatment of paraquat-induced pulmonary fibrosis].

    PubMed

    Shao, Xue; Chen, Jiang-Hua

    2014-11-01

    Paraquat (PQ) is a highly effective herbicide with contact toxicity. PQ mainly accumulates in the lungs after absorption into the blood circulation. The respiratory function failure caused by PQ-induced lung injury, especially the irreversible pulmonary fibrosis in late phase, is the leading cause of death in patients with PQ poisoning. The mechanism of PQ poisoning is still unclear. Now it is speculated that oxidative stress and inflammation injury are the main pathogenic mechanisms, and abnormal gene expression, mitochondrial damage, loss of pulmonary surfactant, cytokine network and unbalanced matrix metalloproteinases/tissue inhibitors may be also involved in the pathogenesis. In addition to reducing poison absorption and increasing its removal, the current clinical treatment is mainly composed of antioxidant and anti-immune response, but has poor therapeutic effects. Although many novel methods of treatment have been proposed, most of them are still in the experimental stage. It is a hot spot to clarify the mechanism of PQ poisoning and to seek safe and effective treatment of pulmonary fibrosis. This article reviews the research progress on pathogenesis and treatment of PQ-induced pulmonary fibrosis. PMID:25644573

  1. Screening and identification of five serum proteins as novel potential biomarkers for cured pulmonary tuberculosis

    PubMed Central

    Wang, Chong; Wei, Li-Liang; Shi, Li-Ying; Pan, Zhi-Fen; Yu, Xiao-Mei; Li, Tian-Yu; Liu, Chang-Ming; Ping, Ze-Peng; Jiang, Ting-Ting; Chen, Zhong-Liang; Mao, Lian-Gen; Li, Zhong-Jie; Li, Ji-Cheng

    2015-01-01

    Rapid and efficient methods for the determination of cured tuberculosis (TB) are lacking. A total of 85 differentially expressed serum proteins were identified by iTRAQ labeling coupled with two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) analysis (fold change >1.50 or <0.60, P < 0.05). We validated albumin (ALB), Rho GDP-dissociation inhibitor 2 (ARHGDIB), complement 3 (C3), ficolin-2 (FCN2), and apolipoprotein (a) (LPA) using the enzyme-linked immunosorbent assay (ELISA) method. Significantly increased ALB and LPA levels (P = 0.036 and P = 0.012, respectively) and significantly reduced ARHGDIB, C3, and FCN2 levels (P < 0.001, P = 0.035, and P = 0.018, respectively) were observed in cured TB patients compared with untreated TB patients. In addition, changes in ALB and FCN2 levels occurred after 2 months of treatment (P < 0.001 and P = 0.030, respectively). We established a cured TB model with 87.10% sensitivity, 79.49% specificity, and an area under the curve (AUC) of 0.876. The results indicated that ALB, ARHGDIB, C3, FCN2, and LPA levels might serve as potential biomarkers for cured TB. Our study provides experimental data for establishing objective indicators of cured TB and also proposes potential markers for evaluating the efficacy of anti-TB drugs. PMID:26499913

  2. Attitudes, knowledge and practices of healthcare workers regarding occupational exposure of pulmonary tuberculosis

    PubMed Central

    Bhebhe, Lesley T.; Van Rooyen, Cornel

    2014-01-01

    Abstract Background Healthcare-associated tuberculosis (TB) has become a major occupational hazard for healthcare workers (HCWs). HCWs are inevitably exposed to TB, due to frequent interaction with patients with undiagnosed and potentially contagious TB. Whenever there is a possibility of exposure, implementation of infection prevention and control (IPC) practices is critical. Objective Following a high incidence of TB among HCWs at Maluti Adventist Hospital in Lesotho, a study was carried out to assess the knowledge, attitudes and practices of HCWs regarding healthcare-associated TB infection and infection controls. Methods This was a cross-sectional study performed in June 2011; it involved HCWs at Maluti Adventist Hospital who were involved with patients and/or sputum. Stratified sampling of 140 HCWs was performed, of whom, 129 (92.0%) took part. A self-administered, semi-structured questionnaire was used. Results Most respondents (89.2%) had appropriate knowledge of transmission, diagnosis and prevention of TB; however, only 22.0% of the respondents knew the appropriate method of sputum collection. All of the respondents (100.0%) were motivated and willing to implement IPC measures. A significant proportion of participants (36.4%) reported poor infection control practices, with the majority of inappropriate practices being the administrative infection controls (> 80.0%). Only 38.8% of the participants reported to be using the appropriate N-95 respirator. Conclusion Poor infection control practices regarding occupational TB exposure were demonstrated, the worst being the first-line administrative infection controls. Critical knowledge gaps were identified; however, there was encouraging willingness by HCWs to adapt to recommended infection control measures. Healthcare workers are inevitably exposed to TB, due to frequent interaction with patients with undiagnosed and potentially contagious TB. Implementation of infection prevention and control practices is

  3. Looking beyond PPHN: the unmet challenge of chronic progressive pulmonary hypertension in the newborn

    PubMed Central

    2013-01-01

    Abstract Infants with forms of pulmonary hypertension (PH) that persist or develop beyond the first week of life are an understudied group of patients with up to 40%–60% mortality. The clinical management of the progressive PH that develops in these infants is challenging because of the nonspecific signs and symptoms of clinical presentation, the limited diagnostic sensitivity of standard echocardiographic techniques, and the lack of proven therapies. The signaling mechanisms that underlie the structural and functional abnormalities in the pulmonary circulation of these infants are not yet clear. The ability to improve outcomes for these patients awaits technological advances to improve diagnostic capabilities and therapeutic discoveries made in basic science laboratories that can be tested in randomized clinical trials. PMID:24618533

  4. Delays in diagnosis and treatment of pulmonary tuberculosis in India: a systematic review

    PubMed Central

    Satyanarayana, Srinath; Subbaraman, Ramnath; Pai, Madhukar

    2014-01-01

    SUMMARY Objective To systematically review Indian literature on delays in TB diagnosis and treatment. Methods We searched multiple sources for studies on delays in pulmonary TB and chest symptomatic patients. Studies were included if numeric data on any delay were reported. Patient delay was defined as the time interval between onset of symptoms and the patient’s first contact with a healthcare provider. Diagnostic delay was defined as the time interval between the first consultation with a healthcare provider and diagnosis. Treatment delay was defined as the time interval between diagnosis and initiation of anti-TB treatment. Total delay was defined as time interval from the onset of symptoms until treatment initiation. Results Among 541 potential citations identified, 23 studies met our inclusion criteria. Included studies used a variety of definitions for onset of symptoms and delays. Median (IQR) estimates of patient, diagnostic and treatment delay were 18.4 (14.3-27.0), 31.0 (24.5-35.4) and 2.5 days (1.9-3.6), respectively, for TB and chest symptomatic patients combined. The median total delay was 55.3 days (46.5-61.5). About 48% of all patients first consulted private providers and 2.7 healthcare providers, on average, were consulted before diagnosis. Number and type of provider first consulted were the most important risk factors for delay. Conclusions These findings underscore the need to develop novel strategies for reducing patient and diagnostic delays and engaging first-contact healthcare providers. PMID:24670558

  5. Trends in mortality from pulmonary tuberculosis before and after antibiotics in the Portuguese sanatorium Carlos Vasconcelos Porto (1918-1991): Archival evidence and its paleopathological relevance.

    PubMed

    Matos, Vítor M J; Santos, Ana Luísa

    2015-06-01

    The comparative study of patients' profiles and outcomes from pulmonary tuberculosis (TB), before and after the discovery of antibiotic therapy, using sanatoria archives is an unexplored approach in paleopathology. Although higher mortality rates are assumed before chemotherapy, scarce information exists regarding the disease's duration in institutionalized patients and to what extent tuberculous sufferers lived enough to develop skeletal lesions. To fill this gap, 315 clinical files from the former male Sanatorium Carlos Vasconcelos Porto, located in São Brás de Alportel, Portugal, were studied. Two periods of hospitalization were considered: 1931-1944 (n = 128, Group 1) and 1955-1961 (n = 187, Group 2). The average duration of hospitalization (350.3 days for Group 1 and 371.8 for Group 2) and the crude mortality (18.2% and 11.2%, respectively in Groups 1 and 2) did not differ significantly between groups. However, Cox's regression revealed significant differences between survival curves, after adjusting for age at admission (14-74 years old), with pre-chemotherapy patients presenting a higher risk of dying during hospitalization (p = 0.037, hazard ratio = 1.94, IC95% = 1.03-3.63). This study also confirms poorer prognoses for pulmonary tuberculosis sufferers hospitalized in sanatoria before antibiotics and reveals that a significant number of patients survived enough time to develop bone lesions.

  6. Active Case Finding of Pulmonary Tuberculosis through Screening of Respiratory Symptomatics Using Sputum Microscopy: Is It Time to Change the Paradigm?

    PubMed Central

    del Portillo-Mustieles, Eva Carolina; Laniado-Laborín, Rafael

    2013-01-01

    Background. One of the main strategies for the early detection of pulmonary tuberculosis (PTB) is through the screening of individuals with symptoms compatible with PTB. Although this is programmatic strategy for active case finding, its yield is not well known. Objective. To determine the yield of pulmonary tuberculosis active case finding through the screening of respiratory symptomatic (RS) patients at a general hospital. Methods. RS patients were defined as subjects complaining of cough and/or sputum for a period of 2 or more weeks. Outpatients and their companions were approached while they waited in the outpatient care areas of the hospital to detect RS. Two samples from different days or 2 samples taken 2 hours apart on the same day were collected. Results. 122 RS patients were identified. Fifty-seven patients (46.7%) had at least one sputum sample analyzed. Three patients presented a positive smear and 2 were culture positive; neither had upper airway symptoms. None of the patients with productive cough and upper airway symptoms had a positive smear (P = 0.07). Only 19 (33.3%) returned to the laboratory to retrieve their results. Conclusion. Current strategy to screen RS patients based only on clinical data has a low compliance. Specific strategies to increase compliance (removal of barriers, incentives, etc.) should be implemented. PMID:23533747

  7. [Evaluation of the efficacy of antiparasitic drugs in the treatment of concurrent parasitic diseases in patients with HIV infection and in those with pulmonary tuberculosis].

    PubMed

    Davis, N A; Giiasov, Kh Z; Islamova, Zh I; Tuĭchiev, L N; Parpieva, N N; Belotserkovets, V G; Dzhuraeva, Z B; Syrov, V N; Faĭzullaeva, D B; Papina, E S; Baimbetov, B N; Osipova, S O

    2013-01-01

    The efficacy of albendazole (400 mg taken once), mebendazole (100 mg taken once), and metronidazole (0.5 g thrice daily for 7 days) was evaluated when treating ascariasis, enterobiosis, and blastocystosis, respectively, in patients with HIV infection and in those with pulmonary tuberculosis. Metronidazole-resistant lambliasis was treated with exdisten (5 mg four times for 10 days) in 30.4% of the patients with HIV infection and in 43.3% of those with tuberculosis. Most HIV infected patients received antiretroviral therapy (ARVT). All the tuberculosis patients took isoniazid, ethambutol, pyrazinamide, rifampicin, and streptomycin. Efficiency was monitored by triple coproscopy at an interval of 5-7 days and by additional examinations using the method of Ritchii et al. There was parasitological cure (decreased infection rate for blastocystosis) and clinical improvement as positive changes in symptoms, such as nausea, weakness, headache, weight loss, and others, in all the patients with concomitant ascariasis, enterobiosis, and lambliasis. ARVT and antituberculosis drugs were observed to be better tolerated in all cases.

  8. Transcriptional profiles discriminate patients with pulmonary tuberculosis from non-tuberculous individuals depending on the presence of non-insulin diabetes mellitus.

    PubMed

    Serrano, Carmen J; Cuevas-Córdoba, Betzaida; Macías-Segura, Noé; González-Curiel, Rosa Angélica; Martínez-Balderas, Víctor Yordani; Enciso-Moreno, Leonor; Small, Peter; Hernández-Pando, Rogelio; Enciso-Moreno, José Antonio

    2016-01-01

    Our objective was to identify transcriptional biomarkers in peripheral blood mononuclear cells (PBMC) that discriminate individuals with latent tuberculosis infection (LTBI) from those with pulmonary tuberculosis (PTB) in subjects with non-insulin-dependent diabetes mellitus (NIDDM) and in individuals without NIDDM. Using gene expression microarrays we identified differentially expressed genes from lungs of mice infected with Mycobacterium tuberculosis (Mtb) or a mutant (ΔsigH) representing a non-inflammatory model. Genes expressed in blood, with inflammatory related functions were evaluated in humans by RT-qPCR. NCF1 and ORM transcripts have the better discriminatory capacity to identify PTB subjects from LTBI and non-infected controls (NICs) independently of the presence of NIDDM. The sequential evaluation of the mRNA levels of NCF1 and ORM as multiple diagnostic tests showed 95% Sensitivity (Se) and 80% Specificity (Sp). In addition, FPR2 promises to be a good biomarker for the PTB detection in subjects with NIDDM (Se=100%; Sp=90%).

  9. An approach to the problems of diagnosing and treating adult smear-negative pulmonary tuberculosis in high-HIV-prevalence settings in sub-Saharan Africa.

    PubMed Central

    Harries, A. D.; Maher, D.; Nunn, P.

    1998-01-01

    The overlap between the populations in sub-Saharan Africa infected with human immunodeficiency virus (HIV) and Mycobacterium tuberculosis has led to an upsurge in tuberculosis cases over the last 10 years. The relative increase in the proportion of notified sputum-smear-negative pulmonary tuberculosis (PTB) cases is greater than that of sputum-smear-positive PTB cases. This is a consequence of the following: the association between decreased host immunity and reduced sputum smear positivity; the difficulty in excluding other HIV-related diseases when making the diagnosis of smear-negative PTB; and an increase in false-negative sputum smears because of overstretched resources. This article examines problems in the diagnosis and treatment of smear-negative PTB in high-HIV-prevalence areas in sub-Saharan Africa. The main issues in diagnosis include: the criteria used to diagnose smear-negative PTB; the degree to which clinicians actually follow these criteria in practice; and the problem of how to exclude other respiratory diseases that can resemble, and be misdiagnosed as, smear-negative PTB. The most important aspect of the treatment of smear-negative PTB patients is abandoning 12-month "standard" treatment regimens in favour of short-course chemotherapy. Operational research is necessary to determine the most cost-effective approaches to the diagnosis and treatment of smear-negative PTB. Nevertheless, substantial improvement could be obtained by implementing the effective measures already available, such as improved adherence to diagnostic and treatment guidelines. PMID:10191561

  10. Transcriptional profiles discriminate patients with pulmonary tuberculosis from non-tuberculous individuals depending on the presence of non-insulin diabetes mellitus.

    PubMed

    Serrano, Carmen J; Cuevas-Córdoba, Betzaida; Macías-Segura, Noé; González-Curiel, Rosa Angélica; Martínez-Balderas, Víctor Yordani; Enciso-Moreno, Leonor; Small, Peter; Hernández-Pando, Rogelio; Enciso-Moreno, José Antonio

    2016-01-01

    Our objective was to identify transcriptional biomarkers in peripheral blood mononuclear cells (PBMC) that discriminate individuals with latent tuberculosis infection (LTBI) from those with pulmonary tuberculosis (PTB) in subjects with non-insulin-dependent diabetes mellitus (NIDDM) and in individuals without NIDDM. Using gene expression microarrays we identified differentially expressed genes from lungs of mice infected with Mycobacterium tuberculosis (Mtb) or a mutant (ΔsigH) representing a non-inflammatory model. Genes expressed in blood, with inflammatory related functions were evaluated in humans by RT-qPCR. NCF1 and ORM transcripts have the better discriminatory capacity to identify PTB subjects from LTBI and non-infected controls (NICs) independently of the presence of NIDDM. The sequential evaluation of the mRNA levels of NCF1 and ORM as multiple diagnostic tests showed 95% Sensitivity (Se) and 80% Specificity (Sp). In addition, FPR2 promises to be a good biomarker for the PTB detection in subjects with NIDDM (Se=100%; Sp=90%). PMID:26628192

  11. Tuberculosis in children.

    PubMed

    Marais, Ben J; Schaaf, H Simon

    2014-09-01

    Many clinicians regard tuberculosis as an adult pulmonary disease, but tuberculosis (TB) is a major cause of disease, both pulmonary and extrapulmonary, and death in young children from TB-endemic countries, especially in areas affected by poverty, social disruption, and human immunodeficiency virus (HIV) infection. This article reviews the disease burden and the natural history of disease in children with TB. It also provides guidance regarding the diagnosis, treatment, and prevention of TB in children. PMID:25037105

  12. The Endothelin System Has a Significant Role in the Pathogenesis and Progression of Mycobacterium tuberculosis Infection

    PubMed Central

    Correa, Andre F.; Bailão, Alexandre M.; Bastos, Izabela M. D.; Orme, Ian M.; Soares, Célia M. A.; Kipnis, Andre

    2014-01-01

    Tuberculosis (TB) remains a major global health problem, and although multiple studies have addressed the relationship between Mycobacterium tuberculosis and the host on an immunological level, few studies have addressed the impact of host physiological responses. Proteases produced by bacteria have been associated with important alterations in the host tissues, and a limited number of these enzymes have been characterized in mycobacterial species. M. tuberculosis produces a protease called Zmp1, which appears to be associated with virulence and has a putative action as an endothelin-converting enzyme. Endothelins are a family of vasoactive peptides, of which 3 distinct isoforms exist, and endothelin 1 (ET-1) is the most abundant and the best-characterized isoform. The aim of this work was to characterize the Zmp1 protease and evaluate its role in pathogenicity. Here, we have shown that M. tuberculosis produces and secretes an enzyme with ET-1 cleavage activity. These data demonstrate a possible role of Zmp1 for mycobacterium-host interactions and highlights its potential as a drug target. Moreover, the results suggest that endothelin pathways have a role in the pathogenesis of M. tuberculosis infections, and ETA or ETB receptor signaling can modulate the host response to the infection. We hypothesize that a balance between Zmp1 control of ET-1 levels and ETA/ETB signaling can allow M. tuberculosis adaptation and survival in the lung tissues. PMID:25267836

  13. The endothelin system has a significant role in the pathogenesis and progression of Mycobacterium tuberculosis infection.

    PubMed

    Correa, Andre F; Bailão, Alexandre M; Bastos, Izabela M D; Orme, Ian M; Soares, Célia M A; Kipnis, Andre; Santana, Jaime M; Junqueira-Kipnis, Ana Paula

    2014-12-01

    Tuberculosis (TB) remains a major global health problem, and although multiple studies have addressed the relationship between Mycobacterium tuberculosis and the host on an immunological level, few studies have addressed the impact of host physiological responses. Proteases produced by bacteria have been associated with important alterations in the host tissues, and a limited number of these enzymes have been characterized in mycobacterial species. M. tuberculosis produces a protease called Zmp1, which appears to be associated with virulence and has a putative action as an endothelin-converting enzyme. Endothelins are a family of vasoactive peptides, of which 3 distinct isoforms exist, and endothelin 1 (ET-1) is the most abundant and the best-characterized isoform. The aim of this work was to characterize the Zmp1 protease and evaluate its role in pathogenicity. Here, we have shown that M. tuberculosis produces and secretes an enzyme with ET-1 cleavage activity. These data demonstrate a possible role of Zmp1 for mycobacterium-host interactions and highlights its potential as a drug target. Moreover, the results suggest that endothelin pathways have a role in the pathogenesis of M. tuberculosis infections, and ETA or ETB receptor signaling can modulate the host response to the infection. We hypothesize that a balance between Zmp1 control of ET-1 levels and ETA/ETB signaling can allow M. tuberculosis adaptation and survival in the lung tissues.

  14. 38 CFR 3.375 - Determination of inactivity (complete arrest) in tuberculosis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... inactivity (complete arrest) in tuberculosis. 3.375 Section 3.375 Pensions, Bonuses, and Veterans' Relief...) in tuberculosis. (a) Pulmonary tuberculosis. A veteran shown to have had pulmonary tuberculosis will...) Nonpulmonary disease. Determination of complete arrest of nonpulmonary tuberculosis requires absence...

  15. 38 CFR 3.375 - Determination of inactivity (complete arrest) in tuberculosis.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... inactivity (complete arrest) in tuberculosis. 3.375 Section 3.375 Pensions, Bonuses, and Veterans' Relief...) in tuberculosis. (a) Pulmonary tuberculosis. A veteran shown to have had pulmonary tuberculosis will...) Nonpulmonary disease. Determination of complete arrest of nonpulmonary tuberculosis requires absence...

  16. 38 CFR 3.375 - Determination of inactivity (complete arrest) in tuberculosis.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... inactivity (complete arrest) in tuberculosis. 3.375 Section 3.375 Pensions, Bonuses, and Veterans' Relief...) in tuberculosis. (a) Pulmonary tuberculosis. A veteran shown to have had pulmonary tuberculosis will...) Nonpulmonary disease. Determination of complete arrest of nonpulmonary tuberculosis requires absence...

  17. 38 CFR 3.375 - Determination of inactivity (complete arrest) in tuberculosis.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... inactivity (complete arrest) in tuberculosis. 3.375 Section 3.375 Pensions, Bonuses, and Veterans' Relief...) in tuberculosis. (a) Pulmonary tuberculosis. A veteran shown to have had pulmonary tuberculosis will...) Nonpulmonary disease. Determination of complete arrest of nonpulmonary tuberculosis requires absence...

  18. 38 CFR 3.375 - Determination of inactivity (complete arrest) in tuberculosis.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... inactivity (complete arrest) in tuberculosis. 3.375 Section 3.375 Pensions, Bonuses, and Veterans' Relief...) in tuberculosis. (a) Pulmonary tuberculosis. A veteran shown to have had pulmonary tuberculosis will...) Nonpulmonary disease. Determination of complete arrest of nonpulmonary tuberculosis requires absence...

  19. Repeated Aerosolized-Boosting with Gamma-Irradiated Mycobacterium bovis BCG Confers Improved Pulmonary Protection against the Hypervirulent Mycobacterium tuberculosis Strain HN878 in Mice

    PubMed Central

    Kim, Jong-Seok; Kim, Hongmin; Kwon, Kee Woong; Han, Seung Jung; Eum, Seok-Yong; Cho, Sang-Nae; Shin, Sung Jae

    2015-01-01

    Mycobacterium bovis bacillus Calmette-Guerin (BCG), the only licensed vaccine, shows limited protection efficacy against pulmonary tuberculosis (TB), particularly hypervirulent Mycobacterium tuberculosis (Mtb) strains, suggesting that a logistical and practical vaccination strategy is urgently required. Boosting the BCG-induced immunity may offer a potentially advantageous strategy for advancing TB vaccine development, instead of replacing BCG completely. Despite the improved protection of the airway immunization by using live BCG, the use of live BCG as an airway boosting agent may evoke safety concerns. Here, we analyzed the protective efficacy of γ-irradiated BCG as a BCG-prime boosting agent for airway immunization against a hypervirulent clinical strain challenge with Mycobacterium tuberculosis HN878 in a mouse TB model. After the aerosol challenge with the HN878 strain, the mice vaccinated with BCG via the parenteral route exhibited only mild and transient protection, whereas BCG vaccination followed by multiple aerosolized boosting with γ-irradiated BCG efficiently maintained long-lasting control of Mtb in terms of bacterial reduction and pathological findings. Further immunological investigation revealed that this approach resulted in a significant increase in the cellular responses in terms of a robust expansion of antigen (PPD and Ag85A)-specific CD4+ T cells concomitantly producing IFN-γ, TNF-α, and IL-2, as well as a high level of IFN-γ-producing recall response via both the local and systemic immune systems upon further boosting. Collectively, aerosolized boosting of γ-irradiated BCG is able to elicit strong Th1-biased immune responses and confer enhanced protection against a hypervirulent Mycobacterium tuberculosis HN878 infection in a boosting number-dependent manner. PMID:26509812

  20. HMGB1/RAGE Signaling and Pro-Inflammatory Cytokine Responses in Non-HIV Adults with Active Pulmonary Tuberculosis

    PubMed Central

    Ip, Margaret; Chu, Yi Jun; Yung, Irene M. H.; Cheung, Catherine S. K.; Zheng, Lin; Lam, Judy S. Y.; Wong, Ka Tak; Sin, Winnie W. Y.; Choi, Kin Wing; Lee, Nelson

    2016-01-01

    Background We aimed to study the pathogenic roles of High-Mobility Group Box 1 (HMGB1) / Receptor-for-Advanced-Glycation-End-products (RAGE) signaling and pro-inflammatory cytokines in patients with active pulmonary tuberculosis (PTB). Methods A prospective study was conducted among non-HIV adults newly-diagnosed with active PTB at two acute-care hospitals (n = 80); age-and-sex matched asymptomatic individuals (tested for latent TB) were used for comparison (n = 45). Plasma concentrations of 8 cytokines/chemokines, HMGB1, soluble-RAGE, and transmembrane-RAGE expressed on monocytes/dendritic cells, were measured. Gene expression (mRNA) of HMGB1, RAGE, and inflammasome-NALP3 was quantified. Patients’ PBMCs were stimulated with recombinant-HMGB1 and MTB-antigen (lipoarabinomannan) for cytokine induction ex vivo. Results In active PTB, plasma IL-8/CXCL8 [median(IQR), 6.0(3.6–15.1) vs 3.6(3.6–3.6) pg/ml, P<0.001] and IL-6 were elevated, which significantly correlated with mycobacterial load, extent of lung consolidation (rs +0.509, P<0.001), severity-score (rs +0.317, P = 0.004), and fever and hospitalization durations (rs +0.407, P<0.001). IL-18 and sTNFR1 also increased. Plasma IL-8/CXCL8 (adjusted OR 1.12, 95%CI 1.02–1.23 per unit increase, P = 0.021) and HMGB1 (adjusted OR 1.42 per unit increase, 95%CI 1.08–1.87, P = 0.012) concentrations were independent predictors for respiratory failure, as well as for ICU admission/death. Gene expression of HMGB1, RAGE, and inflammasome-NALP3 were upregulated (1.2−2.8 fold). Transmembrane-RAGE was increased, whereas the decoy soluble-RAGE was significantly depleted. RAGE and HMGB1 gene expressions positively correlated with cytokine levels (IL-8/CXCL8, IL-6, sTNFR1) and clinico-/radiographical severity (e.g. extent of consolidation rs +0.240, P = 0.034). Ex vivo, recombinant-HMGB1 potentiated cytokine release (e.g. TNF-α) when combined with lipoarabinomannan. Conclusion In patients with active PTB, HMGB1/RAGE

  1. Prevalence, Risk Factors, and Treatment Outcomes of Isoniazid- and Rifampicin- Mono-Resistant Pulmonary Tuberculosis in Lima, Peru

    PubMed Central

    Villegas, Leonela; Huaman, Moises A.; Van der Stuyft, Patrick; Gotuzzo, Eduardo; Seas, Carlos

    2016-01-01

    Background Isoniazid and rifampicin are the two most efficacious first-line agents for tuberculosis (TB) treatment. We assessed the prevalence of isoniazid and rifampicin mono-resistance, associated risk factors, and the association of mono-resistance on treatment outcomes. Methods A prospective, observational cohort study enrolled adults with a first episode of smear-positive pulmonary TB from 34 health facilities in a northern district of Lima, Peru, from March 2010 through December 2011. Participants were interviewed and a sputum sample was cultured on Löwenstein-Jensen (LJ) media. Drug susceptibility testing was performed using the proportion method. Medication regimens were documented for each patient. Our primary outcomes were treatment outcome at the end of treatment. The secondary outcome included recurrent episodes among cured patients within two years after completion of the treatment. Results Of 1292 patients enrolled, 1039 (80%) were culture-positive. From this subpopulation, isoniazid mono-resistance was present in 85 (8%) patients and rifampicin mono-resistance was present in 24 (2%) patients. In the multivariate logistic regression model, isoniazid mono-resistance was associated with illicit drug use (adjusted odds ratio (aOR) = 2.10; 95% confidence interval (CI): 1.1–4.1), and rifampicin mono-resistance was associated with HIV infection (aOR = 9.43; 95%CI: 1.9–47.8). Isoniazid mono-resistant patients had a higher risk of poor treatment outcomes including treatment failure (2/85, 2%, p-value<0.01) and death (4/85, 5%, p<0.02). Rifampicin mono-resistant patients had a higher risk of death (2/24, 8%, p<0.01). Conclusion A high prevalence of isoniazid and rifampicin mono-resistance was found among TB patients in our low HIV burden setting which were similar to regions with high HIV burden. Patients with isoniazid and rifampicin mono-resistance had an increased risk of poor treatment outcomes. PMID:27045684

  2. Multi-state modelling reveals sex-dependent transmission, progression and severity of tuberculosis in wild badgers.

    PubMed

    Graham, J; Smith, G C; Delahay, R J; Bailey, T; McDonald, R A; Hodgson, D

    2013-07-01

    Statistical models of epidemiology in wildlife populations usually consider diseased individuals as a single class, despite knowledge that infections progress through states of severity. Bovine tuberculosis (bTB) is a serious zoonotic disease threatening the UK livestock industry, but we have limited understanding of key epidemiological processes in its wildlife reservoirs. We estimated differential survival, force of infection and progression in disease states in a population of Eurasian badgers (Meles meles), naturally infected with bTB. Our state-dependent models overturn prevailing categorizations of badger disease states, and find novel evidence for early onset of disease-induced mortality in male but not female badgers. Males also have higher risk of infection and more rapid disease progression which, coupled with state-dependent increases in mortality, could promote sex biases in the risk of transmission to cattle. Our results reveal hidden complexities in wildlife disease epidemiology, with implications for the management of TB and other zoonotic diseases.

  3. [Multifocal tuberculosis in immunocompetent patients].

    PubMed

    Rezgui, Amel; Fredj, Fatma Ben; Mzabi, Anis; Karmani, Monia; Laouani, Chadia

    2016-01-01

    Multifocal tuberculosis is defined as the presence of lesions affecting at least two extrapulmonary sites, with or without pulmonary involvement. This retrospective study of 10 cases aims to investigate the clinical and evolutionary characteristics of multifocal tuberculosis. It included 41 cases with tuberculosis collected between 1999 and 2013. Ten patients had multifocal tuberculosis (24%): 9 women and 1 man, the average age was 50 years (30-68 years). Our patients were correctly BCG vaccinated. The evaluation of immunodepression was negative in all patients. 7 cases had lymph node tuberculosis, 3 cases digestive tuberculosis, 2 cases pericardial tuberculosis, 2 cases osteoarticular tuberculosis, 1 case brain tuberculosis, 2 cases urinary tuberculosis, 4 cases urogenital tuberculosis, 1 case adrenal tuberculosis, 1 case cutaneous and 1 case muscle tuberculosis. All patients received anti-tuberculosis treatment for a mean duration of 10 months, with good evolution. Multifocal tuberculosis is difficult to diagnose. It can affect immunocompetent patients but often has good prognosis. Anti-tuberculosis therapy must be initiated as soon as possible to avoid sequelae. PMID:27583077

  4. Serum lysyl oxidase-like 2 levels and idiopathic pulmonary fibrosis disease progression.

    PubMed

    Chien, Jason W; Richards, Thomas J; Gibson, Kevin F; Zhang, Yingze; Lindell, Kathleen O; Shao, Lixin; Lyman, Susan K; Adamkewicz, Joanne I; Smith, Victoria; Kaminski, Naftali; O'Riordan, Thomas

    2014-05-01

    We evaluated whether lysyl oxidase-like 2 (LOXL2), which promotes cross-linking of collagen in pathological stroma, was detectable in serum from idiopathic pulmonary fibrosis (IPF) patients, and assessed its relationship with IPF disease progression. Patients from the ARTEMIS-IPF (n=69) and the Genomic and Proteomic Analysis of Disease Progression in IPF (GAP) (n=104) studies were analysed. Baseline serum LOXL2 (sLOXL2) levels were compared with baseline clinical and physiological surrogates of disease severity, and the association with IPF disease progression was assessed using a classification and regression tree (CART) method. sLOXL2 correlated weakly with forced vital capacity and carbon monoxide diffusion capacity (r -0.24-0.05) in both cohorts. CART-determined thresholds were similar: ARTEMIS-IPF 800 pg·mL(-1) and GAP 700 pg·mL(-1). In ARTEMIS-IPF, higher sLOXL2 (>800 pg·mL(-1)) was associated with increased risk for disease progression (hazard ratio (HR) 5.41, 95% CI 1.65-17.73). Among GAP subjects with baseline spirometric data (n=70), higher sLOXL2 levels (>700 pg·mL(-1)) were associated with more disease progression events (HR 1.78, 95% CI 1.01-3.11). Among all GAP subjects, higher sLOXL2 levels were associated with increased risk for mortality (HR 2.28, 95% CI 1.18-4.38). These results suggest that higher sLOXL2 levels are associated with increased risk for IPF disease progression. However, due to multiple limitations, these results require validation.

  5. A First Insight into High Prevalence of Undiagnosed Smear-Negative Pulmonary Tuberculosis in Northern Ethiopian Prisons: Implications for Greater Investment and Quality Control

    PubMed Central

    Biadglegne, Fantahun; Rodloff, Arne C.; Sack, Ulrich

    2014-01-01

    Background Tuberculosis (TB) transmission in prisons poses significant risks to inmates as well as the general population. Currently, there are no data on smear-negative pulmonary TB cases in prisons and by extension no data on the impact such cases have on TB incidence. This study was designed to obtain initial data on the prevalence of smear-negative cases of TB in prisons as well as preliminary risk factor analysis for such TB cases. Methods This cross-sectional survey was conducted in November 2013 at eight main prisons located in the state of Amhara, Ethiopia. Interviews using a structured and pretested questionnaire were done first to identify symptomatic prisoners. Three consecutive sputum samples were collected and examined using acid fast bacilli (AFB) microscopy at the point of care. All smear-negative sputum samples were taken for culture and Xpert testing. Descriptive and multivariate analysis was done using SPSS version 16. Results Overall the prevalence of smear-negative pulmonary TB cases in the study prisons was 8% (16/200). Using multivariate analysis, a contact history to TB patients in prison, educational level, cough and night sweating were found to be predictors of TB positivity among smear-negative pulmonary TB cases (p≤ 0.05). Conclusions In the studied prisons, high prevalence of undiagnosed TB cases using AFB microscopy was documented, which is an important public health concern that urgently needs to be addressed. Furthermore, patients with night sweating, non-productive cough, a contact history with TB patients and who are illiterate merit special attention, larger studies are warranted in the future to assess the associations more precisely. Further studies are also needed to examine TB transmission dynamics by patients with smear-negative pulmonary TB in a prison setting. PMID:25203007

  6. Clinical significance of smear positivity for acid-fast bacilli after ≥5 months of treatment in patients with drug-susceptible pulmonary tuberculosis

    PubMed Central

    Kang, Hyung Koo; Jeong, Byeong-Ho; Lee, Hyun; Park, Hye Yun; Jeon, Kyeongman; Huh, Hee Jae; Ki, Chang-Seok; Lee, Nam Yong; Koh, Won-Jung

    2016-01-01

    Abstract Patients with pulmonary tuberculosis (TB) with acid-fast bacilli (AFB)-positive sputum smear at 5 months or later during treatment are considered to be cases of treatment failure according to World Health Organization guidelines. This study evaluated the proportion, clinical characteristics, and significance of positive sputum smears after ≥5 months of standard treatment in patients with drug-susceptible pulmonary TB. This was a retrospective cohort study of 1611 patients with culture-confirmed drug-susceptible pulmonary TB who received standard anti-TB treatment from January 2009 to February 2014. Forty-one patients (2.5%) who were smear-positive after ≥5 months of treatment and 123 age- and sex-matched control patients were evaluated. Among the 41 smear-positive patients, culture of the sputum specimens yielded Mycobacterium tuberculosis (MTB) in 1 patient (2.4%), nontuberculous mycobacteria (NTM) in 7 (17.1%), and no growth in the remaining 33 patients (80.5%). Treatment was successfully completed in 40 patients (97.6%) with prolongation of the continuation phase regimens without change to second-line anti-TB treatment. In patients with smear positivity after ≥5 months of treatment compared with controls, cavitation on chest radiographs (53.7% vs. 25.2%, P = 0.001), bilateral involvement (51.2% vs. 30.1%, P = 0.01) and combined pleural effusion (26.8% vs. 10.6%, P = 0.01) were found more frequently at the time of treatment initiation, and paradoxical response occurred more commonly (19.5% vs. 3.3%, P = 0.002) during treatment. Smear-positive sputum after ≥5 months of standard anti-TB treatment was mainly because of nonviable MTB bacilli or NTM in patients with drug-susceptible pulmonary TB. AFB smear alone should not be used to assess treatment failure and careful examination of microbiologic status, including culture and drug susceptibility testing, is needed before making changes to retreatment regimens or empirical second

  7. Clinical significance of smear positivity for acid-fast bacilli after ≥5 months of treatment in patients with drug-susceptible pulmonary tuberculosis.

    PubMed

    Kang, Hyung Koo; Jeong, Byeong-Ho; Lee, Hyun; Park, Hye Yun; Jeon, Kyeongman; Huh, Hee Jae; Ki, Chang-Seok; Lee, Nam Yong; Koh, Won-Jung

    2016-08-01

    Patients with pulmonary tuberculosis (TB) with acid-fast bacilli (AFB)-positive sputum smear at 5 months or later during treatment are considered to be cases of treatment failure according to World Health Organization guidelines. This study evaluated the proportion, clinical characteristics, and significance of positive sputum smears after ≥5 months of standard treatment in patients with drug-susceptible pulmonary TB.This was a retrospective cohort study of 1611 patients with culture-confirmed drug-susceptible pulmonary TB who received standard anti-TB treatment from January 2009 to February 2014. Forty-one patients (2.5%) who were smear-positive after ≥5 months of treatment and 123 age- and sex-matched control patients were evaluated.Among the 41 smear-positive patients, culture of the sputum specimens yielded Mycobacterium tuberculosis (MTB) in 1 patient (2.4%), nontuberculous mycobacteria (NTM) in 7 (17.1%), and no growth in the remaining 33 patients (80.5%). Treatment was successfully completed in 40 patients (97.6%) with prolongation of the continuation phase regimens without change to second-line anti-TB treatment. In patients with smear positivity after ≥5 months of treatment compared with controls, cavitation on chest radiographs (53.7% vs. 25.2%, P = 0.001), bilateral involvement (51.2% vs. 30.1%, P = 0.01) and combined pleural effusion (26.8% vs. 10.6%, P = 0.01) were found more frequently at the time of treatment initiation, and paradoxical response occurred more commonly (19.5% vs. 3.3%, P = 0.002) during treatment.Smear-positive sputum after ≥5 months of standard anti-TB treatment was mainly because of nonviable MTB bacilli or NTM in patients with drug-susceptible pulmonary TB. AFB smear alone should not be used to assess treatment failure and careful examination of microbiologic status, including culture and drug susceptibility testing, is needed before making changes to retreatment regimens or empirical second-line anti

  8. The use of a computer in the organization of a large-scale co-operative controlled clinical trial of the treatment of pulmonary tuberculosis*

    PubMed Central

    Tall, Ruth; Devine, C. Margaret

    1970-01-01

    The organization of controlled clinical trials requires well-defined clerical procedures which, with large-scale studies, are so monotonous that it is difficult to attract and keep staff of a sufficiently high calibre. In a large-scale trial of pulmonary tuberculosis, a computer is being used to undertake much of the routine clerical work, including (1) the preparation of an appointments diary, which also specifies the exact requirements for the trial, and (2) the storage of all the data on magnetic tape so that periodic checks can be made for missing data and interim and final analyses can be produced rapidly. These arrangements reduce the time spent by clerical and statistical staff to a minimum. Although a strict evaluation of the effect of introducing the computer has not yet been made, this approach does appear to be sufficiently promising to warrant further investigations of a similar type. PMID:4921092

  9. Intuitive weights of harm for therapeutic decision making in smear-negative pulmonary Tuberculosis: an interview study of physicians in India, Pakistan and Bangladesh

    PubMed Central

    2014-01-01

    Background To estimate the amount of regret and weights of harm by omission and commission during therapeutic decisions for smear-negative pulmonary Tuberculosis. Methods An interviewer-administered survey was done among young physicians in India, Pakistan and Bangladesh with a previously used questionnaire. The physicians were asked to estimate probabilities of morbidity and mortality related with disease and treatment and intuitive weights of omission and commission for treatment of suspected pulmonary Tuberculosis. A comparison with weights based on literature data was made. Results A total of 242 physicians completed the interview. Their mean age was 28 years, 158 (65.3%) were males. Median probability (%) of mortality and morbidity of disease was estimated at 65% (inter quartile range [IQR] 50-75) and 20% (IQR 8-30) respectively. Median probability of morbidity and mortality in case of occurrence of side effects was 15% (IQR 10-30) and 8% (IQR 5-20) respectively. Probability of absolute treatment mortality was 0.7% which was nearly eight times higher than 0.09% reported in the literature data. The omission vs. commission harm ratios based on intuitive weights, weights calculated with literature data, weights calculated with intuitive estimates of determinants adjusted without and with regret were 3.0 (1.4-5.0), 16 (11-26), 33 (11-98) and 48 (11-132) respectively. Thresholds based on pure regret and hybrid model (clinicians’ intuitive estimates and regret) were 25 (16.7-41.7), and 2(0.75-7.5) respectively but utility-based thresholds for clinicians’ estimates and literature data were 2.9 (1-8.3) and 5.9 (3.7-7.7) respectively. Conclusion Intuitive weight of harm related to false-negatives was estimated higher than that to false-positives. The mortality related to treatment was eightfold overestimated. Adjusting expected utility thresholds for subjective regret had little effect. PMID:25104297

  10. Pharmacodynamic Modeling of Bacillary Elimination Rates and Detection of Bacterial Lipid Bodies in Sputum to Predict and Understand Outcomes in Treatment of Pulmonary Tuberculosis

    PubMed Central

    Sloan, Derek J.; Mwandumba, Henry C.; Garton, Natalie J.; Khoo, Saye H.; Butterworth, Anthony E.; Allain, Theresa J.; Heyderman, Robert S.; Corbett, Elizabeth L.; Barer, Mike R.; Davies, Geraint R.

    2015-01-01

    Background. Antibiotic-tolerant bacterial persistence prevents treatment shortening in drug-susceptible tuberculosis, and accumulation of intracellular lipid bodies has been proposed to identify a persister phenotype of Mycobacterium tuberculosis cells. In Malawi, we modeled bacillary elimination rates (BERs) from sputum cultures and calculated the percentage of lipid body–positive acid-fast bacilli (%LB + AFB) on sputum smears. We assessed whether these putative measurements of persistence predict unfavorable outcomes (treatment failure/relapse). Methods. Adults with pulmonary tuberculosis received standard 6-month therapy. Sputum samples were collected during the first 8 weeks for serial sputum colony counting (SSCC) on agar and time-to positivity (TTP) measurement in mycobacterial growth indicator tubes. BERs were extracted from nonlinear and linear mixed-effects models, respectively, fitted to these datasets. The %LB + AFB counts were assessed by fluorescence microscopy. Patients were followed until 1 year posttreatment. Individual BERs and %LB + AFB counts were related to final outcomes. Results. One hundred and thirty-three patients (56% HIV coinfected) participated, and 15 unfavorable outcomes were reported. These were inversely associated with faster sterilization phase bacillary elimination from the SSCC model (odds ratio [OR], 0.39; 95% confidence interval [CI], .22–.70) and a faster BER from the TTP model (OR, 0.71; 95% CI, .55–.94). Higher %LB + AFB counts on day 21–28 were recorded in patients who suffered unfavorable final outcomes compared with those who achieved stable cure (P = .008). Conclusions. Modeling BERs predicts final outcome, and high %LB + AFB counts 3–4 weeks into therapy may identify a persister bacterial phenotype. These methods deserve further evaluation as surrogate endpoints for clinical trials. PMID:25778753

  11. Cytokine production and mRNA expression in pulmonary tuberculosis patients and their household contacts of younger age group (15-25years).

    PubMed

    Joshi, Lavanya; Ponnana, Meenakshi; Sivangala, Ramya; Chelluri, Lakshmi Kiran; Nallari, Pratibha; Valluri, Vijaya Lakshmi; Gaddam, Sumanlatha

    2016-05-01

    Household contacts of tuberculosis patients are at high risk of infection and development of active disease. In this study we evaluated the cytokine production and mRNA expression of IFN-γ, TNF-α, IL-10&IL-6 stimulated with r32kDa M. bovis BCGAg in active pulmonary tuberculosis patients (APTB), household contacts (HHC) and healthy controls (HC). The results showed the stimulated levels of IFN-γ and TNF-α were low while IL-10 levels were high in APTB and HHC compared to HC. IL-6 has not shown any significant difference. The mRNA expression of TNF- α was 8 fold high in HCs compared to APTB and HHC. The IL-6 expression was 2.2 fold &1 fold less in APTB and HHC compared to HCs. Multinomial logistic regression analysis indicated that the stimulated levels of IFN-γ & IL-6 and sex significantly predicted the HHC group from HCs at p<0.05.In conclusion further follow up studies with r32kd antigen might help to identify the high risk individuals. PMID:26876300

  12. MCP1 SNPs and pulmonary tuberculosis in cohorts from West Africa, the USA and Argentina: lack of association or epistasis with IL12B polymorphisms.

    PubMed

    Velez Edwards, Digna R; Tacconelli, Alessandra; Wejse, Christian; Hill, Philip C; Morris, Gerard A J; Edwards, Todd L; Gilbert, John R; Myers, Jamie L; Park, Yo Son; Stryjewski, Martin E; Abbate, Eduardo; Estevan, Rosa; Rabna, Paulo; Novelli, Giuseppe; Hamilton, Carol D; Adegbola, Richard; Østergaar, Lars; Williams, Scott M; Scott, William K; Sirugo, Giorgio

    2012-01-01

    The monocyte chemotactic protein-1 (MCP-1) is a chemokine that plays an important role in the recruitment of monocytes to M. tuberculosis infection sites, and previous studies have reported that genetic variants in MCP1 are associated with differential susceptibility to pulmonary tuberculosis (PTB). We examined eight MCP1 single nucleotide polymorphisms (SNPs) in a multi-ethnic, case-control design that included: 321 cases and 346 controls from Guinea-Bissau, 258 cases and 271 controls from The Gambia, 295 cases and 179 controls from the U.S. (African-Americans), and an additional set of 237 cases and 144 controls of European ancestry from the U.S. and Argentina. Two locus interactions were also examined for polymorphisms in MCP1 and interleukin 12B (IL12B), another gene implicated in PTB risk. Examination of previously associated MCP1 SNPs rs1024611 (-2581A/G), rs2857656 (-362G/C) and rs4586 (+900C/T) did not show evidence for association. One interaction between rs2857656 and IL12B SNP rs2288831 was observed among Africans but the effect was in the opposite direction in Guineans (OR = 1.90, p = 0.001) and Gambians (OR = 0.64, p = 0.024). Our data indicate that the effect of genetic variation within MCP1 is not clear cut and additional studies will be needed to elucidate its role in TB susceptibility.

  13. Multicenter Evaluation of Anyplex Plus MTB/NTM MDR-TB Assay for Rapid Detection of Mycobacterium tuberculosis Complex and Multidrug-Resistant Isolates in Pulmonary and Extrapulmonary Specimens.

    PubMed

    Sali, Michela; De Maio, Flavio; Caccuri, Francesca; Campilongo, Federica; Sanguinetti, Maurizio; Fiorentini, Simona; Delogu, Giovanni; Giagulli, Cinzia

    2016-01-01

    The rapid diagnosis of tuberculosis (TB) and the detection of drug-resistant Mycobacterium tuberculosis strains are critical for successful public health interventions. Therefore, TB diagnosis requires the availability of diagnostic tools that allow the rapid detection of M. tuberculosis and drug resistance in clinical samples. Here, we performed a multicenter study to evaluate the performance of the Seegene Anyplex MTB/NTM MDR-TB assay, a new molecular method based on a multiplex real-time PCR system, for detection of Mycobacterium tuberculosis complex (MTBC), nontuberculous mycobacteria (NTM), and genetic determinants of drug resistance. In total, the results for 755 samples (534 pulmonary and 221 extrapulmonary samples) were compared with the results of smears and cultures. For pulmonary specimens, the sensitivities of the Anyplex assay and acid-fast bacillus smear testing were 86.4% and 75.0%, respectively, and the specificities were 99% and 99.4%. For extrapulmonary specimens, the sensitivities of the Anyplex assay and acid-fast bacillus smear testing were 83.3% and 50.0%, respectively, and the specificities of both were 100%. The negative and positive predictive values of the Anyplex assay for pulmonary specimens were 97% and 100%, respectively, and those for extrapulmonary specimens were 84.6% and 100%. The sensitivities of the Anyplex assay for detecting isoniazid resistance in MTBC strains from pulmonary and extrapulmonary specimens were 83.3% and 50%, respectively, while the specificities were 100% for both specimen types. These results demonstrate that the Anyplex MTB/NTM MDR-TB assay is an efficient and rapid method for the diagnosis of pulmonary and extrapulmonary TB and the detection of isoniazid resistance.

  14. Multicenter Evaluation of Anyplex Plus MTB/NTM MDR-TB Assay for Rapid Detection of Mycobacterium tuberculosis Complex and Multidrug-Resistant Isolates in Pulmonary and Extrapulmonary Specimens

    PubMed Central

    De Maio, Flavio; Caccuri, Francesca; Campilongo, Federica; Sanguinetti, Maurizio; Fiorentini, Simona; Giagulli, Cinzia

    2015-01-01

    The rapid diagnosis of tuberculosis (TB) and the detection of drug-resistant Mycobacterium tuberculosis strains are critical for successful public health interventions. Therefore, TB diagnosis requires the availability of diagnostic tools that allow the rapid detection of M. tuberculosis and drug resistance in clinical samples. Here, we performed a multicenter study to evaluate the performance of the Seegene Anyplex MTB/NTM MDR-TB assay, a new molecular method based on a multiplex real-time PCR system, for detection of Mycobacterium tuberculosis complex (MTBC), nontuberculous mycobacteria (NTM), and genetic determinants of drug resistance. In total, the results for 755 samples (534 pulmonary and 221 extrapulmonary samples) were compared with the results of smears and cultures. For pulmonary specimens, the sensitivities of the Anyplex assay and acid-fast bacillus smear testing were 86.4% and 75.0%, respectively, and the specificities were 99% and 99.4%. For extrapulmonary specimens, the sensitivities of the Anyplex assay and acid-fast bacillus smear testing were 83.3% and 50.0%, respectively, and the specificities of both were 100%. The negative and positive predictive values of the Anyplex assay for pulmonary specimens were 97% and 100%, respectively, and those for extrapulmonary specimens were 84.6% and 100%. The sensitivities of the Anyplex assay for detecting isoniazid resistance in MTBC strains from pulmonary and extrapulmonary specimens were 83.3% and 50%, respectively, while the specificities were 100% for both specimen types. These results demonstrate that the Anyplex MTB/NTM MDR-TB assay is an efficient and rapid method for the diagnosis of pulmonary and extrapulmonary TB and the detection of isoniazid resistance. PMID:26491178

  15. Fibulin-1 Predicts Disease Progression in Patients With Idiopathic Pulmonary Fibrosis

    PubMed Central

    Unger, Sofia; Corte, Tamera J.; Keller, Michael; Wolters, Paul J.; Richeldi, Luca; Cerri, Stefania; Prêle, Cecilia M.; Hansbro, Philip M.; Argraves, William Scott; Oliver, Rema A.; Oliver, Brian G.; Black, Judith L.; Burgess, Janette K.

    2014-01-01

    BACKGROUND: The underlying mechanisms of idiopathic pulmonary fibrosis (IPF) are unknown. This progressive disease has high mortality rates, and current models for prediction of mortality have limited value in identifying which patients will progress. We previously showed that the glycoprotein fibulin-1 is involved in enhanced proliferation and wound repair by mesenchymal cells and, thus, may contribute to lung fibrosis in IPF. METHODS: Serum, lung tissue, and lung function values were obtained from four independent locations (Sydney, NSW, and Perth, WA, Australia; San Francisco, CA; and Modena, Italy). Patients with IPF were followed for a minimum of 1 year and progression was defined as a significant decline in lung function or death. Primary parenchymal lung fibroblasts of 15 patients with and without IPF were cultured under nonstimulatory conditions. Fibulin-1 levels in serum, and secreted or deposited by fibroblasts, were measured by western blot and in lung tissue by immunohistochemistry. RESULTS: Serum fibulin-1 levels were increased in patients with IPF compared with subjects without lung disease (P = .006). Furthermore, tissue fibulin-1 levels were increased in patients with IPF (P = .02) and correlated negatively with lung function (r = −0.9, P < .05). Primary parenchymal fibroblasts from patients with IPF produced more fibulin-1 than those from subjects without IPF (P < .05). Finally, serum fibulin-1 levels at first blood draw predicted disease progression in IPF within 1 year (area under the curve , 0.71; 95% CI, 0.57-0.86; P = .012). CONCLUSIONS: Fibulin-1 is a novel potential biomarker for disease progression in IPF and raises the possibility that it could be used as a target for the development of new treatments. PMID:24832167

  16. Dynamics of the T cell response to Mycobacterium tuberculosis DosR and Rpf antigens in a Colombian population of household contacts of recently diagnosed pulmonary tuberculosis patients.

    PubMed

    Arroyo, Leonar; Rojas, Mauricio; Ortíz, Blanca L; Franken, Kees L M C; García, Luis F; Ottenhoff, Tom H M; Barrera, Luis F

    2016-03-01

    Immune response to DosR and Rpf antigens from Mycobacterium tuberculosis (Mtb) seems to be important for latency maintenance. Little is known about the dynamics of the immune response to these antigens in an endemic community. Thus, the IFNγ response and cytokine production in response to PPD, Esat6-Cfp10 (E6-C10), DosR and Rpf antigens in healthy HHC of tuberculosis (TB) patients over a 12 (T12) months period (short-term, stLTBI) was investigated. This response was compared with a group of LTBI, who have remained healthy for 5-7 years (long-term, ltLTBI). According to the IFNγ response, two groups of HHCs were identified in stLTBI in response to E6-C10. At T12, E6-C10(+) HHCs displayed a decrease in the IFNγ levels and a generalized decrease in cytokines production. The E6-C10(-) HHC showed an increase in the IFNγ response and cytokine levels. In stLTBI, the responses to E6-C10, DosR, and Rpf may be interpreted as a protective immune response controlling Mtb infection and may be leading to a state of latent infection. Comparing the response of stLTBI and ltLTBI, we observed significant changes in the proportions of CD45RO(+)CD27(+) T cells to specific DosR and Rpf, which may indicate a persistent immune response to Mtb antigens in ltLTBI.

  17. Progressive right ventricular functional and structural changes in a mouse model of pulmonary arterial hypertension.

    PubMed

    Wang, Zhijie; Schreier, David A; Hacker, Timothy A; Chesler, Naomi C

    2013-12-01

    Right ventricle (RV) dysfunction occurs with progression of pulmonary arterial hypertension (PAH) due to persistently elevated ventricular afterload. A critical knowledge gap is the molecular mechanisms that govern the transition from RV adaptation to RV maladaptation, which leads to failure. Here, we hypothesize that the recently established mouse model of PAH, via hypoxia and SU5416 treatment (HySu), captures that transition from adaptive to maladaptive RV remodeling including impairments in RV function and decreases in the efficiency of RV interactions with the pulmonary vasculature. To test this hypothesis, we exposed C57BL6 male mice to 0 (control), 14, 21, and 28 days of HySu and then obtained synchronized RV pressure and volume measurements in vivo. With increasing HySu exposure duration, arterial afterload increased monotonically, leading to a continuous increase in RV stroke work, RV fibrosis, and RV wall stiffening (P < 0.05). RV contractility increased at 14 days of HySu exposure and then plateaued (P < 0.05). As a result, ventricular-vascular coupling efficiency tended to increase at 14 days and then decrease. Our results suggest that RV remodeling may begin to shift from adaptive to maladaptive with increasing duration of HySu exposure, which would mimic changes in RV function with PAH progression found clinically. However, for the duration of HySu exposure used here, no drop in cardiac output was found. We conclude that the establishment of a mouse model for overt RV failure due to PAH remains an important task. PMID:24744862

  18. Cutaneous tuberculosis in children.

    PubMed

    Sethuraman, Gomathy; Ramesh, Venkatesh

    2013-01-01

    Cutaneous tuberculosis is a rare form of extrapulmonary tuberculosis that accounts for 1% to 2% of cases. Childhood skin tuberculosis represents 18% to 82% of all cutaneous tuberculosis cases. Scrofuloderma and lupus vulgaris are the two most common clinical forms in children. An increase in the number of tuberculids, especially lichen scrofulosorum, has been observed in the last several years. Cutaneous tuberculosis in children can be severe and have a protracted course. Multiplicity of lesions and multifocal disseminated involvement in scrofuloderma and lupus vulgaris is common. Scrofuloderma progressing to gummatous lesions (scrofulous gumma) is mostly described in children. Morbidities and deformities are more severe in children.

  19. Tuberculosis in otorhinolaryngology: clinical presentation and diagnostic challenges.

    PubMed

    Michael, Rajiv C; Michael, Joy S

    2011-01-01

    Tuberculosis affects all tissues of the body, although some more commonly than the others. Pulmonary tuberculosis is the most common type of tuberculosis accounting for approximately 80% of the tuberculosis cases. Tuberculosis of the otorhinolaryngeal region is one of the rarer forms of extrapulmonary tuberculosis but still poses a significant clinical and diagnostic challenge. Over three years, only five out of 121 patients suspected to have tuberculosis of the otorhinolaryngeal region (cervical adenitis excluded) had Mycobacterium tuberculosis culture-proven disease. Additional 7 had histology-proven tuberculosis. Only one patient had concomitant sputum-positive pulmonary tuberculosis. We look at the various clinical and laboratory aspects of tuberculosis of the otorhinolaryngeal region that would help to diagnose this uncommon but important form of extrapulmonary tuberculosis.

  20. Bedaquiline and Pyrazinamide Treatment Responses Are Affected by Pulmonary Lesion Heterogeneity in Mycobacterium tuberculosis Infected C3HeB/FeJ Mice

    PubMed Central

    2016-01-01

    BALB/c and Swiss mice are routinely used to validate the effectiveness of tuberculosis drug regimens, although these mouse strains fail to develop human-like pulmonary granulomas exhibiting caseous necrosis. Microenvironmental conditions within human granulomas may negatively impact drug efficacy, and this may not be reflected in non-necrotizing lesions found within conventional mouse models. The C3HeB/FeJ mouse model has been increasingly utilized as it develops hypoxic, caseous necrotic granulomas which may more closely mimic the pathophysiological conditions found within human pulmonary granulomas. Here, we examined the treatment response of BALB/c and C3HeB/FeJ mice to bedaquiline (BDQ) and pyrazinamide (PZA) administered singly and in combination. BALB/c mice consistently displayed a highly uniform treatment response to both drugs, while C3HeB/FeJ mice displayed a bimodal response composed of responsive and less-responsive mice. Plasma pharmacokinetic analysis of dissected lesions from BALB/c and C3HeB/FeJ mice revealed that PZA penetrated lesion types from both mouse strains with similar efficiency. However, the pH of the necrotic caseum of C3HeB/FeJ granulomas was determined to be 7.5, which is in the range where PZA is essentially ineffective under standard laboratory in vitro growth conditions. BDQ preferentially accumulated within the highly cellular regions in the lungs of both mouse strains, although it was present at reduced but still biologically relevant concentrations within the central caseum when dosed at 25 mg/kg. The differential treatment response which resulted from the heterogeneous pulmona