Dempers, Johan; Sens, Mary Ann; Wadee, Shabbir Ahmed; Kinney, Hannah C.; Odendaal, Hein J.; Wright, Colleen A.
The classification of an unexpected infant death as the sudden infant death syndrome (SIDS) depends upon a complete autopsy and death scene investigation to exclude known causes of death. Here we report the death of a four-month-old infant in a tuberculosis endemic area that presented as a sudden unexpected death in infancy (SUDI) with no apparent explanation based on the death scene characteristics. The autopsy, however, revealed progressive primary pulmonary tuberculosis with intrathoracic adenopathy, compression of the tracheobronchial tree and miliary lesions in the liver. This case underscores the clinical difficulties in the diagnosis of infantile tuberculosis, as well as the possibility of sudden death as part of its protean manifestations. The pathology and clinical progression of tuberculosis in infants differs from older children and adults due to the immature immune response in infants. This case dramatically highlights the need for complete autopsies in all sudden and unexpected infant deaths, as well as the public health issues in a sentinel infant tuberculosis diagnosis. PMID:20705406
Maglione, Paul J; Xu, Jiayong; Chan, John
Though much is known about the function of T lymphocytes in the adaptive immune response against Mycobacterium tuberculosis, comparably little is understood regarding the corresponding role of B lymphocytes. Indicating B cells as components of lymphoid neogenesis during pulmonary tuberculosis, we have identified ectopic germinal centers (GCs) in the lungs of infected mice. B cells in these pulmonary lymphoid aggregates express peanut agglutinin and GL7, two markers of GC B cells, as well as CXCR5, and migrate in response to the lymphoid-associated chemokine CXCL13 ex vivo. CXCL13 is negatively regulated by the presence of B cells, as its production is elevated in lungs of B cell-deficient (B cell(-/-)) mice. Upon aerosol with 100 CFU of M. tuberculosis Erdman, B cell(-/-) mice have exacerbated immunopathology corresponding with elevated pulmonary recruitment of neutrophils. Infected B cell(-/-) mice show increased production of IL-10 in the lungs, whereas IFN-gamma, TNF-alpha, and IL-10R remain unchanged from wild type. B cell(-/-) mice have enhanced susceptibility to infection when aerogenically challenged with 300 CFU of M. tuberculosis corresponding with elevated bacterial burden in the lungs but not in the spleen or liver. Adoptive transfer of B cells complements the phenotypes of B cell(-/-) mice, confirming a role for B cells in both modulation of the host response and optimal containment of the tubercle bacillus. As components of ectopic GCs, moderators of inflammatory progression, and enhancers of local immunity against bacterial challenge, B cells may have a greater role in the host defense against M. tuberculosis than previously thought.
Minchella, Peter A; Donkor, Simon; McDermid, Joann M; Sutherland, Jayne S
Early identification of individuals at risk for progressing to active tuberculosis (TB) disease may limit new transmission and improve clinical outcomes. Evidence indicates altered iron homeostasis may identify those at greater risk of disease progression in HIV co-infection. We aimed to investigate iron homeostasis biomarkers as risk factors for progression to TB. Archived plasma samples were analyzed from household contacts of pulmonary TB index cases in The Gambia. Contacts were classified as asymptomatic non-progressors (n = 17) or TB-progressors (n = 10), which included two HIV-infected participants. Iron homeostasis (hemoglobin, ferritin, hepcidin, soluble transferrin receptor, transferrin) was assessed in all contacts at study recruitment. Plasma was collected a median of 910 days prior to TB diagnosis. Low transferrin around the time of known exposure to infectious TB was a disease progression risk factor among all TB-progressors (Poisson incidence rate ratio: 0.55; 95% CI: 0.35-0.89). Iron homeostasis also differed between early and delayed TB-progressors, with higher ferritin and hepcidin concentrations observed among early TB-progressors (mean ferritin 50.2 vs. 26.2 ng/ml; P = 0.027; mean hepcidin 37.7 vs. 5.6 ng/ml; P = 0.036). Iron homeostasis is associated with progression to TB among household contacts. Further studies are needed to elucidate mechanisms and determine the clinical utility of monitoring iron homeostasis biomarkers.
Carrol, E D; Clark, J E; Cant, A J
Tuberculosis (TB) is a serious disease of global importance, with a rising incidence in the developed world in recent years. Tuberculous lymphadenitis, tuberculous meningitis, osteoarticular tuberculosis and miliary tuberculosis are some of the more well-recognised manifestations of non-pulmonary TB in childhood. The diagnosis of non-pulmonary TB poses a particular challenge for clinicians because of the protean ways in which the disease presents. The omission of tuberculosis from the differential diagnosis of patients with obscure illnesses and the relatively insensitive bacteriological methods for detecting Mycobacterium tuberculosis add to the complexity of the problem. A high index of suspicion is required in order to avoid delays in diagnosis which may influence treatment outcome. The advent of DNA amplification techniques such as the polymerase chain reaction may herald a promising new era in the prompt and accurate management of extrapulmonary tuberculosis.
Toujani, S; Ben Salah, N; Cherif, J; Mjid, M; Ouahchy, Y; Zakhama, H; Daghfous, J; Beji, M; Mehiri-Ben Rhouma, N; Louzir, B
Tuberculosis is a major public health problem worldwide. Indeed, a third of the world population is infected with Mycobacterium tuberculosis and more than 8 million new cases of tuberculosis each year. Pulmonary tuberculosis is the most common location. Its diagnosis is difficult and often established with a delay causing a spread of infection. The diagnosis of tuberculosis infection is mainly based on immunological tests represented by the tuberculin skin test and detection of gamma interferon, while the diagnosis of pulmonary tuberculosis is suspected on epidemiological context, lasting general and respiratory symptoms, contrasting usually with normal lung examination, and a chest radiography showing suggestive lesions. The radioclinical feature may be atypical in patients with extreme ages and in case of immunodeficiency. Confirmation of tuberculosis is bacteriological. Conventional bacteriological methods remain the reference. Innovative tests using the technique of molecular biology have improved the diagnosis of tuberculosis in terms of sensitivity and especially speed. However, those techniques are of limited use.
García, Maria de los Angeles; Lanio, Maria E.; Tirado, Yanely; Alvarez, Nadine; Puig, Alina; Aguilar, Alicia; Canet, Liem; Mata Espinoza, Dulce; Barrios Payán, Jorge; Sarmiento, María Elena; Hernández-Pando, Rogelio; Norazmi, Mohd-Nor; Acosta, Armando
A more effective vaccine against tuberculosis (TB) is urgently needed. Based on its high genetic homology with Mycobacterium tuberculosis (Mtb), the nonpathogenic mycobacteria, Mycobacterium smegmatis (Ms), could be an attractive source of potential antigens to be included in such a vaccine. We evaluated the capability of lipid-based preparations obtained from Ms to provide a protective response in Balb/c mice after challenge with Mtb H37Rv strain. The intratracheal model of progressive pulmonary TB was used to assess the level of protection in terms of bacterial load as well as the pathological changes in the lungs of immunized Balb/c mice following challenge with Mtb. Mice immunized with the lipid-based preparation from Ms either adjuvanted with Alum (LMs-AL) or nonadjuvanted (LMs) showed significant reductions in bacterial load (P < 0.01) compared to the negative control group (animals immunized with phosphate buffered saline (PBS)). Both lipid formulations showed the same level of protection as Bacille Calmette and Guerin (BCG). Regarding the pathologic changes in the lungs, mice immunized with both lipid formulations showed less pneumonic area when compared with the PBS group (P < 0.01) and showed similar results compared with the BCG group. These findings suggest the potential of LMs as a promising vaccine candidate against TB. PMID:25548767
We investigated the causes of death of late sequelae of pulmonary tuberculosis. Chronic respiratory failure is one of the most frequent cause of death in the patients of late sequelae of pulmonary tuberculosis. We compared the long term prognosis of chronic respiratory failure in case of emphysema and pulmonary tuberculosis. In the patients with chronic respiratory failure by pulmonary emphysema, the prognosis was poor in those with pulmonary hypertension. But in case of late sequelae of pulmonary tuberculosis, prognosis was not affected by presence or absence of pulmonary hypertension. The determinants of prognosis of late sequelae of pulmonary tuberculosis are the indication of home oxygen therapy, malnutrition, and hypoxemia. Fungal infection, especially aspergilloma, is a common secondary infection of late sequelae of pulmonary tuberculosis. We investigated forty-two cases of aspergilloma as late sequelae of pulmonary tuberculosis, and of those 15 patients died. The causes of death were pneumonia and respiratory failure. Measurement of galactomannan antigen of aspergillus in serum using ELISA or PCR, it was apparent that the outcome was poor in the patients positive for antigen. It suggested that the prognosis of the patients with aspergilloma related with some degree of invasion of Aspergillus in parenchyma. It was reported that neoplasm is closely related to chronic tuberculous empyema. Lymphoma is most frequently complicated with chronic tuberculous empyema, and squamous cell carcinoma, adenocarcinoma, sarcoma and carcinoid were reported as complication of chronic empyema. We reported the case of angiosarcoma, originated from chronic empyema in left thoracic cavity formed after being treated for tuberculosis with artificial pneumothorax. Recently, the number of patients with late sequelae of pulmonary tuberculosis have been decreased, but some severe cases of patients of pulmonary tuberculosis will suffer from late sequelae of pulmonary tuberculosis, and
Elías-López, A L; Marquina, B; Gutiérrez-Ortega, A; Aguilar, D; Gomez-Lim, M; Hernández-Pando, R
Host control of mycobacterial infection, in both human and mouse models, has been shown to be associated with the production of interferon (IFN)-gamma by CD4(+) T cells. Interleukin (IL)-12 is known to be a crucial cytokine in the differentiation of IFN-gamma-producing T helper 1 (Th1) cells. To determine whether continuous administration of IL-12 expressed in transgenic tomato (TT-IL-12) has therapeutic efficacy in a murine model of pulmonary tuberculosis, BALB/c mice were infected with either Mycobacterium tuberculosis H37Rv strain or a multi-drug-resistant clinical isolate (MDR) and treated with a daily oral dose of TT-IL12 crude fruit extracts. For the early H37Rv infection, TT-IL-12 administration was started 1 day before infection and continued for 60 days. In the H37Rv or MDR late infection, treatment was started 60 days after infection and continued for another 60 days. In both phases of infection, TT-IL-12 administration resulted in a reduction of bacterial loads and tissue damage compared with wild-type tomato (non-TT). The Th1 response was increased and the Th2 response was reduced. In the late infection, a long-term treatment with TT-IL-12 was necessary. We demonstrate that TT-IL-12 increases resistance to infection and reduces lung tissue damage during early and late drug-sensitive and drug-resistant mycobacterial infection.
The problems of diagnosis, treatment and management of tuberculosis associated with HIV infection in Africa are placed in perspective by the former director of the Kenya Medical Research Institute. Tuberculosis (TB) has increased as much as 3-fold in many African countries due to heightened susceptibility of HIV patients. HIV infection may both re-activate latent TB, which virtually all Africans harbor, or increase the likelihood of exogenous infection or re-infection by TB. In most of Africa diagnosis by stained sputum smear is standard: in late AIDS, this method may yield false negatives due to non-pulmonary TB, or pulmonary TB with a negative smear. Chest x-rays are also atypical, since cavitation of the upper zones is not as common, but lobar consolidation and lower zone involvement, and various unusual findings are likely. There is no evidence that mycobacterium avium intracellular has occurred in Africa. Treatment in Africa often centers on long-term thiazina (thiacetazone and isoniazid combined). HIV+ patients are more prone to skin rashes or even lethal epidermal neurolysis as a complication of treatment. Treated patients should be monitored for other symptoms such as diarrhea, recurrent fevers, other chest infections, cerebral space occupying lesions, urinary infections. Many can be treated with broad spectrum antibiotics such as chloramphenicol. Nursing HIV-infected young adults is an expensive and burdensome prospect for overworked and underpaid staff, but curing TB in AIDS patients is possible and worthwhile because of the public health advantages.
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
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
Sánchez-Pérez, Héctor J.; Sánchez, Inma; Bedoya, Alfredo; Martín, Miguel
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
Al-Otaibi, Fawzia; El Hazmi, Malak M
Studies from developed countries have reported that extra-pulmonary tuberculosis (EPTB) is on the rise due to the human immunodeficiency virus (HIV) epidemic. However, similar studies from high-burden countries with low prevalence of HIV like Saudi Arabia are lacking. Therefore, we conducted this study to investigate demographic and clinical characteristics of patients with pulmonary and extra-pulmonary tuberculosis. A retrospective analysis was carried out on all patients (n=431) with a culture - proven diagnosis of tuberculosis seen at University teaching hospital, Riyadh, Saudi Arabia from January 2001 to December 2007. A total of 183 (42.5%) pulmonary tuberculosis (PTB) and 248 (57.5%) extra-pulmonary TB (EPTB) cases were compared in terms of age, sex, and nationality. There were 372 Saudis (SA) (86.3%) and the remaining non-Saudis (NSA) 59 (13.7%). The age distribution of the PTB patients had a bimodal distribution. EPTB was more common at young age (20-29 years). The proportion of EPTB cases was significantly higher among NSA patients (72.9%) compared to SA patients (55.1%). Females had higher proportion (59.5%) of EPTB than males (55.6%). The most common site was lymph node tuberculosis (42%). In conclusion, our data suggest that EPTB was relatively common in younger age, female gender and NSA. Tuberculosis (TB) control program may target those populations for EPTB case-finding.
Koyama, Sekiya; Sakaguchi, Nobuki; Hotta, Jyunnichi
Mycobacterium tuberculosis (M. tuberculosis) infects all organs in the body; however, lung infection is the primary lesion. The total number of infections is decreasing, but the percentage of infections in older people is rising. Because this disease is due to infection with M. tuberculosis, the diagnosis requires the presence of M. tuberculosis. Chest X-ray and CT are very powerful tools to suggest the presence of M. tuberculosis infection. Pathological examination of the tissues also shows the typical findings of M. tuberculosis infection; however, the presence of the bacterium was not proven in certain cases of M. tuberculosis infection, and especially in cases of latent infection. Recently, the whole-blood interferon--gamma test (QuantiFERON-TB, QFT) became more popular than the tuberculin skin test. It is reported that the specificity and sensitivity of QFT are similar to or better than the tuberculin skin test. However, it should be noted that QFT positive does not automatically lead to a diagnosis of active M. tuberculosis infection and that QFT is one of the supplementary tests in the diagnosis of M. tuberculosis infection. Currently, massive infection with M. tuberculosis is increasing. The precise responsible linkage in massive infection with M. tuberculosis needs DNA polymorphism analysis using variable numbers of tandem repeats (VNTR) or restricted fragment length polymorphism (RFLP).
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.
Bricha, Myriem; Slimani, Hajar; Hammi, Sanae; Bourkadi, Jamal Eddine
Tuberculosis of the oral cavity is rare. It is associated with clinical polymorphism and poses above all a diagnostic problem. We report the case of a 42-year-old male patient with tubercular cheilitis. This study aims to focus attention on tuberculosis that can be detected exceptionally in specific locations, such as the oral lip.
Xi, Xueyan; Han, Xiqin; Li, Liang; Zhao, Zhendong
Background & objectives: The unique immunological functions of γδ T lymphocytes to contribute immunity against Mycobacterium tuberculosis attracted interest of researchers. However, little is known about the specificity of γδ Τ cell in tuberculosis patients and the lack of exact tuberculosis antigen recognized by γδ T cells limited its application. The analysis of complementary determinant region (CDR)3 sequence characteristic in γδ T cells of tuberculosis patients would contribute to understand the distribution specificity of γδ T cell. In present study, we investigated the diversity of the γ9/δ2 T cell immunorepertoire and analysed the specificity of the expressed CDR3 in pulmonary tuberculosis patients. Methods: The total RNA in peripheral blood mononuclear cell of 50 pulmonary tuberculosis patients and 10 healthy controls was extracted. The polymerase chain reaction was used to specifically amplify the CDR3 region of γ9 and δ2 chain. The PCR products were ligated into the pGEM-T easy vector. The plasmid DNA was sequenced using the ABI3700 and the T7 primer. Results: Our findings showed that predominant CDR3 sequence of δ2 chain in pulmonary tuberculosis patients was CACDTLVSTDKLIFGKG. The sequence specifically exists in almost all pulmonary tuberculosis patients. The conserved hydrophobic acid residue in 97 positions is present in the γδ T cell reactive to M. tuberculosis. The length of δ2 CDR3 in pulmonary tuberculosis patients has no relation with the disease progress. Interpretation & conclusions: Our results suggest that γδ T cells appear to use CDR3 sequence to recognise M. tuberculosis antigen. γδ T cells reactive to M. tuberculosis were diverse and polyclonal. PMID:21985819
Garg, Tinu; Gera, Kamal; Modi, Nikhil; Shah, Ashok
Intrathoracic goitre is an uncommon condition which usually occurs in females in the fifth decade. It can cause compression of several mediastinal structures. A 42-year-old female with goitre since childhood was evaluated for dry cough, occasional wheezing and low grade fever. Imaging showed patchy airspace opacities with cavitation in left lung. Imaging of the neck revealed retrosternal extension of the goitre. Stains and cultures of bronchial aspirate were positive for Mycobacterium tuberculosis. A diagnosis of pulmonary tuberculosis with intrathoracic goitre was established, an unusual association.
Díaz Rojas, F; Córdova Gutiérrez, H; Aguirre Gas, H
This paper reviewed 8 cases of spontaneous pneumothorax, associated to pulmonary tuberculosis during a period of time of two years at the A.L.M. General Hospital of Toluca, Mex. The diagnosis was confirmed by clinical picture, radiology and bacteriology studies. Six males and two females proceding of the low class; farmers all of them. Their age ranged between 18 and 35 years. Two of the patients showed cavitary lesions, five had difusse fibrosis of the lung. We analized the clinical manifestations and reviewed the pathogenic mechanisms as well the medical and surgical treatment. No deaths ocurred en this series. We concluded that the direct relation between active pulmonary tuberculosis and spontaneous pneumothorax is not clear, but their association in this serie suggested further studies to stablished this. We emphasized the importance of this complication rare in the world literature.
Gimeno, F; Kraan, J K; Orie, N G; Peset, R
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
Cherif, J; Mjid, M; Ladhar, A; Toujani, S; Mokadem, S; Louzir, B; Mehiri, N; Béji, M
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.
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
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
Belizario, V; Guan, M; Borja, L; Ortega, A; Leonardia, W
The clinical epidemiology of pulmonary paragonimiasis and tuberculosis was investigated in a known endemic municipality of Sorsogon, Philippines. Records of diagnosed tuberculosis patients on treatment and follow up at the local Rural Health Unit over a two year period from 1993 to 1994 were reviewed to provide an overview of pulmonary tuberculosis in the area, specifically to describe the population at risk, the basis for diagnosis and the proportion of case notification who were sputum negative. Patients from the same group of individuals as well as undiagnosed tuberculosis patients with productive cough, fever with chest and/or back pain, or hemoptysis were examined to look into clinical manifestations, duration of symptoms, history of crab-eating and sputum examination results for acid-fast bacilli and Paragonimus. There was difficulty in determining the number of non-responders as the records did not have any provision for the recording of such. Annual tuberculosis case notification rates for the two years (374 and 401 per 100,000 population) were higher than the national figure in 1991 (325 per 100,000 population) indicating that tuberculosis is still a major health problem in the area and tuberculosis control efforts may have to be more aggressive to better contain the disease. Twenty-six out of 160 individuals surveyed were sputum smear positive for Paragonimus. Paragonimiasis rates were not significantly different in the two groups (15.6% vs 16.9%, respectively) indicating that there is a need for routine sputum examination for Paragonimus which is not available at present. Only six patients surveyed were sputum smear positive for acid-fast bacilli. A high index of suspicion is necessary to diagnose paragonimiasis and to be able to differentiate it from tuberculosis. The diagnosis may be suggested by a patient's place of origin being a known endemic area, a long period of chronic cough and the habit of eating raw or insufficiently cooked crabs or crayfish
Oliveira, Marina Gribel; Delogo, Karina Neves; de Oliveira, Hedi Marinho de Melo Gomes; Ruffino-Netto, Antonio; Kritski, Afranio Lineu; Oliveira, Martha Maria
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
The discovery, some nine years ago, of the highly specific antituberculous drug, isoniazid, marked an important advance in the antimicrobial therapy of tuberculosis, first practised successfully with streptomycin and p-aminosalicylic acid (PAS) in the late 'forties. Isoniazid is relatively non-toxic and, unlike streptomycin, can be administered orally, so that it is eminently suitable for use, either alone or in combination with PAS, in the domiciliary treatment of tuberculous patients. The wisdom of employing it on a large scale in home-treatment programmes, however, has been questioned on the ground that such wide-spread use might result in a spread of tubercle bacilli resistant to the drug. This controversial subject is discussed in some detail in this general review of the chemotherapy of tuberculosis. The author is convinced that, so far, the benefits of isoniazid therapy have outweighed the disadvantages and, though well aware of the possible consequences in terms of isoniazid-resistance, sees no reason at the present time for not making full use of this valuable weapon in the antituberculosis armamentarium. PMID:20604078
Munsiff, Sonal S; Kambili, Chrispin; Ahuja, Shama Desai
Rifapentine is a recently approved antituberculosis drug that has not yet been widely used in clinical settings. Clinical data support intermittent use of rifapentine with isoniazid during the continuation phase of tuberculosis treatment. Patients with culture-positive, noncavitary, pulmonary tuberculosis whose sputum smear is negative for acid-fast bacilli at the end of the 2-month intensive treatment phase are eligible for rifapentine therapy. Rifapentine should not be used in human immunodeficiency virus-infected patients, given their increased risk of developing rifampin resistance with currently recommended dosages. Rifapentine is not currently recommended for children aged <12 years, pregnant or lactating women, or individuals with culture-negative or extrapulmonary tuberculosis. Rifapentine (600 mg) is administered once weekly with isoniazid (900 mg) during the continuation phase of treatment. This combination should only be given under direct observation. As with rifampin, drug-drug interactions are common, and regular patient monitoring is required. Ease of administration makes this regimen attractive both for tuberculosis-control programs and for patients.
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
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
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.
Navarro Ballester, A; Marco Domenech, S F
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.
Dorhoi, Anca; Kaufmann, Stefan H E
Heightened morbidity and mortality in pulmonary tuberculosis (TB) are consequences of complex disease processes triggered by the causative agent, Mycobacterium tuberculosis (Mtb). Mtb modulates inflammation at distinct stages of its intracellular life. Recognition and phagocytosis, replication in phagosomes and cytosol escape induce tightly regulated release of cytokines [including interleukin (IL)-1, tumor necrosis factor (TNF), IL-10], chemokines, lipid mediators, and type I interferons (IFN-I). Mtb occupies various lung lesions at sites of pathology. Bacteria are barely detectable at foci of lipid pneumonia or in perivascular/bronchiolar cuffs. However, abundant organisms are evident in caseating granulomas and at the cavity wall. Such lesions follow polar trajectories towards fibrosis, encapsulation and mineralization or liquefaction, extensive matrix destruction, and tissue injury. The outcome is determined by immune factors acting in concert. Gradients of cytokines and chemokines (CCR2, CXCR2, CXCR3/CXCR5 agonists; TNF/IL-10, IL-1/IFN-I), expression of activation/death markers on immune cells (TNF receptor 1, PD-1, IL-27 receptor) or abundance of enzymes [arginase-1, matrix metalloprotease (MMP)-1, MMP-8, MMP-9] drive genesis and progression of lesions. Distinct lesions coexist such that inflammation in TB encompasses a spectrum of tissue changes. A better understanding of the multidimensionality of immunopathology in TB will inform novel therapies against this pulmonary disease.
Pasoto, S G; Borba, E F; Bonfa, E; Shinjo, S K
The objective of the study was to evaluate risk factors for pulmonary tuberculosis in systemic lupus erythematosus (SLE). Clinical/laboratorial features of 1283 SLE patients (ACR criteria) followed at the Lupus Clinic were obtained from the electronic register database from 2001 to 2009. Pulmonary tuberculosis was diagnosed in 20 patients (1.6%) (TB+ group). As control group (TB-), 40 patients without tuberculosis matched for age, gender, ethnicity, age at SLE diagnosis, and disease duration were arbitrarily selected. All 20 patients of the TB+ group presented confirmed pulmonary tuberculosis from 1 to 23 years after SLE diagnosis (7.6 ± 8.1 years). Frequencies of previous SLE involvements (cutaneous, articular, hematological, renal, pericarditis, pneumonitis, and central nervous system) were alike in TB+ and TB- groups (p > 0.05). In contrast, prior pleuritis was more frequent in the TB+ group (40% vs. 5%, p = 0.001). In fact, pulmonary tuberculosis was diagnosed in 8/10 patients with previous pleuritis. Immunosuppressive and corticosteroid therapies at the moment of tuberculosis diagnosis were also similar in both groups (p > 0.05). We have identified pleuritis as a relevant risk factor for pulmonary tuberculosis, suggesting that previous pleural injury is a critical part of the complex interplay between altered immune system, socio-economic conditions, and increased susceptibility to this mycobacterial infection.
Demikhova, O V; Karpina, N L; Lepekha, L N; Bagirov, M A; Amansakhedov, R B
One of the reasons of dramatic situation with tuberculosis in Russia is untimely diagnostics of tuberculosis. The aim of the study was to identify the causes of diagnostic mistakes when we deal with disseminated pulmonary tuberculosis at current stage and to modernize the diagnostic process. The analysis of the diagnostic activity of the consultative diagnostic center of Central Tuberculosis Research Institute of Russian Academy Medical Sciences for 2011 was performed with special attention on the results of the survey of 505 patients with pulmonary dissemination. The frequency of discrepancies of disseminated pulmonary tuberculosis diagnostics was 96.1%. Based on the studies carried out the main causes diagnostic mistakes in patients with disseminated pulmonary tuberculosis were determined. New directions of improving of tuberculosis diagnostics were developed: overall high-technology examination of patient, adherence to the diagnostic procedure, developed by consultative diagnostic center of Central Tuberculosis Research Institute (CTRI), timely performing fiber-optic bronchoscopy with complex biopsy and diagnostic surgery procedures, further training of primary health care doctors. Implementation of proposed activities will significantly (by 3-5 times) reduce the time for diagnostics of respiratory system disease.
Kimura, Yosuke; Kurosawa, Takayuki; Hosaka, Kiminori
A case of pulmonary Mycobacterium kansasii infection with pleural effusion is very rare. We report a case of pulmonary Mycobacterium kansasii infection with pleural effusion, distinguished from pulmonary tuberculosis. A 44-year-old man presented to a clinic with a productive cough, sputum, and loss of appetite for several months. Chest X-ray and chest computed tomography (CT) showed right pleural effusion, centrilobular nodules and infiltrative shadows with cavities in the bilateral lung fields. The direct smear examination showed positive acid-fast bacilli (Gaffky 5). He was referred to our hospital for suspected recurrent pulmonary tuberculosis. We started anti-tuberculosis drugs because pulmonary tuberculosis complicated with pleurisy was first suspected from the findings of high ADA level (78.6 IU/l) of the effusion and positive result of interferon-gamma release assay (QuantiFERON TB-2G). But Mycobacterium tuberculosis and M. avium complex was not identified by the polymerase chain reaction method and the culture of the sputum was negative. At a later date, Mycobacterium kansasii was detected by sputum culture. The patient was diagnosed as pulmonary Mycobacterium kansasii infection and treatment with anti-tuberculosis drugs including RFP resulted in a good clinical response. This case was a rare case of pulmonary Mycobacterium kansasii infection with pleural effusion, distinguished from pulmonary tuberculosis.
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.
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
Meher, Lalit Kumar; Dalai, Siba Prasad; Nayak, Sachidananda; Tripathy, Sujit Kumar
The haematological abnormalities associated with active pulmonary tuberculosis were known to human beings since decades but Immune Thrombocytopenic Purpura (ITP) secondary to pulmonary tuberculosis have been reported only in a couple of instances. We report a 27 year-old male patient who was admitted to our hospital with fever, shortness of breath, haematuria, epistaxis and generalized petechiae. The sputum positivity for Acid Fast Bacilli (AFB) and chest X-ray reports were suggestive of active pulmonary tuberculosis in our patient. Clinical and laboratory parameters including bone marrow aspiration cytology diagnosed the case to be ITP. Patient was put on Directly Observed Treatment and Short course (DOTS) category-1 Anti-Tuberculosis Therapy (ATT) and prednisone following which thrombocytopenia was corrected and there was complete recovery of the patient without recurrence of thrombocytopenia. PMID:27891382
Ono, Hidemaro; Murakami, Reiko; Tsuruwaka, Mia; Suzuki, Yoshihiko
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.
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...
Chang, Jung Hyun; Kim, Jung Hyun; Kang, Ju Wan; Kim, Jeong Hong
Tuberculosis is an important cause of morbidity and mortality world-wide. We report the case of a 52-year-old man who presented with a two month history of sore throat without other general or respiratory symptoms. Oral ex- amination revealed ulcerative and granulomatous lesions on the soft palate and tonsils. Histological examination of the lesions showed granulomatous tissue with caseaous necrosis consistent with tuberculosis. A chest x-ray and computed to- mography of the chest showed miliary tuberculosis of both lungs. The oral lesions improved with antituberculous medication by one month. Tuberculosis should be considered in the differential diagnosis of oral lesions which do not respond to appropriate antibiotic therapy. Pulmonary tuberculosis should also be considered in patients with oral tuberculosis even if they do not have respiratory symptoms.
... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Pulmonary tuberculosis... Rating Considerations Relative to Specific Diseases § 3.370 Pulmonary tuberculosis shown by X-ray in... connection for pulmonary tuberculosis. When under consideration, all available service department films...
Behr, Marcel A; Waters, W Ray
Tuberculosis most commonly presents as a pulmonary disease, in which infection, persistence, and induction of transmissible pathology all occur in the lungs. If viewed as a pulmonary disease, enlarged lymph nodes represent reactive adenitis, and extrapulmonary forms of tuberculosis (including lymphatic tuberculosis) are not transmissible, hence representing an evolutionary dead-end for the pathogen. In an alternative theory, Mycobacterium tuberculosis passes asymptomatically through the lungs and rapidly establishes a chronic lymphatic infection. After a period of weeks to decades secondary lung pathology develops, ultimately allowing transmission to occur. Evidence that supports this lymphatic model includes historical descriptions of human tuberculosis from the preantibiotic era, analogy with other mycobacterial infections, observations of tuberculosis in non-human hosts, and experimental models of tuberculosis disease. At a fundamental level, a lymphocentric model proposes that spread of organisms outside the lung parenchyma is essential to induce adaptive immunity, which is crucial for the generation of transmissible pathology. Furthermore, a lymphatic model could explain why the lesion associated with primary infection (Ghon focus) is anatomically separated from the most common site of reactivation disease (the apex). More practically, an alternative perspective that classes tuberculosis as a lymphatic disease might affect strategies for preclinical and clinical assessment of novel diagnostics, drugs, and vaccines.
Karmakar, Partha Sarathi; Sherpa, Pasang Lahmu; Ray, Achintya Narayan; Saha, Bikram Kr; Santra, Tuhin; Saha, Sanchita; Chakrabarti, Indranil
Mycobacterium tuberculosis infection is a common infection in developing countries, including India. It can induce several cutaneous reactions such as erythema nodosum, and erythema induratum; however, association of tuberculosis with Sweet's syndrome (also known as acute febrile neutrophilic dermatosis) is extremely rare. Here we present an interesting case of sputum-positive pulmonary tuberculosis with Sweet's syndrome. A 55-year-old female who was receiving a regimen of four antitubercular drugs (isoniazid, rifampicin, pyrazinamide, ethambutol- HRZE) for six weeks for sputum-positive pulmonary tuberculosis developed new onset high-grade fever for 15 days along with multiple reddish brown plaques and nodules involving the face as well as all four limbs of the body. Histopathology of the skin lesion was suggestive of Sweet's syndrome. The patient responded well to immunosuppressive steroid therapy.
Kant, Surya; Gupta, Harshita; Ahluwalia, Savita
Malnutrition and tuberculosis are both problems mostly of the developing countries. Tuberculosis can lead to malnutrition and malnutrition may predispose to tuberculosis. Poor nutrition leads to protein-energy malnutrition and micronutrients deficiencies which lead to immunodeficiency. This secondary immunodeficiency increases the host's susceptibility to infection and hence increase the risk for developing tuberculosis. Tuberculosis itself leads to reduction in appetite, nutrient malabsorption, micronutrient malabsorption, and altered metabolism leading to wasting and poor nutritional status. Nutritional status and dietary intake and hence nutritional status of patients get improved during antituberculosis treatment.
Barbareschi, M; Denti, F; Bottelli, S; Greppi, F
A seventy-four-year-old patient had lupus vulgaris associated with the nodular, confluent ulcerated type of pulmonary tuberculosis. The diagnosis had been missed on several occasions. The presence of cutaneous tuberculosis in developed countries is emphasized again. It is also stressed that chronic dermatosis of unknown nature in an immunocompetent patient may have a tubercular origin. Complete resolution of the disease was achieved after almost two years of anti-tubercular therapy.
Bloom, Chloe I.; Graham, Christine M.; Berry, Matthew P. R.; Rozakeas, Fotini; Redford, Paul S.; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A.; Wilkinson, Robert J.; Kendrick, Yvonne; Devouassoux, Gilles; Ferry, Tristan; Miyara, Makoto; Bouvry, Diane; Dominique, Valeyre; Gorochov, Guy; Blankenship, Derek; Saadatian, Mitra; Vanhems, Phillip; Beynon, Huw; Vancheeswaran, Rama; Wickremasinghe, Melissa; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Ho, Ling-pei; Lipman, Marc; O’Garra, Anne
Rationale New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. Objectives To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. Methods We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. Measurements and Main Results An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Conclusions Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the
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.
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
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
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.
Wang, Ping-Huai; Wang, Hao-Chien; Liao, Chun-Hsing
Clinical deterioration during the treatment of tuberculosis remains a diagnostic challenge. We describe the case of a 46-year-old man with a history of oral cancer status after a radical operation who had pulmonary tuberculosis with pleura and neck lymph node involvement. The clinical condition improved after antituberculosis therapy. However, the patient suffered from low-grade fever, progressive dyspnea, and cough after 7 weeks of the therapy. The findings of chest plain films were relapse and progression of left lung haziness. The deterioration was caused by disseminated Penicillium marneffei infection. Disseminated P. marneffei in a non-HIV patient with tuberculosis is rarely seen, and the manifestations are similar to a paradoxical response and relapse of pulmonary tuberculosis, thereby making it difficult to establish a diagnosis.
Sanyika, Charles; Corr, Peter; Royston, Duncan; Blyth, David F.
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.
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...
Ramarokoto, H; Andrianasolo, D; Rasolonavalona, T; Ramaroson, F; Razafitsiarovana, I; Vincent, V; Ratsimba, L; Rasolofo Razanamparany, V
We report a chronic case of pulmonary tuberculosis in a Malagasy citizen from Antsohihy (West of Madagascar), who was infected with a multi-drug resistant Mycobacterium bovis strain. This is the first case reported of the isolation of such a strain in Madagascar.
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
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
de Jong, Bouke C.; Hill, Philip C.; Aiken, Alex; Awine, Timothy; Antonio, Martin; Adetifa, Ifedayo M.; Jackson-Sillah, Dolly J.; Fox, Annette; DeRiemer, Kathryn; Gagneux, Sebastien; Borgdorff, Martien W.; McAdam, Keith P.W.J.; Corrah, Tumani; Small, Peter M.; Adegbola, Richard A.
Considerable variability exists in the outcome of M. tuberculosis infection. We hypothesized that M. africanum was less likely than M. tuberculosis to transmit and progress to tuberculosis disease. In a cohort study of tuberculosis patients and their household contacts in the Gambia, we categorized 1,808 HIV negative tuberculosis contacts according to exposure to M. tuberculosis or to M. africanum. A positive skin test indicated transmission and development of tuberculosis during 2 years of follow-up indicated progression to disease. Transmission was similar, but progression to disease was significantly lower in contacts exposed to M. africanum than to M. tuberculosis (1.0% vs 2.9%; Hazard Ratio (HR) 3.1, 95% CI 1.1–8.7). Within M. tuberculosis sensu stricto, contacts exposed to a Beijing family strain were most likely to progress to disease (5.6%; HR 6.7 (2.0–22) relative to M. africanum). M. africanum and M. tuberculosis transmit equally well to household contacts, but contacts exposed to M. africanum are less likely to progress to tuberculosis disease than those exposed to M. tuberculosis. The variable rate of progression by lineage suggests that TB variability matters in clinical settings and should be taken into account in studies evaluating tuberculosis vaccines and treatment regimens for latent tuberculosis infection. PMID:18702608
Piva, Silvana Gomes Nunes; Costa, Maria da Conceição Nascimento; Barreto, Florisneide Rodrigues; Pereira, Susan Martins
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
Bajaj, Darshan K.; Verma, Ajay K.; Jaiswal, Riddhi; Kant, Surya; Patel, Anand; Asnani, Mona
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
Orme, I M; McMurray, D N; Belisle, J T
Recent years have seen a renewed effort to develop new vaccines against tuberculosis. As a result, several promising avenues of research have developed, including the production of recombinant vaccines, auxotrophic vaccines, DNA vaccines and subunit vaccines. In this article we briefly review this work, as well as consider the pros and cons of the animal models needed to test these new vaccines. Screening to date has been carried out in mouse and guinea pig models, which have been used to obtain basic information such as the effect of the vaccine on bacterial load, and whether the vaccine can prevent or reduce lung pathology. The results to date lead us to be optimistic that new candidate vaccines could soon be considered for evaluation in clinical trials.
Razvodovskiĭ, Iu E
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.
Abidi, Maheen Z; Haque, Javeria; Varma, Parvathi; Olteanu, Horatiu; Guru Murthy, Guru Subramanian; Dhakal, Binod; Hari, Parameswaran
Ruxolitinib is widely in use for treatment of myeloproliferative disorders. It causes inhibition of the Janus kinase (JAK) signal transducer and activation of transcription (STAT) pathway, which plays a key role in the underlying pathophysiology of myeloproliferative diseases. We describe a case of reactivation pulmonary tuberculosis in a retired physician while on treatment with ruxolitinib. We also review the literature on opportunistic infections following use of ruxolitinib. Our case highlights the importance of screening for latent tuberculosis in patients from highly endemic areas prior to start of therapy with ruxolitinib.
Haque, Javeria; Varma, Parvathi; Guru Murthy, Guru Subramanian; Dhakal, Binod; Hari, Parameswaran
Ruxolitinib is widely in use for treatment of myeloproliferative disorders. It causes inhibition of the Janus kinase (JAK) signal transducer and activation of transcription (STAT) pathway, which plays a key role in the underlying pathophysiology of myeloproliferative diseases. We describe a case of reactivation pulmonary tuberculosis in a retired physician while on treatment with ruxolitinib. We also review the literature on opportunistic infections following use of ruxolitinib. Our case highlights the importance of screening for latent tuberculosis in patients from highly endemic areas prior to start of therapy with ruxolitinib. PMID:27843657
Pulmonary tuberculosis (TB) persists as a great public health problem in Korea. Increases in the overall age of the population and the rise of drug-resistant TB have reinforced the need for rapid diagnostic improvements and new modalities to detect TB and drug-resistant TB, as well as to improve TB control. Standard guidelines and recent advances for diagnosing pulmonary TB are summarized in this article. An early and accurate diagnosis of pulmonary TB should be established using chest X-ray, sputum microscopy, culture in both liquid and solid media, and nucleic acid amplification. Chest computed tomography, histopathological examination of biopsy samples, and new molecular diagnostic tests can be used for earlier and improved diagnoses, especially in patients with smear-negative pulmonary TB or clinically-diagnosed TB and drug-resistant TB. PMID:25861338
Rakotosamimanana, Sitraka; Mandrosovololona, Vatsiharizandry; Rakotonirina, Julio; Ramamonjisoa, Joselyne; Ranjalahy, Justin Rasolofomanana; Randremanana, Rindra Vatosoa; Rakotomanana, Fanjasoa
Introduction Tuberculosis infection may remain latent, but the disease is nevertheless a serious public health issue. Various epidemiological studies on pulmonary tuberculosis have considered the spatial component and taken it into account, revealing the tendency of this disease to cluster in particular locations. The aim was to assess the contribution of Knowledge Attitude and Practice (KAP) to the distribution of tuberculosis and to provide information for the improvement of the National Tuberculosis Program. Methods We investigated the role of KAP to distribution patterns of pulmonary tuberculosis in Antananarivo. First, we performed spatial scanning of tuberculosis aggregation among permanent cases resident in Antananarivo Urban Township using the Kulldorff method, and then we carried out a quantitative study on KAP, involving TB patients. The KAP study in the population was based on qualitative methods with focus groups. Results The disease still clusters in the same districts identified in the previous study. The principal cluster covered 22 neighborhoods. Most of them are part of the first district. A secondary cluster was found, involving 18 neighborhoods in the sixth district and two neighborhoods in the fifth. The relative risk was respectively 1.7 (p<10−6) in the principal cluster and 1.6 (p<10−3) in the secondary cluster. Our study showed that more was known about TB symptoms than about the duration of the disease or free treatment. Knowledge about TB was limited to that acquired at school or from relatives with TB. The attitude and practices of patients and the population in general indicated that there is still a stigma attached to tuberculosis. Conclusion This type of survey can be conducted in remote zones where the tuberculosis-related KAP of the TB patients and the general population is less known or not documented; the findings could be used to adapt control measures to the local particularities. PMID:25386655
Chen, Guo; He, Jian-Qing
Abstract Rationale: Disseminated intravascular coagulation (DIC) induced by daily rifampicin therapy is rare, especially the patient is absent of malignancy, severe infection, and prior exposure to rifampicin. Patient concerns: We report a case of DIC induced by daily rifampicin treatment for pulmonary tuberculosis. A 22-year-old, previously healthy man received an anti-tuberculosis therapy consisting of isoniazid, rifampicin, ethambutol, and pyrazinamide on the daily dose recommended by the World Health Organization tuberculosis guidelines after a diagnosis of pulmonary tuberculosis. Two weeks later, he was transferred to the West China Hospital with nasal hemorrhage for 1 week, hematochezia, hematuria, and petechiae for 5 days. Diagnoses: Laboratory data and symptoms on admission indicated DIC. Interventions: The anti-tuberculosis drugs were discontinued after admission and he was initiated with targeted treatment for DIC, omeprazole and polyene hosphatidylcholine infusion, as well as nutrition supportive treatment. Five days after admission, ethambutol, moxifloxacin, and amikacin were added to the patient without further active hemorrhage. Eight days after admission, the platelet count had risen gradually. Isoniazid was administered on 24 days after admission, while his liver function tests and platelet counts returned to normal. No recurrence of DIC occurred. The diagnosis of rifampicin-induced DIC was confirmed. Outcomes: The patient recovered and left hospital with isoniazid, ethambutol, levofloxacin, and streptomycin after 4 weeks of hospitalization. There was no recurrence of DIC or hemorrhage during the 8 months of follow-up. The literature review revealed that there were 10 other cases of rifampicin-induced DIC. Only 4 cases received rifampicin on a daily basis for pulmonary tuberculosis treatment and the others were on intermittent dosing schedule for pulmonary tuberculosis or leprosy treatment. Lessons: As a rare adverse effect, DIC induced by
Leylabadlo, Hamed Ebrahimzadeh; Kafil, Hossein Samadi; Yousefi, Mehdi; Aghazadeh, Mohammad; Asgharzadeh, Mohammad
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.
Jones, F.L. Jr.
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.
Achkar, Jacqueline M.; Dong, Yuxin; Holzman, Robert S.; Belisle, John; Kourbeti, Irene S.; Sherpa, Tsering; Condos, Rany; Rom, William N.; Laal, Suman
The 81-kDa malate synthase (MS; Rv 1837c) and the 27-kDa MPT51 (Rv 3803c) of Mycobacterium tuberculosis are immunodominant antigens recognized by serum antibodies from ∼80% of human immunodeficiency virus-negative smear-positive tuberculosis patients from India. We now provide evidence that the use of the MS/MPT51-based serodiagnostic assay can serve as an adjunct to sputum microscopy in the rapid diagnosis of pulmonary tuberculosis. PMID:17090645
Gera, Kamal; Roshan, Rahul; Varma-Basil, Mandira; Shah, Ashok
Klebsiella species infrequently cause acute community acquired pneumonia (CAP). The chronic form of the disease caused by K. pneumoniae (Friedlander's bacillus) was occasionally seen in the pre-antibiotic era. K. oxytoca is a singularly uncommon cause of CAP. The chronic form of the disease caused by K. oxytoca has been documented only once before. A 50-year-old immunocompetent male smoker presented with haemoptysis for 12 months. Imaging demonstrated a cavitary lesion in the right upper lobe with emphysematous changes. Sputum stains and cultures for Mycobacterium tuberculosis were negative. However, three sputum samples for aerobic culture as well as bronchial aspirate cultured pure growth of K. oxytoca. A diagnosis of chronic pneumonia due to K. oxytoca was established and with appropriate therapy, the patient was largely asymptomatic. The remarkable clinical and radiological similarity to pulmonary tuberculosis can result in patients with chronic Klebsiella pneumonia erroneously receiving anti-tuberculous therapy.
Ugurlu, E; Altinisik, G; Aydogmus, U; Bir, F
A 19-year-old male patient was observed due to having central diabetes insipidus (DI) for five years. He had a history of smoking 5-10 cigarettes a day for two years, but stopped smoking from the last month. The computerized tomography revealed thin-walled cystic lesions in different sizes more dominantly in the upper lobes and consolidated areas in the left upper and lower lobes. The wedge resection from the right lower lobe revealed pulmonary langerhans cell histiocytosis. Follow-up acid-fast bacteria (AFB) examinations revealed (+++) and antituberculous treatment was started. On the 40th day of the anti-tuberculosis treatment, the patient applied once again due to fever and chest pain. Although infiltrations persisted in the left upper and middle zones in the postero-anterior lung rontgenogram, right-sided pneumothorax was detected. The case is considered tuberculosis and the patient continued to receive anti-TB treatment under the close supervision.
Thanachartwet, Vipa; Desakorn, Varunee; Duangrithi, Duangjai; Chunpongthong, Pongsak; Phojanamongkolkij, Kamol; Jitruckthai, Pasakorn; Kasetjaroen, Yuttichai; Pitisuttithum, Punnee
In tuberculosis endemic areas, patients with sputum positive for acid-fast bacilli (AFB) are usually diagnosed and treated for pulmonary tuberculosis. The diagnosis of nontuberculous mycobacteria (NTM) lung disease is often ascertained only after lung disease progression occurs, increasing the risk of severe morbidity and mortality. We conducted a matched case-control study among a prospective cohort of 300 patients with newly diagnosed AFB-positive sputum in Thailand during 2010-2012. We compared clinical and laboratory parameters and outcomes among patients with pulmonary tuberculosis, NTM lung disease and NTM colonization. A mycobacterial culture was performed in all patients. Ten patients with NTM lung disease were compared to 50 patients with pulmonary tuberculosis and 10 patients with NTM colonization. The presence of diabetes mellitus or human immunodeficiency virus infection, were associated with NTM lung disease (p = 0.030). Patients with NTM lung disease had a significantly lower body weight prior to treatment (p = 0.021), a higher body weight change from baseline (p = 0.038), and were more likely to have cavitations on chest radiograph (p = 0.033) than those with NTM colonization. In tuberculosis endemic areas, mycobacterial identification should be performed among patients with impaired immune function. NTM lung disease treatment should be considered in patients with NTM sputum isolates who have a history of significant weight loss or cavitations on chest radiography.
Srilohasin, Prapaporn; Chaiprasert, Angkana; Tokunaga, Katsushi; Nishida, Nao; Prammananan, Therdsak; Smittipat, Nat; Mahasirimongkol, Surakameth; Chaiyasirinroje, Boonchai; Yanai, Hideki; Palittapongarnpim, Prasit
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.
Pavan Kumar, Nathella; Nair, Dina; Banurekha, V V; Dolla, Chandrakumar; Kumaran, Paul; Sridhar, Rathinam; Babu, Subash
Type 2 diabetes mellitus (T2DM) is recognized as major risk factor for the progress of active pulmonary tuberculosis (PTB), although the mechanistic link between diabetes and tuberculosis remains poorly characterized. Moreover, the influence of poorly controlled diabetes on the baseline levels of adipocytokines in the context of tuberculosis has not been explored in detail. To characterize the influence of coexistent DM on adipocytokine levels in pulmonary or latent TB (LTB), we examined circulating levels of adipocytokines in the plasma of individuals with PTB-DM or LTB-DM and compared them with those without DM (PTB or LTB). PTB-DM or LTB-DM is characterized by diminished circulating levels of adiponectin and adipsin and/or heightened circulating levels of leptin, visfatin and PAI-1. In addition, adiponectin and adipsin exhibit a significant negative correlation, whereas leptin, visfatin and PAI-1 display a significant positive correlation with HbA1C levels and random blood glucose levels. Therefore, our data reveal that PTB-DM or LTB-DM is characterized by alterations in the systemic levels of adipocytokines, indicating that altered adipose tissue inflammation underlying Type 2 diabetes potentially contributes to pathogenesis of TB disease.
Aamir, Siddiqua; Aisha
The need to recognize and manage psychiatric co-morbidity in tuberculosis (TB) patients in primary care settings in order to improve adherence to the treatment is now well documented. Pulmonary TB patients at the District TB Control Office and TB Centre in Haripur from December 2007 to March 2008 were evalute in order to assess the frequency of anxiety and depression and continuation of treatment. Forty seven out of 65 (72%) TB patients had severe/moderate level of anxiety and depression according to Hospital Anxiety and Depression Scale (HADS). Fourteen (22%) TB patients with co-morbid anxiety and depression showed multi drug-resistance (MDR-TB).
Lin, Chun-Yu; Chen, Tun-Chieh; Lu, Po-Liang; Lai, Chung-Chih; Yang, Yi-Hsin; Lin, Wei-Ru; Huang, Pei-Ming; Chen, Yen-Hsu
Most cases of adult-onset tuberculosis (TB) result from reactivation of a pre-existing Mycobacterium tuberculosis infection. Mycobacterium tuberculosis usually invades the respiratory tract and most patients develop intrapulmonary TB; however, some patients develop concurrent pulmonary and extra-pulmonary TB. The purpose of the present study was to identify the demographic and clinical factors associated with an increased risk of concurrent extra-pulmonary diseases in patients with pulmonary TB. We compared patients who had isolated pulmonary TB with patients who had concurrent pulmonary and extra-pulmonary TB. We initially analyzed one-million randomly selected subjects from the population-based Taiwan National Health Insurance database. Based on analysis of 5414 pulmonary TB patients in this database, women were more likely than men to have concurrent extra-pulmonary TB (OR: 1.30, p = 0.013). A separate analysis of the Kaohsiung Medical University Hospital database, which relied on sputum culture-proven pulmonary TB, indicated that women were more likely than men to have concurrent extra-pulmonary TB (OR: 1.62, p = 0.039). There was no significant gender difference in extra-pulmonary TB for patients younger than 45 years in either database. However, for patients 45 years and older, women were more likely than men to have concurrent extra-pulmonary TB (insurance database: 9.0% vs. 6.8%, p = 0.016, OR: 1.36; hospital database: 27.3% vs. 16.0%, p = 0.008, OR = 1.98). Our results indicate that among patients who have pulmonary TB, older females have an increased risk for concurrent extra-pulmonary TB.
Realpe, Teresa; Correa, Nidia; Rozo, Juan Carlos; Ferro, Beatriz Elena; Gomez, Verónica; Zapata, Elsa; Ribon, Wellman; Puerto, Gloria; Castro, Claudia; Nieto, Luisa María; Diaz, Maria Lilia; Rivera, Oriana; Couvin, David; Rastogi, Nalin; Arbelaez, Maria Patricia; Robledo, Jaime
Background Phylogeographic composition of M. tuberculosis populations reveals associations between lineages and human populations that might have implications for the development of strategies to control the disease. In Latin America, lineage 4 or the Euro-American, is predominant with considerable variations among and within countries. In Colombia, although few studies from specific localities have revealed differences in M. tuberculosis populations, there are still areas of the country where this information is lacking, as is a comparison of Colombian isolates with those from the rest of the world. Principal Findings A total of 414 M. tuberculosis isolates from adult pulmonary tuberculosis cases from three Colombian states were studied. Isolates were genotyped using IS6110-restriction fragment length polymorphism (RFLP), spoligotyping, and 24-locus Mycobacterial interspersed repetitive units variable number tandem repeats (MIRU-VNTRs). SIT42 (LAM9) and SIT62 (H1) represented 53.3% of isolates, followed by 8.21% SIT50 (H3), 5.07% SIT53 (T1), and 3.14% SIT727 (H1). Composite spoligotyping and 24-locus MIRU- VNTR minimum spanning tree analysis suggest a recent expansion of SIT42 and SIT62 evolved originally from SIT53 (T1). The proportion of Haarlem sublineage (44.3%) was significantly higher than that in neighboring countries. Associations were found between M. tuberculosis MDR and SIT45 (H1), as well as HIV-positive serology with SIT727 (H1) and SIT53 (T1). Conclusions This study showed the population structure of M. tuberculosis in several regions from Colombia with a dominance of the LAM and Haarlem sublineages, particularly in two major urban settings (Medellín and Cali). Dominant spoligotypes were LAM9 (SIT 42) and Haarlem (SIT62). The proportion of the Haarlem sublineage was higher in Colombia compared to that in neighboring countries, suggesting particular conditions of co-evolution with the corresponding human population that favor the success of this
Muller, Beatriz Lima Alezio; Ramalho, Daniela Maria de Paula; dos Santos, Paula Fernanda Gonçalves; Mesquita, Eliene Denites Duarte; Kritski, Afranio Lineu; Oliveira, Martha Maria
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
Huang, Xiaoying; Xu, Xiaomei; Yu, Chang; Fan, Rong; Lu, Yuanyuan; Lu, Sansan; Wang, Liangxing
Pulmonary sequestration is a relatively rare malformation. The incidence of common pyogenic infection in this anomaly is very high. We describe a non-symptomatic, 19-year-old man who was misdiagnosed with left lower lobe pneumonia, which was treated with antibiotics for nearly one month. Contrast-enhanced computed tomography (CT) with multiplanar reconstruction showed an aberrant artery originated from the left side of the descending aorta, and went through the infiltration of the left lower lobe. The patient underwent surgical removal of the affected lobe. Microscopy demonstrated resected sequestrated lung tissue that was mainly composed of caseous necrosis with Langhans cells. And the tuberculosis was just confined to the sequestrated lung without any other sites of lung tuberculous infection. The patient received subsequent antituberculous chemotherapy after his operation. At 4-month follow-up, his clinical status was excellent. There are few reports of sequestration combined with tuberculosis. This case showed us two things: first, a persistent infiltration or consolidation in a same segment, especially in the lower lobe, reminds us of the possibility of sequestration; and second, even if the diagnosis of sequestrated lung is confirmed, we should consider whether the patient has any other diseases, besides the tuberculosis.
Chowdhury, Imran Hussain; Ahmed, Albin Mostaque; Choudhuri, Subhadip; Sen, Aditi; Hazra, Avijit; Pal, Nishith Kumar; Bhattacharya, Basudev; Bahar, Bojlul
Active pulmonary tuberculosis (APTB) is associated with a failure of the host immune system to control the invading Mycobacterium tuberculosis (Mtb). The objective of this study was to quantify and assess the role of serum inflammatory cytokines in active pulmonary tuberculosis patients following anti-tuberculosis drug (ATD) therapy. Blood samples were collected from APTB patients and normal healthy subjects (NHS) (total n=204) at baseline and 2, 4 and 6 months post-therapy and the abundance of serum inflammatory cytokines were measured by cytokine specific ELISA. Compared to NHS, APTB patients at baseline had higher levels of serum pro-inflammatory cytokines IL-12p40 (P<0.001), IFN-γ (P<0.001), TNF-α (P<0.01), IL-1β (P<0.001) and IL-6 (P<0.001) and anti-inflammatory cytokines IL-10 (P<0.001) and TGF-β1 (P<0.001) while there was no change in the level of IL-4. In APTB patients, the serum levels of IFN-γ, TNF-α, IL-6 and TGF-β1 directly relate to the bacterial load while the TNF-α, IL-1β, IL-6 and TGF-β1 relate to radiological severity. At baseline, the IL-6 level in NHS and APTB patients differed most and following ATD therapy, this level rapidly decreased and stabilized by 4-month in APTB patients. It is concluded that a subtle reduction in the serum level of IL-6 of the APTB patients following ATD therapy might play a vital role in immune-protection of the host against Mtb infection and hence the serum IL-6 level can be a useful marker to diagnose the effectiveness of therapy in the patients.
Arnedo-Pena, A; Juan-Cerdán, J V; Romeu-García, A; García-Ferrer, D; Holguín-Gómez, R; Iborra-Millet, J; Gil-Fortuño, M; Gomila-Sard, B; Roach-Poblete, F
A prospective cohort study was conducted from 2009 to 2012 to assess the relationship between serum baseline 25-hydroxivytamin D (vitamin D) status and the incidence of tuberculosis (TB) among 572 contacts of 89 pulmonary TB patients in Castellon, Spain. Three new cases of pulmonary TB occurred, with an incidence density of 3.6 per 1000 person-years. Mean vitamin D status was 13.7 ng/ml for cases and 25.7 ng/ml for non-cases. Vitamin D status showed a significant inverse association with TB incidence (adjusted HR 0.88, 95%CI 0.80-0.97). This result is in line with the hypothesis that vitamin D deficiency is associated with TB incidence.
Hu, H; Teng, G L; Gai, L Z; Yang, Y; Zhu, C J
The aim of this study was to explore the diagnostic and differential diagnosis value of surfactant protein-A (SP-A) in the serum and sputum for pulmonary tuberculosis. A total of 101 patients with pulmonary tuberculosis, 85 healthy volunteers, and 30 chronic obstructive pulmonary disease (COPD) patients were divided into pulmonary tuberculosis group, healthy control group, and COPD group, respectively. SP-A was determined in the serum and sputum in the three groups by enzyme-linked immunosorbent assay. The expression of SP-A in serum was significantly higher (P < 0.05) in the pulmonary tuberculosis group than in the healthy control and COPD groups. There were no differences in the SP-A expression in the sputum among the three groups. There was no significant effect of gender, age, tubercle bacillus antibodies, tuberculin purified protein derivative trial, leukocyte count, neutrophilic granulocyte, lymphocyte percentage, or lung cavities on SP-A levels in serum or sputum for the pulmonary tuberculosis group (P > 0.05). The detection of SP-A in serum and sputum was shown to be of great value for the diagnosis and differential diagnosis of pulmonary tuberculosis, and therefore merits further investigation.
Mengiste, Bezatu; Mesfin, Frehiwot; Godana, Wanzahun
Objectives The aim of this study was to determine factors associated with active pulmonary tuberculosis seen in cases in Ambo Hospital, Ethiopia. Design A facility-based prospective case-control study. Setting Patients attending Ambo Hospital from 01 December 2011 to 29 March 2012. Participants The sample included 312 adult patients attending Ambo Hospital. The main outcome measure was presence of active pulmonary tuberculosis (TB). Explanatory measures Age, gender, occupation, educational status, marital status, place of residence, patient history of TB, family history of TB, human immunodeficiency virus (HIV) infection, smoking, alcohol intake, khat chewing, body mass index (BMI), employment, diabetes, history of asthma, previous history of worm infestation, history of hospitalisation, number of adults living in the household (HH), person per room, housing condition. Results A total of 312 study participants, including 104 active pulmonary tuberculosis (PTB) cases (cases) and 208 non-active PTB cases (controls), were recruited for the present study. Having one or more family member with a history of TB (OR = 4.4; 95% CI: 1.50–12.90), marital status (OR = 7.6; 95% CI: 2.2–12.6), male gender (OR = 3.2; 95% CI: 1.4–7), rural residence (OR = 3.3; P = 0.012), being a current or past smoker (OR = 2.8; 95% CI: 1.1–7.2), BMI < 18.5 (OR = 2.1; 95% CI: 1.03–4.2), HIV infection (OR = 8.8; 95% CI: 2.4–23.8) and a history of worm infestation (OR = 6.4; 95% CI: 2.6–15.4) remained significant independent host-related factors for active PTB. Conclusion Patients who came from a compound with more than two HHs were more likely to develop active PTB than those who came from a compound with only one HH. Those who lived in houses with no windows were more likely to develop active PTB than those who lived in houses with one or more windows, had a family history of TB, lived in rural areas. Sex of the patient was a predicting factor. Not being the owner of the house was
Ahmad, Nawaid; Srinivasan, Koottalai; Panayi, Jeannette; Moudgil, Harmesh
Lumbo-sacral spinal disease due to bovine tuberculosis (TB) in a patient with concurrent pulmonary disease is rare. We report this unpredicted finding in an immunocompetent patient and discuss the natural history in an area of low prevalence.
Altraja, Alan; Jürgenson, Katre; Roosipuu, Retlav; Laisaar, Tanel
Pulmonary foreign body granulomatosis following intravenous administration of medications meant for oral use among drug addicts has been occasionally reported. This condition is often misdiagnosed because of its rarity, but rather due to its similarity to other pulmonary diseases that are more common. Here we report a case of pulmonary intravascular talcosis mimicking miliary tuberculosis in a young male intravenous drug addict from North-Eastern Estonia, known as a hotspot for tuberculosis and drug misuse. The condition was caused by intravenous administration of crushed tablets of diphenhydramine, but miliary tuberculosis was misdiagnosed on patient's demographical, clinical and radiological grounds and a decision to start treatment with four first-line antituberculosis drugs followed. The current report refers to the importance of considering rare causes of pulmonary disseminations with attempts to identify the causative agent and warns against the use of antituberculosis treatment without confirmation of microbiological diagnosis of tuberculosis. PMID:24713715
Altraja, Alan; Jürgenson, Katre; Roosipuu, Retlav; Laisaar, Tanel
Pulmonary foreign body granulomatosis following intravenous administration of medications meant for oral use among drug addicts has been occasionally reported. This condition is often misdiagnosed because of its rarity, but rather due to its similarity to other pulmonary diseases that are more common. Here we report a case of pulmonary intravascular talcosis mimicking miliary tuberculosis in a young male intravenous drug addict from North-Eastern Estonia, known as a hotspot for tuberculosis and drug misuse. The condition was caused by intravenous administration of crushed tablets of diphenhydramine, but miliary tuberculosis was misdiagnosed on patient's demographical, clinical and radiological grounds and a decision to start treatment with four first-line antituberculosis drugs followed. The current report refers to the importance of considering rare causes of pulmonary disseminations with attempts to identify the causative agent and warns against the use of antituberculosis treatment without confirmation of microbiological diagnosis of tuberculosis.
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
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
Gorospe, Luis; Ayala-Carbonero, Ana María; Rodríguez-Díaz, Ricardo; García Latorre, Raquel; Muñoz-Molina, Gemma María; Cabañero-Sánchez, Alberto
A 62-year-old woman presented to our hospital with an anterior chest wall swelling. Computed tomography (CT) and magnetic resonance imaging showed findings consistent with an infectious arthritis of the manubriosternal joint, and CT images also demonstrated multiple centrilobular nodules in both lungs, suggesting an infectious bronchiolitis. A CT-guided fine needle aspiration of a presternal mass yielded growth of Mycobacterium tuberculosis. Bronchoalveolar lavage confirmed an active pulmonary tuberculosis. Septic arthritis of the manubriosternal joint is exceedingly rare.
Owczarek, Witold; Targowski, Tomasz; Kozera-Zywczyk, Anna; Paluchowska, Elwira; Patera, Janusz
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.
Holden, Helen M.; Quinlan, J. J.; Hiltz, J. E.
Eighty patients with carcinoma of the lung have been treated at the Nova Scotia Sanatorium since 1940; in 15, coexisting active pulmonary tuberculosis was present. No characteristic clinical or roentgenological findings indicated that the tuberculous individual also had lung cancer. In four cases cancer was not diagnosed until the lung was examined by the pathologist. In the others a considerable interval elapsed before carcinoma was suspected. Only four patients with known cancer were considered suitable for thoracotomy. In three, an attempt at curative resection was made. One survived over seven years before accidental death; one is alive less than one year after operation; the third died as a result of the surgery. Bronchogenic carcinoma should be suspected in every tuberculous patient over the age of 50; diagnostic investigations should include bronchoscopy and cytological studies of bronchial secretion and sputum. Suspicion of carcinoma in any such patient constitutes an indication for early resection of the tuberculous disease. PMID:5843871
The authors analyze the results of surgical treatment for bilateral destructive pulmonary tuberculosis in 234 patients who have under- gone 449 lung operations. A study group comprised 156 patients who received mini-invasive surgical treatments via mini-accesses under video-assisted thoracoscopic control. A comparison group included 78 patients operated on through standard approaches by the conventional procedures. In the study group, surgery of less duration was attended by less blood loss, a need for fewer blood transfusions, and the lower incidence and severity of intraoperative complications. Complications following mini-invasive surgery occurred 4 times less frequently and postoperative mortality was 5 times less than that in the comparison group. With mini-invasive surgical techniques, a complete clinical effect at surgical hospital discharge was achieved 1.5-fold more frequently and it was more steady-state in the late period.
Esmail, H; Lai, RP; Lesosky, M; Wilkinson, KA; Graham, CM; Coussens, AK; Oni, T; Warwick, JM; Said-Hartley, Q; Koegelenberg, CF; Walzl, G; Flynn, JL; Young, DB; Barry, CE; O’Garra, A; Wilkinson, RJ
Tuberculosis is classically divided into states of latent infection and active disease. Using combined positron emission and computed tomography in 35 asymptomatic, antiretroviral therapy naïve, HIV-1 infected adults with latent tuberculosis, we identified ten individuals with pulmonary abnormalities suggestive of subclinical, active disease who were significantly more likely to progress to clinical disease. Our findings challenge the conventional two-state paradigm and may aid future identification of biomarkers predictive of progression. PMID:27595321
Ostanin, Alexander A.; Khonina, Nataliya A.; Norkin, Maxim N.; Leplina, Olga Yu.; Nikonov, Sergey D.; Ogirenko, Anatoly P.; Chernykh, Helen R.
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.
... 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...
... 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...
... 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...
... 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...
... 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...
Volchegorskiĭ, I A; Novoselov, P N; Astakhova, T V
The aim of this prospective placebo-controlled randomized study was to assess the effectiveness of ascorbic acid or emoxipin in the regimen of the therapy of infiltrative pulmonary tuberculosis. Emoxipin vs. ascorbic acid favored the eradication of tuberculosis mycobacteria. Both preparations decreased the blood level of the contra-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), shortened time to the closure of degeneration cavities in tubercular infiltrations, decreased the risk of the development of destructive forms, and lowered the need for surgical interventions for infiltrative pulmonary tuberculosis.
Keflie, Tibebe Seyoum; Ameni, Gobena
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
Akhtar, Saeed; Mohammad, Hameed GHH
Background There is a paucity of published data on the pattern of pulmonary tuberculosis among migrant workers entering Middle Eastern countries particularly Kuwait. The objectives of this study were to use routine health surveillance data i) to estimate the prevalence of pulmonary tuberculosis among migrant workers at entry in Kuwait and ii) to determine the occurrence of any time trends in the proportions of pulmonary tuberculosis positive workers over the study period. Methods The monthly aggregates of daily number of migrants tested and the number of pulmonary tuberculosis cases detected during routine health examinations of migrant workers from tuberculosis high-prevalence countries were used to generate the monthly series of proportions (per 100,000) of pulmonary tuberculosis cases over 120 months between January 1, 1997 and December 31, 2006 and analysed using time series methods. Results The overall prevalence (per 100,000) of documented pulmonary tuberculosis cases among screened migrants was 198 (4608/2328582). Year-specific prevalence (per 100,000) of tuberculosis cases consistently declined from 456 (95% CI: 424 – 490) in 1997 to 124 (95% CI: 110 – 140) in 2002 before showing a steady increase up to 183 (95% CI: 169–197) in 2006. The second-order polynomial regression model revealed significant (P < 0.001) initial decline, followed by a significant (P < 0.001) increasing trend thereafter in monthly proportions of tuberculosis cases among migrant workers. Conclusion The proportions of documented tuberculosis cases among migrant workers showed a significant nonlinear pattern, with an initial decline followed by a significant increasing trend towards the end of the study period. These findings underscore the need to maintain the current policy of migrants' screening for tuberculosis at entry. The public health authorities in Kuwait and perhaps other countries in the region may consider complementing the current screening protocol with interferon
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
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
Grigorian, V A; Golovchenko, R N; Ustinov, A I
The case histories of 428 patients operated on for tuberculosis were analyzed. Three groups were identified. They were as follows: 1) 121 patients untreated with bactericidal drugs before surgery; 2) 247 patients treated less than 6 months before it; 3) 160 patients treated more than 6 months before surgery. Various complications due to resection of the lung were observed in 30 (7%) patients undergone surgery. They were 6.6, 6.8, and 7.5% in Groups 1, 2, and 3, respectively. A clinical effect was achieved in 99.8% of cases. The late outcomes of surgical intervention were studied within 1 to 10 years in 354 patients, including 102, 119, and 133 patients in Groups 1, 2, and 3, respectively. Progressive and recurrent tuberculosis was revealed in 7 (6.8%), 11 (9.2%), and 18 (13.5%), respectively. Thus, immediate and late outcomes of surgical treatment were not worse in patients with tuberculomas untreated with bactericidal drugs before surgery than in those who receive long-term therapy that substantially reduces the duration of therapy, which is a most important task of modern phthisiology. So patients should be operated on when they are found to have pulmonary tuberculomas without signs of a progressive tuberculous process.
Hamada, Manabu; Urabe, Kazunori; Moroi, Yoichi; Koga, Tetsuya; Takeishi, Masaaki; Fujita, Masaki; Nakanishi, Yoichi; Furue, Masutaka
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).
Zhang, Liqun; Pang, Yu; Yu, Xia; Wang, Yufeng; Lu, Jie; Gao, Mengqiu; Huang, Hairong; Zhao, Yanlin
Pulmonary cavitation is one of the most frequently observed clinical characteristics in tuberculosis (TB). The objective of this study was to investigate the potential risk factors associated with cavitary TB in China. A total of 385 smear-positive patients were enrolled in the study, including 192 (49.9%) patients with cavitation as determined by radiographic findings. Statistical analysis revealed that the distribution of patients with diabetes in the cavitary group was significantly higher than that in the non-cavitary group (adjusted odds ratio (OR) (95% confidence interval (CI)):12.08 (5.75–25.35), P<0.001). Similarly, we also found that the proportion of individuals with multidrug-resistant TB in the cavitary group was also higher than that in the non-cavitary group (adjusted OR (95% CI): 2.48 (1.52–4.07), P<0.001). Of the 385 Mycobacterium tuberculosis strains, 330 strains (85.7%) were classified as the Beijing genotype, which included 260 strains that belonged to the modern Beijing sublineage and 70 to the ancient Beijing sublineage. In addition, there were 80 and 31 strains belonging to large and small clusters, respectively. Statistical analysis revealed that cavitary disease was observed more frequently among the large clusters than the small clusters (P=0.037). In conclusion, our findings demonstrate that diabetes and multidrug resistance are risk factors associated with cavitary TB. In addition, there was no significant difference in the cavitary presentation between patients infected with the Beijing genotype strains and those infected with the non-Beijing genotype strains. PMID:27729644
Malherbe, Stephanus T.; Shenai, Shubhada; Ronacher, Katharina; Loxton, Andre G.; Dolganov, Gregory; Kriel, Magdalena; Van, Tran; Chen, Ray Y.; Warwick, James; Via, Laura E.; Song, Taeksun; Lee, Myungsun; Schoolnik, Gary; Tromp, Gerard; Alland, David; Barry, Clifton E.; Winter, Jill; Walzl, Gerhard
The absence of a gold standard to determine when antibiotics have induced sterilizing cure confounds the development of new approaches to treat pulmonary tuberculosis (PTB). We detected PET-CT imaging response patterns consistent with active disease along with the presence of Mycobacterium tuberculosis mRNA in sputum and bronchoalveolar lavage samples in a substantial proportion of adult, HIV-negative PTB patients after standard 6-month treatment plus one year follow-up, including patients with a durable cure and others who later developed recurrent disease. The presence of MTB mRNA in the context of non-resolving and intensifying lesions on PET-CT might indicate ongoing transcription, suggesting that even apparently curative PTB treatment may not eradicate all organisms in most patients. This suggests an important complementary role for the immune response in maintaining a disease-free state. Sterilizing drugs or host-directed therapies and better treatment response markers are likely needed for the successful development of improved and shortened PTB treatment strategies. PMID:27595324
Zhao, Wei; Tian, Yuke; Peng, Feng; Long, Jianlin; Liu, Lan; Lu, You
Pulmonary infections and lung cancer can resemble each other on radiographic images, which makes it difficult to diagnosis accurately and apply an appropriate therapy. Here we report two cases that two postoperative patients with lung adenocarcinoma developed diffuse nodules in bilateral lungs in a month which needed to be distinguished between metastatic malignancies and infectious diseases. Although there are much similarities in disease characteristics of two cases, patient in case one was diagnosed as acute miliary pulmonary tuberculosis (TB) while patient in case two was diagnosed as metastatic disease. The symptoms and pulmonary foci on CT scan of patient in case one improved distinctly after the immediate anti-TB treatment, but the disease of patient in case two progressed after chemotherapy. These findings caution us that differential diagnosis is crucial and have significance in guiding clinical work. PMID:28275493
Seddon, Jo; Kasprowicz, Victoria; Walker, Naomi F.; Yuen, Ho Ming; Sunpath, Henry; Tezera, Liku; Meintjes, Graeme; Wilkinson, Robert J.; Bishai, William R.; Friedland, Jon S.; Elkington, Paul T.
Background. Tuberculosis is transmitted by patients with pulmonary disease. Matrix metalloproteinases (MMPs) drive lung destruction in tuberculosis but the resulting matrix degradation products (MDPs) have not been studied. We investigate the hypothesis that MMP activity generates matrix turnover products as correlates of lung pathology. Methods. Induced sputum and plasma were collected prospectively from human immunodeficiency virus (HIV) positive and negative patients with pulmonary tuberculosis and controls. Concentrations of MDPs and MMPs were analyzed by ELISA and Luminex array in 2 patient cohorts. Results. Procollagen III N-terminal propeptide (PIIINP) was 3.8-fold higher in induced sputum of HIV-uninfected tuberculosis patients compared to controls and desmosine, released during elastin degradation, was 2.4-fold higher. PIIINP was elevated in plasma of tuberculosis patients. Plasma PIIINP correlated with induced sputum MMP-1 concentrations and radiological scores, demonstrating that circulating MDPs reflect lung destruction. In a second patient cohort of mixed HIV seroprevalence, plasma PIIINP concentration was increased 3.0-fold above controls (P < .001). Plasma matrix metalloproteinase-8 concentrations were also higher in tuberculosis patients (P = .001). Receiver operating characteristic analysis utilizing these 2 variables demonstrated an area under the curve of 0.832 (P < .001). Conclusions. In pulmonary tuberculosis, MMP-driven immunopathology generates matrix degradation products. PMID:23922364
Muñoz-Torrico, Marcela; Rendon, Adrian; Centis, Rosella; D'Ambrosio, Lia; Fuentes, Zhenia; Torres-Duque, Carlos; Mello, Fernanda; Dalcolmo, Margareth; Pérez-Padilla, Rogelio; Spanevello, Antonio; Migliori, Giovanni Battista
ABSTRACT The role of tuberculosis as a public health care priority and the availability of diagnostic tools to evaluate functional status (spirometry, plethysmography, and DLCO determination), arterial blood gases, capacity to perform exercise, lesions (chest X-ray and CT), and quality of life justify the effort to consider what needs to be done when patients have completed their treatment. To our knowledge, no review has ever evaluated this topic in a comprehensive manner. Our objective was to review the available evidence on this topic and draw conclusions regarding the future role of the "post-tuberculosis treatment" phase, which will potentially affect several million cases every year. We carried out a non-systematic literature review based on a PubMed search using specific keywords (various combinations of the terms "tuberculosis", "rehabilitation", "multidrug-resistant tuberculosis", "pulmonary disease", "obstructive lung disease", and "lung volume measurements"). The reference lists of the most important studies were retrieved in order to improve the sensitivity of the search. Manuscripts written in English, Spanish, and Russian were selected. The main areas of interest were tuberculosis sequelae following tuberculosis diagnosis and treatment; "destroyed lung"; functional evaluation of sequelae; pulmonary rehabilitation interventions (physiotherapy, long-term oxygen therapy, and ventilation); and multidrug-resistant tuberculosis.The evidence found suggests that tuberculosis is definitively responsible for functional sequelae, primarily causing an obstructive pattern on spirometry (but also restrictive and mixed patterns), and that there is a rationale for pulmonary rehabilitation. We also provide a list of variables that should be discussed in future studies on pulmonary rehabilitation in patients with post-tuberculosis sequelae. PMID:27812638
Opanasenko, M S; Levanda, L I; Kononenko, V A; KYimenko, V I; Tereshkovych, O V; Kalenychenko, M I; Konik, V M; Obrems'ka, O K; Demus, R S; Kshanovs'kyĭ, O E
Actual issue, concerning coexistent pulmonary tuberculosis and diabetes mellitus, was studied. The data about the rate of various types of diabetes mellitus in phthysiosurgery were adduced. The results of surgical treatment of 116 patients, suffering pulmonary tuberculosis on the diabetes mellitus background, were summarized. Total efficacy of the treatment have constituted 96.0%. The surgical complications rate was 12.2%.
Raveendran, Reena; Oberoi, Jaswinder Kaur; Wattal, Chand
Background & objectives: Multidrug-resistant tuberculosis (MDR-TB) is a public health problem of great significance in India. In the present study an attempt was made to analyse the progression of MDR-TB pattern during a course of 13 years (2000-2012) among the patient population at a tertiary care centre in New Delhi, India. Methods: Mycobacterial isolates obtained on Lowenstein-Jensen (L-J) medium/BacT/ALERT 3D were identified using AccuProbe molecular identification system, routine biochemical tests or GenoType Mycobacteria CM. Antimycobacterial susceptibility testing was performed using resistance ratio method on L-J medium (2000-2004) and one per cent proportion method on BacT/ALERT 3D system (2005-2012). Results: Of the total 14,849 samples subjected to mycobacterial culture, 6569 pulmonary and 8280 extrapulmonary, 2364 were detected positive for mycobacteria. The average percentage positivity rate was 15.9 per cent (18.9 and 13.6% in case of pulmonary and extrapulmonary samples, respectively). Our study revealed a significant increase (P<0.001) in multidrug resistance by 12 per cent (4.7% in 2000 to 19.8% in 2012). MDR-TB was more in case of pulmonary (28.2%) than extrapulmonary (11.6%) TB (P<0.001). Only 6.5 per cent (154) of mycobacterial isolates were non-tuberculous mycobacteria and rapid growers represented by Mycobacterium fortuitum and M. abscessus were the most commonly isolated species. Interpretation & conclusions: Increase in prevalence of MDR-TB by 12 per cent in the past 13 years is alarming. Policy modifications may have to be done to strengthen the existing TB control programmes to encourage contact tracing and culture and drug susceptibility testing for all smear positive pulmonary cases to ensure early and appropriate therapy. PMID:26658593
Ishibatake, H; Onizuka, R
We experienced small outbreaks of M. tuberculosis infection in two bars. 9 patients were diagnosed as tuberculosis by identifying M. tuberculosis from their sputa. Six of them were regular customers or employees of the bar, one of them was a family members. Each outbreak within the two bars was suspected of the common source of infection, because one patient was a regular customer of the both bars. The analysis of restriction fragment length polymorphism (RFLP) was done on 5 strains of M. tuberculosis which were isolated from five of 9 patients. The result unexpectedly showed that 5 isolates were classified into 3 groups. Within each group, identical fingerprints were shown. It does mean that each outbreak in two bars was originated from independent source. There was also one relapsed case of tuberculosis. He was suspected of relapsed tuberculosis after a period of 7 years because of the similarity of drug resistance compared with his primary tuberculosis. It was cleared up that 3 different strains of M. tuberculosis were concerned with these outbreaks in the two bars. In this case, almost all patients were heavy drinkers, however, liver dysfunction and malnutrition were not recognized among them. These experiences indicate that a place like bar may be a space of infection of M. tuberculosis. We should always keep in mind a spread of tuberculosis in a place like a bar as one of problems in tuberculosis control.
Hatherill, Mark; Hawkridge, Tony; Whitelaw, Andrew; Tameris, Michele; Mahomed, Hassan; Moyo, Sizulu; Hanekom, Willem; Hussey, Gregory
Objective To evaluate the frequency and clinical significance of non-tuberculous mycobacteria (NTM) isolates among children investigated for pulmonary tuberculosis in a rural South African community. Methods Children were investigated for pulmonary tuberculosis as part of a tuberculosis vaccine surveillance program (2001–2005). The clinical features of children in whom NTM were isolated, from induced sputum or gastric lavage, were compared to those with culture-proven M. tuberculosis. Results Mycobacterial culture demonstrated 114 NTM isolates from 109 of the 1,732 children investigated, a crude yield of 6% (95% CI 5–7). The comparative yield of positive NTM cultures from gastric lavage was 40% (95% CI 31–50), compared to 67% (95% CI 58–76) from induced sputum. 95% of children with NTM isolates were symptomatic. Two children were HIV-infected. By contrast, M. tuberculosis was isolated in 187 children, a crude yield of 11% (95% CI 9–12). Compared to those with culture-proven M. tuberculosis, children with NTM isolates were less likely to demonstrate acid-fast bacilli on direct smear microscopy (OR 0.19; 95% 0.0–0.76). Children with NTM were older (p<0.0001), and more likely to demonstrate constitutional symptoms (p = 0.001), including fever (p = 0.003) and loss of weight or failure to gain weight (p = 0.04), but less likely to demonstrate a strongly positive tuberculin skin test (p<0.0001) or radiological features consistent with pulmonary tuberculosis (p = 0.04). Discussion NTM were isolated in 6% of all children investigated for pulmonary tuberculosis and in more than one third of those with a positive mycobacterial culture. NTM may complicate the diagnosis of PTB in regions that lack capacity for mycobacterial species identification. The association of NTM isolates with constitutional symptoms suggestive of host recognition requires further investigation. PMID:17183648
Padilla-Velázquez, Rosario; Valle-Alvarado, Gabriel; Arriaga-Nieto, Lumumba; Rojas-Mendoza, Teresita; Rosado-Quiab, Ulises; Grajales-Muñiz, Concepción
Background Tuberculosis and HIV remain a public health problem in developed countries. The objective of this study was to analyze the incidence trends of pulmonary TB and HIV comorbidity and treatment outcomes according to HIV during the period 2006 to 2014 in the Mexican Institute of Social Security. Methods Analyzed data from this registry including pulmonary tuberculosis patients aged 15 years and older who had been diagnosed during the years 2006 to 2014 in the Mexican Institute of Social Security. The outcomes that we use were incidents rate, failure to treatment and death. Regression models were used to quantify associations between pulmonary tuberculosis and HIV mortality. Results During the study period, 31,352 patients were registered with pulmonary tuberculosis. The incidence rate observed during 2014 was 11.6 case of PTB per 100,000. The incidence rate for PTB and HIV was 0.345 per 100,000. The PTB incidence rate decreased by 0.07%, differences found in the PTB incidence rate by sex since in women decreased by 5.52% and in man increase by 3.62%. The pulmonary TB with HIV incidence rate decreased by 16.3% during the study period (In women increase 4.81% and in man decrease 21.6%). Analysis of PTB associated with HIV by age groups revealed that the highest incidence rates were observed for the 30 to 44 years old group. Meanwhile, the highest incidence rates of PTB without HIV occurred among the 60 and more years old individuals. We did not find statistically significant differences between treatment failure and PTB patients with HIV and without HIV. The treatment failure was associated with sex and the region of the patient. We found a strong association between HIV and the probability of dying during treatment. Our data suggested that patients suffering from both conditions (PTB and HIV) have no difference in the probability of failure of treatment contrary to other reports. Hypotheses to this is adherence to tuberculosis treatment with people living with
Essential facts Tuberculosis (TB) is an infection caused by a bacterium, mycobacterium tuberculosis. While it can affect any part of the body, only pulmonary TB is infectious. According to the charity TB Alert, there were 5,758 cases of TB in the UK in 2015 and 39% of them were in London. This represented a fall from a peak of 8,919 cases in 2011. Left untreated, TB is life-threatening, but is usually curable with antibiotics. The sooner it is diagnosed and treated, the better, both for the person's health and in preventing them from passing the infection on to others.
Essential facts Tuberculosis (TB) is an infection caused by a bacterium, mycobacterium tuberculosis. While it can affect any part of the body, only pulmonary TB is infectious. According to the charity TB Alert, there were 5,758 cases of TB in the UK in 2015 and 39% of them were in London. This represented a fall from a peak of 8,919 cases in 2011. Left untreated, TB is life-threatening, but is usually curable with antibiotics. The sooner it is diagnosed and treated, the better, both for the person's health and in preventing them from passing the infection on to others.
Zar, Heather J.; Workman, Lesley J.; Little, Francesca; Nicol, Mark P.
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
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
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
Meyer, Christian G; Scarisbrick, Genevieve; Niemann, Stefan; Browne, Edmund N L; Chinbuah, Margaret Amanua; Gyapong, John; Osei, Ivy; Owusu-Dabo, Ellis; Kubica, Tanja; Rüsch-Gerdes, Sabine; Thye, Thorsten; Horstmann, Rolf D
Although Mycobacterium africanum is being isolated in a significant proportion of cases of pulmonary tuberculosis in West Africa, its pathogenic potential remains a matter of discussion. Recent reports leave the question of whether M. africanum causes more severe pathology than M. tuberculosis or resembles opportunistic pathogens and might gain importance in the course of the HIV pandemic. Patients with pulmonary tuberculosis associated with M. africanum (n=556) and M. tuberculosis (n=1350) were studied in Ghana, West Africa, and compared regarding self-reported signs and symptoms, chest radiography, HIV status, mycobacterial drug resistance and mycobacterial clustering as determined by spoligotyping and IS6110 fingerprints. The rate of M. africanum infections was similar in HIV-positive (27%) and HIV-negative (30%) patients. M. africanum clustered less than M. tuberculosis (21% vs 79%; OR, 0.38; 95% CI, 0.3-0.5; p<0.001) corresponding to its lower prevalence (29% vs 70%). Clinically and radiographically, no significant differences were found except that M. africanum caused lower-lobe disease less frequently than M. tuberculosis (OR, 0.39; 95% CI, 0.2-0.7; Pc=0.01), whereby this association applied to HIV-negative patients only. No difference in virulence, as assessed by the severity of radiological presentation, was found when the two M. africanum subtypes West African 1 and West African 2 were compared. In the population studied, M. africanum closely resembled M. tuberculosis in pathology and cannot be considered an opportunistic pathogen.
Khukhunaishvili, R; Tskvitinidze, S; Nagervadze, M; Akhvlediani, L; Koridze, M
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.
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
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
Binesh, Fariba; Jalali, Hadi; Zare, Mohammad Reza; Behravan, Farhad; Tafti, Arefeh Dehghani; Behnaz, Fatemah; Tabatabaee, Mohammad; Shahcheraghi, Seyed Hossein
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
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
Nguen, V Kh; Stroganov, P V; Geshelin, S A
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.
Orofino-Costa, Rosane; Unterstell, Natasha; Carlos Gripp, Alexandre; de Macedo, Priscila Marques; Brota, Arles; Dias, Emylli; de Melo Teixeira, Marcus; Felipe, Maria Sueli; Bernardes-Engemann, Andréa R; Lopes-Bezerra, Leila Maria
A 32-year-old HIV negative male presented with multiple pulmonary cavitation and skin abscesses up to 15 cm in diameter mimicking tuberculosis. Sporothrix brasiliensis was isolated and patient responded well to amphotericin B followed by itraconazole, except the skin lesions that had to be surgical drained to obtain cure. PMID:24432220
...: Developing Drugs for Treatment; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice... industry entitled ``Pulmonary Tuberculosis: Developing Drugs for Treatment.'' The purpose of the draft guidance is to assist sponsors in the development of antimycobacterial drugs for the treatment of...
... connection for pulmonary tuberculosis. When under consideration, all available service department films and subsequent films will be secured and read by specialists at designated stations who should have a current examination report and X-ray. Resulting interpretations of service films will be accorded the...
... connection for pulmonary tuberculosis. When under consideration, all available service department films and subsequent films will be secured and read by specialists at designated stations who should have a current examination report and X-ray. Resulting interpretations of service films will be accorded the...
... connection for pulmonary tuberculosis. When under consideration, all available service department films and subsequent films will be secured and read by specialists at designated stations who should have a current examination report and X-ray. Resulting interpretations of service films will be accorded the...
Aggarwal, Deepak; Chander, Jagdish; Janmeja, Ashok K.; Katyal, Rahul
Uncontrolled diabetes mellitus is associated with a variety of infections which pose management difficulties. Herein, we report a case of diabetic patient who developed combined pulmonary tuberculosis and mucormycosis. The case illustrates management of this rare co-infection which despite being potentially fatal was treated successfully. PMID:25624598
Aggarwal, Deepak; Chander, Jagdish; Janmeja, Ashok K; Katyal, Rahul
Uncontrolled diabetes mellitus is associated with a variety of infections which pose management difficulties. Herein, we report a case of diabetic patient who developed combined pulmonary tuberculosis and mucormycosis. The case illustrates management of this rare co-infection which despite being potentially fatal was treated successfully.
Schulthess, G; Osterwalder, P; Valentini, T; Bicik, I; Widmer, U
A 21-year-old woman suffered from cramplike abdominal pain, flatulence and occasional diarrhoea for about one year. Over the past few weeks the abdominal symptoms exacerbated, besides productive cough and subfebrile temperatures developed. Coloscopy revealed two isolated, short ulcers in the proximal colon. The histological examination of the biopsies taken from these ulcers indicated granulomatous inflammation. Moreover small acinar infiltrates in both pulmonary apices were visualized. The findings in this patient originating from Turkey were suspicious for intestinal and pulmonary tuberculosis. Though sensitive methods were used (Ziehl-Neelson stam, amplified M. tuberculosis direct test, a polymerase chain reaction) direct tests allowed no detection of mycobacteria. Antituberculous therapy was initiated on a probatory basis to which the patient responded well and promptly. The diagnosis was confirmed by culture results: M. tuberculosis was grown from colonic biopsies, morning sputa and bronchioalveolar lavage.
Shkurupiĭ, V A; Odintsova, O A; Kazarinova, N V; Tkrachenko, K G
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.
Yang, Jinghui; Chen, Jin; Yue, Jun; Liu, Lirong; Han, Min; Wang, Hongxiu
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.
Arghir, Oana Cristina; Niţu, Mimi; Trenchea, Mihaela; Ciobotaru, Camelia
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.
This is a case report on a 42-year old West. German woman suspected of suffering from an extrapulmonary manifestation of mucous membrane tuberculosis of the ethmoid sinuses. The condition did not improve after application of specific chemotherapy. Only after histological examination of several tissue samples was a direct connection with initial stage Wegeners granulomatosis established. Attention must be drawn to the fact that in isolated cases the differentiation between the histological diagnosis of tuberculosis versus Wegeners disease is complex and often faulty.
Mandal, Sanjay Kumar; Ghosh, Sudip; Mondal, Soumya Sarathi; Chatterjee, Sumanta
Tuberculosis and sarcoidosis are multisystem diseases having different aetiology and management; however, they have similar clinical and histological characteristics. Very rarely they may coexist. We report a rare case of a 38-year-old woman who presented with chronic cough, low-grade fever and respiratory distress that was initially diagnosed as miliary tuberculosis. Diagnosis was supported by positive mycobacterial culture and initially responded to antitubercular treatment, but later recurrences led to further investigations and the diagnosis of coexisting sarcoidosis.
Dietze, Reynaldo; Hadad, David Jamil; McGee, Bryan; Molino, Lucilia Pereira Dutra; Maciel, Ethel Leonor Noia; Peloquin, Charles A.; Johnson, Denise F.; Debanne, Sara M.; Eisenach, Kathleen; Boom, W. Henry; Palaci, Moises; Johnson, John L.
Rationale: Linezolid, the first oxazolidinone approved for clinical use, has effective in vitro and promising in vivo activity against Mycobacterium tuberculosis. Objectives: To evaluate the early and extended early bactericidal activity of linezolid in patients with pulmonary tuberculosis. Methods: Randomized open label trial. Thirty patients with newly diagnosed smear-positive pulmonary tuberculosis (10 per arm) were assigned to receive isoniazid (300 mg daily) and linezolid (600 mg twice daily or 600 mg once daily) for 7 days. Sputum for quantitative culture was collected for 2 days before and then daily during 7 days of study drug administration. Bactericidal activity was estimated by measuring the decline in bacilli during the first 2 days (early bactericidal activity) and the last 5 days of study drug administration (extended early bactericidal activity). Measurements and Main Results: The mean early bactericidal activity of isoniazid (0.67 log10 cfu/ml/d) was greater than that of linezolid twice and once daily (0.26 and 0.18 log10 cfu/ml/d, respectively). The extended early bactericidal activity of linezolid between Days 2 and 7 was minimal. Conclusions: Linezolid has modest early bactericidal activity against rapidly dividing tubercle bacilli in patients with cavitary pulmonary tuberculosis during the first 2 days of administration, but little extended early bactericidal activity. Clinical trial registered with www.clinicaltrials.gov (NCT00396084). PMID:18787216
Tyne, Anneliese S; Chan, John Gar Yan; Shanahan, Erin R; Atmosukarto, Ines; Chan, Hak-Kim; Britton, Warwick J; West, Nicholas P
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.
Jiménez Borré, Gustavo; Gómez Camargo, Doris; Chalavé Jiménez, Neylor; Bellido Rodríguez, Javier; Cuadrado Cano, Bernarda; Navarro Gómez, Shirley
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
Hernández-Pando, R; Orozco-Esteves, H; Maldonado, H A; Aguilar-León, D; Vilchis-Landeros, M M; Mata-Espinosa, D A; Mendoza, V; López-Casillas, F
Transforming growth factor-beta (TGF-β) and prostaglandins (PG) regulate the cell-mediated immune response, so it has been proposed that they affect the progression of pulmonary tuberculosis. Here we report that the administration of soluble betaglycan, a potent TGF-β antagonist, and niflumic acid, a PG synthesis inhibitor, during the chronic phase of experimental murine tuberculosis enhanced Th1 and decreased Th2 cytokines, increased the expression of iNOS and reduced pulmonary inflammation, fibrosis and bacillary load. This immunotherapeutic approach resulted in significant control of the disease comparable to that achieved by anti-microbial treatment alone. Importantly, the combination of immunotherapy and anti-microbials resulted in an accelerated clearance of bacilli from the lung. These results confirm that TGF-β and PG have a central pathophysiological role in the progression of pulmonary tuberculosis in the mouse and suggest that the addition of immunotherapy to conventional anti-microbial drugs might result in improved treatment of the disease. PMID:16634800
Sweeney, Timothy E; Braviak, Lindsay; Tato, Cristina M; Khatri, Purvesh
Summary Background Active pulmonary tuberculosis is difficult to diagnose and treatment response is difficult to effectively monitor. A WHO consensus statement has called for new non-sputum diagnostics. The aim of this study was to use an integrated multicohort analysis of samples from publically available datasets to derive a diagnostic gene set in the peripheral blood of patients with active tuberculosis. Methods We searched two public gene expression microarray repositories and retained datasets that examined clinical cohorts of active pulmonary tuberculosis infection in whole blood. We compared gene expression in patients with either latent tuberculosis or other diseases versus patients with active tuberculosis using our validated multicohort analysis framework. Three datasets were used as discovery datasets and meta-analytical methods were used to assess gene effects in these cohorts. We then validated the diagnostic capacity of the three gene set in the remaining 11 datasets. Findings A total of 14 datasets containing 2572 samples from 10 countries from both adult and paediatric patients were included in the analysis. Of these, three datasets (N=1023) were used to discover a set of three genes (GBP5, DUSP3, and KLF2) that are highly diagnostic for active tuberculosis. We validated the diagnostic power of the three gene set to separate active tuberculosis from healthy controls (global area under the ROC curve (AUC) 0·90 [95% CI 0·85–0·95]), latent tuberculosis (0·88 [0·84–0·92]), and other diseases (0·84 [0·80–0·95]) in eight independent datasets composed of both children and adults from ten countries. Expression of the three-gene set was not confounded by HIV infection status, bacterial drug resistance, or BCG vaccination. Furthermore, in four additional cohorts, we showed that the tuberculosis score declined during treatment of patients with active tuberculosis. Interpretation Overall, our integrated multicohort analysis yielded a three
Katz, Dolly; Ghosh, Smita; Blumberg, Henry; Tamhane, Ashutosh; Sevilla, Anna; Reves, Randall
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
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
Shao, Yan; Peng, Hong; Chen, Cheng; Zhu, Tao; Ji, Ming; Jiang, Wei; Zhu, Wei; Zhai, Xiang Jun; Lu, Wei
Tuberculosis is one of the most common infectious diseases in China, while delayed patient finding obstructed disease control, especially for smear-negative patients. The current study was undertaken to evaluate the diagnostic accuracy of GeneXpert MTB/RIF compared with conventional methods in the detection of pulmonary tuberculosis patients. A total of 295 spot sputum samples from confirmed pulmonary tuberculosis patients were evaluated from September 2014 to June 2015. Each sample was examined by acid-fast bacillus smear microscopy, culture and GeneXpert MTB/RIF. The sputum culture on Löwenstein-Jensen (L-J) was considered as the gold-standard. After testing by smear, 68.81% (203/295) was negative and 31.19% (92/295) was positive. As the gold-standard, L-J culture detected 37.97% (112/295) positive of all specimens, while the positivity for GeneXpert MTB/RIF was 46.44% (137/295). Compared with L-J culture, the combined sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for GeneXpert MTB/RIF were 94.64%, 82.97%, 77.37% and 96.18% respectively. For smear-negative specimens, the sensitivity, specificity, PPV and NPV for GeneXpert MTB/RIF were 96.00%, 83.05%, 44.44% and 99.32%; while for smear-positive specimens, the corresponding accuracy values were 94.25%, 80.00%, 98.80% and 44.44%. The findings of study indicated that GeneXpert MTB/RIF assay demonstrated a high sensitivity in detecting Mycobacterium tuberculosis compared to smear method and a high NPV among smear negative patients.
Kolomiets, V M; Abramov, A V; Rachina, N V; Rubleva, N V
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.
Thuong, N T T; Tram, T T B; Dinh, T D; Thai, P V K; Heemskerk, D; Bang, N D; Chau, T T H; Russell, D G; Thwaites, G E; Hawn, T R; Caws, M; Dunstan, S J
Macrophage receptor with collagenous structure (MARCO) has an important role in the phagocytosis of Mycobacterium tuberculosis (M. tuberculosis). We hypothesized that MARCO polymorphisms are associated with phagocytosis, tuberculosis (TB) disease susceptibility and presentation, and infecting lineage. We used a human cellular model to examine how MARCO genotype mediates the immune response; a case–control study to investigate tuberculosis host genetic susceptibility; and a host–pathogen genetic analysis to study host–pathogen interactions. Two MARCO heterozygous (AG) genotypes (single-nucleotide polymorphisms rs2278589 and rs6751745) were associated with impaired phagocytosis of M. tuberculosis trehalose 6,6'-dimycolate-cord factor and β-glucan-coated beads in macrophages. The heterozygous genotypes of rs2278589 and rs6751745 were also associated with increased risk of pulmonary TB (PTB; rs2278589, P=0.001, odds ratio (OR)=1.6; rs6751745, P=0.009, OR=1.4), and with severe chest X-ray abnormalities (P=0.007, OR=1.6). These two genotypes were also associated with the Beijing lineage (rs2278589, P=0.001, OR=1.7; rs6751745, P=0.01, OR=1.5). Together, these results suggest that MARCO polymorphisms may regulate phagocytosis of M. tuberculosis and susceptibility and severity of PTB. They also suggest MARCO genotype and Beijing strains may interact to increase the risk of PTB. PMID:27853145
Kim, Jihyun; Lee, In Jae; Kim, Joo-Hee
PURPOSE We aimed to assess computed tomography (CT) findings of pulmonary tuberculosis (TB) and TB pleurisy in diabetes mellitus (DM) patients and to evaluate the effect of duration of DM on radiologic findings of pulmonary TB and TB pleurisy. METHODS Ninety-three consecutive patients diagnosed as active pulmonary TB with underlying DM were enrolled in our study. As a control group, 100 pulmonary TB patients without DM were randomly selected. TB patients with DM were subdivided into two subgroups depending on diabetes duration of ≥10 years or <10 years. Medical records and CT scans of the patients were retrospectively reviewed and compared. RESULTS Bilateral pulmonary involvement (odds ratio [OR]=2.39, P = 0.003), involvement of all lobes (OR=2.79, P = 0.013), and lymph node enlargement (OR=1.98, P = 0.022) were significantly more frequent CT findings among TB patients with DM compared with the controls. There were no statistically significant differences in CT findings of pulmonary TB depending on the duration of DM. CONCLUSION Bilateral pulmonary involvement, involvement of all lobes, and lymph node enlargement are significantly more common CT findings in TB patients with underlying DM than in patients without DM. Familiarity with the CT findings may be helpful to suggest prompt diagnosis of pulmonary TB in DM patients. PMID:28185999
Lin, Chao-Shun; Yeh, Chun-Chieh; Chung, Chi-Li; Hung, Chih-Jen; Chen, Ta-Liang
Background The association between pulmonary tuberculosis (TB) and postoperative outcomes remains unknown. This study investigated outcomes following non-chest surgeries in patients with previous pulmonary TB. Methods Using Taiwan’s National Health Insurance Research Database, we analyzed 6911 patients (aged ≥ 20 years) with preoperative diagnosis of pulmonary TB and 6911 propensity score-matched controls receiving non-chest surgeries in 2008–2010. Postoperative outcomes were compared between patients with or without pulmonary TB by calculating adjusted odds ratios (ORs) and 95% confidence intervals (CIs) in the multivariate logistic regressions. Results Surgical patients with pulmonary TB had a significantly higher postoperative complication rates than controls, including septicemia, pneumonia, acute renal failure, deep wound infection, overall complications, and 30-day postoperative mortality (OR 1.41; 95% CI 1.07–1.86). The ORs of patients with low-income status were as high as 2.27 (95% CI 1.03–5.03). Preoperative use of TB drugs and TB-related medical expenditure also associated with higher postoperative mortality among surgical patients with pulmonary TB. Conclusions Surgical patients with pulmonary TB have significantly increased risks of postoperative complications and mortality after non-chest surgeries. This study suggests the need to improve postoperative care for surgical patients with pulmonary TB. PMID:26172153
Goussard, Pierre; Gie, Robert
Pulmonary tuberculosis (TB) is the commonest clinical form of childhood TB occurring in approximately 80% of cases. Traditionally, bronchoscopy in pediatric TB suspects was used to collect specimens for mycobacterial culture using especially bronchoalveolar lavage. New data have described the role of bronchoscopy as a more comprehensive instrument for the diagnosis and management of pulmonary TB in children. Flexible bronchoscopy is an important intervention to evaluated airways disease, collect samples for culture, relieve critical threatening airway obstruction and aid in the management of complicated pulmonary TB disease in children. Airway involvement in children suspected of pulmonary TB has been described in 41-63% of cases. The commonest airways involved are bronchus intermedius, left main bronchus and the trachea. Bronchoscopy is safe in children with severe airway obstruction. As bronchoscope images improve, the working channel size increases new applications for bronchoscopy will be developed making them more applicable in small children.
Voloshyn, Ia M; Kovalenchenko, V F; Podhaievs'kyĭ, S H
Peculiarities of the operations performance and the postoperative period conduction in 128 patients with pulmonary tuberculosis and diabetes mellitus (DM) were enlightened. After the operation in majority of patients it is expedient on the background of diet and insulin therapy to continue conventional chemotherapy. In patients with severe DM, focal pulmonary changes, chronic alcoholism and those to whom the preliminary chemotherapy was not conducted, it is mandatory to prescribe an intensive chemotherapy. For correction of the carbohydrate metabolism disorders it is expedient to conduct electrophoresis of 6% solution of sodium salicilate and 5000 U of heparin according to the elaborated method.
Pravada, N S; Budritskiĭ, A M; Sukhanov, D S
Clinical and immunological efficacy of meglumine acridonacetate (cycloferon) tablets was evaluated in complex treatment of patients with newly diagnosed advanced pulmonary tuberculosis. It was shown that the use of cycloferon according to our scheme increased the efficacy of the therapy (earlier disappearance of the disease symptoms and bacteria isolation, shorter-terms of cavern healing, more pronounced positive radiographic dynamics vs. the patients under the etiotropic therapy). The use of cycloferon normalized the number of gamma interferon receptors, increased the gamma interferon serum levels, reduced the incidence of the side effects (liver damage) due to the use of TB drugs. Such a use of cycloferon was cost effective. The use of sycloferon is possible in the complex treatment of outpatients with advanced pulmonary tuberculosis.
The intricate relationship between tuberculosis (TB) and immune system remains poorly understood. It is generally believed that weakening of the immune response against Mycobacterium tuberculosis leads to reactivation of latent infection into the active pulmonary disease. However, heterogeneous nature of TB and failure of rationally designed vaccines in clinical trials raises serious questions against the simplistic view of TB as an outcome of weakened immunity. In the wake of accumulating human TB data, it is argued here that a hyperactive antimycobacterial immune response is to blame for the pathogenesis of pulmonary TB in immunocompetent adults. Direct and indirect evidence supporting this notion is presented in this article. Revisiting the role of immune system in TB pathogenesis will pave the way for effective anti-TB vaccines.
Background Tuberculosis is classified as either pulmonary or extra-pulmonary (EPTB). While much focus has been paid to pulmonary tuberculosis, EPTB has received scant attention. Moreover, EPTB is viewed as one wastebasket diagnosis, as “the other” which is not pulmonary. Methods This is a retrospective cohort study of all patients treated for EPTB in the state of Texas between January 2000 and December 2005, who had no pulmonary disease. Clinical and epidemiological factors were abstracted from electronic records of the Report of Verified Case of Tuberculosis. The long-term outcome, which is death by December 2011, was established using the Social Security Administration Death Master File database. Survival in EPTB patients was compared to those with latent tuberculosis, as well as between different types of EPTB, using Cox proportional hazard models. A hybrid of the machine learning method of classification and regression tree analyses and standard regression models was used to identify high-order interactions and clinical factors predictive of long-term all-cause mortality. Results Four hundred and thirty eight patients met study criteria; the median study follow-up period for the cohort was 7.8 (inter-quartile range 6.0-10.1) years. The overall all-cause mortality rate was 0.025 (95% confidence interval [CI]: 0.021-0.030) per 100 person-year of follow-up. The significant predictors of poor long-term outcome were age (hazard ratio [HR] for each year of age-at-diagnosis was 1.05 [CI: 1.04-1.06], treatment duration, type of EPTB and HIV-infection (HR = 2.16; CI: 1.22, 3.83). Mortality in genitourinary tuberculosis was no different from latent tuberculosis, while meningitis had the poorest long-term outcome of 46.2%. Compared to meningitis the HR for death was 0.50 (CI: 0.27-0.91) for lymphatic disease, 0.42 (CI: 0.21-0.81) for bone/joint disease, and 0.59 (CI: 0.27-1.31) for peritonitis. The relationship between mortality and therapy duration for each type
Astekar, Madhusudan; Bhatiya, Priyanka Sharma; Sowmya, GV
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
da Costa, Ana Roberta Fusco; Falkinham, Joseph O.; Lopes, Maria Luiza; Barretto, Adriana Rodrigues; Felicio, João Soares; Sales, Lúcia Helena Messias; Bahia, Jeann Ricardo da Costa; Conceição, Emilyn Costa; Lima, Karla Valéria Batista
The majority of investigations of the epidemiology of nontuberculous mycobacteria (NTM) have focused on highly developed nations with a low prevalence of tuberculosis. In contrast, the Para state of north Brazil represents an area of high tuberculosis prevalence and increasing NTM incidence. Toward the goal of understanding the dynamics of infection by all Mycobacterium species, we report patient characteristics and the identification of NTM strains isolated from sputum samples from patients that were residents of Para, a state in the Amazon region, Northern of Brazil, over the period January 2010 through December 2011 (2 years). The 29 NTM patients comprised 13.5% of positive mycobacterial cultures over the 2-year period. A major risk factor for NTM pulmonary disease was previous tuberculosis (76%). Further, the average age of NTM patients (52 years) was significantly higher than that of tuberculosis patients (39 years) and more were female (72.4% vs. 37.4%). Unlike other Brazilian states, NTM pulmonary patients in Para were infected with a different spectrum of mycobacteria; primarily the rapidly growing Mycobacterium massiliense and Mycobacterium simiae complex. PMID:23875055
Turner, Oliver C.; Basaraba, Randall J.; Orme, Ian M.
Pulmonary tuberculosis in guinea pigs is similar to the disease in humans and is accordingly widely used as a model to test tuberculosis vaccines. The primary site of expression of acquired immunity and the hallmark of tuberculosis is the granuloma. Granuloma morphology is well described, but there is limited information regarding T-cell subset influx. We monitored the course of pulmonary tuberculosis in guinea pigs and observed four distinct immunohistopathological stages. In all stages there were similar numbers and arrangement of CD4 and CD8 T cells. There were only small numbers of apoptotic lymphocytes, scattered around and within the necrotic core, and acid-fast bacilli were visible both within macrophages and free within airway debris. A key finding of the study was the observation that the development of the necrotic core was an early event and almost certainly preceded the emergence of the acquired immune response. This in turn suggests that innate mechanisms are the basis of the early lesions and that subsequent acquired responses are unable to moderate them. This hypothesis differs from the current dogma that excessive activity of T cells mediates delayed-type hypersensitivity and that cellular cytolysis is the root cause of the necrosis. PMID:12540568
Smith, Allan H; Marshall, Guillermo; Yuan, Yan; Liaw, Jane; Ferreccio, Catterina; Steinmaus, Craig
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.
Chen, Guozhong; Wu, Chunling; Luo, Zhiying; Teng, Yiming; Mao, Suping
Background In recent decades, morbidity and mortality have been found to be significantly increased in patients with chronic obstructive pulmonary disease (COPD) complicated with pulmonary tuberculosis (PTB). Platelet–lymphocyte ratio (PLR) is an indicator for inflammatory diseases. This study aims to investigate whether PLR could act as a potential marker for patients with COPD complicated with PTB. Methods In this retrospective study, laboratory characteristics of 87 COPD patients complicated with PTB (determined by Mycobacterium tuberculosis positive culture from sputum or bronchial lavage fluid) and 83 COPD patients (as the control group, determined by M. tuberculosis culture negativity from sputum or bronchial lavage fluid) were investigated. Data obtained on the day of admission were analyzed. Results PLR >216.82 was identified as the optimal cutoff value for discriminating COPD patients with PTB (sensitivity 92.4%, specificity 84.5%, positive-predictive value 91.6%, negative-predictive value 86.2%, and area under the curve [AUC] was 0.87) from patients with COPD alone. The AUC of PLR was significantly greater than that of neutrophil–lymphocyte count ratio (AUC, 0.74; 95% confidence interval, 0.67–0.81; P<0.01). Conclusion PLR could be developed as a valuable maker for identifying tuberculosis infection in COPD patients. PMID:27843310
Sharma, Sumedha; Ryndak, Michelle B.; Aggarwal, Ashutosh N.; Yadav, Rakesh; Sethi, Sunil; Masih, Shet; Laal, Suman; Verma, Indu
Pulmonary tuberculosis, the disease caused by Mycobacterium tuberculosis, still retains a top rank among the deadliest communicable diseases. Sputum expectorated during the disease continues to be a primary diagnostic specimen and also serves as a reservoir of bacteria. The expression pattern of mycobacteria in sputum will lead to an insight into bacterial adaptation at the most highly transmissible stage of infection and can also help in identifying newer diagnostic as well as drug targets. Thus, in the present study, a whole genome microarray of Mycobacterium tuberculosis was used to elucidate the transcriptional profile of mycobacteria in the sputum samples of smear positive pulmonary tuberculosis patients. Overall, the mycobacteria in sputum appeared to be in a low energy and low replicative state as compared to in vitro grown log phase M. tb with downregulation of genes involved in ATP synthesis, aerobic respiration and translational machinery. Simultaneously, downregulation was also seen in the genes involved in secretion machinery of mycobacteria along with the downregulation of genes involved in the synthesis of phthiocerol dimycocerosate and phenol glycolipids. In contrast, the majority of the genes which showed an upregulation in sputum mycobacteria were of unknown function. Further identification of these genes may provide new insights into the mycobacterial behavior during this phase of infection and may help in deciphering candidates for development of better diagnostic and drug candidates. PMID:28282458
Lachi, Tatiana; Nakayama, Mauro
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
Binesh, Fariba; Halvani, Abolhassan
Current diagnostic tests for tuberculosis (TB) are time-consuming. The aim of this study was to evaluate the diagnostic usefulness of ADA in bronchoalveolar lavage fluid in patients with pulmonary TB. A cross-sectional study was performed in Yazd, Iran, between 2009 and 2010. Patients suspected of pulmonary TB with negative sputum smear for AFB were included in the study. Mean ADA levels in BAL fluids were measured and compared between study groups. Sixty-three patients were enrolled in the study among which 15 cases had pulmonary TB, 33 had pulmonary diseases other than TB, and 15 subjects with normal bronchoscopy results were considered as controls. Mean ADA levels in BAL fluid were 4.13 ± 2.55, 2.42 ± 1.06, and 1.93 ± 0.88, respectively. This rate was significantly higher in the pulmonary TB group compared to the other two groups (P = 0.001). Using ROC curve with a cut-off value of 3.5 IU/L, the highest sensitivity (57%) and specificity (84%) were obtained in diagnosis of TB. The results showed that although ADA activity in BAL fluid of pulmonary TB patients was higher than those seen in other diseases, a negative test does not rule out pulmonary TB.
Mesfin, Mengiste M; Newell, James N; Walley, John D; Gessessew, Amanuel; Madeley, Richard J
Background Delays seeking care increase transmission of pulmonary tuberculosis and hence the burden of tuberculosis, which remains high in developing countries. This study investigates patterns of health seeking behavior and determines risk factors for delayed patient consultation at public health facilities in 10 districts of Ethiopia. Methods New pulmonary TB patients ≥ 15 years old were recruited at 18 diagnostic centres. Patients were asked about their health care seeking behaviour and the time from onset of symptoms to first consultation at a public health facility. First consultation at a public health facility 30 days or longer after onset of symptoms was regarded as prolonged patient delay. Results Interviews were held with 924 pulmonary patients. Of these, 537 (58%) were smear positive and 387 (42%) were smear negative; 413 (45%) were female; 451 (49%) were rural residents; and the median age was 34 years. Prior to their first consultation at a public health facility, patients received treatment from a variety of informal sources: the Orthodox Church, where they were treated with holy water (24%); private practitioners (13%); rural drug vendors (7%); and traditional healers (3%). The overall median patient delay was 30 days (mean = 60 days). Fifty three percent [95% Confidence Intervals (CI) (50%, 56%)] of patients had delayed their first consultation for ≥ 30 days. Patient delay for women was 54%; 95% CI (54%, 58%) and men 51%; 95% CI (47%, 55%). The delay was higher for patients who used informal treatment (median 31 days) than those who did not (15 days). Prolonged patient delay (≥ 30 days) was significantly associated with both patient-related and treatment-related factors. Significant patient-related factors were smear positive pulmonary disease [Adjusted Odds Ratio (AOR) 1.4; 95% CI (1.1 to 1.9)], rural residence [AOR 1.4; 95% CI (1.1 to 1.9)], illiteracy [AOR 1.7; 95% CI (1.2 to 2.4)], and lack of awareness/misperceptions of causes of
Fukuda, Hozumi Ibukuro, Kenji; Tsukiyama, Toshitaka; Ishii, Rei
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.
Ibarburen González-Arenas, C; Zapatero Gaviria, A; Gómez Santos, D; García-Castaño, B; Tomás Ros, M; Merino Morales, F
Pulmonar tuberculosis still being one of the diseases more frequent in our area, this producing different clinical and radiological presentation. A case with posterior uveitis and bilateral lungs nodules which required a thoracotomy to perform a diagnosis, is presented.
Tang, Shenjie; Xiao, Heping; Fan, Yihu; Wu, Furong; Zhang, Zhongshun; Li, Hong; Yang, Yan
OBJECTIVE To investigate the characteristics and clinical value of serum tumor necrosis factor-alpha (TNF-alpha) and its receptor (sTNF-R), interleukin-1beta(IL-1beta) and its receptor(IL-1R), interleukin-6(IL-6) and its receptor(IL-6R) in patients with pulmonary tuberculosis, and to evaluate their role in the immunopathogenesis of tuberculosis. METHODS The serum levels of TNF-alpha, sTNF-R Iota IL-1beta,IL-1R, IL-6 and IL-6R were measured using the sandwich ABC-ELISA method in 41 cases of active tuberculosis, 21 cases of inactive tuberculosis and 20 normal controls. The serum levels of the cytokines in 17 cases of active tuberculos is were followed. RESULTS The serum levels of TNF-alpha sTNF-RIota IL-1beta,IL-1R, IL-6 IL-6R and the TNF-alpha/sTNF-RIota ratio were significantly higher in both the active and the inactive tuberculosis groups than those in normal controls (P <0.01 approximately 0.05). The TNF-alpha sTNF-R Iota IL-1 beta, IL-1R, IL-6 IL-6R levels and the TNF-alpha/sTNF-R Iota ratio in the active tuberculosis group were significantly higher than those in the inactive tuberculosis(P <0.01 approximately 0.05). The serum levels of TNF-alpha sTNF-R Iota, IL-1beta and IL-6 and the TNF-alpha,/sTNF-R Iota ratio were significantly lower in cavernous tuberculosis than those in non- cavernous tuberculosis (P < 0.01 approximately 0.05). After 2 months' antituberculosis treatment, the serum levels of TNF-alpha,sTNF-R Iota IL-1 beta, IL-1R,IL-6, IL-6R and the TNF-alpha/sTNF-R Iota ratio in 15(15/17) cases were significantly lower than those before treatment(P < 0.01 approximately 0.05). CONCLUSIONS TNF-alpha, IL-1 beta, IL-6 and their receptors may be involved in the immunopathogenesis of tuberculosis. Measuring the serum levels of proinflammatory cytokines and their receptors may be useful in evaluating the activity, the clinical pattern, and the prognosis of the disease and monitoring the clinical effect of antituberculous therapy.
Narain, Raj; Nair, S. S.; Naganna, K.; Chandrasekhar, P.; Rao, G. Ramanatha; Lal, Pyare
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
Lovacheva, O V; Erokhin, V V; Chernichenko, N V; Evgushchenko, G V; Lepekha, L N; Rozenberg, O A
Many years' experience in studying the surfactant system in patients with pulmonary tuberculosis has allowed recommendation of using surfactant agents in the treatment of tuberculosis. The purpose of the study was to evaluate the efficacy of surfactant-BL (Russia) as a pathogenetic agent in chemotherapy in patients with destructive pulmonary tuberculosis. The results of treatment were compared in two groups of 70 persons in each, which were matched by gender, age, the extent of a tuberculous process, and the presence of drug resistance in the causative agent, including multidrug resistance. In the study group, the patients received surfactant inhalations (8 weeks) during chemotherapy while the control patients had only chemotherapy. Drugs were chosen on an individual basis, by taking into account the pathogen's drug sensitivity and a patient's tolerability of a drug. The cumulative dose of the surfactant was 700 mg. There were no adverse reactions to the surfactant in the study group of patients. After 2-5 surfactant inhalations, the amount of sputum increase, its discharge became easier, and cough diminished. Following 4 weeks, the level of bacterial isolation decreased in 49 (70.0%) patients from the study group and in 20 (28.6%) from the control one. Two months of treatment, bacterial isolation ceased in 82.9 and 64.3% in the study and control groups, respectively. In the study group, X-ray trend in infiltration resolution and cavernous closure was significantly better in the study group. By month 4, cavernous closure was achieved in 72.9% in the study group and in 41.4% in the control one. The changes in the cellular composition of the lung in surfactant-treated and untreated patients were analyzed by the data on broncho-alveolar lavage. The findings indicate that inhaled Surfactant-BL as a two-month therapy has a pathogenetic effect and during chemotherapy improves the efficiency of treatment reduces its time in pulmonary tuberculosis.
Kathirvel, Maruthai; Kommoju, Vallayyachari; Brammacharry, Usharani; Ravibalan, Thirumurugan; Ravishankar, Nandikolla; Radhakrishnan, Balu; Muthaiah, Muthuraj
Rapid and sensitive detection of Mycobacterium tuberculosis from patient samples is vital for clinical diagnosis and treatment. The emergence of M. tuberculosis strains with either no copies or only a single copy of IS6110 in Asian countries makes the standard PCR based diagnosis of M. tuberculosis using IS6110 not reliable. We studied the diagnostic efficacy of the in-house PCR amplification of the candidate gene mtp40 as an alternative to IS6110 element based diagnosis. Clinical samples included pulmonary and extra-pulmonary specimens from TB suspected patients residing in Puducherry, South India and were analyzed using in-house PCR procedures targeting IS6110 element and mtp40 genes. Out of 317 clinical specimens analyzed, 132 (41.6 %) and 114 (36 %) were found positive for mtp40 PCR and IS6110 PCR, respectively. However, 18 specimens that were found to negative for IS6110 PCR were found positive for mtp40 PCR, which was further confirmed by DNA sequencing method. PCR amplification of mtp40 gene for the diagnosis of M. tuberculosis in clinical samples is fast, sensitive, and further identified clinical strains that lack IS6110 element in this region. It is clearly demonstrated that there is a significant difference between the two PCR procedures and the sensitivity and specificity levels of mtp40 PCR were found to be higher when compared with DNA sequencing method. Thus, mtp40 based PCR technique will be beneficial in diagnosis of TB where M. tuberculosis strains lack of IS6110 element is predominant.
Lavín-Alconero, Lucía; Sánchez-Velasco, Pablo; Guerrero-Alonso, M.-Ángeles; Ausín, Fernando; Fariñas, M.-Carmen; Leyva-Cobián, Francisco
Mannose-binding lectin is a central molecule of the innate immune system. Mannose-binding lectin 2 promoter polymorphisms and structural variants have been associated with susceptibility to tuberculosis. However, contradictory results among different populations have been reported, resulting in no convincing evidence of association between mannose-binding lectin 2 and susceptibility to tuberculosis. For this reason, we conducted a study in a well genetically conserved Spanish population in order to shed light on this controversial association. We analysed the six promoter and structural mannose-binding lectin 2 gene variants in 107 patients with pulmonary tuberculosis and 441 healthy controls. Only D variant and HYPD haplotype were significantly more frequents in controls which would indicate that this allele could confer protection against pulmonary tuberculosis, but this difference disappeared after statistical correction. Neither the rest of alleles nor the haplotypes were significantly associated with the disease. These results would indicate that mannose-binding lectin promoter polymorphisms and gene variants would not be associated with an increased risk to pulmonary tuberculosis. Despite the slight trend of the D allele and HYPD haplotype in conferring protection against pulmonary tuberculosis, susceptibility to this disease would probably be due to other genetic factors, at least in our population. PMID:23304495
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
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.
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
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
Brhane, Mussie; Kebede, Ameha; Petros, Yohannes
Background Molecular methods that target drug resistance mutations are suitable approaches for rapid drug susceptibility testing to detect multidrug-resistant tuberculosis (MDR-TB). The aim of the study was to determine MDR-TB cases and to analyze the frequency of gene mutations associated with rifampicin (RIF) and/or isoniazid (INH) resistance of Mycobacterium tuberculosis among smear-positive pulmonary tuberculosis patients. Methods Institution-based cross-sectional study design was employed. Sputum specimens were collected, and using a pretested questionnaire, data for associated risk factors for drug resistance were collected from 105 consecutive smear-positive pulmonary tuberculosis patients in Karamara General Hospital. Specimens were transported to Harar Health Research and Regional Laboratory, Harar, where molecular drug susceptibility testing was performed using GenoType® MTBDRplus assay. Results Of the total 105 sputum specimens, 98 (93.3%) gave interpretable results, in which 67 (68.4%) were new cases and 31 (31.6%) were previously treated cases. Of these, 80 (81.6%) were sensitive to both drugs and 18 (18.4%) were resistant to RIF and/or INH. The prevalences of MDR-TB in total cases, new, and previously treated cases were 10 (10.2%), 3 (4.5%), and 7 (22.6%), respectively. Among the ten total RIF-resistant specimens, eight (80%) had resulted because of absence of rpoB WT8 and presence of MUT3 and in all specimens, the amino acids changed were Ser531Lue. Of the 18 total INH-resistant specimens, 15 (83.3%) had mutations in the katG gene (katG MUT1, Ser315Thr1), indicating high-level resistance, while 3 (14.7%) had mutations in the inhA promoter gene (Cys15Thr), indicating low-level resistance. Conclusion Among the mutations associated with resistance to RIF and INH, the majority were in codon 531 of the rpoB gene and codon 315 of the katG gene. Relatively high prevalence of MDR-TB was observed in the study. PMID:28331348
Bisero, Elsa D; Luque, Graciela F; Rizzo, Cristina N; Zapata, Alejandra E; Cuello, María S
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.
Soldá, P A; Rojo, S C; Cosiansi, M C; Barnes, A I
Tuberculosis continues to be a serious problem of public health causing nearly three million deaths per year all over the world. Despite technologic improvements in the diagnostic methods, it is not possible to control the disease in the absence of surveillance and treatment follow-up programs supervising the ending of treatments, and definitive cure of patients. The frequency of pulmonary and extrapulmonary tuberculosis, and simultaneous pulmonary and extrapulmonary tuberculosis localization among patients assisted at Tránsito Cáceres de Allende Hospital during thirteen years (1991-2003), was determined. The benefit of inoculating the specimens on Stonebrink medium for the best recuperation of Mycobacterium bovis was herein observed, and the contribution of Ziehl Neelsen staining in extrapulmonary materials was tested as well. Out of 790 cases of tuberculosis diagnosed, 723 were pulmonary, and 48 were extrapulmonary localization (pleural 31, renal 7, ganglionar 5, meningeal 2, genital 1, pericardial 1 and digestive 1), and 19 patients presented both, pulmonary and extrapulmonary tuberculosis. Out of the 723 pulmonary cases, 9 were caused by M. bovis. All M. bovis isolates grew on Stonebrink medium, and only one grew also on Lowenstein Jensen. Smear microscopy using Ziehl Neelsen staining resulted positive in 4 extrapulmonary specimens.
Dawson, Rod; Condos, Rany; Tse, Doris; Huie, Maryann L.; Ress, Stanley; Tseng, Chi-Hong; Brauns, Clint; Weiden, Michael; Hoshino, Yoshihiko; Bateman, Eric; Rom, William N.
Background Current treatment regimens for pulmonary tuberculosis require at least 6 months of therapy. Immune adjuvant therapy with recombinant interferon-γ1b (rIFN-γb) may reduce pulmonary inflammation and reduce the period of infectivity by promoting earlier sputum clearance. Methodology/Principal Findings We performed a randomized, controlled clinical trial of directly observed therapy (DOTS) versus DOTS supplemented with nebulized or subcutaneously administered rIFN-γ1b over 4 months to 89 patients with cavitary pulmonary tuberculosis. Bronchoalveolar lavage (BAL) and blood were sampled at 0 and 4 months. There was a significant decline in levels of inflammatory cytokines IL-1β, IL-6, IL-8, and IL-10 in 24-hour BAL supernatants only in the nebulized rIFN-γ1b group from baseline to week 16. Both rIFN-γ1b groups showed significant 3-fold increases in CD4+ lymphocyte response to PPD at 4 weeks. There was a significant (p = 0.03) difference in the rate of clearance of Mtb from the sputum smear at 4 weeks for the nebulized rIFN-γ1b adjuvant group compared to DOTS or DOTS with subcutaneous rIFN-γ1b. In addition, there was significant reduction in the prevalence of fever, wheeze, and night sweats at 4 weeks among patients receiving rFN-γ1b versus DOTS alone. Conclusion Recombinant interferon-γ1b adjuvant therapy plus DOTS in cavitary pulmonary tuberculosis can reduce inflammatory cytokines at the site of disease, improve clearance of Mtb from the sputum, and improve constitutional symptoms. Trial Registration ClinicalTrials.gov NCT00201123 PMID:19753300
Kim, Yi-Suk; Lee, In Sun; Oh, Chang Seok; Kim, Myeung Ju; Cha, Soon Chul; Shin, Dong Hoon
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.
Mahato, Roshan Kumar; Koju, Rajendra; Vaeteewootacharn, Kriangsak
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
Mooventhan, A; Khode, Vitthal; Nivethitha, L
A 24-year-old, unmarried woman diagnosed of pulmonary tuberculosis (PTB) visited our hospital out-patient department in the month of August-2013. Patient came with the complaint of sever cough with expectoration; evening raise of temperature; gradual loss of appetite and weight since 2-weeks. We referred the patient to our hospital's Revised National Tuberculosis Program, direct observed treatment short-course center for sputum fluorescence microscopic examination (FME). FME report suggested the new smear positive, 2+ PTB. Our patient received yogic breathing techniques (YBT) for 45-min daily under the supervision for three alternate-days/week with anti-tuberculosis treatment (ATT) for the period of 8-weeks. After intervention our result showed better improvement in weight gain, body mass index, symptom scores, pulmonary function and health related quality of life with conversion of positive to negative FME for acid fast bacilli. It suggests YBT with ATT are effective in treating PTB and further studies required to warrant this effect.
Zeng, Jin-Cheng; Lin, Dong-Zi; Yi, Lai-Long; Liu, Gan-Bin; Zhang, Hui; Wang, Wan-Dang; Zhang, Jun-Ai; Wu, Xian-Jing; Xiang, Wen-Yu; Kong, Bin; Chen, Zheng W; Wang, Cong-Yi; Xu, Jun-Fa
Despite past extensive studies, the role of B and T lymphocyte attenuator (BTLA) in αβ T cells in patients with active pulmonary tuberculosis (ATB) remains poorly understood. Here we demonstrate that BTLA expression on αβ T cells is decreased in patients with M. tuberculosis (Mtb) infection. Particularly, BTLA expression levels are likely critical for αβ T cells to manifest and maintain an active central memory phenotype with high capacity for secretion of IFN-γ and perforin, which are important for immune memory against TB infection. BTLAhigh αβ T cells also exhibited higher capacity in response to Mtb peptide stimulation. In contrast to the role of BTLA played for negative regulation of immune responses, our data in the current studies suggest that BTLA expression on αβ T cells is likely associated with protective immune memory against Mtb infection in the setting of patients with active pulmonary tuberculosis. This previous unappreciated role for BTLA may have implications for prevention and treatment of patients with Mtb infection. PMID:25360214
Shah, S A; Mujeeb, S A; Mirza, A; Nabi, K G; Siddiqui, Q
Jail inmates may be at increased risk of contracting tuberculosis (TB). We studied 386 detainees (mean age 17.7 years) in Karachi juvenile jail to determine the prevalence of TB and possible risk factors for contracting TB. We found a 3.9% prevalence of TB among the inmates, significantly higher than the estimated 1.1% prevalence in the general population of Pakistan. Positive family history of TB was a significant risk factor for TB. Poor adherence of previously diagnosed patients to anti-TB treatment was found. Our study highlights the vulnerability of inmates to TB owing to the presence of highly infectious cases, along with environmental conditions such as overcrowding and poor ventilation. This study strongly indicates the need for an effective treatment programme in the jails as well in the general community.
Caminero Luna, J A
Tuberculosis (TB) remains the most important human infectious disease. Currently, the TB diagnosis is still based on the clinical presentation, radiographic findings and microbiological results; all of which have sensitivity or specificity issues. For that reason, the immediate future involves rapid molecular microbiological techniques, in particular GeneXpert (which is more sensitive than bacilloscopy and is able to detect rifampicin resistance) and GenoType. The current six-month treatment for TB has remained unchanged for decades. Attempts to shorten this treatment have failed. In recent years, new drugs have been reported that could contribute to TB treatment in the near future, and are already being used in multi-drug-resistance TB.
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
The high-output pathway of nitric oxide production helps protect mice from infection by several pathogens, including Mycobacterium tuberculosis. However, based on studies of cells cultured from blood, it is controversial whether human mononuclear phagocytes can express the corresponding inducible nitric oxide synthase (iNOS;NOS2). The present study examined alveolar macrophages fixed directly after bronchopulmonary lavage. An average of 65% of the macrophages from 11 of 11 patients with untreated, culture-positive pulmonary tuberculosis reacted with an antibody documented herein to be monospecific for human NOS2. In contrast, a mean of 10% of bronchoalveolar lavage cells were positive from each of five clinically normal subjects. Tuberculosis patients' macrophages displayed diaphorase activity in the same proportion that they stained for NOS2, under assay conditions wherein the diaphorase reaction was strictly dependent on NOS2 expression. Bronchoalveolar lavage specimens also contained NOS2 mRNA. Thus, macrophages in the lungs of people with clinically active Mycobacterium tuberculosis infection often express catalytically competent NOS2. PMID:8642338
Background Changes in respiratory tract microbiota have been associated with diseases such as tuberculosis, a global public health problem that affects millions of people each year. This pilot study was carried out using sputum, oropharynx, and nasal respiratory tract samples collected from patients with pulmonary tuberculosis and healthy control individuals, in order to compare sample types and their usefulness in assessing changes in bacterial and fungal communities. Findings Most V1-V2 16S rRNA gene sequences belonged to the phyla Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Fusobacteria, with differences in relative abundances and in specific taxa associated with each sample type. Most fungal ITS1 sequences were classified as Ascomycota and Basidiomycota, but abundances differed for the different samples. Bacterial and fungal community structures in oropharynx and sputum samples were similar to one another, as indicated by several beta diversity analyses, and both differed from nasal samples. The only difference between patient and control microbiota was found in oropharynx samples for both bacteria and fungi. Bacterial diversity was greater in sputum samples, while fungal diversity was greater in nasal samples. Conclusions Respiratory tract microbial communities were similar in terms of the major phyla identified, yet they varied in terms of relative abundances and diversity indexes. Oropharynx communities varied with respect to health status and resembled those in sputum samples, which are collected from tuberculosis patients only due to the difficulty in obtaining sputum from healthy individuals, suggesting that oropharynx samples can be used to analyze community structure alterations associated with tuberculosis. PMID:25225609
Macovei, Lilia; Kanunfre, Kelly; Dhiman, Rakesh; Restrepo, Blanca I.; Zarate, Izelda; Pino, Paula A.; Mora-Guzman, Francisco; Fujiwara, Ricardo T.; Michel, Gerd; Kashino, Suely S.
The development of an accurate antigen detection assay for the diagnosis of active tuberculosis (TB) would represent a major clinical advance. Here, we demonstrate that the Mycobacterium tuberculosis Rv1681 protein is a biomarker for active TB with potential diagnostic utility. We initially identified, by mass spectroscopy, peptides from the Rv1681 protein in urine specimens from 4 patients with untreated active TB. Rabbit IgG anti-recombinant Rv1681 detected Rv1681 protein in lysates and culture filtrates of M. tuberculosis and immunoprecipitated it from pooled urine specimens from two TB patients. An enzyme-linked immunosorbent assay formatted with these antibodies detected Rv1681 protein in unconcentrated urine specimens from 11/25 (44%) TB patients and 1/21 (4.8%) subjects in whom TB was initially clinically suspected but then ruled out by conventional methods. Rv1681 protein was not detected in urine specimens from 10 subjects with Escherichia coli-positive urine cultures, 26 subjects with confirmed non-TB tropical diseases (11 with schistosomiasis, 5 with Chagas' disease, and 10 with cutaneous leishmaniasis), and 14 healthy subjects. These results provide strong validation of Rv1681 protein as a promising biomarker for TB diagnosis. PMID:23390284
Peter, C R; Schultz, E; Moser, K; Cox, M; Freeman, R; Ramirez-Zetina, M; Lomeli, M R
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
Faccenda, J; Watt, B; Leitch, A G
In Edinburgh in 1991 a relative excess of pulmonary TB cases in the 15-34 year age group was recorded. Five of 17 notifications in this age group were of overseas students of higher education: three aged 21-29 from Central Africa, one 27-year-old Asian and one 26-year-old Western European. One of the African students was seropositive for HIV infection. Disease presented clinically on average 31 months after entry to the U.K. (range 6-48 months). Four students had smear positive disease. Two patients had had normal chest radiographs 1 and 2 years previously on entry to the U.K.; three students had not previously been radiologically screened. We suggest that students from countries with a high prevalence of tuberculosis should be screened on entry to their course of education and that student health services should develop and maintain a high index of suspicion for tuberculosis in these students.
Bogue, Patrick; Bolland, Mhairi; How, Peter; Benziger, Harrison
Post-operative fever is common following emergency surgery. Investigation and management of post-operative fever can be challenging when a clear source of sepsis is not evident or the underlying source of infection is not recognised. We herein report a case of secondary pulmonary tuberculosis presenting as post-operative fever following emergency laparotomy for a perforated duodenal ulcer. This case of tuberculosis was diagnosed on day 41 post-operatively and prior inconclusive results meant that we relied mainly on re-visiting history and examination in order to identify 3 targeted investigations: plain chest X-ray, sputum sample and blood test. Accordingly, the co-management of this complex patient achieved a good outcome.
Satyanarayana, S; Nagaraja, S B; Kelamane, S; Jaju, J; Chadha, S S; Chander, K; Vishnu, H; Wilson, N C; Harries, A D
To assess response to anti-tuberculosis treatment as per national guidelines, a retrospective record review was undertaken in four districts of Andhra Pradesh, India, in December 2009 to determine whether pulmonary tuberculosis (PTB) patients reported as successfully treated (cured or treatment completed) underwent all scheduled follow-up sputum smear examinations. In a quarterly cohort of 3000 PTB patients reported as successfully treated, 1847 (61.5%) underwent all follow-up sputum examinations, with a higher proportion of new cases (65%) than retreatment cases (45%). The mid-continuation phase follow-up sputum examinations were commonly missed, and 11% patients had not undergone end-of-treatment follow-up sputum examinations.
Jarvela, Jessica R; Tuscano, Lori; Lee, Hung; Silver, Richard F
In this study, we used ELISPOT to quantify frequencies of bronchoalveolar lavage (BAL) and peripheral blood T cells capable of producing IFNγ in response to PPD, antigen 85B, and Mtb-specific antigens CFP-10 and ESAT-6 in individuals with latent tuberculosis infection (LTBI) and Mtb-naïve controls. Compared to peripheral blood, BAL cells of LTBI subjects displayed significant enrichment for T cells responding to PPD, antigen 85B, and CFP-10, but not to ESAT-6. Baseline BAL cells of LTBI subjects displayed significant production of Mig (CXCL9) in response to PPD, antigen 85B, and CFP-10 as well. These findings suggest that enrichment for Mtb-specific T cells within BAL is not unique to active pulmonary tuberculosis and may, to the contrary, contribute to protection from re-infection in Mtb immune individuals.
Koretskaia, N M
A total of 1150 cases of new-onset pulmonary tuberculosis were analyzed. A higher liability to the disease was shown in young females and males of ripe age. There was evidence for that the severer pattern of clinical forms and the nature of the process were directly proportional to the age of patients. Age-specific differences were found in the ways of detecting the disease and in the regularity of control fluorographic studies. The inclusion of persons aged 60 years or older into an increased risk group was justified. A severer pattern of clinical forms and characteristics of the process were established in males, which are largely caused by that the latter had irregularly underwent control fluorographic studies. Age- and gender-specific features of tuberculosis, which are typical of this region, have been identified.
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.
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
Cheng, Jun; Wang, Lixia; Zhang, Hui; Xia, Yinyin
Objective To evaluate the diagnostic value of symptom screening for tuberculosis (TB) case finding defined in National Tuberculosis Control Program in China (China NTP) among elderly people(≥65 years) and younger people(<65 years). Methods We made a secondary analysis in a population-based TB prevalence survey in China in 2010. Questionnaire including information for cough and haemoptysis was completed by face to face interview, and then chest radiography was conducted in all eligible participants. Sputum smear and culture were followed for all TB suspects. We calculated the odds ratios (OR), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and the area under the receiver operating characteristic curve (AUC) of using different symptoms for screening to detect bacteriologically positive TB in subpopulations stratified by age 65, to evaluate the performance of symptom screening for TB. Findings Of 315 newly diagnosed bacteriologically positive TB, 131 patients (41.59%) were elderly, and 48.57% of TB patients were asymptomatic. Nearly 50% patients did not present cough of any duration, and less than half present cough more than 2 weeks, a defined suspected symptom in China NTP. Cough of any duration was reported more in patients aged under 65 than those in elderly, especially for the acute cough (9.78% vs 6.87%). Those symptoms defined by China NTP were reported by less than half participants in two subpopulations. Acute cough (<2 weeks) was an independent predictor of TB in people aged under 65 (adjusted OR: 3.3, 95% CI: 2.0-5.5), but not in those aged 65 and above (adjusted OR: 1.4, 95% CI: 0.7-2.9). The specificity for each symptom was significantly higher in participants aged under 65 (P<0.01), and sensitivities of most symptoms were significantly higher among elderly (P<0.05 or P<0.01). When compared with cough for 2 weeks and more, using cough of any duration for symptom screening increased the sensitivity from 42
Rulaningtyas, Riries; Suksmono, Andriyan B.; Mengko, Tati L. R.; Saptawati, Putri
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)%.
Mabiala-Babela, J R; M'Pemba Loufoua, A B; Mouko, A; Senga, P
Little information is available on pulmonary tuberculosis in infants in sub-Saharan Africa. This retrospective study was conducted in infants ranging in age from 1 to 23 months admitted to the Paediatric Departments of the University Hospital Centre in Brazzaville, Congo for pulmonary tuberculosis between January 1, 1999 and July 1, 2004. Tuberculosis was diagnosed on the basis of epidemiological, clinical, radiological, and follow-up data. All children over 12 months old underwent HIV testing. In case of positive test results, children between the ages of 12 and 18 months were retested after the age of 18 months. Of a total of 803 children admitted for tuberculosis during the study period, 117 (14.6%) were under the age of 24 months (53% males). Mean age was 17.5 months. The BCG test was mentioned in 75.2% of cases. Determination of the contagion in 50.4% of cases indicated that transmission was intrafamilial in 69.3% of cases. The mean delay for hospitalization was 2.6 months (range, 21 days to 16 months). Eighty-one patients (69.2%) presented severe malnutrition. Intrathoracic forms accounted for most cases with bronchopneumopathy (72.6%) and mediastinal adenopathy (40.2%). The incidence of bronchopneumonopathy and isolated forms was significantly higher in children over one year old than in children under one year old: 78.3% versus 21.7 % (p<0.01) and 62.8% versus 37.2% (p<0.001) respectively. A total of 35 children (43.8%) over the age of 12 months presented HIV infection. In comparison with HIV-negative children, HIV-positive children were more likely to present malnutrition and presented a statistically higher incidence of mediastinal adenopathy and multifocal forms. All associated extrathoracic lesions (21.4% of cases) occurred in HIV-positive children. Outcome was favourable in all HIV-negative children while 7 HIV-positive children (20%) died during treatment. Pulmonary tuberculosis in infants in Brazzaville is characterized by frequent association with
Subotic, Dragan; Yablonskiy, Piotr; Sulis, Giorgia; Cordos, Ioan; Petrov, Danail; Centis, Rosella; D’Ambrosio, Lia; Sotgiu, Giovanni
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
Oliveira, Cláudia Di Lorenzo; de Melo, Angelita Cristine; de Oliveira, Lílian Ruth Silva; Froede, Emerson Lopes; Camargos, Paulo
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
Varghese, Bright; Al-Hajoj, Sahal
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.
Duzhiy, I D; Grehsko, I Ya; Kravets, O V; Oleshchenko, G P; Glazunova, N I
In coincidence of chronic phthisic pleuritis in a rigid stage with pulmonary tuberculosis operative intervention is indicated of a pleuropulmonectomy type, what is a complex situation for performance and preservation of the patient's functional state. Pleuropulmonectomy in some patients is complicated by empyema and pathological processes in bronchi. Possibilities of operative interventions application, alternative to pleuropulmonectomy, were studied. Of 48 patients, to whom pleuropulmonectomy is indicated in accordance to data of clinic-roentgenological investigations, in 7--simultant operative treatment were conducted with positive results.
Balestrino, E. A.; Daniel, T. M.; de Latini, M. D. S.; Latini, O. A.; Ma, Y.; Scocozza, J. B.
IgG antibody to Mycobacterium tuberculosis antigen 5 and tuberculin purified protein derivative (PPD) was measured, by enzyme-linked immunosorbent assay (ELISA), in serum samples from 86 patients with active pulmonary tuberculosis and 91 non-tuberculous control subjects from Santa Fé, Argentina. The geometric mean titre for the tuberculosis patients was 74.6 with antigen 5 and 99.5 with PPD. In 91 control subjects the geometric mean titres were 3.6 and 15.6 respectively. Titres were not related to tuberculin reactor status or prior BCG vaccination. At a serum dilution end-point of 1:40, ELISA with antigen 5 had a sensitivity of 81.4% and a specificity of 93.4% for tuberculosis. At 1:40, ELISA with PPD showed a sensitivity of 82.6% and a specificity of 54.9% for tuberculosis. Applied at a serum dilution of 1:40 to a hypothetical model population with a tuberculosis prevalence of 2%, ELISA using antigen 5 would correctly classify 93.2% of persons and ELISA with PPD, 55.5%. At a dilution of 1:80, accuracy is increased to 99.3% with antigen 5 and 83.3% with PPD, but sensitivity decreases to 64.0% with antigen 5 and 72.1% with PPD. Thus, antigen 5 is more accurate than PPD for the diagnosis of tuberculosis using ELISA. PMID:6439426
Gupta, Amitesh; Mrigpuri, Parul; Faye, Abhishek; Bandyopadhyay, Debdutta; Singla, Rupak
One-third of patients with symptomatic venous thromboembolism (VTE) manifest pulmonary embolism, whereas two-thirds manifest deep vein thrombosis (DVT). Overall, 25%–50% of patients with first-time VTE have an idiopathic condition, without a readily identifiable risk factor, and its association with tuberculosis (TB) is a rare occurrence. Deep venous thrombosis has been associated with 1.5%–3.4% cases of TB. Early initiation of anti-TB treatment along with anticoagulant therapy decreases the overall morbidity and mortality associated with the disease. We report three cases of DVT associated with pulmonary TB who were diagnosed due to high index of suspicion as the risk factors for the development of DVT were present in these cases. PMID:28144063
Montez, Ana Sofia José; Coutinho, Daniel; Velez, Jorge; Freitas, Filomena; Oliveira, Célia
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.
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
Zychowicz, Michael E
Mycobacterium tuberculosis has affected humans for much of our existence. The incidence of global tuberculosis infection continues to rise, especially in concert with HIV coinfection. Many disease processes, such as diabetes, increase the likelihood of tuberculosis infection. Tuberculosis bacteria can infect any bone, joint, tendon, or bursa; however, the most common musculoskeletal site for infection includes the spine and weight-bearing joints of the hip and knee. Many patients who present with osteoarticular tuberculosis infection will have a gradual onset of pain at the site of infection. Many patients who develop a musculoskeletal tuberculosis infection will have no evidence of a pulmonary tuberculosis infection on x-ray film and many will have very mild symptoms with the initial infection. Healthcare providers must remember that many patients who develop tuberculosis infection do not progress to active tuberculosis disease; however, the latent infection may become active with immune compromise.
Aguilo, Nacho; Alvarez-Arguedas, Samuel; Uranga, Santiago; Marinova, Dessislava; Monzón, Marta; Badiola, Juan; Martin, Carlos
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.
Ong, Catherine W M; Elkington, Paul T; Brilha, Sara; Ugarte-Gil, Cesar; Tome-Esteban, Maite T; Tezera, Liku B; Pabisiak, Przemyslaw J; Moores, Rachel C; Sathyamoorthy, Tarangini; Patel, Vimal; Gilman, Robert H; Porter, Joanna C; Friedland, Jon S
Pulmonary cavities, the hallmark of tuberculosis (TB), are characterized by high mycobacterial load and perpetuate the spread of M. tuberculosis. The mechanism of matrix destruction resulting in cavitation is not well defined. Neutrophils are emerging as key mediators of TB immunopathology and their influx are associated with poor outcomes. We investigated neutrophil-dependent mechanisms involved in TB-associated matrix destruction using a cellular model, a cohort of 108 patients, and in separate patient lung biopsies. Neutrophil-derived NF-kB-dependent matrix metalloproteinase-8 (MMP-8) secretion was up-regulated in TB and caused matrix destruction both in vitro and in respiratory samples of TB patients. Collagen destruction induced by TB infection was abolished by doxycycline, a licensed MMP inhibitor. Neutrophil extracellular traps (NETs) contain MMP-8 and are increased in samples from TB patients. Neutrophils lined the circumference of human pulmonary TB cavities and sputum MMP-8 concentrations reflected TB radiological and clinical disease severity. AMPK, a central regulator of catabolism, drove neutrophil MMP-8 secretion and neutrophils from AMPK-deficient patients secrete lower MMP-8 concentrations. AMPK-expressing neutrophils are present in human TB lung biopsies with phospho-AMPK detected in nuclei. These data demonstrate that neutrophil-derived MMP-8 has a key role in the immunopathology of TB and is a potential target for host-directed therapy in this infectious disease.
Carniel, F; Dalla Costa, E R; Lima-Bello, G; Martins, C; Scherer, L C; Rossetti, M L
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.
Soto, Alonso; Solari, Lely; Díaz, Javier; Mantilla, Alberto; Matthys, Francine; van der Stuyft, Patrick
Background Clinical suspects of pulmonary tuberculosis in which the sputum smears are negative for acid fast bacilli represent a diagnostic challenge in resource constrained settings. Our objective was to validate an existing clinical-radiographic score that assessed the probability of smear-negative pulmonary tuberculosis (SNPT) in high incidence settings in Peru. Methodology/Principal Findings We included in two referral hospitals in Lima patients with clinical suspicion of pulmonary tuberculosis and two or more negative sputum smears. Using a published but not externally validated score, patients were classified as having low, intermediate or high probability of pulmonary tuberculosis. The reference standard for the diagnosis of tuberculosis was a positive sputum culture in at least one of 2 liquid (MGIT or Middlebrook 7H9) and 1 solid (Ogawa) media. Prevalence of tuberculosis was calculated in each of the three probability groups. 684 patients were included. 184 (27.8%) had a diagnosis of pulmonary tuberculosis. The score did not perform well in patients with a previous history of pulmonary tuberculosis. In patients without, the prevalence of tuberculosis was 5.1%, 31.7% and 72% in the low, intermediate and high probability group respectively. The area under de ROC curve was 0.76 (95% CI 0.72–0.80) and scores ≥6 had a positive LR of 10.9. Conclusions/Significance In smear negative suspects without previous history of tuberculosis, the clinical-radiographic score can be used as a tool to assess the probability of pulmonary tuberculosis and to guide the decision to initiate or defer treatment or to requesting additional tests. PMID:21483690
Shiratori, Beata; Zhao, Jingge; Okumura, Masao; Chagan-Yasutan, Haorile; Yanai, Hideki; Mizuno, Kazue; Yoshiyama, Takashi; Idei, Tadashi; Ashino, Yugo; Nakajima, Chie; Suzuki, Yasuhiko; Hattori, Toshio
Elevated matricellular proteins (MCPs), including osteopontin (OPN) and galectin-9 (Gal-9), were observed in the plasma of patients with Manila-type tuberculosis (TB) previously. Here, we quantified plasma OPN, Gal-9, and soluble CD44 (sCD44) by enzyme-linked immunosorbent assay (ELISA), and another 29 cytokines by Luminex assay in 36 patients with pulmonary TB, six subjects with latent tuberculosis (LTBI), and 19 healthy controls (HCs) from Japan for a better understanding of the roles of MCPs in TB. All TB subjects showed positive results of enzyme-linked immunospot assays (ELISPOTs). Spoligotyping showed that 20 out of 36 Mycobacterium tuberculosis (MTB) strains belong to the Beijing type. The levels of OPN, Gal-9, and sCD44 were higher in TB (positivity of 61.1%, 66.7%, and 63.9%, respectively) than in the HCs. Positive correlations between OPN and Gal-9, between OPN and sCD44, and negative correlation between OPN and ESAT-6-ELISPOT response, between chest X-ray severity score of cavitary TB and ESAT-6-ELISPOT response were observed. Instead of OPN, Gal-9, and sCD44, cytokines G-CSF, GM-CSF, IFN-α, IFN-γ, IL-12p70, and IL-1RA levels were higher in Beijing MTB-infected patients. These findings suggest immunoregulatory, rather than inflammatory, effect of MCPs and can advance the understanding of the roles of MCPs in the context of TB pathology. PMID:28025511
Atif, M; Sulaiman, Sas; Shafi, Aa; Muttalif, Ar; Ali, I; Saleem, F
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.
Ryan, Alan J.; Shi, Lei; Glogauer, Michael; Neighbors, Jeffrey D.; Hohl, Raymond; Carter, A. Brent
Fibrotic remodeling in lung injury is a major cause of morbidity. The mechanism that mediates the ongoing fibrosis is unclear, and there is no available treatment to abate the aberrant repair. Reactive oxygen species (ROS) have a critical role in inducing fibrosis by modulating extracellular matrix deposition. Specifically, mitochondrial hydrogen peroxide (H2O2) production by alveolar macrophages is directly linked to pulmonary fibrosis as inhibition of mitochondrial H2O2 attenuates the fibrotic response in mice. Prior studies indicate that the small GTP-binding protein, Rac1, directly mediates H2O2 generation in the mitochondrial intermembrane space. Geranylgeranylation of the C-terminal cysteine residue (Cys189) is required for the for Rac1 activation and mitochondrial import. We hypothesized that impairment of geranylgeranylation would limit mitochondrial oxidative stress, and, thus, abrogate progression of pulmonary fibrosis. By targeting the isoprenoid pathway with a novel agent, digeranyl bisphosphonate (DGBP), which impairs geranylgeranylation, we demonstrate that Rac1 mitochondrial import, mitochondrial oxidative stress, and progression of the fibrotic response to lung injury are significantly attenuated. These observations reveal that targeting the isoprenoid pathway to alter Rac1 geranylgeranylation halts the progression of pulmonary fibrosis after lung injury. PMID:25958207
... Loss Surgery? A Week of Healthy Breakfasts Shyness Tuberculosis KidsHealth > For Teens > Tuberculosis A A A What's in this article? TB ... Duration When to Call the Doctor en español Tuberculosis TB Basics Tuberculosis (also known as "TB") is ...
... Loss Surgery? A Week of Healthy Breakfasts Shyness Tuberculosis KidsHealth > For Teens > Tuberculosis Print A A A What's in this article? ... Duration When to Call the Doctor en español Tuberculosis TB Basics Tuberculosis (also known as "TB") is ...
Gallardo, Carmen R; Rigau Comas, David; Valderrama Rodríguez, Angélica; Roqué i Figuls, Marta; Parker, Lucy Anne; Caylà, Joan; Bonfill Cosp, Xavier
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
Soto, Alonso; Salazar, Daniela; Acurio, Vilma; Segura, Patricia; Van der Stuyft, Patrick
We evaluated the diagnostic yield of fiberoptic bronchoscopy for the diagnosis of smear-negative pulmonary tuberculosis in patients treated at a referral hospital in Lima, Peru. Of the 611 patients who underwent the procedure, 140 (23%) were diagnosed with tuberculosis based on the analysis of BAL samples. Being young and being male were significantly associated with positive cultures. In addition, 287 patients underwent post-bronchoscopic sputum smear testing for AFB, the results of which increased the diagnostic yield by 22% over that obtained through the analysis of BAL samples alone. We conclude that the analysis of BAL samples and post-bronchoscopic sputum samples provides a high diagnostic yield in smear-negative patients suspected of having pulmonary tuberculosis.
Rao, V G; Bhat, J; Yadav, R; Muniyandi, M; Bhondeley, M K; Wares, D F
A cross-sectional tuberculosis prevalence survey was undertaken in Jabalpur district, Madhya Pradesh, central India. All individuals were questioned for chest symptoms. Sputum samples were collected and examined for microscopy and culture. Overall prevalence of sputum positive pulmonary tuberculosis was found to be 255.3 per 100,000 population. Cough, with or without other symptoms, was present in 75.5% individuals and yielded 88.2% of the detected pulmonary tuberculosis cases. Elicitation of a previous history of treatment yielded 5.9%, and chest pain 4.5% cases. History of fever alone yielded no cases. The findings suggest that a history of fever alone may be safely excluded from the list of symptoms to be elicited in future TB prevalence surveys in India.
Kerimov, R V; Badalov, R K; Medzhidov, F A; Mamedov, R I
Immediate and long-term outcomes of repeated and multistage operations were analyzed in 190 patients with pulmonary tuberculosis. The aspects of work rehabilitation were studied in these patients. The efficiency of repeated and stage surgical interventions in patients both with disseminated and complicated types of tuberculosis and with pleural empyemas and in those with uncomplicated postoperative disease is 87.5 and 92.2%, respectively. The long-term results indicated that the complete clinical effect preserved in 79.2% of patients. Work rehabilitation was achieved in 64.8% of the examinees in the long-term postoperative period. The use of repeated and stage surgical interventions in patients with pulmonary tuberculosis may rehabilitate a rather large proportion of those operated on, assuming a great socioeconomic significance.
Zhang, Z X; Sng, L-H; Yong, Y; Lin, L M; Cheng, T W; Seong, N H; Yong, F K
Diagnostic and treatment delays increase the severity and transmission of pulmonary tuberculosis (PTB). This study aimed to evaluate TB diagnostic and treatment delays in acid-fast bacilli (AFB) smear-negative patients.
This was a retrospective observational study. Patients with positive AFB culture of Mycobacterium tuberculosis complex (MTC) were selected from among hospitalised patients with a diagnosis of pneumonia. Admission ward, anti-tuberculosis treatment and the duration of AFB culture were compared between smear-positive and smear-negative patients.
Of the 70 patients with positive isolation of MTC in AFB culture, 27 (38.5%) were smear-negative; of these, 18 (66.7%) were not isolated while in hospital, and 17 (63%) were neither diagnosed nor treated for TB. In contrast, 41 of the 43 smear-positive patients (95.3%) were directly admitted or quickly transferred to the isolation room and started on anti-tuberculosis treatment (P < 0.001). Samples from smear-negative patients required more time to grow MTC in AFB culture than those of smear-positive patients (23 days vs. 14 days, P < 0.001). Diabetes was significantly associated with AFB smear positivity, with an odds ratio of 12.2.
Negative AFB smears caused significant diagnostic and treatment delay. Patients staying in the general ward were exposed to TB patients who were not diagnosed in time.
Aliannejad, Rasoul; Bahrmand, Ahmadreza; Abtahi, Hamidreza; Seifi, Mahnaz; Safavi, Enayat; Abdolrahimi, Farid; Shahriaran, Shahriyar
Background and Objectives: Tuberculosis (TB) is a major problem in the world. Treatment and control of TB needs detection of the Mycobacterium tuberculosis (MT) in the proper samples. While smear doesn’t have enough sensitivity, culture and PCR are expensive, time consuming and unavailable in many centers. Recent development of a rapid TB antigen detection test (PrTBK) at Pasteur Institute of Iran could give a simple way for diagnosis of TB in about two hours. In this test the antigen-antibody complex will change color when gold conjugated mouse anti-rabbit antibody detects specific MT cell wall antigen in suspected samples. Materials and Methods: We evaluated the diagnostic accuracy of PrTBK for diagnosis of pulmonary TB in comparison with smear, culture and PCR techniques in 56 consecutive samples (47 BAL and 13 sputum samples) obtained from patients with clinical suspicion of active TB. Results: Twentynine patients (52%) were female and seven patients were HIV positive. PrTBK was positive in 17 culture positive and 4 culture negative samples (100% sensitivity, 89% specificity and 92% accuracy in comparison with culture method). In two out of four patients with negative culture who were positive for PrTBK, PCR and anti-tuberculosis drugs trial therapy responses were in favor of tuberculosis. If we take this finding into account, the accuracy of PrTBK will rise. Conclusion: High sensitivity and accuracy of PrTBK test enable us to initiate treatment on the basis of this convenient and rapid test. PMID:28210462
Subbian, Selvakumar; Tsenova, Liana; Holloway, Jennifer; Peixoto, Blas; O'Brien, Paul; Dartois, Véronique; Khetani, Vikram; Zeldis, Jerome B.; Kaplan, Gilla
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
Man, Dede K W; Chow, Michael Y T; Casettari, Luca; Gonzalez-Juarrero, Mercedes; Lam, Jenny K W
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.
Nicol, Mark P; Allen, Veronica; Workman, Lesley; Isaacs, Washiefa; Munro, Jacinta; Pienaar, Sandra; Black, Faye; Adonis, Layla; Zemanay, Widaad; Ghebrekristos, Yonas; Zar, Heather J
Summary Background Urine tests for mycobacterial lipoarabinomannan might be useful for point-of-care diagnosis of tuberculosis in adults with advanced HIV infection, but have not been assessed in children. We assessed the accuracy of urine lipoarabinomannan testing for the diagnosis of pulmonary tuberculosis in HIV-positive and HIV-negative children. Methods We prospectively recruited children (aged ≤15 years) who presented with suspected tuberculosis at a primary health-care clinic and paediatric referral hospital in South Africa, between March 1, 2009, and April 30, 2012. We assessed the diagnostic accuracy of urine lipoarabinomannan testing with lateral flow assay and ELISA, with mycobacterial culture of two induced sputum samples as the reference standard. Positive cultures were identified by acid-fast staining and tested to confirm Mycobacterium tuberculosis and establish susceptibility to rifampicin and isoniazid. Findings 535 children (median age 42·5 months, IQR 19·1–66·3) had urine and two induced specimens available for testing. 89 (17%) had culture-confirmed tuberculosis and 106 (20%) had HIV. The lateral flow lipoarabinomannan test showed poor accuracy against the reference standard, with sensitivity of 48·3% (95% CI 37·6–59·2), specificity of 60·8% (56·1–65·3), and an area under the receiver operating characteristic curve of 0·53 (0·46–0·60) for children without HIV and 0·64 (0·51–0·76) for children with HIV. ELISA had poor sensitivity in children without HIV (sensitivity 3·0%, 95% CI 0·4–10·5) and children with HIV (0%, 0·0–14·3); overall specificity was 95·7% (93·4–97·4). Interpretation Urine lipoarabinomannan tests have insufficient sensitivity and specificity to diagnose HIV-positive and HIV-negative children with tuberculosis and should not be used in this patient population. Funding US National Institutes of Health, the National Health Laboratory Services Research Trust, the Medical Research Council of
Hunter, Robert L.
Lack of access to human tissues with untreated tuberculosis (TB) has forced generations of researchers to use animal models and to adopt a paradigm that granulomas are the characteristic lesion of both primary and post primary TB. An extended search of studies of human lung tissues failed to find any reports that support this paradigm. We found scores of publications from gross pathology in 1804 through high resolution CT scans in 2015 that identify obstructive lobular pneumonia, not granulomas, as the characteristic lesion of developing post-primary TB. This paper reviews this literature together with other relevant observations to formulate a new paradigm of TB with three distinct stages: a three-act play. First, primary TB, a war of attrition, begins with infection that spreads via lymphatics and blood stream before inducing systemic immunity that contains and controls the organisms within granulomas. Second, post-primary TB, a sneak attack, develops during latent TB as an asymptomatic obstructive lobular pneumonia in persons with effective systemic immunity. It is a paucibacillary process with no granulomas that spreads via bronchi and accumulates mycobacterial antigens and host lipids for 1–2 years before suddenly undergoing caseous necrosis. Third, the fallout, is responsible for nearly all clinical post primary disease. It begins with caseous necrotic pneumonia that is either retained to become the focus of fibrocaseous disease or is coughed out to leave a cavity. This three-stage paradigm suggests testable hypotheses and plausible answers to long standing questions of immunity to TB. PMID:26980490
Hunter, Robert L
Lack of access to human tissues with untreated tuberculosis (TB) has forced generations of researchers to use animal models and to adopt a paradigm that granulomas are the characteristic lesion of both primary and post primary TB. An extended search of studies of human lung tissues failed to find any reports that support this paradigm. We found scores of publications from gross pathology in 1804 through high resolution CT scans in 2015 that identify obstructive lobular pneumonia, not granulomas, as the characteristic lesion of developing post-primary TB. This paper reviews this literature together with other relevant observations to formulate a new paradigm of TB with three distinct stages: a three-act play. First, primary TB, a war of attrition, begins with infection that spreads via lymphatics and blood stream before inducing systemic immunity that contains and controls the organisms within granulomas. Second, post-primary TB, a sneak attack, develops during latent TB as an asymptomatic obstructive lobular pneumonia in persons with effective systemic immunity. It is a paucibacillary process with no granulomas that spreads via bronchi and accumulates mycobacterial antigens and host lipids for 1-2 years before suddenly undergoing caseous necrosis. Third, the fallout, is responsible for nearly all clinical post primary disease. It begins with caseous necrotic pneumonia that is either retained to become the focus of fibrocaseous disease or is coughed out to leave a cavity. This three-stage paradigm suggests testable hypotheses and plausible answers to long standing questions of immunity to TB.
Han, Yi; Zhen, Dezhi; Liu, Shuku; Qin, Ming; Zhou, Shijie; Yu, Daping; Song, Xiaoyun; Li, Yunsong; Xiao, Ning; Su, Chongyu; Shi, Kang
Objective To compare video-assisted thoracoscopic surgery (VATS) lobectomy and conventional open lobectomy in patients with pulmonary tuberculosis (TB) who require surgery. Methods Forty patients with pulmonary TB who required lobectomy were randomized to receive either VATS or open lobectomy. Patient demographic, pulmonary function, operative, and postoperative data were compared between the groups. Results There were 20 patients who received VATS lobectomy (median age 31.5 years, range 19-67 years) and 20 that received open lobectomy (median age 33.5 years, range 16-60 years). The two groups were similar with respect to gender, age and pulmonary function (all, P>0.05). Lobectomy was completed by VATS in 19 of 20 patients (95%), and by thoracoscope-assisted mini-incision lobectomy in 1 patient. The median intraoperative blood loss was 345 mL (range, 100-800 mL), and the median duration of pleural cavity closed drainage was 5 days (range, 3-7 days). All open lobectomies were completed successfully, and the median intraoperative blood loss was 445 mL (range, 150-950 mL) and the median duration of pleural cavity closed drainage was 5 days (range, 3-9 days). No statistically significant differences were found between the groups with respect to operation completion rates, type of lung resection, intraoperative blood loss, closed pleural drainage duration and volume of postoperative chest drainage. The operation time, number of postoperative complications, postoperative pain index at 24 hours after surgery and postoperative hospital stay were all significantly less in the VATS group. With a median follow-up duration of 14 months (range, 8-18 months) no positive sputum examination results were found in either group. Conclusions VATS lobectomy is an effective and minimally invasive method for treating patients with pulmonary TB. PMID:26380771
Rosati, Yuri; Fabiani, Andrea; Taccari, Tommaso; Ranaldi, Renzo; Mammana, Gabriele; Tubaldi, Alberto
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.
Zhou, A T; Ma, W L; Zhang, P Y; Cole, R A
A rapid membrane-based serologic assay using the 38-kDa antigen from Mycobacterium tuberculosis for the diagnosis of tuberculosis (TB) was evaluated with 201 patients with pulmonary TB, 67 patients with extrapulmonary TB, 79 Mycobacterium bovis BCG-vaccinated healthy controls, and 77 non-TB respiratory patients. The overall sensitivities, specificities, and positive and negative predictive values were, respectively, 92, 92, 84, and 96% for sputum-positive TB patients; 70, 92, 87, and 79% for sputum-negative TB patients; and 76, 92, 80, and 90% for extrapulmonary-TB patients. Only 2% (1 of 44) of the healthy control BCG-vaccinated subjects gave weak positive signals in the assay, indicating that this rapid serological assay is a valuable aid in clinical diagnosis for both pulmonary and extrapulmonary TB. PMID:8705680
Santos-Neto, Marcelino; Yamamura, Mellina; Garcia, Maria Concebida da Cunha; Popolin, Marcela Paschoal; Silveira, Tatiane Ramos dos Santos; Arcêncio, Ricardo Alexandre
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
Nakao, Makoto; Sone, Kazuki; Kagawa, Yusuke; Kurokawa, Ryota; Sato, Hidefumi; Kunieda, Takefumi; Muramatsu, Hideki
Diagnosing active tuberculosis in elderly patients presents problems due to nonspecific symptoms and complications such as aspiration pneumonia. The current study presents two cases of pulmonary tuberculosis with bilateral pulmonary infiltrates associated with aspiration pneumonia. The two elderly patients developed acute respiratory distress syndrome as a result of aspiration pneumonia. The diagnoses of pulmonary tuberculosis were delayed in both cases, as the patients were diagnosed with active tuberculosis following discharge from hospital. The sputum test for acid-fast bacillus at the time of administration was smear-negative/culture-positive in these patients. They were treated with isoniazid, rifampicin and ethambutol, and nosocomial transmission of tuberculosis from these patients was not reported. The number of elderly patients with aspiration pneumonia is predicted to increase rapidly, and aspiration pneumonia combined with pulmonary tuberculosis is a major medical and healthcare concern in Japan. The present study concludes that physicians should always consider the complication of pulmonary tuberculosis when treating pneumonia patients, in particular in treating elderly patients with pulmonary infiltrates.
Nakao, Makoto; Sone, Kazuki; Kagawa, Yusuke; Kurokawa, Ryota; Sato, Hidefumi; Kunieda, Takefumi; Muramatsu, Hideki
Diagnosing active tuberculosis in elderly patients presents problems due to nonspecific symptoms and complications such as aspiration pneumonia. The current study presents two cases of pulmonary tuberculosis with bilateral pulmonary infiltrates associated with aspiration pneumonia. The two elderly patients developed acute respiratory distress syndrome as a result of aspiration pneumonia. The diagnoses of pulmonary tuberculosis were delayed in both cases, as the patients were diagnosed with active tuberculosis following discharge from hospital. The sputum test for acid-fast bacillus at the time of administration was smear-negative/culture-positive in these patients. They were treated with isoniazid, rifampicin and ethambutol, and nosocomial transmission of tuberculosis from these patients was not reported. The number of elderly patients with aspiration pneumonia is predicted to increase rapidly, and aspiration pneumonia combined with pulmonary tuberculosis is a major medical and healthcare concern in Japan. The present study concludes that physicians should always consider the complication of pulmonary tuberculosis when treating pneumonia patients, in particular in treating elderly patients with pulmonary infiltrates. PMID:27446284
The purpose of our study was to investigate the association between a functional single nucleotide polymorphism (SNP) in the interleukin-23 receptor gene (IL23R; rs11209026, 1142 Gwild type → Areduced function, Arg381Gln) and disease severity outcome in pulmonary tuberculosis (TB) in the Tunisian population. SNP was investigated in a population of 168 patients with active pulmonary TB (cases were stratified into patients with minimal/moderate lung involvement, i.e., patients with minimal/moderate disease [Pmd], and patients with extensive lung involvement, i.e., patients with active disease [Pad]) and 150 healthy subjects. Genotype analyses were carried out using the PCR-restriction fragment length polymorphism method. We have found that the IL23R reduced-function allele 1142A and genotypes AA and AG were overrepresented, especially in the Pad subgroup compared with the control group (51% versus 18% [P = 10−8], 33% versus 5% [P = 10−8], and 36% versus 26% [P = 5 × 10−3], respectively). Additionally, comparison of the Pad and the Pmd groups showed that the A allele and AA genotype seemed to be associated with 2.79-fold (P = 4 × 10−5) and 7.74-fold (P = 10−5) increased risks of TB with minimal/moderate lung involvement, respectively. Our results demonstrate that the reduced-function polymorphism 1142G → A encoded by IL23R influences the outcome of disease severity of active pulmonary TB in Tunisian patients. PMID:22695161
Winetsky, Daniel E.; Almukhamedov, Olga; Pulatov, Dilshod; Vezhnina, Natalia; Dooronbekova, Aizhan; Zhussupov, Baurzhan
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
Zadbuke, Sonali Sudhir; Set, Reena; Khan, Nishat; Shastri, Jayanthi
BACKGROUND: Methods for detection and drug susceptibility of tuberculosis (TB) with solid media are inexpensive but slow and laborious. Rapid methods to diagnose TB and multidrug-resistant TB (MDR-TB) are a global priority for TB control. OBJECTIVES: A study was performed to compare the sensitivity of detection of mycobacterial growth and time of culture positivity by microscopic observation of drug susceptibility (MODS) assay with that of Lowenstein–Jensen (LJ) culture in pulmonary and extrapulmonary TB and to evaluate the concordance of the susceptibilities to isoniazid (INH) and rifampicin (RIF) by MODS and proportion method on LJ. MATERIALS AND METHODS: A prospective, laboratory-based study was conducted on a total of 300 samples from suspected cases of pulmonary and extrapulmonary TB. Samples were inoculated on LJ medium as per the standard guidelines and MODS assay was performed. RESULTS: Sensitivity of MODS assay was 80% and 83.3% and specificity was 92.9% and 83.3% for pulmonary and extrapulmonary samples, respectively. Difference between mean time to detection of Mycobacterium TB (MTB) by LJ medium and MODS was statistically significant, with MODS being faster. drug susceptibility testing (DST) by MODS when compared to economic variant of proportion method was 87.87% for RIF, 90.9% for INH, and 96.96% for MDR-TB detection. CONCLUSION: MODS assay provides rapid, safe, and sensitive detection of TB faster than the existing gold standard. It is extremely promising in effectively diagnosing MDR-TB. PMID:28367022
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
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
Background Delayed diagnosis and treatment of tuberculosis increase both the severity of the disease and the duration of infectivity. A number of studies have addressed the issue of health system delays in the treatment of tuberculosis, but mostly in countries with a high or low incidence of the disease. Our understanding of delay is quite limited in settings with an intermediate burden of tuberculosis. We explore the duration and factors associated with delays in the Croatian health system which has free health care and a sufficient network of health services providing tuberculosis diagnosis and care. Methods A total of 241 consecutive adults with culture-confirmed pulmonary tuberculosis were interviewed in seven randomly selected Croatian counties and their medical records were evaluated. A health system delay was defined as the number of days from the first consultation with a physician to the initiation of anti-tuberculosis treatment. A long delay was defined as a period exceeding the median delay, while an extreme delay was considered to be above the 75th percentile delay. Results The median health system delay was 15 days while the 75th percentile was 42 days (the 5th and 95th percentile being 1 and 105 days respectively). Almost 30% of tuberculosis patients remained undiagnosed for more than 30 days after the initial health care visit. Female patients (p = 0.005), patients with a negative sputum smear (p = 0.002) and patients having symptoms other than the usual ones (0.027) were found to be in significant correlation with a long delay. In a multivariate model, a long delay remained associated with the same variables (p = 0.008, p = 0.003, and p = 0.037, respectively). A significant association was demonstrated between both the female gender (p = 0.042) and a negative sputum smear (p < 0.001) and extreme delay, while only a negative sputum smear (p < 0.001) remained significant in the multivariate analysis. Conclusions Our
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
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
Mahato, Roshan Kumar; Koju, Rajendra
Introduction Health system delay is the time for complete diagnosis of the disease after patient approaches a health care provider. Aim The study aims to identify the characteristics and the determinants of unacceptable health system delay (≥ 7 days delay from health system) in diagnosis of new pulmonary tuberculosis patients attending in Direct Observation Treatment Short course (DOTS) centers of Nepal. Materials and Methods An analytical cross-sectional study was conducted by administrating a structured questionnaire interview and reviewing the medical record of the new sputum smear positive pulmonary tuberculosis cases during January–May 2015. The generalized linear model (GLM) was applied to control the clustering effects. Multiple logistic regressions were performed to identify the association between variables with ≥ 7 days of unacceptable health system delay. Results Of the 374 new sputum smear positive pulmonary tuberculosis cases, the factors that were associated with unacceptable health system delay (time ≥ 7 days) were doing business (adj.OR= 1.61, 95% CI: 1.22-2.11; p-value <0.001) and unemployed (adj.OR= 3.04, 95% CI: 1.53-6.04; p-value <0.001) had chances of health system delay. However, getting support from parents (adj.OR= 0.55, 95% CI: 0.44-0.68; p-value <0.001), consultation with the private practitioners/ pharmacists (adj.OR= 0.24, 95% CI: 0.07-0.81; p-value 0.021), visiting government health facilities (adj.OR= 0.31, 95% CI: 0.13-0.73; p-value 0.008), using X-ray (adj.OR= 0.69, 95% CI: 0.49-0.97; p-value 0.032) and advance technologies for diagnosis of TB (adj.OR= 0.60, 95% CI: 0.39-0.94; p-value 0.024) were found contributing to reduce health system delay while controlling socio-economic, knowledge, presence of symptoms and attitude factors. Conclusion About a quarter of new TB patients faced health system delay problems. Socioeconomic factors, unemployment, influences the health system delay when controlled for other covariates. PMID
Porto dos Santos, Maisa; de Melo Silva, Cláudia Maria; Alves de Almeida, Vanessa; Assumpção Antunes, Irineide
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
Muñoz-Torrico, Marcela; Rendon, Adrian; Centis, Rosella; D'Ambrosio, Lia; Fuentes, Zhenia; Torres-Duque, Carlos; Mello, Fernanda; Dalcolmo, Margareth; Pérez-Padilla, Rogelio; Spanevello, Antonio; Migliori, Giovanni Battista
The role of tuberculosis as a public health care priority and the availability of diagnostic tools to evaluate functional status (spirometry, plethysmography, and DLCO determination), arterial blood gases, capacity to perform exercise, lesions (chest X-ray and CT), and quality of life justify the effort to consider what needs to be done when patients have completed their treatment. To our knowledge, no review has ever evaluated this topic in a comprehensive manner. Our objective was to review the available evidence on this topic and draw conclusions regarding the future role of the "post-tuberculosis treatment" phase, which will potentially affect several million cases every year. We carried out a non-systematic literature review based on a PubMed search using specific keywords (various combinations of the terms "tuberculosis", "rehabilitation", "multidrug-resistant tuberculosis", "pulmonary disease", "obstructive lung disease", and "lung volume measurements"). The reference lists of the most important studies were retrieved in order to improve the sensitivity of the search. Manuscripts written in English, Spanish, and Russian were selected. The main areas of interest were tuberculosis sequelae following tuberculosis diagnosis and treatment; "destroyed lung"; functional evaluation of sequelae; pulmonary rehabilitation interventions (physiotherapy, long-term oxygen therapy, and ventilation); and multidrug-resistant tuberculosis.The evidence found suggests that tuberculosis is definitively responsible for functional sequelae, primarily causing an obstructive pattern on spirometry (but also restrictive and mixed patterns), and that there is a rationale for pulmonary rehabilitation. We also provide a list of variables that should be discussed in future studies on pulmonary rehabilitation in patients with post-tuberculosis sequelae. RESUMO O papel da tuberculose como uma prioridade de saúde pública e a disponibilidade de ferramentas diagnósticas para avaliar o estado
Ray, Animesh; Suri, J C; Sen, M K; Chakrabarti, S; Gupta, Ayush; Capoor, Malini
Many disorders can present as cavitating lesions in the lung. In this case report, a case of mixed infection with drug resistant tuberculosis and invasive pulmonary aspergillosis in a post-partum patient has been presented.
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
Jiménez‐Corona, M‐E; García‐García, L; DeRiemer, K; Ferreyra‐Reyes, L; Bobadilla‐del‐Valle, M; Cano‐Arellano, B; Canizales‐Quintero, S; Martínez‐Gamboa, A; Small, P M; Sifuentes‐Osornio, J; Ponce‐de‐León, A
Background In most low income countries there are twice as many cases of tuberculosis (TB) reported among men than among women, a difference commonly attributed to biological and epidemiological characteristics as well as socioeconomic and cultural barriers in access to health care. The World Health Organization has encouraged gender specific comparisons in TB rates to determine whether women with TB are less likely than men with TB to be diagnosed, reported, and treated. A study was undertaken to identify gender based differences in patients with pulmonary TB and to use this information to improve TB control efforts. Methods Individuals with a cough for more than 2 weeks in southern Mexico were screened from March 1995 to April 2003. Clinical and mycobacteriological information (isolation, identification, drug susceptibility testing and IS6110 based genotyping, and spoligotyping) was collected from those with bacteriologically confirmed pulmonary TB. Patients were treated in accordance with official norms and followed to ascertain treatment outcome, retreatment, and vital status. Results 623 patients with pulmonary TB were enrolled. The male:female incidence rate ratio for overall, reactivated, and recently transmitted disease was 1.58 (95% CI 1.34 to 1.86), 1.64 (95% CI 1.36 to 1.98), and 1.41 (95% CI 1.01 to 1.96), respectively. Men were more likely than women to default from treatment (adjusted OR 3.30, 95% CI 1.46 to 7.43), to be retreated (hazard ratio (HR) 3.15, 95% CI 1.38 to 7.22), and to die from TB (HR 2.23, 95% CI 1.25 to 3.99). Conclusions Higher rates of transmitted and reactivated disease and poorer treatment outcomes among men are indicators of gender differentials in the diagnosis and treatment of pulmonary TB, and suggest specific strategies in endemic settings. PMID:16449260
Nevin, Remington L; Silvestri, John W; Hu, Zheng; Tobler, Steven K; Trotta, Richard F
Military personnel serving at remote camps in the border regions of northeastern Afghanistan may experience crowded living conditions and may have frequent interaction with local national (LN) workers, increasing the risk of exposure to multiple endemic diseases including tuberculosis (TB). In January 2007, pulmonary TB was clinically suspected in a LN worker who had close contact with a company of 92 U.S. Army personnel at a remote camp in Konar province, Afghanistan, over 4 months. This report describes the results of the contact investigation conducted by the U.S. Army, in which four U.S. personnel were found to have evidence of TB exposure. This investigation raises concerns arising from the high prevalence of drug-resistant TB in the region and in neighboring North West Frontier Province, Pakistan, and demonstrates the challenges of conducting contact investigations and using LN workers in deployed wartime environments.
Suntornsut, Pornpan; Kasemsupat, Kriangsak; Silairatana, Santi; Wongsuvan, Gumphol; Jutrakul, Yaowaruk; Wuthiekanun, Vanaporn; Day, Nicholas P J; Peacock, Sharon J; Limmathurotsakul, Direk
The clinical and radiological features of pulmonary melioidosis can mimic tuberculosis. We prospectively evaluated 118 patients with suspected pulmonary tuberculosis who were acid-fast bacilli (AFB) smear negative at Udon Thani Hospital, northeast Thailand. Culture of residual sputum from AFB testing was positive for Burkholderia pseudomallei in three patients (2.5%; 95% confidence interval [CI] 0.5-7.3%). We propose that in melioidosis-endemic areas, residual sputum from AFB testing should be routinely cultured for B. pseudomallei.
Tong, Xiang; Yan, Zhipeng; Zhou, Qilong; Liu, Sitong; Han, Jing; Ma, Yao; Yang, Xue; Fan, Hong
Many studies have indicated that Macrophage migration inhibitory factor (MIF)-173G/C gene polymorphisms are associated with susceptibility to pulmonary tuberculosis (PTB). Additionally, some studies have suggested that there are higher levels of serum MIF in patients with PTB than the controls. However, the results of these studies were underpowered. The current study aimed to precisely evaluate the association between the MIF-173G/C polymorphism and serum MIF concentrations with PTB. Therefore, a systematic literature search was preformed to identify studies involving the indicated association. Eleven articles (1316 cases and 1272 controls) were included in the study. The results indicated that the MIF-173G/C polymorphism was significantly associated with PTB susceptibility, especially in Asians. Interestingly, the results further detected that circulating MIF levels were significantly higher in patients with PTB than in healthy controls, but this was only the case among Asians. Moreover, the statistical significance was also similar to that of the high quality group. The present study indicated that the MIF-173G/C polymorphism may contribute to the development of PTB. Furthermore, significantly higher serum MIF levels were observed in PTB patients than in controls, which further indicated that the MIF may play an important role in PTB progression, particularly in Asians.
Alavi, Seyed Mohammad; Salmanzadeh, Shokrollah; Bakhtiyariniya, Pejman; Albagi, Ali; Hemmatnia, Fatemeh; Alavi, Leila
Background: Knowledge about childhood tuberculosis (TB) in Iran is limited. This study aimed to determine the proportion of tuberculosis in children living in Khuzestan in southwest of Iran and its treatment outcomes. Methods: In this retrospective study, the child’s medical records registered in national TB program (NTP) unit of Khuzestan Health Center (KHC) for TB treatment from 2005 to 2010 were studied. Data including demographic, clinical presentation, laboratory test results, and treatment outcomes were extracted from the files and were analyzed. Results: Of total 4104 new TB cases registered in KHC, 203 (4.9%) were children. The mean age was 10.7±4.3 years, and 75.7% of them were females. More than 84% of TB children cases were 10 years or older, whereas, young children (< 5 years old) accounted for 5.6%. Of the total studied cases, 57.1% were pulmonary TB and 42.9% were extra pulmonary, 91.7% were successfully treated and 8.3% had poor treatment outcome. The main risk factors for poor treatment outcome were: age <5 years (OR: 0.17, 95% CI, 0.04-0.76), low body weight (OR: 0.08, 95% CI, 0.01-0.60), household contact with cases of TB treatment failure (OR: 0.13, 95% CI, 0.03-0.52), and exposure to cigarette smoke odor inside the home (OR: 0.17, 95% CI, 0.05-0.56). Conclusion: The proportion of pediatric TB in the region was lower than expected. The treatment success rate was higher than the rate defined in NTP. Special attention should be given to children aged less than five years, low body weight, contact with TB treatment failure cases, and exposure to cigarette smoke. PMID:26644895
Li, Lei; Liu, Dan; Zhu, Yingying; Li, Weimin
Ground-glass nodules (GGNs) was a special type of pulmonary nodules. With the progress of high resolution CT (HRCT), it achieved a higher positive rate and attracted much attention in recent years. For lacking characteristic symptoms, the early diagnosis of lung cancer was difficult even nowadays. However, it had been proved that GGNs was well associated with lung cancer in previous studies. Therefore, optimized managements of GGNs could help diagnosis and treatments of lung cancer at early stage. In this review, we summarized the definition, classification, imaging characteristics, growing history, molecular pathological features and suggested managements of GGNs.
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
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.
Ordonez, Alvaro A.; Tasneen, Rokeya; Pokkali, Supriya; Xu, Ziyue; Converse, Paul J.; Klunk, Mariah H.; Mollura, Daniel J.; Nuermberger, Eric L.
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
Kruyt, M. L.; Kruyt, N. D.; Boeree, M. J.; Harries, A. D.; Salaniponi, F. M.; van Noord, P. A.
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
Atif, M; Sulaiman, SAS; Shafi, AA; Muttalif, AR; Ali, I; Saleem, F
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
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
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
Tsenova, Liana; O'Brien, Paul; Holloway, Jennifer; Peixoto, Blas; Soteropoulos, Patricia; Fallows, Dorothy; Subbian, Selvakumar
Treatment of chronic inflammatory diseases with tumor necrosis factor alpha (TNF-α) antagonists has been associated with increased risk of tuberculosis (TB). We examined the usefulness of the rabbit model of active pulmonary TB for studying the impact of the human immune modulatory reagent etanercept on the host immune response. Control of Mycobacterium tuberculosis (Mtb) infection, disease pathology, and the global transcriptional response in Mtb-infected lungs of rabbits were studied. Etanercept treatment exacerbated disease pathology and reduced bacillary control in the lungs, compared with infected untreated animals. Reduced collagen and fibrin deposition in the granulomas was associated with significant downregulation of the collagen metabolism and fibrosis network genes and upregulation of genes in the inflammatory response and cell recruitment networks in the lungs of etanercept treated, compared with untreated rabbits. Our results suggest that targeting the TNF-α signaling pathway disrupts the tissue remodeling process, which is required for the formation and maintenance of well-differentiated granulomas and for control of Mtb growth in the lungs. These results validate the use of the rabbit model for investigating the impact of selected human immune modulatory drugs, such as a TNF-α antagonist, on the host immune response and pathogenesis in TB. PMID:24831609
Shirodkar, S.; Anande, L.; Dalal, A.; Desai, C.; Corrêa, G.; Laxmeshwar, C.; Mansoor, H.; Remartinez, D.; Trelles, M.; Isaakidis, P.
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
Bonacci, Robert A.; Cruz-Hervert, Luis Pablo; García-García, Lourdes; Reynales-Shigematsu, Luz Myriam; Ferreyra-Reyes, Leticia; Bobadilla-del-Valle, Miriam; Canizales-Quintero, Sergio; Ferreira-Guerrero, Elizabeth; Báez-Saldaña, Renata; Téllez-Vázquez, Norma; Mongua-Rodríguez, Norma; Montero-Campos, Rogelio; Delgado-Sánchez, Guadalupe; Martínez-Gamboa, Rosa Areli; Cano-Arellano, Bulmaro; Sifuentes-Osornio, José; de León, Alfredo Ponce
Objectives To examine the relationship between cigarette smoking and incidence and mortality rates of pulmonary tuberculosis (TB) and treatment outcomes. Materials From 1995-2010, we analyzed data from 1062 patients with TB and from 2001-2004, 2951 contacts in Southern Mexico. Patients with acid-fast bacilli or Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and mycobacteriological evaluation and received treatment by the local DOTS program. Results Consumers of 1-10 (LS) or 11 or more (HS) cigarettes per day incidence (1.75 and 11.79) and mortality (HS,17.74) smoker-nonsmoker rate ratios were significantly higher for smokers. Smoker population was more likely to experience unfavorable treatment outcomes (HS, adjusted OR 2.36) and retreatment (LS and HS, adjusted hazard ratio (HR) 2.14 and 2.37). Contacts that smoked had a higher probability of developing active TB (HR 2.38) during follow up. Conclusions Results indicate the need of incorporating smoking prevention and cessation, especially among men, into international TB control strategies. PMID:22982014
Yin, Qing-Qin; Jiao, Wei-Wei; Han, Rui; Jiao, An-Xia; Sun, Lin; Tian, Jian-Ling; Ma, Yu-Yan; Rao, Xiao-Chun; Shen, Chen; Li, Qin-Jing; Shen, A-Dong
In order to evaluate the diagnostic accuracy of the Xpert MTB/RIF assay on childhood pulmonary tuberculosis (PTB) using bronchoalveolar lavage fluid (BALF), we evaluated the sensitivity, specificity, positive predictive value, and negative predictive value of Xpert MTB/RIF assay using BALF in comparison with acid-fast bacilli (AFB) microscopy and Mycobacterium tuberculosis (MTB) culture for diagnosing childhood PTB using Chinese "composite clinical reference standard" (CCRS) as reference standard. Two hundred fifty-five children with suspected PTB were enrolled at Beijing Children's Hospital from September 2010 to July 2013. Compared with Chinese CCRS, the sensitivity of AFB microscopy, MTB culture, and Xpert MTB/RIF assay was 8.4%, 28.9%, and 53.0%, respectively. The specificity of three assays was all 100%. Xpert MTB/RIF assay could detect 33.9% of cases with negative MTB culture, and 48.7% of cases with negative AFB microscopy. Younger age (<3 years), absence of BCG scar, and contact with TB patient were found significantly associated with a positive result of Xpert MTB/RIF assay. In conclusion, Xpert MTB/RIF assay using BALF can assist in diagnosing childhood PTB much faster when fiberoptic bronchoscopy is necessary according to the chest radiograph.
Shirodkar, S; Anande, L; Dalal, A; Desai, C; Corrêa, G; Das, M; Laxmeshwar, C; Mansoor, H; Remartinez, D; Trelles, M; Isaakidis, P
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.
Ko, Yousang; Shin, Jeong Hwan; Lee, Hyun-Kyung; Lee, Young Seok; Lee, Suh-Young; Park, So Young; Mo, Eun-Kyung; Kim, Changhwan
Background A sputum culture is the most reliable indicator of the infectiousness of pulmonary tuberculosis (PTB); however, a spontaneous sputum specimen may not be suitable. The aim of this study was to evaluate the infectious period in patients with non–drug-resistant (DR) PTB receiving adequate standard chemotherapy, using induced sputum (IS) specimens. Methods We evaluated the duration of infectiousness of PTB using a retrospective cohort design. Results Among the 35 patients with PTB, 22 were smear-positive. The rates of IS culture positivity from baseline to the sixth week of anti-tuberculosis medication in the smear-positive PTB group were 100%, 100%, 91%, 73%, 36%, and 18%, respectively. For smear-positive PTB cases, the median time of conversion to culture negativity was 35.0 days (range, 28.0–42.0 days). In the smear-negative PTB group (n=13), the weekly rates of positive IS culture were 100%, 77%, 39%, 8%, 0%, and 0%, respectively, and the median time to conversion to culture-negative was 21.0 days (range, 17.5–28.0 days). Conclusion The infectiousness of PTB, under adequate therapy, may persist longer than previously reported, even in patients with non-DR PTB. PMID:28119744
... you have come into contact with the TB bacteria. It does not mean that you have active ... Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health Page last updated: ...
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.
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
Chisti, Mohammod Jobayer; Ahmed, Tahmeed; Pietroni, Mark A C; Faruque, Abu S G; Ashraf, Hasan; Bardhan, Pradip K; Hossain, Iqbal; Das, Sumon Kumar; Salam, Mohammed Abdus
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
Goyal, Vipin; Goel, Shewtank
Introduction Even a single case of pulmonary Tuberculosis (TB) can infect many others. Hence, to ensure better control of the disease, it is imperative that all patients dispose their sputum safely. Outcomes of this study would highlight the gaps need to be bridged in order to curtail transmission of TB. Aim To analyse and ascertain perceptions about the disease and determine the sputum collection and disposal practices followed by sputum-positive TB patients. Materials and Methods In this cross-sectional study, 422 sputum-positive TB patients aged more than 15 years registered in the Tuberculosis Unit Ambala city from January 2012 – September 2012 formed the study population. After enrolment, at the end of one month, they were assessed for sputum collection and disposal practices by a trained person at their place of residences. Questionnaire was framed to collect relevant data. Results Safe sputum disposal was practised by 46.4% of the study subjects. More females than males disposed of sputum safely (70.4% vs. 29.6%), as did more subjects of low than middle socio-economic status (74.1% vs. 25.9%). 70.9% (n=66) of the subjects with a family history of TB practiced safe sputum disposal methods as compared to 39.5% (n=130) subjects without a family history of TB practiced the same. Similarly more literate than illiterate subjects (n=150, 57.5% vs. n=46, 28.6%) practiced safe sputum disposal methods. (p< 0.001). Regarding knowledge of causation of TB only 63% of the study subjects were in the view that this disease is caused by germs. Conclusion The study demonstrated that a large number of pulmonary TB patients practiced unsafe sputum disposal. Unsafe sputum disposal was higher among males, illiterate patients and those belonging to the lower socio-economic group. Therefore, it is need of the hour to launch Information, Education and Communication (IEC) activities so as to improve the sputum disposal practices among tuberculosis patients. PMID:28208887
Mursalova, G Kh
The differential diagnostic signs of disseminated pulmonary processes were defined by computed tomography. A hundred and sixty-seven patients, including 117 (70%) with disseminated pulmonary tuberculosis (DPT) and 50 (30%) with alveolitis, were examined. Their mean age was 32.3 +/- 5.1 years; the history of disease averaged 4.6 +/- 1.2 years. Acute, subacute, and chronic DPT was observed in 17 (14.5%), 32 (27.3%), and 68 (58.1%) patients, respectively. Idiopathic fibrosing alveolitis (IFA) was seen in 38 patients; 12 patients had exogenous allergic alveolitis (EAA). IFA and EAA were chronic. Patients with DPT had most commonly signs, such as focal masses (45.3%), intra- and interlobular septal thickening (35%), lung tissue reticulation (35%), centrilobular empyema (29%), only focal masses being detected in its acute form, and other signs being more pronounced in its subacute and particularly chronic form. Glassy dark patches, the opal glass syndrome, were a common sign in patients with alveolitis. Septal thickening, lung tissue meshwork, and centrilobular emphysema were encountered only in patients with IDA and small-nodular focal masses and bronchial wall thickening were present in those with EAA.
Thomas, Beena E.; Adinarayanan, Srividya; Manogaran, C.; Swaminathan, Soumya
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
Otchere, ID; Asante-Poku, A; Osei-Wusu, S; Aboagye, SY; Yeboah-Manu, D
Background Nontuberculous mycobacterial (NTM) species are assuming public health importance in pulmonary diseases; they are increasingly being isolated, and importantly, most NTMs do not respond to routine tuberculosis (TB) drugs. This study aimed to identify NTMs isolated from pulmonary TB cases and also determine their susceptibility to streptomycin (STR), isoniazid (INH), and rifampicin (RIF). Methods A total of 1755 mycobacterial isolates, obtained between August 2012 and July 2014, from 2036 smear-positive pulmonary cases were identified using polymerase chain reaction amplification of IS6110, and hsp65 gene sequencing analysis. Drug susceptibility testing (DST) was then performed for the identified NTMs against STR, INH, and RIF using microplate Alamar blue assay. The results were analyzed against patients’ biodata for statistical associations. Results Of the 1755 analyzed isolates, we identified 43 (2.5%) NTMs, which included 18 (41.9%) Mycobacterium intracellulare, 13 (30.2%) Mycobacterium avium subs. paratuberculosis, 5 (11.3%) Mycobacterium abscessus, 3 (7.0%) each of Mycobacterium mucogenicum and Mycobacterium colombiense, and 1 (2.3%) Mycobacterium simiae. Patients infected with NTMs (52.0%) were more likely to be human immunodeficiency virus-positive (P = 0.001, odds ratio = 6.6, 95% confidence interval = 2.7–16.2) than those infected with M. tuberculosis complex (5.8%). All the 43 (100%) NTMs were resistant to INH, whereas 32 (74%) and 19 (44%) were resistant to RIF and STR, respectively. Furthermore, 16 (37.2%) NTMs were resistant to all three drugs, 20 were resistant to INH and RIF, and 3 were resistant to STR and INH. All the M. abscessus isolates were resistant to all the three drugs, whereas all the M. avium isolates were resistant to INH and RIF, but only three were resistant to STR. Among the M. intracellulare isolates, 8, 18, and 15 isolates were resistant to STR, INH, and RIF, respectively. Conclusion The observed high-resistance level to
Gao, Limin; Li, Huifang; Li, Gandi; Liu, Weiping; Li, Jinnan; Zhang, Wenyan
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.
Lee, Sang Cjeol
Background This study aimed to investigate the treatment outcomes and influence of old pulmonary tuberculosis (TB) in elderly patients (over 70 years) with secondary spontaneous pneumothorax (SSP). Methods A retrospective analysis was performed on patients with SSP between January 2002 and December 2014. Treatment outcomes including chest tube duration (CTD), type and complication of surgery, recurrence and survival rate were obtained from the review of medical records and analyzed statistically. Results Two hundred and sixteen consecutive cases were recruited. Of these, 134 (62.0%) did not have old pulmonary TB [non-tuberculosis (NTB) group], and the other 82 (38.0%) had experienced pulmonary TB (TB group). More thoracoscopic surgeries had been performed in the NTB group (P=0.038). More postoperative complications developed in the TB group (P=0.038). Total CTD and postoperative CTD in the TB group were significantly longer (P=0.015 and 0.030, respectively). However, recurrence-free survival and overall survival rate were not significantly different between the TB and NTB groups. Conclusions Old pulmonary TB in elderly patients with SSP made their treatment more complicated. However, surgery might be considered in highly selected patients regardless of old pulmonary TB, and could be conducted with acceptable morbidity and mortality. PMID:27867567
Ben-Selma, Walid; Boukadida, Jalel
The purpose of our study was to investigate the association between a functional single nucleotide polymorphism (SNP) in the interleukin-23 receptor gene (IL23R; rs11209026, 1142 G(wild type) → A(reduced function), Arg381Gln) and disease severity outcome in pulmonary tuberculosis (TB) in the Tunisian population. SNP was investigated in a population of 168 patients with active pulmonary TB (cases were stratified into patients with minimal/moderate lung involvement, i.e., patients with minimal/moderate disease [Pmd], and patients with extensive lung involvement, i.e., patients with active disease [Pad]) and 150 healthy subjects. Genotype analyses were carried out using the PCR-restriction fragment length polymorphism method. We have found that the IL23R reduced-function allele 1142A and genotypes AA and AG were overrepresented, especially in the Pad subgroup compared with the control group (51% versus 18% [P = 10(-8)], 33% versus 5% [P = 10(-8)], and 36% versus 26% [P = 5 × 10(-3)], respectively). Additionally, comparison of the Pad and the Pmd groups showed that the A allele and AA genotype seemed to be associated with 2.79-fold (P = 4 × 10(-5)) and 7.74-fold (P = 10(-5)) increased risks of TB with minimal/moderate lung involvement, respectively. Our results demonstrate that the reduced-function polymorphism 1142G → A encoded by IL23R influences the outcome of disease severity of active pulmonary TB in Tunisian patients.
Price, Dominique N.; Kusewitt, Donna F.; Lino, Christopher A.; McBride, Amber A.; Muttil, Pavan
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
Adzhemian, A A; Markarian, N R; Mkrtchian, M M
250 patients in need of retreatment for pulmonary tuberculosis were enrolled in the study. The later indicated that there was a preponderance of males constituting all-bodied age population groups aged 25 to 64 years in the age and gender structure of the examinees. The major factors contributing to reactivation of the tuberculous process and poor outcomes of a previous course of specific therapy were extensive X-ray changes in the lung, drug resistance of the pathogens of tuberculosis to first-line drugs, and neglect of X-ray findings in the determinants of the duration of treatment. The use of the standard short-term course of chemotherapy was found to result in incomplete cure of disseminated and moderately disseminated processes, particularly in drug resistance of Mycobacterium tuberculosis and in concomitant diseases, which becomes a cause of early and late recurrences.
Yang, Wen-fang; Han, Fei; Zhang, Xiao-hui; Zhang, Ping; Chen, Jiang-hua
The diagnosis of extra-pulmonary tuberculosis (TB) seems relatively difficult due to the absence of specific symptoms and signs in patients on peritoneal dialysis or hemodialysis. We report four cases of extra-pulmonary tuberculosis on dialysis, with two cases on peritoneal dialysis and two cases on hemodialysis. The presentations, therapy, and outcomes of TB infection in these patients were reviewed. Otherwise, the English literature published in the PubMed database associating extra-pulmonary tuberculosis on dialysis over the last three decades is reviewed. A total of 61 studies containing 70 cases were included. The most common primary disease was diabetic nephropathy (22.86%, 16/70). The peritoneum (31.42%, 22/70), bone (21.42%, 15/70), and lymph node (20%, 14/70) were the most frequently infected. Single organ infection was common (90%, 63/70). Fever (58.57%, 41/70), pain (35.71%, 25/70), and enlarged lymph node (20%, 14/70) were the most common symptoms. Biopsy (67.14%, 47/70) and culture (40%, 28/70) provided most reliable methods for clear diagnosis of tuberculosis. The combined treatment of isoniazid, rifampicin, pyrazinamide, and ethambutol (44.29%, 31/70) was the most common therapy. The majority of patients improved (82.86%, 58/70); however, 12 cases got worse (17.14%), with 10 of them dying (14.29%). Physicians should be aware of the non-specific symptoms and location of infection, and consider tuberculosis in their differential diagnoses in dialysis patients presenting with symptoms such as fever, pain, and weight loss.
Koro Koro, Francioli; Um Boock, Alphonse; Kaiyven, Afi Leslie; Noeske, Juergen; Gutierrez, Cristina; Kuaban, Christopher; Etoa, François-Xavier; Eyangoh, Sara Irène
Background. Cameroon this last decade continues to present a low contribution of M. africanum and M. bovis in human tuberculosis (TB), while M. bovis was prevalent in cattle but all these pieces of information only concerned West and Center regions. Methods. We carried out the first study in Adamaoua, one of the most rearing regions of Cameroon, on the genetic structure and drug susceptibility of the MTBC strains isolated from newly diagnosed sputum smear-positive patients aged 15 years and above. For that purpose, spoligotyping, a modified 15 standard MIRU/VNTR loci typing, and the proportion method were used. Results. Four hundred and thirty-seven MTBC isolates were analyzed by spoligotyping. Of these, 423 were identified as M. tuberculosis, within the Cameroon family being dominant with 278 (65.7%) isolates; twelve (2.75%) isolates were classified as M. africanum and two as M. bovis. MIRU/VNTR typing of the most prevalent sublineage (SIT 61) suggested that this lineage is not a unique clone as thought earlier but could constitute a group of strains implicated to different pocket of TB transmission. Only M. tuberculosis sublineages were associated with antituberculosis drug resistance. Conclusion. These results showed the weak contribution of M. africanum and M. bovis to human active pulmonary tuberculosis in Cameroon even in the rearing region.
Um Boock, Alphonse; Noeske, Juergen; Gutierrez, Cristina; Kuaban, Christopher; Etoa, François-Xavier; Eyangoh, Sara Irène
Background. Cameroon this last decade continues to present a low contribution of M. africanum and M. bovis in human tuberculosis (TB), while M. bovis was prevalent in cattle but all these pieces of information only concerned West and Center regions. Methods. We carried out the first study in Adamaoua, one of the most rearing regions of Cameroon, on the genetic structure and drug susceptibility of the MTBC strains isolated from newly diagnosed sputum smear-positive patients aged 15 years and above. For that purpose, spoligotyping, a modified 15 standard MIRU/VNTR loci typing, and the proportion method were used. Results. Four hundred and thirty-seven MTBC isolates were analyzed by spoligotyping. Of these, 423 were identified as M. tuberculosis, within the Cameroon family being dominant with 278 (65.7%) isolates; twelve (2.75%) isolates were classified as M. africanum and two as M. bovis. MIRU/VNTR typing of the most prevalent sublineage (SIT 61) suggested that this lineage is not a unique clone as thought earlier but could constitute a group of strains implicated to different pocket of TB transmission. Only M. tuberculosis sublineages were associated with antituberculosis drug resistance. Conclusion. These results showed the weak contribution of M. africanum and M. bovis to human active pulmonary tuberculosis in Cameroon even in the rearing region. PMID:28119925
Banu, Sayera; Rahman, Md. Toufiq; Uddin, Mohammad Khaja Mafij; Khatun, Razia; Khan, Md. Siddiqur Rahman; Rahman, Md. Mojibur; Uddin, Syed Iftekhar; Ahmed, Tahmeed; Heffelfinger, James D.
Background Understanding tuberculosis (TB) transmission dynamics is essential for establishing effective TB control strategies in settings where the burden and risk of transmission are high. The objectives of this study were to evaluate the effect of active screening on controlling TB transmission and also to characterize Mycobacterium tuberculosis strains for investigating transmission dynamics in a correctional setting. Methods The study was carried out in Dhaka Central Jail (DCJ), from October 2005 to February 2010. An active case finding strategy for pulmonary TB was established both at the entry point to the prison and inside the prison. Three sputum specimens were collected from all pulmonary TB suspects and subjected to smear microscopy, culture, and drug susceptibility testing as well as genotyping which included deletion analysis, spoligotyping and analysis of mycobacterial interspersed repetitive units (MIRU). Results A total of 60,585 inmates were screened during the study period. We found 466 inmates with pulmonary TB of whom 357 (77%) had positive smear microscopy results and 109 (23%) had negative smear microscopy results but had positive results on culture. The number of pulmonary TB cases declined significantly, from 49 cases during the first quarter to 8 cases in the final quarter of the study period (p=0.001). Deletion analysis identified all isolates as M. tuberculosis and further identified 229 (70%) strains as ‘modern’ and 100 (30%) strains as ‘ancestral’. Analysis of MIRU showed that 347 strains (85%) exhibited unique patterns, whereas 61 strains (15%) clustered into 22 groups. The largest cluster comprised eight strains of the Beijing M. tuberculosis type. The rate of recent transmission was estimated to be 9.6%. Conclusions Implementation of active screening for TB was associated with a decline in TB cases in DCJ. Implementation of active screening in prison settings might substantially reduce the national burden of TB in Bangladesh
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
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
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
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.
Chigutsa, Emmanuel; Patel, Kashyap; Denti, Paolo; Visser, Marianne; Maartens, Gary; Kirkpatrick, Carl M J; McIlleron, Helen; Karlsson, Mats O
Days to positivity in automated liquid mycobacterial culture have been shown to correlate with mycobacterial load and have been proposed as a useful biomarker for treatment responses in tuberculosis. However, there is currently no quantitative method or model to analyze the change in days to positivity with time on treatment. The objectives of this study were to describe the decline in numbers of mycobacteria in sputum collected once weekly for 8 weeks from patients on treatment for tuberculosis using days to positivity in liquid culture. One hundred forty-four patients with smear-positive pulmonary tuberculosis were recruited from a tuberculosis clinic in Cape Town, South Africa. A nonlinear mixed-effects repeated-time-to-event modeling approach was used to analyze the time-to-positivity data. A biexponential model described the decline in the estimated number of bacteria in patients' sputum samples, while a logistic model with a lag time described the growth of the bacteria in liquid culture. At baseline, the estimated number of rapidly killed bacteria is typically 41 times higher than that of those that are killed slowly. The time to kill half of the rapidly killed bacteria was about 1.8 days, while it was 39 days for slowly killed bacteria. Patients with lung cavitation had higher bacterial loads than patients without lung cavitation. The model successfully described the increase in days to positivity as treatment progressed, differentiating between bacteria that are killed rapidly and those that are killed slowly. Our model can be used to analyze similar data from studies testing new drug regimens.
The case was 71-year-old woman. She was diagnosed as drug sensitive pulmonary tuberculosis (bII3 by the GAKKAI classification) and the chemotherapy with INH, RFP, EB and PZA was started. Two months later back pain and hemiparesis of both lower limbs appeared and it was diagnosed as caries of the 10th thoracic vertebrae. Because she was confined to bed and impossible to eat orally, the parenteral-hyperalimentaiton therapy was started with the central vein catheter. Howerer, nutritional state, pulmonary tuberculosis lesions and caries symptoms deteriorated. Then percutaneous endoscopic gastrostomy was performed and enteral nutrition was started. Since then nutritional state and tuberculosis lesions including caries improved gradually. It was estimated that the enteral nutrition brought about recovery of function and immunity of her digestive tract. For patients with advanced tuberculosis with poor nutritional state, the enteral nutrition is a useful adjuvant therapy, and the gastrostoma is considered to be one of the effective administrational routes when oral ingestion is difficult.
Tseng, Yau-Lin; Chang, Jia-Ming; Liu, Yi-Sheng; Cheng, Lili; Chen, Ying-Yuan; Wu, Ming-Ho; Lu, Chung-Lan; Yen, Yi-Ting
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
Background At present, much of the attention within tuberculosis (TB) management is spent on microbiological cure, and its impact on health-related quality of life (HRQoL) is either undervalued or seldom considered. The aim of this study was to evaluate the impact of TB treatment on HRQoL of new smear positive pulmonary tuberculosis (PTB) patients. Moreover, we also aimed to determine whether the selected socio-demographic and clinical variables were predictive of variability in the HRQoL scores over time. Methods This was a prospective follow-up of new smear positive PTB patients who were diagnosed at the chest clinic of Penang General Hospital between March 2010 and February 2011. All eligible patients (i.e., a new case of smear positive PTB, literate and aged 18 years or above) were asked to self-complete the SF-36v2 questionnaire at the start of their treatment, and then subsequently after the intensive phase and at the end of the treatment. A score on a health domain or component summary measure that was less than 47 norm-based scoring (NBS) point was considered indicative of impaired function within that health domain or dimension. Likewise, an individual having mental component summary (MCS) score ≤ 42 NBS point was considered to be at the risk of depression. Repeated measures ANOVA test was performed to examine how the summary scores varied over time, and to determine whether independent variables were predictive of variability in the physical component summary (PCS) and MCS scores over time. Results A total of 216 patients completed the SF-36v2 questionnaire at the start of their treatment. Out of these, 177 and 153 completed the questionnaire at the second and third follow-ups, respectively. The mean PCS scores at the start of the treatment, after the intensive phase and at the end of treatment were 41.9 (SD 5.1), 45.8 (SD 4.8) and 46.0 (SD 6.9), respectively. Similarly, the mean MCS scores at the start of the treatment, after the intensive phase
Valente, Ilaria C.; Norbis, Luca; Sotgiu, Giovanni; Bosu, Roberta; Ambrosi, Alessandro; Codecasa, Luigi R.; Goletti, Delia; Matteelli, Alberto; Ntinginya, Elias N.; Aloi, Francesco; Heinrich, Norbert; Reither, Klaus; Cirillo, Daniela M.
Several studies showed that assessing levels of specific circulating microRNAs (miRNAs) is a non-invasive, rapid, and accurate method for diagnosing diseases or detecting alterations in physiological conditions. We aimed to identify a serum miRNA signature to be used for the diagnosis of tuberculosis (TB). To account for variations due to the genetic makeup, we enrolled adults from two study settings in Europe and Africa. The following categories of subjects were considered: healthy (H), active pulmonary TB (PTB), active pulmonary TB, HIV co-infected (PTB/HIV), latent TB infection (LTBI), other pulmonary infections (OPI), and active extra-pulmonary TB (EPTB). Sera from 10 subjects of the same category were pooled and, after total RNA extraction, screened for miRNA levels by TaqMan low-density arrays. After identification of “relevant miRNAs”, we refined the serum miRNA signature discriminating between H and PTB on individual subjects. Signatures were analyzed for their diagnostic performances using a multivariate logistic model and a Relevance Vector Machine (RVM) model. A leave-one-out-cross-validation (LOOCV) approach was adopted for assessing how both models could perform in practice. The analysis on pooled specimens identified selected miRNAs as discriminatory for the categories analyzed. On individual serum samples, we showed that 15 miRNAs serve as signature for H and PTB categories with a diagnostic accuracy of 82% (CI 70.2–90.0), and 77% (CI 64.2–85.9) in a RVM and a logistic classification model, respectively. Considering the different ethnicity, by selecting the specific signature for the European group (10 miRNAs) the diagnostic accuracy increased up to 83% (CI 68.1–92.1), and 81% (65.0–90.3), respectively. The African-specific signature (12 miRNAs) increased the diagnostic accuracy up to 95% (CI 76.4–99.1), and 100% (83.9–100.0), respectively. Serum miRNA signatures represent an interesting source of biomarkers for TB disease with the
Nepal, A K; Gyawali, N; Poudel, B; Mahato, R V; Lamsal, M; Gurung, R; Baral, N; Majhi, S
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.
Castro, Simone; Cafezeiro, Aparecida S.; Daltro, Carla; Netto, Eduardo M.; Kornfeld, Hardy; Andrade, Bruno B.
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
Yuliwulandari, Rika; Sachrowardi, Qomariyah; Nakajima, Humiaki; Kashiwase, Koichi; Hirayasu, Kouyuki; Mabuchi, Akihiko; Sofro, Abdul Salam Mudzakir; Tokunaga, Katsushi
Genetic studies of pulmonary tuberculosis (PTB), including those of human leukocyte antigen (HLA) genes, have been reported in several populations. Some studies also have reported these genes to have a stronger role in severe tuberculosis. We investigated HLA class I and II alleles and haplotypes to ascertain their role in susceptibility and resistance to new and recurrent PTB in 257 PTB patients (216 new and 41 recurrent PTB patients) and 236 healthy controls in Western Javanese (Indonesia). HLA-B*4006 was associated with new PTB (p = 0.044, p(adj) = ns), whereas HLA-B*1802, HLA-B*4001 and HLA-DRB1*1101 were associated with recurrent PTB (p = 0.013, p(adj) = 0.016; p = 0.015, p(adj) = 0.028; and p = 0.008, p(adj) = 0.027 for new PTB vs recurrent PTB, respectively). Except for HLA-B*4006, those associations remained significant after adjustment for age and gender by logistic regression analysis, although they disappeared after correction for multiple testing. Haplotype HLA-B*1802-DRB1*1202 was associated with susceptibility to recurrent PTB (p = 0.014, odds ratio = 3.8, 95% confidence interval = 1.18-12.27). In contrast, HLA-DRB1*1202 in the absence of HLA-B*1802 showed a significant association with resistance to recurrent PTB (p = 8.2 x 10(-4), odds ratio = 0.32, 95% confidence interval = 0.16-0.64), suggesting that stronger susceptibility effect of HLA-B*1802 masked the protective effect of HLA-DRB1*1202. Further studies using larger number of patients with recurrent PTB will be needed to confirm our findings.
Anai, Satoshi; Hashisako, Mikiko; Ikegame, Satoshi; Wakamatsu, Kentarou; Nagata, Nobuhiko; Nakanishi, Yoichi; Kajiki, Akira
A 78-year-old Japanese woman was admitted to our hospital for fever, dry cough, and right pleural effusion. She was diagnosed with mantle cell lymphoma (MCL) at 73 years of age and was treated with carcinostatics, but MCL was refractory. Chest computed tomography (CT) on admission revealed a localized trabecular shadow in the middle lobe of the right lung and right pleural effusion with thickened visceral pleura. Right pleural effusion was exudative, lymphocytes were dominant, and adenosine deaminase isoenzymes were elevated. (18)F-fluorodeoxyglucose positron emission tomography/CT revealed positive findings in the right thickened visceral pleura and right middle lobe. We suspected tuberculosis, but bronchoscopy revealed that the washing fluid was negative for Ziehl-Neelsen staining. Thoracoscopy under local anesthesia revealed redness on the parietal and visceral pleura and fibrin network. Pathological findings from pleural biopsy included granulomas, Langhans-type giant cells, and diffuse invasion of lymphocytes with atypical nuclei. Immunophenotypes were CD5(+), CD10(-), CD19(+), CD20(+), λ(+), CD25(+) by flow cytometry and CD20(+), CD45RO(-), cyclin D1(+), bcl2(+), bcl6(-) by immunohistochemistry. We diagnosed MCL involvement of the pleura, and highly suspected tuberculous pleurisy. The patient received antituberculosis therapy with rifampicin, isoniazid, pyrazinamide, and ethambutol. After 4 weeks, culture of bronchoscopy washing fluid was positive for Mycobacterium tuberculosis. We diagnosed pulmonary tuberculosis. Patients with malignant lymphoma are vulnerable to tuberculosis. In addition to diagnosing MCL involvement of the pleura, it is important to consider the possibility of complication with tuberculosis.
Wang, Min; Xu, Guisheng; Lü, Lingshuang; Xu, Kun; Chen, Yongzhong; Pan, Hongqiu; Burstrom, Bo; Burstrom, Kristina; Wang, Jianming
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
Rajan, Jiby; Mathai, Ashok Thomas; Prasad, P V S; Kaviarasan, P K
Tuberculosis has been a well-known affliction of human kind, since antiquity. Cutaneous tuberculosis constitutes only a small proportion of extra pulmonary tuberculosis and multifocal involvement of cutaneous tuberculosis is an even rarer manifestation. We report one such case of multifocal tuberculosis verrucosa cutis in a 17-year old male patient in the absence of any primary tuberculous focus. PMID:21772603
Ballester, Marie; Nembrini, Chiara; Dhar, Neeraj; de Titta, Alexandre; de Piano, Cyntia; Pasquier, Miriella; Simeoni, Eleonora; van der Vlies, André J; McKinney, John D; Hubbell, Jeffrey A; Swartz, Melody A
Vaccines that drive robust T-cell immunity against Mycobacterium tuberculosis (Mtb) are needed both for prophylactic and therapeutic purposes. We have recently developed a synthetic vaccine delivery platform with Pluronic-stabilized polypropylene sulfide nanoparticles (NPs), which target lymphoid tissues by their small size (∼ 30 nm) and which activate the complement cascade by their surface chemistry. Here we conjugated the tuberculosis antigen Ag85B to the NPs (NP-Ag85B) and compared their efficacy in eliciting relevant immune responses in mice after intradermal or pulmonary administration. Pulmonary administration of NP-Ag85B with the adjuvant CpG led to enhanced induction of antigen-specific polyfunctional Th1 responses in the spleen, the lung and lung-draining lymph nodes as compared to soluble Ag85B with CpG and to the intradermally-delivered formulations. Mucosal and systemic Th17 responses were also observed with this adjuvanted NP formulation and vaccination route, especially in the lung. We then evaluated protection induced by the adjuvanted NP formulation following a Mtb aerosol challenge and found that vaccination with NP-Ag85B and CpG via the pulmonary route displayed a substantial reduction of the lung bacterial burden, both compared to soluble Ag85B with CpG and to the corresponding intradermally delivered formulations. These findings highlight the potential of administrating NP-based formulations by the pulmonary route for TB vaccination.
Rohner, Peter; Jahn, Esther I. M.; Ninet, Beatrice; Ionati, Concetta; Weber, Rainer; Auckenthaler, Raymond; Pfyffer, Gaby E.
The LCx MTB amplification assay is a nucleic acid amplification test intended for the direct detection of Mycobacterium tuberculosis complex in respiratory specimens. We evaluated its performance on 2,001 consecutive respiratory specimens; 78 were culture positive for M. tuberculosis. Sensitivity, specificity, and positive and negative predictive values of this assay for all specimens compared to culture results were 88.5, 97.7, 60.5, and 99.5%, respectively. When referred to resolved clinical diagnosis of active tuberculosis, these values improved to 90.2, 98.4, 72.8, and 99.5%, respectively. PMID:9738065
Baylor, Peter A; Sobenes, Juan R; Vallyathan, Val
We present a case of interstitial pulmonary fibrosis accompanied by radiographic evidence of progressive massive fibrosis in a patient who had a 15-20 year history of almost daily recreational inhalation of methamphetamine. Mineralogical analysis confirmed the presence of talc on biopsy of the area of progressive massive fibrosis. The coexistence of interstitial pulmonary fibrosis and progressive massive fibrosis suggests that prolonged recreational inhalation of methamphetamine that has been "cut" with talc can result in sufficient amount of talc being inhaled to result in interstitial pulmonary fibrosis and progressive massive fibrosis in the absence of other causes.
Zheng, Meng-Li; Zhou, Nai-Kang; Luo, Cheng-Hua
In our study, we aimed to profile a panel microRNAs (miRNAs) as potential biomarkers for the early diagnosis of pulmonary tuberculosis (PTB) and to illuminate the molecular mechanisms in the development of PTB. Firstly, gene expression profile of E-GEOD-49951 was downloaded from ArrayExpress database, and quantile-adjusted conditional maximum likelihood method was utilized to identify statistical difference between miRNAs of Mycobacterium tuberculosis (MTB)-infected individuals and healthy subjects. Furthermore, in order to assess the performance of our methodology, random forest (RF) classification model was utilized to identify the top 10 miRNAs with better Area Under The Curve (AUC) using 10-fold cross-validation method. Additionally, Monte Carlo Cross-Validation was repeated 50 times to explore the best miRNAs. In order to learn more about the differentially-expressed miRNAs, the target genes of differentially-expressed miRNAs were retrieved from TargetScan database and Ingenuity Pathways Analysis (IPA) was used to screen out biological pathways where target genes were involved. After normalization, a total of 478 miRNAs with higher than 0.25-fold quantile average across all samples were required. Based on the differential expression analysis, 38 differentially expressed miRNAs were identified when the significance was set as false discovery rate (FDR) < 0.01. Among the top 10 differentially expressed miRNAs, miRNA-155 obtained a highest AUC value 0.976, showing a good performance between PTB and control groups. Similarly, miRNA-449a, miRNA-212 and miRNA-132 revealed also a good performance with AUC values 0.947, 0.931 and 0.930, respectively. Moreover, miRNA-155, miRNA-449a, miRNA-29b-1* and miRNA-132 appeared in 50, 49, 49 and 48 bootstraps. Thus, miRNA-155 and miRNA-132 might be important in the progression of PTB and thereby, might present potential signatures for diagnosis of PTB.
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
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 R = 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.
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
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
Dheda, Keertan; Barry, Clifton E; Maartens, Gary
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.
Zeka, Arzu N; Tasbakan, Sezai; Cavusoglu, Cengiz
Mycobacterium tuberculosis remains one of the most significant causes of death from an infectious agent. The rapid diagnosis of tuberculosis and detection of rifampin (RIF) resistance are essential for early disease management. The GeneXpert MTB/RIF assay is a novel integrated diagnostic device for the diagnosis of tuberculosis and rapid detection of RIF resistance in clinical specimens. We determined the performance of the MTB/RIF assay for rapid diagnosis of tuberculosis and detection of rifampin resistance in smear-positive and smear-negative pulmonary and extrapulmonary specimens obtained from possible tuberculosis patients. Two hundred fifty-three pulmonary and 176 extrapulmonary specimens obtained from 429 patients were included in the study. One hundred ten (89 culture positive and 21 culture negative for M. tuberculosis) of the 429 patients were considered to have tuberculosis. In pulmonary specimens, sensitivities were 100% (27/27) and 68.6% (24/35) for smear-positive and smear-negative specimens, respectively. It had a lower sensitivity with extrapulmonary specimens: 100% for smear-positive specimens (4/4) and 47.7% for smear-negative specimens (21/44). The test accurately detected the absence of tuberculosis in all 319 patients without tuberculosis studied. The MTB/RIF assay also detected 1 RIF-resistant specimen and 88 RIF-susceptible specimens, and the results were confirmed by drug susceptibility testing. We concluded that the MTB/RIF test is a simple method, and routine staff with minimal training can use the system. The test appeared to be as sensitive as culture with smear-positive specimens but less sensitive with smear-negative pulmonary and extrapulmonary specimens that include low numbers of bacilli.
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
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.
da Costa, Lucas Laux; 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.
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
Capone, Domenico; Mafort, Thiago; Mogami, Roberto; Rodrigues, Rosana de Souza; Menna Barreto, Miriam
Objectives. To evaluate tomographic changes in pulmonary tuberculosis (TB), degree of agreement among three radiologists regarding tomographic diagnoses, and sequelae following treatment. Methods. Cross-sectional and descriptive study of 74 TB patients confirmed by sputum culture and chest computed tomography before (CT1) and 6 months after (CT2) drug therapy. Results were performed by three radiologists blinded to clinical and laboratory results. Results. Main findings in CT1 included nodules indicating the presence of a tree-in-bud pattern in 93% of cases, ill-defined nodules in 84% of cases, consolidation in 77% of cases, architectural distortion in 71% of cases, cavitary lesions in 62% of cases, and ground glass opacities in 37% of cases. Airway involvement, characterized by increased thickness and dilatation of the bronchial walls, occurred in 93% of cases. Pleural involvement occurred in 54%. There was an agreement on active TB among the three radiologists in 85% of cases. The results in CT2 indicated the presence of architectural distortion in 91% of cases and cylindrical bronchiectasis in 86%. Conclusions. The study established a tomographic pattern for diagnosis of active TB characterized by the presence of airway nodules, consolidation, architectural distortion, and cavitary lesions, and an almost complete degree of agreement (Kappa) was observed among the radiologists (0.85). CT after treatment assists in defining the cure. PMID:28261498
Nájera-Ortiz, J C; Sánchez-Pérez, H J; Ochoa-Díaz-López, H; Leal-Fernández, G; Navarro-Giné, A
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.
Kibrisli, Erkan; Bez, Yasin; Yilmaz, Ahmet; Aslanhan, Hamza; Taylan, Mahsuk; Kaya, Halide; Tanrikulu, Abdullah Cetin; Abakay, Ozlem
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.
Nájera-Ortiz, J. C.; Sánchez-Pérez, H. J.; Ochoa-Díaz-López, H.; Leal-Fernández, G.; Navarro-Giné, A.
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
Sassaki, Cinthia Midori; Scatena, Lucia Marina; Gonzales, Roxana Isabel Cardozo; Ruffino-Netto, Antonio; Hinos, Paula; Villa, Tereza Cristina Scatena
Based on data available in the Information System for Notifiable Diseases, predictive factors of favorable results were identified in the treatment of pulmonary tuberculosis, diagnosed between 2001 and 2004 and living in Recife-PE, Brazil. Uni- and multivariate logistic regression methods were used. In multivariate analysis, the following factors remained: Age (years), 0 to 9 (OR = 4.27; p = 0.001) and 10 to 19 (OR = 1.78; p = 0.011), greater chance of cure than over 60; Education (years), 8 to 11 (OR = 1.52; p = 0.049), greater chance of cure than no education; Type of entry, ne wcase s (OR = 3.31; p < 0.001) and relapse (OR = 3.32; p < 0.001), greater chances of cure than restart after abandonment; Time (months) 2, 5--6 (OR = 9.15; p < 0.001); 6--9 (OR = 27.28; p < 0.001) and More than 9 (OR = 24.78; p < 0.001), greater chances of cure than less than 5; Health Unit District, DSII (OR = 1.60; p = 0.018) and DSIIV (OR = 2.87; p < 0.001), greater chance sof cure than DS II.
Background There is reason to expect strong genetic influences on the risk of developing active pulmonary tuberculosis (TB) among latently infected individuals. Many of the genome wide linkage and association studies (GWAS) to date have been conducted on African populations. In order to identify additional targets in genetically dissimilar populations, and to enhance our understanding of this disease, we performed a multi-stage GWAS in a Southeast Asian cohort from Indonesia. Methods In stage 1, we used the Affymetrix 100 K SNP GeneChip marker set to genotype 259 Indonesian samples. After quality control filtering, 108 cases and 115 controls were analyzed for association of 95,207 SNPs. In stage 2, we attempted validation of 2,453 SNPs with promising associations from the first stage, in 1,189 individuals from the same Indonesian cohort, and finally in stage 3 we selected 251 SNPs from this stage to test TB association in an independent Caucasian cohort (n = 3,760) from Russia. Results Our study suggests evidence of association (P = 0.0004-0.0067) for 8 independent loci (nominal significance P < 0.05), which are located within or near the following genes involved in immune signaling: JAG1, DYNLRB2, EBF1, TMEFF2, CCL17, HAUS6, PENK and TXNDC4. Conclusions Mechanisms of immune defense suggested by some of the identified genes exhibit biological plausibility and may suggest novel pathways involved in the host containment of infection with TB. PMID:22239941
Zhou, Chengchao; Chu, Jie; Geng, Hong; Wang, Xingzhou; Xu, Lingzhong
Objective A timely initiation of treatment is crucial to better control tuberculosis (TB). The aim of this study is to describe treatment delay among migrant patients with TB and to identify factors associated with treatment delay, so as to provide evidence for strategy development and improvement of TB control among migrants in China. Design A cross-sectional study was conducted in Shandong province of China. A total of 314 confirmed smear positive migrant patients with pulmonary TB were included. Univariate logistic regression was used to analyse the association of variables with treatment delay among migrant patients with TB. A multilogistic regression model was developed to further assess the effect of variables on treatment delay. Results Of 314 migrant patients with TB, 65.6% experienced treatment delay (>1 day). Household income level, diagnosis symptom severity, understanding of whether TB is curable or not and knowledge about the free TB treatment policy are factors significantly associated with treatment delay. Conclusions Economic status and knowledge about TB are key barriers to accessing TB treatment. An integrated policy of carrying out TB-related health education and publicising the free TB treatment policy among migrants is needed. Health insurance schemes for migrants should be modified to make them transferrable and pro-poor. PMID:25534210
Ahmed, Tahmeed; Pietroni, Mark A.C.; Faruque, Abu S.G.; Ashraf, Hasan; Bardhan, Pradip K.; Hossain, Md. Iqbal; Das, Sumon Kumar; Salam, Mohammed Abdus
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
Chang, Hung; Liao, Tzu-Yao; Wen, Ming-Sheng; Yu, Chih-Teng
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
Cao, Donglin; Hu, Liangshan; Lin, Maorui; Li, Mingyou; Ye, Zebing; Sun, Hongtao; Huang, Jiwei; Yang, Huawen; Tian, Junzhang
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.
Greif, Gonzalo; Iraola, Gregorio; Berná, Luisa; Coitinho, Cecilia; Rivas, Carlos M.; Naya, Hugo
Despite efficient control programs, large clonal outbreaks of tuberculosis (TB) may arise in low-risk populations. Recently, an unusual TB outbreak was reported in Uruguay, reaching an elevated disease attack rate (53 to 69%). Here, we report the genome sequence of the Mycobacterium tuberculosis strain associated with this rapidly progressing outbreak, named MtURU-001. PMID:24459279
Staring, M. Bakker, M. E.; Shamonin, D. P.; Reiber, J. H. C.; Stoel, B. C.; Stolk, J.
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
Báez-Saldaña, Renata; Delgado-Sánchez, Guadalupe; García-García, Lourdes; Cruz-Hervert, Luis Pablo; Montesinos-Castillo, Marlene; Ferreyra-Reyes, Leticia; Bobadilla-del-Valle, Miriam; Canizales-Quintero, Sergio; Ferreira-Guerrero, Elizabeth; Téllez-Vázquez, Norma; Montero-Campos, Rogelio; Yanes-Lane, Mercedes; Mongua-Rodriguez, Norma; Martínez-Gamboa, Rosa Areli; Sifuentes-Osornio, José; Ponce-de-León, Alfredo
Background Isoniazid mono-resistance (IMR) is the most common form of mono-resistance; its world prevalence is estimated to range between 0.0 to 9.5% globally. There is no consensus on how these patients should be treated. Objective To describe the impact of IMR tuberculosis (TB) on treatment outcome and survival among pulmonary TB patients treated under programmatic conditions in Orizaba, Veracruz, Mexico. Materials and Methods We conducted a prospective cohort study of pulmonary TB patients in Southern Mexico. From 1995 to 2010 patients with acid-fast bacilli or culture proven Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and microbiological evaluation. We included patients who harbored isoniazid mono-resistant (IMR) strains and patients with strains susceptible to isoniazid, rifampicin, ethambutol and streptomycin. All patients were treated following Mexican TB Program guidelines. We performed annual follow-up to ascertain treatment outcome, recurrence, relapse and mortality. Results Between 1995 and 2010 1,243 patients with pulmonary TB were recruited; 902/1,243 (72.57%) had drug susceptibility testing; 716 (79.38%) harbored pan-susceptible and 88 (9.75%) IMR strains. Having any contact with a person with TB (adjusted odds ratio (aOR)) 1.85, 95% Confidence interval (CI) 1.15–2.96) and homelessness (adjusted odds ratio (aOR) 2.76, 95% CI 1.08–6.99) were associated with IMR. IMR patients had a higher probability of failure (adjusted hazard ratio (HR) 12.35, 95% CI 3.38–45.15) and death due to TB among HIV negative patients (aHR 3.30. 95% CI 1.00–10.84). All the models were adjusted for socio-demographic and clinical variables. Conclusions The results from our study provide evidence that the standardized treatment schedule with first line drugs in new and previously treated cases with pulmonary TB and IMR produces a high frequency of treatment failure and death due to tuberculosis. We recommend re-evaluating the optimal
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
Amaral, Eduardo P; Ribeiro, Simone C M; Lanes, Verônica R; Almeida, Fabrício M; de Andrade, Marcelle R M; Bomfim, Caio Cesar Barbosa; Salles, Erika M; Bortoluci, Karina R; Coutinho-Silva, Robson; Hirata, Mario H; Alvarez, José M; Lasunskaia, Elena B; D'Império-Lima, Maria Regina
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.
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
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.
El Daker, Sary; Sacchi, Alessandra; Tempestilli, Massimo; Carducci, Claudia; Goletti, Delia; Vanini, Valentina; Colizzi, Vittorio; Lauria, Francesco Nicola; Martini, Federico; Martino, Angelo
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
Marzo, Elena; Vilaplana, Cristina; Tapia, Gustavo; Diaz, Jorge; Garcia, Vanessa; Cardona, Pere-Joan
Tuberculosis was studied using an experimental model based on the C3HeB/FeJ mouse strain, which mimics the liquefaction of caseous necrosis occurring during active disease in immunocompetent adults. Mice were intravenously infected with 2 × 10(4) Colony Forming Units of Mycobacterium tuberculosis and their histopathology, immune response, bacillary load, and survival were evaluated. The effects of the administration of drugs with anti-inflammatory activity were examined, and the C3H/HeN mouse strain was also included for comparative purposes. Massive intra-alveolar neutrophilic infiltration led to rapid granuloma growth and coalescence of lesions into superlesions. A central necrotic area appeared showing progressive cellular destruction, the alveoli cell walls being initially conserved (caseous necrosis) but finally destroyed (liquefactive necrosis). Increasing levels of pro-inflammatory mediators were detected in lungs. C3HeB/FeJ treated with anti-inflammatory drugs and C3H/HeN animals presented lower levels of pro-inflammatory mediators such as TNF-α, IL-17, IL-6 and CXCL5, a lower bacillary load, better histopathology, and increased survival compared with untreated C3HeB/FeJ. The observation of massive neutrophilic infiltration suggests that inflammation may be a key factor in progression towards active tuberculosis. On the basis of our findings, we consider that the C3HeB/FeJ mouse model would be useful for evaluating new therapeutic strategies against human tuberculosis.
Yan, Liping; Xiao, Heping; Zhang, Qing
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.
Khera, Amandeep K; Afkhami, Sam; Lai, Rocky; Jeyanathan, Mangalakumari; Zganiacz, Anna; Mandur, Talveer; Hammill, Joni; Damjanovic, Daniela; Xing, Zhou
Emerging evidence suggests a role of B cells in host defense against primary pulmonary tuberculosis (TB). However, the role of B cells in TB vaccine-induced protective T cell immunity still remains unknown. Using a viral-vectored model TB vaccine and a number of experimental approaches, we have investigated the role of B cells in respiratory mucosal vaccine-induced T cell responses and protection against pulmonary TB. We found that respiratory mucosal vaccination activated Ag-specific B cell responses. Whereas respiratory mucosal vaccination elicited Ag-specific T cell responses in the airway and lung interstitium of genetic B cell-deficient (Jh(-/-) knockout [KO]) mice, the levels of airway T cell responses were lower than in wild-type hosts, which were associated with suboptimal protection against pulmonary Mycobacterium tuberculosis challenge. However, mucosal vaccination induced T cell responses in the airway and lung interstitium and protection in B cell-depleted wild-type mice to a similar extent as in B cell-competent hosts. Furthermore, by using an adoptive cell transfer approach, reconstitution of B cells in vaccinated Jh(-/-) KO mice did not enhance anti-TB protection. Moreover, respiratory mucosal vaccine-activated T cells alone were able to enhance anti-TB protection in SCID mice, and the transfer of vaccine-primed B cells alongside T cells did not further enhance such protection. Alternatively, adoptively transferring vaccine-primed T cells from Jh(-/-) KO mice into SCID mice only provided suboptimal protection. These data together suggest that B cells play a minimal role, and highlight a central role by T cells, in respiratory mucosal vaccine-induced protective immunity against M. tuberculosis.
Wobeser, W; Yuan, L; Naus, M
BACKGROUND: Completion of treatment of active cases of tuberculosis (TB) is the most important priority of TB control programs. This study was carried out to assess treatment completion for active cases of pulmonary TB in Toronto. METHODS: Consecutive cases of culture-proven pulmonary TB were obtained from the microbiology laboratories of 5 university-affiliated tertiary care centres in Toronto in 1992/93. A standard data-collection tool was used to abstract information from inpatient and outpatient charts. For patients who were transferred to other treatment centres or lost to follow-up, the local health unit was contacted for information about treatment completion. If incomplete information was obtained from these sources, data from the provincial Reportable Disease Information System were also reviewed. The main outcome analysed was treatment outcome, with cases classified as completed (record of treatment completion noted), transferred (patient transferred to another centre but no treatment results available), defaulted (record of defaulting in patient chart but no record of treatment completion elsewhere, or patient still receiving treatment more than 15 months after diagnosis) or dead (patient died before treatment completion). RESULTS: Of the 145 patients 84 (58%) completed treatment, 25 (17%) died, 22 (15%) defaulted and 14 (10%) were transferred. The corresponding values for the 22 patients with HIV coinfection were 6 (27%), 5 (23%), 8 (36%) and 3 (14%). Independent predictors of failure to complete treatment were injection drug use (adjusted odds ratio [OR] 5.7, 95% confidence interval [CI] 1.5 to 22.0), HIV infection (adjusted OR 4.6, 95% CI 1.4 to 14.7) and adverse drug reaction (adjusted OR 2.9, 95% CI 1.1 to 7.9). Independent predictors of death included age more than 50 years (adjusted OR 16.7, 95% CI 2.6 to 105.1), HIV infection (adjusted OR 16.1, 95% CI 3.9 to 66.4), immunosuppressive therapy (adjusted OR 8.0, 95% CI 1.9 to 34.4) and infection with
Ormerod, L P; Green, R M; Broadfield, E
The effects of the policy change in X-ray follow-up of adult tuberculin-positive close contacts of sputum microscopy positive pulmonary tuberculosis made by the Joint Tuberculosis Committee of the British Thoracic Society in 2000 were monitored prospectively from late 2000 until the end of 2003. No cases in contacts that could have been detected by interval X-rays at three and 12 months were found. The data, on 291 cases, support the abandonment of X-ray follow-up in favour of an 'inform and advise' strategy after an initial normal chest X-ray in this category of tuberculosis contact.
Zvada, Simbarashe P; Denti, Paolo; Geldenhuys, Hennie; Meredith, Sandra; van As, Danelle; Hatherill, Mark; Hanekom, Willem; Wiesner, Lubbe; Simonsson, Ulrika S H; Jindani, Amina; Harrison, Thomas; McIlleron, Helen M
We described the population pharmacokinetics of moxifloxacin and the effect of high-dose intermittent rifapentine in patients with pulmonary tuberculosis who were randomized to a continuation-phase regimen of 400 mg moxifloxacin and 900 mg rifapentine twice weekly or 400 mg moxifloxacin and 1,200 mg rifapentine once weekly. A two-compartment model with transit absorption best described moxifloxacin pharmacokinetics. Although rifapentine increased the clearance of moxifloxacin by 8% during antituberculosis treatment compared to that after treatment completion without rifapentine, it did not result in a clinically significant change in moxifloxacin exposure.
Zvada, Simbarashe P.; Denti, Paolo; Geldenhuys, Hennie; Meredith, Sandra; van As, Danelle; Hatherill, Mark; Hanekom, Willem; Wiesner, Lubbe; Simonsson, Ulrika S. H.; Jindani, Amina; Harrison, Thomas
We described the population pharmacokinetics of moxifloxacin and the effect of high-dose intermittent rifapentine in patients with pulmonary tuberculosis who were randomized to a continuation-phase regimen of 400 mg moxifloxacin and 900 mg rifapentine twice weekly or 400 mg moxifloxacin and 1,200 mg rifapentine once weekly. A two-compartment model with transit absorption best described moxifloxacin pharmacokinetics. Although rifapentine increased the clearance of moxifloxacin by 8% during antituberculosis treatment compared to that after treatment completion without rifapentine, it did not result in a clinically significant change in moxifloxacin exposure. PMID:22585223
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, ...
Tamhane, Ashutosh; Ambe, Girish; Vermund, Sten H; Kohler, Connie L; Karande, Alka; Sathiakumar, Nalini
Purpose: To determine the factors responsible for patient delay and treatment delay in newly diagnosed sputum smear-positive pulmonary tuberculosis (TB) patients. Methods: Study subjects (N = 150) were randomly selected from municipal health centers in Mumbai, India. Duration of symptoms, treatment, and reason for delay were assessed using interviews and medical records. We defined patient delay as presentation to a health care provider (HCP) >20 days of the onset of TB-related symptoms and treatment delay as therapy initiated more than 14 days after the first consultation (for TB-related symptoms) with an HCP. Results: Of the 150 subjects, 29% had patient delays and 81% had treatment delays. In multivariable analysis, patient delay was significantly associated with the self-perception that initial symptoms were due to TB [odds ratio (OR) = 3.8, 95% confidence interval (CI) = 1.1–12.6] and perceived inability to pay for care (OR = 2.9, 95% CI = 1.2–7.1). Treatment delay was significantly associated with consulting a non-allopathic provider (OR = 12.3, 95% CI = 1.4–105) and consulting >3 providers (OR = 5.0, 95% CI = 1.4–17.4). Patient interval was half the treatment interval (median days: 15 vs. 31). Women were slightly more likely to experience patient and treatment delays than men. For two-thirds of the patients, another TB patient was a source of TB-related knowledge, while health education material (16%) and television (10%) played a smaller role. Conclusion: Treatment delay, primarily due to diagnosis delay, was a greater problem than patient delay. Expanding public–public and public–private partnerships and regular training sessions for HCPs might decrease treatment delay. Media coverage and cured TB patients as peer advocates may help to reinforce TB-related health education messages. PMID:22973488
Hong, Eun Pyo; Go, Min Jin; Kim, Hyung-Lae
A complex interplay among host, pathogen, and environmental factors is believed to contribute to the risk of developing pulmonary tuberculosis (PTB). The lack of replication of published genome-wide association study (GWAS) findings limits the clinical utility of reported single nucleotide polymorphisms (SNPs). We conducted a GWAS using 467 PTB cases and 1,313 healthy controls obtained from two community-based cohorts in Korea. We evaluated the performance of PTB risk models based on different combinations of genetic and nongenetic factors and validated the results in an independent Korean population comprised of 179 PTB cases and 500 healthy controls. We demonstrated the polygenic nature of PTB and nongenetic factors such as age, sex, and body mass index (BMI) were strongly associated with PTB risk. None of the SNPs achieved genome-wide significance; instead, we were able to replicate the associations between PTB and ten SNPs near or in the genes, CDCA7, GBE1, GADL1, SPATA16, C6orf118, KIAA1432, DMRT2, CTR9, CCDC67, and CDH13, which may play roles in the immune and inflammatory pathways. Among the replicated SNPs, an intergenic SNP, rs9365798, located downstream of the C6orf118 gene showed the most significant association under the dominant model (OR = 1.59, 95% CI 1.32–1.92, P = 2.1×10−6). The performance of a risk model combining the effects of ten replicated SNPs and six nongenetic factors (i.e., age, sex, BMI, cigarette smoking, systolic blood pressure, and hemoglobin) were validated in the replication set (AUC = 0.80, 95% CI 0.76–0.84). The strategy of combining genetic and nongenetic risk factors ultimately resulted in better risk prediction for PTB in the adult Korean population. PMID:28355295
Aryanpur, Mahshid; Mortaz, Esmaeil; Hosseini, Mostafa; Jamaati, Hmidreza; Tabarsi, Payam; Soori, Hamid; Heydari, Gholam Reza; Kazempour-Dizaji, Mehdi; Emami, Habib; Mozafarian, Alireza
Background: Several studies have shown that smoking, as a modifiable risk factor, can affect tuberculosis (TB) in different aspects such as enhancing development of TB infection, activation of latent TB and its related mortality. Since willingness to quit smoking is a critical stage, which may lead to quit attempts, being aware of smokers’ intention to quit and the related predictors can provide considerable advantages. Materials and Methods: In this cross-sectional study, subjects were recruited via a multi-stage cluster sampling method. Sampling was performed during 2012–2014 among pulmonary TB (PTB) patients referred to health centers in Tehran implementing the directly observed treatment short course (DOTS) strategy and a TB referral center. Data analysis was conducted using SPSS version 22 and the factors influencing quit intention were assessed using bivariate regression and multiple logistic regression models. Results: In this study 1,127 newly diagnosed PTB patients were studied; from which 284 patients (22%) were current smokers. When diagnosed with TB, 59 (23.8%) smokers quit smoking. Among the remaining 189 (76.2%) patients who continued smoking, 52.4% had intention to quit. In the final multiple logistic regression model, living in urban areas (OR=8.81, P=0.003), having an office job (OR= 7.34, P=0.001), being single (OR=4.89, P=0.016) and a one unit increase in the motivation degree (OR=2.60, P<0.001) were found to increase the intention to quit smoking. Conclusion: The study found that PTB patients who continued smoking had remarkable intention to quit. Thus, it is recommended that smoking cessation interventions should be started at the time of TB diagnosis. Understanding the associated factors can guide the consultants to predict patients’ intention to quit and select the most proper management to facilitate smoking cessation for each patient. PMID:27403174
Chen, Wei; Shu, Wen; Wang, Min; Hou, Yongchun; Xia, Yinyin; Xu, Weiguo; Bai, Liqiong; Nie, Shaofa; Cheng, Shiming; Xu, Yihua
The incidence of tuberculosis (TB) and its risk factors in China remains unclear. This study examined TB incidence and relative risk factors in rural areas of China. Participants (n = 177,529) were recruited in Xiangtan County (in the central area of China) and in Danyang County (in the eastern area of China) in 2009 and a followed-up study was conducted for one year. The incidence density of pulmonary TB and smear-positive TB were 91.6 (95% CI: 78.7, 106.0) per 100,000 person-year and 36.7 (95% CI: 33.1, 52.4) per 100,000 person-year respectively in Xiangtan, and 47.3 (95% CI: 38.2, 57.5) per 100,000 person-year and 22.7 (95% CI: 16.5, 30.8) per 100,000 person-year in Danyang. The medical history of TB was associated with TB, with the relative risk (RR) of 7.00 (95% CI: 2.76, 17.18) in Xiangtan and that of 31.08 (95% CI: 13.22, 73.10) in Danyang. The association between TB and per capita living space over median was found in Xiangtan, with the RR of 1.86 (95% CI: 1.15, 3.01). No association was found between TB and the insurance status, the contact history with TB, the history of diabetes, smoking, or per capita annual income. The host genetic susceptibility, and social factors such as education and income could be considered in future studies.
Li, Xin-Xu; Ren, Zhou-Peng; Wang, Li-Xia; Zhang, Hui; Jiang, Shi-Wen; Chen, Jia-Xu; Wang, Jin-Feng; Zhou, Xiao-Nong
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
Wang, Min; Hou, Yongchun; Xia, Yinyin; Xu, Weiguo; Bai, Liqiong; Nie, Shaofa; Cheng, Shiming; Xu, Yihua
The incidence of tuberculosis (TB) and its risk factors in China remains unclear. This study examined TB incidence and relative risk factors in rural areas of China. Participants (n = 177,529) were recruited in Xiangtan County (in the central area of China) and in Danyang County (in the eastern area of China) in 2009 and a followed-up study was conducted for one year. The incidence density of pulmonary TB and smear-positive TB were 91.6 (95% CI: 78.7, 106.0) per 100,000 person-year and 36.7 (95% CI: 33.1, 52.4) per 100,000 person-year respectively in Xiangtan, and 47.3 (95% CI: 38.2, 57.5) per 100,000 person-year and 22.7 (95% CI: 16.5, 30.8) per 100,000 person-year in Danyang. The medical history of TB was associated with TB, with the relative risk (RR) of 7.00 (95% CI: 2.76, 17.18) in Xiangtan and that of 31.08 (95% CI: 13.22, 73.10) in Danyang. The association between TB and per capita living space over median was found in Xiangtan, with the RR of 1.86 (95% CI: 1.15, 3.01). No association was found between TB and the insurance status, the contact history with TB, the history of diabetes, smoking, or per capita annual income. The host genetic susceptibility, and social factors such as education and income could be considered in future studies. PMID:23554875
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
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.
Li, Cuiping; He, Xiao; Li, Hongtao; Zhou, Yi; Zang, Ning; Hu, Shuixiu; Zheng, Yanyan; He, Min
Pulmonary tuberculosis (PTB) is a chronic disease and has remained a severe threat to public health. Valuable biomarkers for improving the detection rate are crucial for controlling this disease. The purpose of this study was to discover potential biomarkers in sera from PTB patients compared with pneumonia patients and normal healthy controls. A total of 336 human serum specimens were enrolled in this study. Differentially expressed proteins were identified using iTRAQ method combining with MALDI-TOF-MS. Data was analyzed using relative bioinformatics methods. Potential biomarkers were further validated by IHC, ELISA and Western blot. As a result, 489 non-redundant proteins were identified in the sera, and 159 of which could be quantified by calculating their iTRAQ ratios. Compared to the controls, 26 differentially expressed proteins were recognized among PTB patients, including 16 overexpressed proteins and 10 downregulated proteins. Analysis of their functional interactions revealed that 12 proteins appeared in the center of the functional network. One of these key proteins, sex hormone binding globulin (SHBG), was found to be significantly elevated among PTB patients as compared with the controls examined by IHC, ELISA and Western blot. This result was consistent with the iTRAQ result. An independent blinded testing set to examine serum SHBG by ELISA achieved an accuracy of 78.74%, sensitivity of 75.6% and specificity of 91.5% in diagnosing PTB. In summary, iTRAQ in combination with MALDI-TOF-MS technology can efficiently screen differentially expressed proteins in sera from the PTB patients. SHBG is suggested to be a possible and novel serum biomarker for PTB.
Havumaki, Joshua; Ha, Dang Thi Minh; Caceres, Tatiana; Hang, Pham Thu; Collantes, Jimena; Thi Ngoc Lan, Nguyen; Gotuzzo, Eduardo; Denkinger, Claudia M.
Background Improved and affordable diagnostic or triage tests are urgently needed at the microscopy centre level. Automated digital microscopy has the potential to overcome issues related to conventional microscopy, including training time requirement and inconsistencies in results interpretation. Methods For this blinded prospective study, sputum samples were collected from adults with presumptive pulmonary tuberculosis in Lima, Peru and Ho Chi Minh City, Vietnam. TBDx performance was evaluated as a stand-alone and as a triage test against conventional microscopy and Xpert, with culture as the reference standard. Xpert was used to confirm positive cases. Findings A total of 613 subjects were enrolled between October 2014 and March 2015, with 539 included in the final analysis. The sensitivity of TBDx was 62·2% (95% CI 56·6–67·4) and specificity was 90·7% (95% CI 85·9–94·2) compared to culture. The algorithm assessing TBDx as a triage test achieved a specificity of 100% while maintaining sensitivity. Interpretation While the diagnostic performance of TBDx did not reach the levels obtained by experienced microscopists in reference laboratories, it is conceivable that it would exceed the performance of less experienced microscopists. In the absence of highly sensitive and specific molecular tests at the microscopy centre level, TBDx in a triage-testing algorithm would optimize specificity and limit overall cost without compromising the number of patients receiving up-front drug susceptibility testing for rifampicin. However, the algorithm would miss over one third of patients compared to Xpert alone. PMID:28253302
Chang, Tsui-Ming; Mou, Chih-Hsin; Shen, Te-Chun; Yang, Chien-Lung; Yang, Min-Hui; Wu, Fang-Yang; Sung, Fung-Chang
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.
Bartow, R A; McMurray, D N
Outbred (Hartley) and inbred (strain 2 and 13) guinea pigs were vaccinated with Mycobacterium bovis BCG and placed on isocaloric, purified diets containing either 10 or 30% ovalbumin or on commercial guinea pig chow. Six weeks later, the animals were challenged by the respiratory route with virulent M. tuberculosis H37Rv. At intervals postchallenge, groups were tuberculin tested and sacrificed. Thymus-dependent (T) lymphocytes were enumerated either by rosette formation with rabbit erythrocytes or by the indirect immunofluorescence assay (IFA) with a guinea pig pan-T-cell monoclonal antibody, 8BE6. Protein-deficient guinea pigs of all three strains had significantly fewer erythrocyte rosette-forming (CD2+) T cells in the peripheral blood, and malnourished strain 2 and Hartley guinea pigs exhibited reduced levels of CD2+ T cells in the thymus. In contrast, animals of all three strains fed the low-protein diet harbored more CD2+ T cells in the bronchotracheal lymph nodes than did their control-fed counterparts. A larger proportion of lymphocytes from the blood and lymph nodes of all three strains were IFA positive than formed erythrocyte rosettes regardless of diet treatment. Diet had no effect on IFA-positive lymphocytes in those organs. Protein deficiency is associated with significant alterations in the number and/or distribution of T lymphocytes expressing functional CD2-receptors in BCG-vaccinated animals exposed to virulent mycobacteria by the pulmonary route. These alterations may contribute to the reduction in BCG vaccine efficacy observed in this model. PMID:1971259
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.
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. PMID:24808236
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
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.
Cluver, Lucie; Orkin, Mark; Moshabela, Mosa; Kuo, Caroline; Boyes, Mark
Millions of children in sub-Saharan Africa undertake personal and medical care for family members who are unwell with AIDS. To date, no research has investigated whether such care provision places children at heightened risk for pulmonary tuberculosis. This study aimed to address this gap by identifying risk factors for paediatric pulmonary tuberculosis symptomatology. In 2009-2011, 6002 children aged 10-17 years were surveyed using door-to-door household sampling of census enumeration areas. These were randomly sampled from six urban and rural sites with over 30% HIV prevalence, within South Africa's three highest tuberculosis-burden provinces. Validated scales and clinical tuberculosis symptom checklists were modelled in multivariate logistic regressions, controlling for socio-demographic co-factors. Findings showed that, among children, severe pulmonary tuberculosis symptomatology was predicted by primary caregiver HIV/AIDS-illness [odds ratio (OR): 1.63, confidence interval (CI): 1.23-2.15, p<0.001], and AIDS-orphanhood (OR: 1.44, CI: 1.04-2.00, p<0.029). Three-fold increases in severe tuberculosis symptoms were predicted by the child's exposure to body fluids through providing personal or medical care to an ill adult (OR: 3.12, CI: 1.96-4.95, p<0.001). Symptoms were also predicted by socio-economic factors of food insecurity (OR: 1.52, CI: 1.15-2.02, p<0.003) and household overcrowding (OR: 1.35, CI: 1.06-1.72, p<0.017). Percentage probability of severe tuberculosis symptoms rose from 1.4% amongst least-exposed children, to 18.1% amongst those exposed to all above-stated risk factors, independent of biological relationship of primary caregiver-child and other socio-demographics. Amongst symptomatic children, 75% had never been tested for tuberculosis. These findings identify the risk of tuberculosis among children providing home medical care to their unwell caregivers, and suggest that there are gaps in the health system to screen and detect these cases of
Luo, Fayong; Le, Ngoc-Bao; Mills, Tingting; Chen, Ning-Yuan; Karmouty-Quintana, Harry; Molina, Jose G; Davies, Jonathan; Philip, Kemly; Volcik, Kelly A; Liu, Hong; Xia, Yang; Eltzschig, Holger K; Blackburn, Michael R
Idiopathic pulmonary fibrosis is a devastating lung disease with limited treatment options. The signaling molecule adenosine is produced in response to injury and serves a protective role in early stages of injury and is detrimental during chronic stages of disease such as seen in lung conditions such as pulmonary fibrosis. Understanding the association of extracellular adenosine levels and the progression of pulmonary fibrosis is critical for designing adenosine based approaches to treat pulmonary fibrosis. The goal of this study was to use various models of experimental lung fibrosis to understand when adenosine levels are elevated during pulmonary fibrosis and whether these elevations were associated with disease progression and severity. To accomplish this, extracellular adenosine levels, defined as adenosine levels found in bronchioalveolar lavage fluid, were determined in mouse models of resolvable and progressive pulmonary fibrosis. We found that relative bronchioalveolar lavage fluid adenosine levels are progressively elevated in association with pulmonary fibrosis and that adenosine levels diminish in association with the resolution of lung fibrosis. In addition, treatment of these models with dipyridamole, an inhibitor of nucleoside transporters that potentiates extracellular adenosine levels, demonstrated that the resolution of lung fibrosis is blocked by the failure of adenosine levels to subside. Furthermore, exacerbating adenosine levels led to worse fibrosis in a progressive fibrosis model. Increased adenosine levels were associated with elevation of IL-6 and IL-17, which are important inflammatory cytokines in pulmonary fibrosis. These results demonstrate that extracellular adenosine levels are closely associated with the progression of experimental pulmonary fibrosis and that this signaling pathway may mediate fibrosis by regulating IL-6 and IL-17 production.
Ben-Selma, Walid; Harizi, Hedi; Boukadida, Jalel
Monocyte chemoattractant protein-1 (MCP-1) plays crucial role in protective immunity against Mycobacterium tuberculosis (MT). In this study, we examined whether single nucleotide polymorphism (SNP) -2518 A/G (rs 1024611) of MCP-1 affect the susceptibility to active tuberculosis (TB) in Tunisian populations. Genomic DNA from patients with active TB (168 cases of pulmonary TB and 55 cases of extrapulmonary TB) and ethnically controls (150 cases) was genotyped for the MCP-1 -2518 A/G SNP by polymerase chain reaction fragment length polymorphism (PCR-RFLP). We observed that -2518 G allele and GG genotype (high MCP-1 producer) frequencies were significantly more elevated in active pulmonary TB group in comparison to control group [34 vs. 22%; P = 0.0007; 15 vs. 5%, P corrected for the number of genotypes (Pc) = 0.015; respectively]. Additionally, they were associated with increased risk development of this clinical form of TB [odds ratio (OR) = 1.83, 95% confidence intervals (CI) = 1.26-2.66; OR = 3.1, 95% CI = 1.28-7.76; respectively]. However, wild type allele -2518 A and AA genotype were over-represented in control group (78 and 62%) and seem to be protective factors against TB. Moreover, -2518 AA genotype was more frequent in control group and was associated with resistance against development of active pulmonary TB (OR = 0.56, 95% CI = 0.35-0.89, Pc = 0.03). Our findings confirm the key role of -2518 A/G SNP of MCP-1 and support its association with resistance/susceptibility to the development of active pulmonary TB in the Tunisian population.
Nikitina, Irina Yu; Kondratuk, Natalya A.; Kosmiadi, George A.; Amansahedov, Rasul B.
Background Effector CD4 T cells represent a key component of the host’s anti-tuberculosis immune defense. Successful differentiation and functioning of effector lymphocytes protects the host against severe M. tuberculosis (Mtb) infection. On the other hand, effector T cell differentiation depends on disease severity/activity, as T cell responses are driven by antigenic and inflammatory stimuli released during infection. Thus, tuberculosis (TB) progression and the degree of effector CD4 T cell differentiation are interrelated, but the relationships are complex and not well understood. We have analyzed an association between the degree of Mtb-specific CD4 T cell differentiation and severity/activity of pulmonary TB infection. Methodology/Principal Findings The degree of CD4 T cell differentiation was assessed by measuring the percentages of highly differentiated CD27low cells within a population of Mtb- specific CD4 T lymphocytes (“CD27lowIFN-γ+” cells). The percentages of CD27lowIFN-γ+ cells were low in healthy donors (median, 33.1%) and TB contacts (21.8%) but increased in TB patients (47.3%, p<0.0005). Within the group of patients, the percentages of CD27lowIFN-γ+ cells were uniformly high in the lungs (>76%), but varied in blood (12–92%). The major correlate for the accumulation of CD27lowIFN-γ+ cells in blood was lung destruction (r = 0.65, p = 2.7×10−7). A cutoff of 47% of CD27lowIFN-γ+ cells discriminated patients with high and low degree of lung destruction (sensitivity 89%, specificity 74%); a decline in CD27lowIFN-γ+cells following TB therapy correlated with repair and/or reduction of lung destruction (p<0.01). Conclusions Highly differentiated CD27low Mtb-specific (CD27lowIFN-γ+) CD4 T cells accumulate in the lungs and circulate in the blood of patients with active pulmonary TB. Accumulation of CD27lowIFN-γ+ cells in the blood is associated with lung destruction. The findings indicate that there is no deficiency in CD4 T cell
Sawadogo, Bernard; Tint, Khin San; Tshimanga, Mufuta; Kuonza, Lazarus; Ouedraogo, Laurent
Introduction In Burkina Faso, the tuberculosis (TB) treatment failure rate increased from 2.5% in 2000 to 8.3% in 2006. The risk factors for TB treatment failure in the country are not well known. The study aims to determine the risk factors for treatment failure among pulmonary tuberculosis patients in four health region of Burkina Faso and to recommend appropriate interventions. Methods A case control study was conducted among pulmonary TB patients who began TB treatment in 2009. A case was any patient who remained smear-positive at fifth month of TB treatment and a control was a patient who tested smear-negative at fifth month of treatment. A structured questionnaire was administered to one hundred cases and one hundred controls to collect information on exposure factors. Odds ratio were calculated using bivariate and multivariate analysis to determine the association between exposures and outcome. Results Multivariate analysis showed that independent risk factors for TB treatment failure were fail to take TB drugs for more than 14 consecutive days (OR = 18.53; 95% CI:4.56 - 75.22), sputum smear-positive at two months of treatment (OR = 11.52; 95%CI:5.18-25.60), existence of comorbidity (OR = 5.74; 95%CI:1.69-19.44), and use of traditional medicines or herbs (OR = 2.97; 95%CI:1.12-7.85). Conclusion Early identification of patients with the above risk factors for intense case management will improve TB treatment outcome. Patient with smear positive at 2ndnd month of treatment require more intense follow-up, and involving traditional healers who provide traditional medicines or herbs in the educational programme on TB are required. The national referral laboratory capacity needs to be strengthened to do drug susceptibility testing and routine drug monitoring on cases of non conversion at 2nd month of treatment. PMID:26327989
Porter, Brian O.; Chandrasekhar, Chockalingam; Venkatesan, Perumal; Menon, Pradeep A.; Subramanian, Sudha; Anbalagan, Selvaraj; Bhavani, Kannabiran P.; Sekar, Sathiyavelu; Padmapriyadarshini, Chandrasekaran; Kumar, Satagopan; Ravichandran, Narayanan; Raja, Krishnaraj; Bhanu, Kesavamurthy; Mahilmaran, Ayyamperumal; Sekar, Lakshmanan; Sher, Alan; Sereti, Irini; Swaminathan, Soumya
Background The incidence, manifestations, outcome and clinical predictors of paradoxical TB-IRIS in patients with HIV and culture confirmed pulmonary tuberculosis (PTB) in India have not been studied prospectively. Methods HIV+ patients with culture confirmed PTB started on anti-tuberculosis therapy (ATT) were followed prospectively after anti-retroviral therapy (ART) initiation. Established criteria for IRIS diagnosis were used including decline in plasma HIV RNA at IRIS event. Pre-ART plasma levels of interleukin (IL)-6 and C-reactive protein (CRP) were measured. Univariate and multivariate logistic regression models were used to evaluate associations between baseline variables and IRIS. Results Of 57 patients enrolled, 48 had complete follow up data. Median ATT-ART interval was 28 days (interquartile range, IQR 14–47). IRIS events occurred in 26 patients (54.2%) at a median of 11 days (IQR: 7–16) after ART initiation. Corticosteroids were required for treatment of most IRIS events that resolved within a median of 13 days (IQR: 9–23). Two patients died due to CNS TB-IRIS. Lower CD4+ T-cell counts, higher plasma HIV RNA levels, lower CD4/CD8 ratio, lower hemoglobin, shorter ATT to ART interval, extra-pulmonary or miliary TB and higher plasma IL-6 and CRP levels at baseline were associated with paradoxical TB-IRIS in the univariate analysis. Shorter ATT to ART interval, lower hemoglobin and higher IL-6 and CRP levels remained significant in the multivariate analysis. Conclusion Paradoxical TB–IRIS frequently complicates HIV-TB therapy in India. IL-6 and CRP may assist in predicting IRIS events and serve as potential targets for immune interventions. PMID:23691062
Rewata, Lidya; Rutherford, Merrin; Apriani, Lika; Janssen, Willem; Rahmadi, Andri; Parwati, Ida; Yuwono, Arto; van Crevel, Reinout
HIV infection hampers diagnosis of pulmonary tuberculosis (PTB) because many pathogens cause pulmonary infection in HIV people and the load of Mycobacterium tuberculosis is lower in HIV patients. We conducted a literature review and prospectively examined clinical, radiological, and laboratory diagnosis of PTB in 71 HIV-patients (29 inpatients and 42 outpatients) in a teaching hospital in West Java, Indonesia. For both in- and outpatients, signs and symptoms were sensitive but not specific for PTB. Chest X-ray (CXR) was sensitive but less specific. Among hospitalized PTB suspects, 28,8% could not expectorate sputum. Compared to culture, ZN had a sensitivity of 11.1% and 66.7% for in- and outpatients, respectively. From the literature, fluorescence microscopy, liquid culture, and nucleic acid assays can improve diagnosis of PTB in HIV, while IFNg-release assays lack sensitivity, especially in advanced HIV. The current practice of using CXR and microscopy lacks sensitivity for diagnosing PTB in HIV patients. Sputum culture is more sensitive but slow. Fluorescence microscopy might be a quick, relatively sensitive and feasible option in Indonesia. However, because of the frequent absence of sputum, especially in patients with advanced HIV-AIDS patients, there is an urgent need for alternative diagnostic methods using blood or urine.
Bartow, R A; McMurray, D N
Inbred strain 2 guinea pigs were vaccinated with Mycobacterium bovis BCG or were left unvaccinated and challenged 6 weeks later by the respiratory route with virulent Mycobacterium tuberculosis. By using a double rosette assay with isotype-specific antibody-coated ox and uncoated rabbit erythrocytes, the proportions of T lymphocytes bearing Fc receptors for immunoglobulin G (IgG) (T gamma cells) or IgM (T mu cells) were quantified in tissues taken from animals that were killed within 4 weeks postchallenge. Tuberculin reactivity in vivo and in vitro and antimycobacterial resistance were also measured. BCG vaccination protected the guinea pigs and resulted in significantly enhanced proportions of T mu cells in the blood during the first 3 weeks and in the spleen during weeks 2 and 3 postchallenge. Levels of T gamma cells declined in all tissues during the first 3 weeks of infection and were unaffected by prior vaccination with BCG. Increased proportions of T mu cells in the blood were accompanied by dramatic tuberculin skin reactions and purified protein derivative-induced lymphoproliferation in BCG-vaccinated guinea pigs during the first 2 weeks following virulent pulmonary challenge. Peak levels of T mu cells in the spleens of vaccinated animals at 2 weeks coincided with the first appearance of virulent mycobacteria in that organ. BCG vaccination appears to influence immunoregulatory events in pulmonary tuberculosis through effects on the distribution of IgM Fc receptor-bearing (T mu cell) T lymphocytes. PMID:2523350
Xiong, Xiaowei; Morita, Craig T; Bukowski, Jack F; Brenner, Michael B; Dascher, Christopher C
Guinea pigs are an alternative small animal model for many disease studies. Here we describe a pan-gammadelta monoclonal antibody (anti-TCRdelta1) specific for the constant region of human T cell receptor delta chains that cross-reacts with a subpopulation of guinea pig (Cavia porcellus) lymphocytes. The phenotype and distribution of this subpopulation is consistent with the guinea pig gammadelta T cell subset. FACS analysis of fresh PBMC and splenocytes from naïve guinea pigs revealed the presence of a subset of cells that stained with the anti-TCRdelta1 mAb. The relative percentage of anti-TCRdelta1 positive cells in PBMC and tissues is similar to that described for gammadelta T cells in other species. Immunohistochemistry of tissues also revealed a distribution of anti-TCRdelta1 positive cells consistent with gammadelta T cells. These data are further supported by staining of a polyclonal guinea pig T cell line that became progressively CD4 and CD8 negative in long-term culture. Analysis of PBMC from guinea pigs following aerosol infection with virulent Mycobacterium tuberculosis revealed no apparent changes in the steady-state percentage of blood gammadelta+ T cells. Taken together, these data suggest that the anti-TCRdelta1 antibody recognizes the gammadelta T cell subset in guinea pigs. This reagent may be useful for examining gammadelta T cells in various disease models where the guinea pig is a more desirable model for study.
Farnia, Parissa; Mohammadi, Foroazan; Mirsaedi, Mehdi; Zarife, Abolhasan Zia; Tabatabee, Javad; Bahadori, Katayoon; Bahadori, Muslem; Masjedi, Mohammad Reza; Velayati, Ali Akbar
By oxidation-reduction assay, the viability of Mycobacterium tuberculosis in sputum specimens was evaluated. The technique is based on the Alamar Blue and Malachite Green dyes, which change their color in response to M. tuberculosis growth. The method is simple, permits visual reading of results, and is applicable for laboratories with limited resources. PMID:15243106
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.
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
Background Nucleic acid amplification assays including PCR have revolutionized the detection of Mycobacterium tuberculosis (MTB). Tuberculosis spread to almost every organ of the body and is characterized on the basis of localization of infection. Therefore, different types of body fluids and tissues can be used for the detection of MTB. From 2004 to 2010 total 766 different types of smear negative samples from patients, clinically suspected for tuberculosis were received and investigated at Division of Molecular Diagnostics, University of the Punjab Lahore for the diagnosis of tuberculosis. Mycobacterial DNA was extracted followed by PCR amplification. Findings A total of 356 (46.5%) samples were found positive by PCR for MTB. These included; serum (4.8%), blood (36.3%), urine (46.6%), cerebro spinal fluid (CSF) (42.1%), ascetic fluid (67.6%), pleural fluid (52%), pericardial fluid (30%), pus (38.6%), bone marrow (60%), sputum (38.8%) and bronchoalveolar lavage (BAL) (70%). Over all there was no significant difference in males and females neither in different age groups for the identification of MTB. Conclusion We conclude that PCR is a useful and sensitive tool for the early diagnosis of MTB in variety of clinical samples. PMID:21899772
Keratinocyte growth factor administration attenuates murine pulmonary mycobacterium tuberculosis infection through granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent macrophage activation and phagolysosome fusion.
Pasula, Rajamouli; Azad, Abul K; Gardner, Jason C; Schlesinger, Larry S; McCormack, Francis X
Augmentation of innate immune defenses is an appealing adjunctive strategy for treatment of pulmonary Mycobacterium tuberculosis infections, especially those caused by drug-resistant strains. The effect of intranasal administration of keratinocyte growth factor (KGF), an epithelial mitogen and differentiation factor, on M. tuberculosis infection in mice was tested in prophylaxis, treatment, and rescue scenarios. Infection of C57BL6 mice with M. tuberculosis resulted in inoculum size-dependent weight loss and mortality. A single dose of KGF given 1 day prior to infection with 10(5) M. tuberculosis bacilli prevented weight loss and enhanced pulmonary mycobacterial clearance (compared with saline-pretreated mice) for up to 28 days. Similar effects were seen when KGF was delivered intranasally every third day for 15 days, but weight loss and bacillary growth resumed when KGF was withdrawn. For mice with a well established M. tuberculosis infection, KGF given every 3 days beginning on day 15 postinoculation was associated with reversal of weight loss and an increase in M. tuberculosis clearance. In in vitro co-culture experiments, M. tuberculosis-infected macrophages exposed to conditioned medium from KGF-treated alveolar type II cell (MLE-15) monolayers exhibited enhanced GM-CSF-dependent killing through mechanisms that included promotion of phagolysosome fusion and induction of nitric oxide. Alveolar macrophages from KGF-treated mice also exhibited enhanced GM-CSF-dependent phagolysosomal fusion. These results provide evidence that administration of KGF promotes M. tuberculosis clearance through GM-CSF-dependent mechanisms and enhances host defense against M. tuberculosis infection.
Banerji, D.; Andersen, Stig
In 39 randomly selected villages and towns in Tumkur District, South India, approximately 2000 persons, tuberculosis cases and matched controls, were interviewed in order to determine how many had symptoms suggestive of tuberculosis. Approximately 70% of the bacteriologically confirmed cases and over half the radiologically active or probably active cases had at least one major symptom. The authors discuss these findings in the light of the results of certain other studies they have carried out—for example, on present action-taking among tuberculosis sufferers. They conclude that under present circumstances in India, it is epidemiologically and economically justified to base tuberculosis control programmes on the persons who seek assistance because of worry over symptoms. Only when services satisfying the needs of the already worried tuberculosis sufferers are well developed, may mass case-finding be considered as an additional measure. PMID:14102040
Adenager, Getinet Shewaseged; Alemseged, Fessahaye; Asefa, Henok
Background. Early detection and diagnosis of tuberculosis (TB) and the timely commencement of antituberculosis (anti-TB) treatment are the parts of efficient tuberculosis prevention and control program. Delay in the commencement of anti-TB treatment worsens the prognosis and increases the risk of death and the chance of transmission in the community and among health care workers. Objective. To assess tuberculosis treatment delay and associated factors among pulmonary TB patients in Addis Ababa, Ethiopia. Methods. A cross-sectional study was conducted in 10 public and 10 private health facilities that provide TB treatment. The data were collected from 425 newly registered pulmonary TB patients using pretested structured questionnaire from April to June 2012. Data were entered in EPI info version 3.5.1 and analyzed using SPSS version 16.0. Findings. The median durations of a patient, health care system, and total treatment delays were 17, 9, and 35 days, respectively. Overall 179 (42.1%), 233 (54.8%), and 262 (61.6%) of patients experienced patient delay, health care system delay, and total treatment delay, respectively. Distance more than 2.5 km from TB treatment health facility [AOR = 1.6, 95% CI (1.1–2.5)] and the presence of TB-associated stigma [AOR = 2.1, 95% CI (1.3, 3.4)] indicate higher odds of patient delay, whereas, being unemployed, patients with the hemoptysis symptom complain indicated lower odds of health care system delay [AOR = 0.41, 95% CI (0.24, 0.70)] and [AOR = 0.61 (0.39, 0.94)], respectively. Conclusions. A significant proportion of clients experienced patient and health care system delay. Thus, there is a need for designing and implementing appropriate strategies to decrease the delays. Efforts to reduce delays should give focus on integrating prevention programs such as active case detection and expanding access to TB care. PMID:28348887
Huang, Huichang; Yang, Rui; Yao, Lan
Tuberculosis (TB) remains as a leading infectious disease worldwide. Our previous study showed interferon (IFN)-γ and CD3 T cell impairment in patients with severe cavitary pulmonary TB (PTB). However, the cause of the change in immune responses during the progression of TB is still poorly understood. In this study, eight newly diagnosed patients with severe cavitary and mild lesion non-cavity PTB were recruited, and three healthy volunteers were recruited as the control. RNA extracted from blood was tested by whole genome oligo microarrays. A PCR array was used to further test the same samples. Two additional groups of patients were recruited according to the same criteria with healthy control(HC) recruited as well and subjected to peripheral blood mononuclear cell isolation (PBMC)and analysis of TCF-7, β-catenin, cyclin D2, IFN-γ, and tumor necrosis factor (TNF)-α expression in CD14- cells (lymphocytes) and CD14+ cells by quantitative PCR. The changes of expression of β-catenin, CD69+ and IFN-γ by CD3+, CD14- and CD14+ cells in vitro with stimulation of LiCl were tested by flow cytometry. Whole genome oligo microarrays showed a significant decrease in expression of the Wnt signaling pathway in severe PTB patients. Further analysis of the Wnt pathway by PCR array indicated that TCF-7, β-catenin, and cyclin D2 expression was significantly reduced in severe PTB patients compared with mild PTB patients. In the additionally recruited patients, TCF-7, β-catenin, and cyclin D2 were expressed in both CD14+ and CD14- cells, while β-catenin was decreased significantly in CD14- cells compared with CD14+ cells in severe PTB patients, and IFN-γ and TNF-α expression in CD14- cells was also reduced significantly in severe PTB patients. β-catenin can directly trigger T cell activation and IFN-γsecretion in PBMCs stimulated for 24 hours. These findings indicate that Wnt pathway and its key genes, such as β-catenin, were impaired in blood cells of patients with
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.
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
Jacobson, Karen R
This issue provides a clinical overview of tuberculosis, focusing on screening, prevention, diagnosis, and treatment. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.
Si, Zhuang-Li; Kang, Ling-Ling; Shen, Xu-Bo; Zhou, Yuan-Zhong
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
Yin, Yongmei; Kuai, Shougang; Liu, Jun; Zhang, YingYing; Shan, Zhongbao; Gu, Lan; Huang, Qiusheng
Introduction The neutrophil-to-lymphocyte ratio (NLR) is a readily available biomarker associated with recurrence and survival in various diseases. The objective of this study was to investigate the relationship between NLR and pulmonary tuberculosis (PTB) retreatment. Material and methods This was a case-control study that included 306 newly diagnosed cases of PTB in the clinical database of the Infectious Hospital of Wuxi from December 2009 to December 2011. Of the 306 patients, a total of 68 cases were followed up with TB retreatment. The remaining 238 PTB patients who completed anti-TB treatment and were cured without retreatment were selected as controls. Results According to the ROC curve, the best cut-off value of NLR was 2.53, with a sensitivity of 70.6% and a specificity of 45.4%. The NLR ≥ 2.53 before anti-TB treatment was associated with PTB retreatment (OR = 1.994, 95% CI: 1.116–3.564; adjusted OR (AOR) = 2.409, 95% CI: 1.212–4.788). The retreatment rates with NLR ≥ 2.53 and NLR < 2.53 were 27.1% and 15.5%, respectively, with a significant difference (log-rank test; p = 0.010). Additionally, cavitation on chest X-ray (OR = 2.922, 95% CI: 1.654–5.411; AOR = 2.482, 95% CI: 1.230–5.007), history of smoking (OR = 2.202, 95% CI: 1.158–3.493; AOR = 2.321, 95% CI: 1.135–4.745) and age ≥ 60 (OR = 3.828, 95% CI: 1.626–9.015; AOR = 2.931, 95% CI: 1.122–7.653) were also associated with PTB retreatment. Conclusions NLR ≥ 2.53 is predictive of PTB retreatment. Otherwise, initial cavitation on chest X-ray, history of smoking, and age of ≥ 60 are also risk factors for PTB retreatment. PMID:28261295
Cáceres, Omar; Rastogi, Nalin; Bartra, Carlos; Couvin, David; Galarza, Marco; Asencios, Luis; Mendoza-Ticona, Alberto
Background Peru holds the fourth highest burden of tuberculosis in the Americas. Despite an apparently well-functioning DOTS control program, the prevalence of multidrug resistant tuberculosis (MDR-TB) continues to increase. To worsen this situation, cases of extensively drug resistance tuberculosis (XDR-TB) have been detected. Little information exists about the genetic diversity of drug-susceptible vs. MDR-TB and XDR-TB. Methods Cryopreserved samples of XDR strains from 2007 to 2009 (second semester), were identified and collected. Starting from 227 frozen samples, a total of 142 XDR-TB strains of Mycobacterium tuberculosis complex (MTBC; 1 isolate per patient) were retained for this study. Each strain DNA was analyzed by spoligotyping and the 15-loci Mycobacterial Interspersed Repetitive Unit (MIRU-15). Results Among the 142 isolates analyzed, only 2 samples (1.41%) could not be matched to any lineage. The most prevalent sublineage was Haarlem (43.66%), followed by T (27.46%), LAM (16.2%), Beijing (9.15%), and X clade (1.41%). Spoligotype analysis identified clustering for 128/142 (90.1%) isolates vs. 49/142 (34.5%) with MIRUs. Of the samples, 90.85% belonged to retreated patients. The drug resistant profile demonstrated that 62.67% showed resistance to injectable drugs capreomycin (CAP) and kanamycin (KAN) vs. 15.5% to CAP alone and 21.8% to KAN alone. The SIT219/T1 and SIT50/H3 were the most prevalent patterns in our study. The spoligoforest analysis showed that SIT53/T1 was at the origin of many of the T lineage strains as well as a big proportion of Haarlem lineage strains (SIT50/H3, followed by SIT47/H1, SIT49/H3, and SIT2375/H1), as opposed to the SIT1/Beijing strains that did not appear to evolve into minor Beijing sublineages among the XDR-TB strains. Conclusion In contrast with other Latin-American countries where LAM sublineage is the most predominant, we found the Haarlem to be the most common followed by T sublineage among the XDR-TB strains. PMID
Ben Selma, Walid; Harizi, Hedi; Bougmiza, Iheb; Hannachi, Naila; Ben Kahla, Imen; Zaieni, Radhia; Boukadida, Jalel
Interferon gamma (IFN-γ) is a key cytokine involved mainly in the defense against intracellular pathogens such as Mycobacterium tuberculosis. Given its key role in the control of tuberculosis (TB), in the present article we have investigated a possible association between IFN-γ gene single-nucleotide polymorphism linked to high and low producer phenotypes (IFN-γ [+874T(high) → A(low)]) (rs2430561) and risk development of active TB in Tunisian patients. Genomic DNA samples were obtained from 223 patients with active TB (168 pulmonary and 55 extrapulmonary cases) and 150 healthy blood donors. Genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism method. The +874 AA genotype (low IFN-γ producer) was significantly associated with increased risk of developing of active pulmonary TB (odds ratio [OR] = 2.18; 95% confidence intervals [CI], 1.33-3.57; P corrected for the number of genotypes [Pc] = 0.003). By contrast, the AT genotype was found to be significantly associated with resistance to pulmonary TB (OR = 0.46; 95% CI, 0.28-0.74; Pc = 0.0018) and extrapulmonary TB development (OR = 0.46; 95% CI, 0.23-0.91; Pc = 0.045). Collectively, our data showed that the IFN-γ +874T/A polymorphism is a determinant in the resistance or susceptibility to the development of active TB in the studied population.
Davila, Sonia; Hibberd, Martin L.; Hari Dass, Ranjeeta; Wong, Hazel E. E.; Sahiratmadja, Edhyana; Bonnard, Carine; Alisjahbana, Bachti; Szeszko, Jeffrey S.; Balabanova, Yanina; Drobniewski, Francis; van Crevel, Reinout; van de Vosse, Esther; Nejentsev, Sergey; Ottenhoff, Tom H. M.; Seielstad, Mark
Despite high rates of exposure, only 5–10% of people infected with Mycobacterium tuberculosis will develop active tuberculosis (TB) disease, suggesting a significant role for genetic variation in the human immune response to this infection. Here, we studied TB association and expression of 18 genes involved in the Toll-like receptor (TLR) pathways. Initially, we genotyped 149 sequence polymorphisms in 375 pulmonary TB patients and 387 controls from Indonesia. We found that four polymorphisms in the TLR8 gene on chromosome X showed evidence of association with TB susceptibility in males, including a non-synonymous polymorphism rs3764880 (Met1Val; P = 0.007, odds ratio (OR) = 1.8, 95% c.i. = 1.2–2.7). We genotyped these four TLR8 polymorphisms in an independent collection of 1,837 pulmonary TB patients and 1,779 controls from Russia and again found evidence of association in males (for rs3764880 P = 0.03, OR = 1.2, 95% c.i. = 1.02–1.48). Combined evidence for association is P = 1.2×10−3–6×10−4. In addition, a quantitative PCR analysis indicated that TLR8 transcript levels are significantly up-regulated in patients during the acute phase of disease (P = 9.36×10−5), relative to baseline levels following successful chemotherapy. A marked increase in TLR8 protein expression was also observed directly in differentiated macrophages upon infection with M. bovis bacille Calmette-Guérin (BCG). Taken together, our results provide evidence, for the first time, of a role for the TLR8 gene in susceptibility to pulmonary TB across different populations. PMID:18927625
The fight against tuberculosis in the German Democratic Republic was performed from the very beginning as a task of the state and the society; it was developed according to the progress of economic possibilities and the epidemiological situation. The contribution of the community and of the social-economic development on tuberculosis epidemiology has proved to be decisively important factors in tuberculosis control. The specific methods applied in tuberculosis control in the course of more than 30 years have changed in their importance effectiveness and efficiency with the reduction of the tuberculosis problem and the development of new techniques. Therefore a continuous evaluation of the tuberculosis situation is necessary to recognize the most effective approach. By reducing the estimated annual infection rate to less than 0.05%, the incidence of smear positive pulmonary tuberculosis to less than 5/100,000 and the practical disappearance of tuberculosis among children tuberculosis has become an endemic localized disease among predominantly old citizens. People's mass x-ray examinations have considerably lost their value for finding tuberculosis. Early coverage and examination of persons with respiratory symptoms (21-days-coughers), of contact persons and high risk groups will determine the future activities of the chest clinics. Their integration into the system of outpatient clinics and the system of primary health care were an important step on this way. Successful treatment of each case of tuberculosis is now possible and must be attained. Early case finding + treatment considered as an united activity has become the decisively important measure in the control of tuberculosis. The endemic foci of tuberculosis in some communities have to be surveyed and eliminated with priority. Moreover, the cooperation of all physicians of public health is necessary. Only by this way tuberculosis can be eradicated in GDR in a defined time. (Aim of WHO and IUaT: 1 case of
Anochie, Philip Ifesinachi; Onyeneke, Edwina Chinwe; Onyeozirila, Anthony Chidiebere; Igbolekwu, Leonard Chibuzo; Onyeneke, Bestman Chukwuemeka; Ogu, Angelina Chinyere
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
Dietrich, Jes; Roy, Sugata; Rosenkrands, Ida; Lindenstrøm, Thomas; Filskov, Jonathan; Rasmussen, Erik Michael; Cassidy, Joseph; Andersen, Peter
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.
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
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.
Bernal-Fernandez, German; Espinosa-Cueto, Patricia; Leyva-Meza, Rosario; Mancilla, Nathalie; Mancilla, Raul
Patients with tuberculosis frequently develop anergy, a state of T-cell hyporesponsiveness in which defective T-cell costimulation could be a factor. To know if the expression of T-cell costimulatory molecules was altered in tuberculosis, we analyzed the peripheral blood T-cell phenotype of 23 Mexican patients with pulmonary tuberculosis. There was severe CD4 (P < .001) and CD8 (P < .01) lymphopenia and upregulation of costimulatory molecule CD30 on CD4 and CD8 T cells (P < .05); this increase was higher in relapsing tuberculosis. The main finding was severe downregulation of the major costimulatory molecule CD28 on both CD8 and CD4 T cells (P < .001). Depletion of the CD4/CD28 subset, a hitherto undescribed finding, is relevant because CD4 T cells constitute the main arm of the cell-mediated antimycobacterial immune response. PMID:22567259
Shih, W.J.; DeLand, F.H.; Domstad, P.A.; Mac Vandiviere, H.; Dillon, M.L.
Most causes of superior vena caval (SVC) obstruction are caused by malignant mediastinal neoplasms, especially bronchogenic carcinoma. Less frequently SVC obstruction results from a non-malignant lesion such as mediastinal goiter or tuberculosis. We present a case of mediastinal tuberculosis which progressively enlarged as shown in consecutive Ga-67 citrate studies. As a result, SVC obstruction developed, exhibited by radionuclide SV Cavagram, and demonstrated ''hot'' spots in the radiocolloid scans.
Kubler, Andre; Larsson, Christer; Luna, Brian; Andrade, Bruno B; Amaral, Eduardo P; Urbanowski, Michael; Orandle, Marlene; Bock, Kevin; Ammerman, Nicole C; Cheung, Laurene S; Winglee, Kathryn; Halushka, Marc; Park, Jin Kyun; Sher, Alan; Friedland, Jon S; Elkington, Paul T; Bishai, William R
Cavitation in tuberculosis enables highly efficient person-to-person aerosol transmission. We performed transcriptomics in the rabbit cavitary tuberculosis model. Among 17 318 transcripts, we identified 22 upregulated proteases. Five type I collagenases were overrepresented: cathepsin K (CTSK), mast cell chymase-1 (CMA1), matrix metalloproteinase 1 (MMP-1), MMP-13, and MMP-14. Studies of collagen turnover markers, specifically, collagen type I C-terminal propeptide (CICP), urinary deoxypyridinoline (DPD), and urinary helical peptide, revealed that cavitation in tuberculosis leads to both type I collagen destruction and synthesis and that proteases other than MMP-1, MMP-13, and MMP-14 are involved, suggesting a key role for CTSK. We confirmed the importance of CTSK upregulation in human lung specimens, using immunohistochemical analysis, which revealed perigranulomatous staining for CTSK, and we showed that CTSK levels were increased in the serum of patients with tuberculosis, compared with those in controls (3.3 vs 0.3 ng/mL; P = .005).
Mahishale, Vinay; Avuthu, Sindhuri; Patil, Bhagyashri; Lolly, Mitchelle; Eti, Ajith; Khan, Sujeer
Background: There is growing evidence that diabetes mellitus (DM) is an important risk factor for tuberculosis (TB). A significant number of DM patients have poor glycemic control. This study was carried out to find the impact of poor glycemic control on newly diagnosed smear-positive pulmonary tuberculosis patients with type-2 diabetes mellitus in a tertiary care hospital. Methods: In a hospital-based prospective study, newly diagnosed smear-positive pulmonary TB with DM patients were classified as poorly controlled diabetes (HBA1C≥7%) and optimal control diabetics (HbA1c<7%). Patients were started on anti-TB treatment and followed for 2 years for severity and treatment outcome. ANOVA was used for numerical variables in the univariable analysis. Logistic regression analysis was used for multivariable analysis of treatment outcome. The significance level was kept at a P≤0.05. Results: A total of 630 individuals who met the inclusion criteria were analyzed; of which 423 patients had poor glycemic control (PGC) and 207 patients had optimal glycemic control (OGC). The average HbA1c was 10±2.6 and 5±1.50 in the PGC and OGC groups, respectively. The mean symptom score was significantly higher in the PGC group compared with patients in the OGC group (4.55±0.80 vs. 2.70±0.82, P<0.001). PGC was associated with more extensive lung disease, lung cavitation, and positive sputum smear at the baseline. In PGC, sputum smears were significantly more likely to remain positive after 2 months of treatment. PGC patients had significantly higher rates of treatment failure (adj. OR 0.72, 95% CI 0.58-0.74, P<0.001) and relapse (adj. OR 2.83, 95% CI 2.60-2.92, P<0.001). Conclusion: Poor glycemic control is associated with an increased risk of advanced and more severe TB disease in the form of lung cavitations, positive sputum smear, and slower smear conversion. It has a profound negative effect on treatment completion, cure, and relapse rates in patients with pulmonary
Trujillo, Glenda; Meneghin, Alessia; Flaherty, Kevin R.; Sholl, Lynette M.; Myers, Jeffrey L.; Kazerooni, Ella A.; Gross, Barry H.; Oak, Sameer R.; Coelho, Ana Lucia; Evanoff, Holly; Day, Elizabeth; Toews, Galen B.; Joshi, Amrita D.; Schaller, Matthew A.; Waters, Beatrice; Jarai, Gabor; Westwick, John; Kunkel, Steve L.; Martinez, Fernando J.; Hogaboam, Cory M.
Idiopathic pulmonary fibrosis is a generally progressive disorder with highly heterogeneous disease progression. The most common of the idiopathic interstitial pneumonias, idiopathic pulmonary fibrosis is characterized by a steady worsening of lung function and gas exchange cause by diffuse alveolar damage and severe fibrosis. We examined clinical features of patients with idiopathic pulmonary fibrosis to classify them as exhibiting rapid or slowly progressive over the first year of follow-up. We identified differences between the two groups in order to investigate the mechanism of rapid progression. Previous work from our laboratory has demonstrated that Toll-like receptor 9, a pathogen recognition receptor, promotes myofibroblast differentiation in lung fibroblasts cultured from biopsies of patients with idiopathic pulmonary fibrosis. Therefore, we hypothesized that TLR9 functions as both a sensor of pathogenic molecules and a profibrotic signal in rapidly progressive idiopathic pulmonary fibrosis. TLR9 was present at higher concentrations in surgical lung biopsies from rapidly progressive patients than in tissue from normal controls. Fibroblasts from rapid progressors were more responsive to the TLR9 agonist, CpG, than were fibroblasts from control patients. We used a humanized SCID mouse and demonstrated that there was increased fibrosis in murine lungs receiving human lung fibroblasts from rapid progressors than in mice receiving normal fibroblasts. This fibrosis was exacerbated by intranasal CpG challenges. Furthermore, CpG induced the differentiation of blood monocytes into fibrocytes and the epithelial-to-mesenchymal transition of A549 lung epithelial cells. These data suggest that TLR9 may drive the pathogenesis of rapidly progressive idiopathic pulmonary fibrosis and is a potential indicator of this subset of the disease. PMID:21068441
Kalo, Deepika; Kant, Surya; Srivastava, Kanchan; Sharma, Ajay K
Background: Tuberculosis (TB), a highly contagious disease that sees no gender, age, or race is mainly a disease of lungs. According to World Health Organization, a TB patient can be completely cured with 6–9 months of anti-TB treatment under directly observed treatment short course. Objectives: The aim of this study was to check the mono, multi- and triple-drug resistance to first line drugs (FLDs) among TB patients and to access their genetic profile using DR 3074, DR 0270, DR 0642, DR 2068, and DR 4110 using molecular techniques. Material and Methods: To gain a better understanding of drug resistant TB, we characterized 121 clinical isolates recovered from 159 drug resistant pulmonary tuberculosis patients by IS6110 genotyping. MTB isolates recovered from HIV- negative, and smear positive cases of both genders, age varied from 18 to 70 years with drug resistant-TB that was refractory to chemotherapy given for > 12 months. Of a total of 159 sputum smear positive patients sum number of male and female patients was 121 (76.10%) and 38 (23.89%), respectively. Among these patients, number of literate and illiterate patients were 123 (77.3%) and 36 (22.6%). 25 (15.7%) patients had farming as their occupation, 80 (50.3%) had nonagricultural occupation and 54 (33.9%) women were housewives. Results: Mono drug resistant, multi-drug resistant, and totally drug resistant (TDR) cases of TB were calculated as 113.83%, 125.1%, and 67.9%. Isoniazid showed the highest percentage of resistance among the patients. Conclusion: Any noncompliance to TB medications, lack of knowledge, and poor management in health centers, etc., results in the emergence of deadly direct repeat forms of TB, which are further complicated and complex to treat. PMID:28360464
Leepiyasakulchai, Chaniya; Taher, Chato; Chuquimia, Olga D.; Mazurek, Jolanta; Söderberg-Naucler, Cecilia; Fernández, Carmen; Sköld, Markus
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
Savic, R M; Weiner, M; MacKenzie, W R; Engle, M; Whitworth, W C; Johnson, J L; Nsubuga, P; Nahid, P; Nguyen, N V; Peloquin, C A; Dooley, K E; Dorman, S E
Rifapentine is a highly active antituberculosis antibiotic with treatment-shortening potential; however, exposure-response relations and the dose needed for maximal bactericidal activity have not been established. We used pharmacokinetic/pharmacodynamic data from 657 adults with pulmonary tuberculosis participating in treatment trials to compare rifapentine (n = 405) with rifampin (n = 252) as part of intensive-phase therapy. Population pharmacokinetic/pharmacodynamic analyses were performed with nonlinear mixed-effects modeling. Time to stable culture conversion of sputum to negative was determined in cultures obtained over 4 months of therapy. Rifapentine exposures were lower in participants who were coinfected with human immunodeficiency virus, black, male, or fasting when taking drug. Rifapentine exposure, large lung cavity size, and geographic region were independently associated with time to culture conversion in liquid media. Maximal treatment efficacy is likely achieved with rifapentine at 1,200 mg daily. Patients with large lung cavities appear less responsive to treatment, even at high rifapentine doses.
Volchegorskiĭ, I A; Novoselov, P N; Bolotov, A A
The authors have studied whether an indirect clinical-and-laboratory assessment of the extent of a destructive process in the tuberculous infiltrates and that of concomitant pleural affection can be made from the values of the lipid peroxidation-antioxidative defense (PLO-AOD) system in the blood of patients with infiltrative pulmonary tuberculosis (IPT). Regression analysis has indicated that PLO-AOD values significantly reflect the extent of X-ray verified destructions in the tuberculous infiltrates, concomitant pleural involvements, the specific features of immunity of patients with IPT. The neural network technology used to analyze the baseline PLO-AOD values has been ascertained to permit a reliable prognosis of decay cavity closure 4 months after the initiation of medical treatment and of a need for surgical treatment for IPT.
Background Mycobacterium tuberculosis is a necessary, but not sufficient, cause of tuberculosis. A number of studies have addressed the issue of risk factors for tuberculosis development. Croatia is a European country with an incidence rate of 14/100 000 which is slowly decreasing. The aim of this study is to evaluate the potential demographic, socioeconomic, behavioural and biological risk factors for tuberculosis in Croatia in comparison to other high-income, low-incidence European countries. Methods A total of 300 tuberculosis patients were matched for age, sex and county of residence to 300 controls randomly selected from general practitioners’ registers. They were interviewed and their medical records were evaluated for variables broadly described as potential risk factors. Results In multiple logistic regression, the following factors were significant: parents born in a particular neighbouring county (Bosnia and Herzegovina) (OR = 3.90, 95% CI 2.01-7.58), the lowest level of education (OR = 3.44, 95% CI 1.39-8.50), poor household equipment (OR = 4.72, 95% CI 1.51-14.76), unemployment (OR = 2.69, 95% CI 1.18-6.16), contact with tuberculosis (OR = 2.19, 95% CI 1.27-3.77), former (OR = 2.27, 95% CI 1.19-4.33) and current smoking habits (OR = 2.35, 95% CI 1.27-4.36), diabetes (OR = 2.38, 95% CI 1.05-5.38), a malignant disease (OR = 5.79, 95% CI 1.49-22.42), being underweight in the previous year (OR = 13.57, 95% CI 1.21-152.38). Conclusion In our study, the identified risk groups for tuberculosis reflect a complex interaction between socioeconomic conditions, lifestyle and non-communicable diseases. Interventions focused on poverty will undoubtedly be useful, but not sufficient. Tuberculosis control would benefit from a combination of broad public health activities aimed at the prevention and control of risky lifestyles and non-communicable diseases, interventions outside the health sector, and efforts to constantly
Han, Min; Yue, Jun; Lian, Yuan-Yuan; Zhao, Yan-Lin; Wang, Hong-Xiu; Liu, Li-Rong
Interleukin-18 (IL-18) is a multi-functional cytokine capable of inducing either Th1 or Th2 polarization depending on the immunologic milieu. IL-18 may influence the host response to Mycobacterium tuberculosis (M.tb) infection. To investigate the relationship between single nucleotide polymorphisms of the IL-18 and susceptibility to pulmonary tuberculosis in the Chinese Han population, the IL-18 gene was sequenced to detect polymorphisms and to examine the genotype frequencies in 300 patients and 702 healthy controls. DNA sequencing revealed three IL-18 variants: rs1946518, rs5744247, and rs549908. It also revealed that allele A of rs1946518 confers a 1.47-fold increased risk of developing tuberculosis (TB) (P = 0.0001, OR [95%CI] = 1.47 [1.21-1.78]), and that the C allele of rs5744247 confers a 0.77-fold decreased risk of disease (P = 0.01, R [95%CI] = 0.77 [0.632-0.937]). The genotypes rs1946518, rs5744247 and rs549908 were found to be significantly associated with TB. Estimation of the frequencies of haplotypes revealed a potential risk haplotype AGA (P = 0.01, OR [95%CI] = 1.41 [1.15-1.72]) and a protective haplotype CCA (P = 0.01, OR [95%CI] = 0.70 [0.57-0.85]) for TB. The present findings suggest that polymorphisms in the IL-18 gene may affect susceptibility to TB and increase the risk of developing the disease in the Chinese Han population.
Wu, Jiun-Ting; Chiu, Chien-Tung; Wei, Yu-Feng; Lai, Yung-Fa
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
Nooshabadi, Fatemeh; Yang, Hee-Jeong; Cheng, Yunfeng; Durkee, Madeleine S; Xie, Hexin; Rao, Jianghong; Cirillo, Jeffrey D; Maitland, Kristen C
Tuberculosis is a pulmonary disease with an especially high mortality rate in immuno-compromised populations, specifically children and HIV positive individuals. The causative agent, Mycobacterium tuberculosis (Mtb), is a very slow growing and difficult organism to work with, making both diagnosis and development of effective treatments cumbersome. We utilize a fiber-optic fluorescence microendoscope integrated with a whole-body imaging system for in vivo Mtb detection. The system exploits an endogenous enzyme of Mtb (β-lactamase, or BlaC) using a BlaC-specific NIR fluorogenic substrate. In the presence of BlaC, this substrate is cleaved and becomes fluorescent. Using intravital illumination of the lung to excite this probe, sensitivity of the optical system increases over trans- and epi-illumination methods of whole-body fluorescence imaging. We demonstrate that integration of these imaging technologies with BlaC-specific fluorescent reporter probe improves the level of detection to ∼100 colony forming units, a 100× increase in sensitivity in comparison to epi-illumination and a 10× increase in sensitivity in comparison to previous work in intravital excitation of tdTomato-expressing Mtb. This lower detection threshold enables the study of early stage bacterial infections with clinical strains of Mtb and longitudinal studies of disease pathogenesis and therapeutic efficacy with multiple time points in a single animal.
Khazaei, Salman; Soheilyzad, Mokhtar; Molaeipoor, Leila; Khazaei, Zaher; Rezaeian, Shahab; Khazaei, Somayeh
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
Singh, Netrapal; Sreenivas, Vishnubhatla; Gupta, Krishna B; Chaudhary, Anil; Mittal, Anshu; Varma-Basil, Mandira; Prasad, Rajendra; Gakhar, Surender K; Khuller, Gopal K; Mehta, Promod K
We developed a novel indirect sandwich immuno-polymerase chain reaction (I-PCR) assay for the detection of mycobacterial antigen 85B (Ag85B, 30kDa, Rv1886c) in pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) patients. The amino-modified reporter DNA was covalently attached with the antidetection antibody through a heterobifunctional cross-linking agent succinimidyl 4-[N-maleimidomethyl]-cyclohexane-1-carboxylate. The detection limit of Ag85B by I-PCR was found to be 1 femtogram (fg)/mL, which was 10(6)-fold lower than an analogous enzyme-linked immunosorbent assay (ELISA). The sensitivities of 85% and 77% with I-PCR and 77.6% and 62.5% with ELISA were observed in smear-positive and smear-negative PTB patients, respectively, with high specificity. On the other hand, sensitivities of 84% and 63.7% with I-PCR and 68% and 47.5% with ELISA were observed in confirmed and clinically suspected EPTB cases, respectively, with high specificity.
Xia, YinYin; Goel, Sonu; Harries, Anthony D.; Zhang, ZhiGuo; Gao, TieJie; Wang, LiXia; Cheng, ShiMing; Lin, Yan; Du, Xin
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
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
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.
Via, Laura E; Weiner, Danielle M; Schimel, Daniel; Lin, Philana Ling; Dayao, Emmanuel; Tankersley, Sarah L; Cai, Ying; Coleman, M Teresa; Tomko, Jaime; Paripati, Praveen; Orandle, Marlene; Kastenmayer, Robin J; Tartakovsky, Michael; Rosenthal, Alexander; Portevin, Damien; Eum, Seok Yong; Lahouar, Saher; Gagneux, Sebastien; Young, Douglas B; Flynn, Joanne L; Barry, Clifton E
Existing small-animal models of tuberculosis (TB) rarely develop cavitary disease, limiting their value for assessing the biology and dynamics of this highly important feature of human disease. To develop a smaller primate model with pathology similar to that seen in humans, we experimentally infected the common marmoset (Callithrix jacchus) with diverse strains of Mycobacterium tuberculosis of various pathogenic potentials. These included recent isolates of the modern Beijing lineage, the Euro-American X lineage, and M. africanum. All three strains produced fulminant disease in this animal with a spectrum of progression rates and clinical sequelae that could be monitored in real time using 2-deoxy-2-[(18)F]fluoro-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT). Lesion pathology at sacrifice revealed the entire spectrum of lesions observed in human TB patients. The three strains produced different rates of progression to disease, various extents of extrapulmonary dissemination, and various degrees of cavitation. The majority of live births in this species are twins, and comparison of results from siblings with different infecting strains allowed us to establish that the infection was highly reproducible and that the differential virulence of strains was not simply host variation. Quantitative assessment of disease burden by FDG-PET/CT provided an accurate reflection of the pathology findings at necropsy. These results suggest that the marmoset offers an attractive small-animal model of human disease that recapitulates both the complex pathology and spectrum of disease observed in humans infected with various M. tuberculosis strain clades.
Steingart, Karen R; Schiller, Ian; Horne, David J; Pai, Madhukar; Boehme, Catharina C; Dendukuri, Nandini
Background Accurate, rapid detection of tuberculosis (TB) and TB drug resistance is critical for improving patient care and decreasing TB transmission. Xpert® MTB/RIF assay is an automated test that can detect both TB and rifampicin resistance, generally within two hours after starting the test, with minimal hands-on technical time. The World Health Organization (WHO) issued initial recommendations on Xpert® MTB/RIF in early 2011. A Cochrane Review on the diagnostic accuracy of Xpert® MTB/RIF for pulmonary TB and rifampicin resistance was published January 2013. We performed this updated Cochrane Review as part of a WHO process to develop updated guidelines on the use of the test. Objectives To assess the diagnostic accuracy of Xpert® MTB/RIF for pulmonary TB (TB detection), where Xpert® MTB/RIF was used as both an initial test replacing microscopy and an add-on test following a negative smear microscopy result. To assess the diagnostic accuracy of Xpert® MTB/RIF for rifampicin resistance detection, where Xpert® MTB/RIF was used as the initial test replacing culture-based drug susceptibility testing (DST). The populations of interest were adults presumed to have pulmonary, rifampicin-resistant or multidrug-resistant TB (MDR-TB), with or without HIV infection. The settings of interest were intermediate- and peripheral-level laboratories. The latter may be associated with primary health care facilities. Search methods We searched for publications in any language up to 7 February 2013 in the following databases: Cochrane Infectious Diseases Group Specialized Register; MEDLINE; EMBASE; ISI Web of Knowledge; MEDION; LILACS; BIOSIS; and SCOPUS. We also searched the metaRegister of Controlled Trials (mRCT) and the search portal of the WHO International Clinical Trials Registry Platform to identify ongoing trials. Selection criteria We included randomized controlled trials, cross-sectional studies, and cohort studies using respiratory specimens that allowed for
Pachi, Argiro; Bratis, Dionisios; Moussas, Georgios; Tselebis, Athanasios
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
Dumonceaux, Genevieve A; St Leger, Judy; Olsen, John H; Burton, Michael S; Ashkin, David; Maslow, Joel N
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.
Adane, Kelemework; Spigt, Mark; Ferede, Semaw; Asmelash, Tsehaye; Abebe, Markos; Dinant, Geert-Jan
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
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
Kadihasanoglu, Mustafa; Yildiz, Tekin; Atahan, Safak; Ausmus, Andrew; Atahan, Ozcan
Genitourinary tuberculosis (TB) is a common type of extrathoracic TB and can be found in isolation or associated with pulmonary TB. It contributes to 10-14% of extrapulmonary TB. Prostate TB is rare and usually found incidentally following transurethral resection of the prostate for treatment of benign prostatic obstruction as an isolated lesion in immunocompetant patient. The authors report a case of prostatic and pulmonary TB in animmunocompetant patient investigating for the positive positron emission tomography in lung and prostate. To our knowledge, this is the first case reported in the literature presenting with simultaneous hypermetabolic lesions in the prostate and lung.
Kumar, Nathella P; Sridhar, Rathinam; Nair, Dina; Banurekha, Vaithilingam V; Nutman, Thomas B; Babu, Subash
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.
Reddy, Yogesh N V; Lunawat, Deepika; Abraham, Georgi; Matthew, Milly; Mullasari, Ajith; Nagarajan, Prethivee; Reddy, Yuvaram N V
The aim of this retrospective study was to compare the prevalence of pulmonary hypertension in a cohort of patients with end-stage renal disease (ESRD) prior to and following renal transplantation and to identify the possible risk factors. Of the 425 renal transplantations performed between 2001 and 2007, Doppler echocardiographic findings were available in 124. The echocardiographic data, collected both pre- and post-transplant, included the pulmonary artery pressure (PAP), ejection fraction and left ventricular hypertrophy. The data analyzed included age, gender, hypertension, diabetes, smoking status, along with blood urea, creatinine, glomerular filtration rate, hemoglobin, hemodialysis duration, urine albumin, arterio-venous access and body mass index (BMI). Chi-square test was used for discrete variables and ANOVA was used for continuous variables. Of the patients studied, males comprised 72%; the mean age was 43.3 ± 13.02 years; 87% were hypertensive, 30% were diabetic and 4% were smokers. Statistical analysis revealed a significant reduction of the PAP, irrespective of its severity, following renal transplantation (P <0.05). The PAP had no significant correlation with any of the parameters analyzed, with the exception of BMI (P <0.05). Our study suggests that the PAP gets reduced in patients with ESRD after renal transplantation.
Johnson, J. L.; Okwera, A.; Nsubuga, P.; Nakibali, J. G.; Whalen, C. C.; Hom, D.; Cave, M. D.; Yang, Z. H.; Mugerwa, R. D.; Ellner, J. J.
SUMMARY SETTING National Tuberculosis Treatment Centre, Mulago Hospital, Kampala, Uganda. OBJECTIVE To assess the efficacy of a daily, self-administered 8-month rifampicin-containing regimen for the treatment of pulmonary tuberculosis (TB) in human immunodeficiency virus (HIV) infected adults. DESIGN Treatment outcomes in patients with pulmonary TB treated with a single 8-month regimen and followed in a prospective epidemiological study. RESULTS Two hundred and sixty-five HIV-infected and 26 non-HIV-infected adults with initial episodes of pulmonary tuberculosis were treated with 2 months of daily isoniazid (INH), rifampicin (RMP), ethambutol and pyrazinamide followed by 6 months of daily INH + RMP. Median follow-up was 17.8 months. Ninety-five per cent of the HIV-infected and all of the non-HIV-infected patients who had sputum examined were sputum culture negative after 2 months of treatment. Twenty-two HIV-infected and no non-HIV-infected patients died during treatment. Relapse rates were 8.4% (5.9 per 100 person-years of observation [PYO], 95%CI 3.2–8.6) among HIV-infected patients and 4.5% (2.1/100 PYO, 95%CI 0–7.8) for non-HIV-infected patients. Adverse drug reactions occurred in 37% of the HIV-infected patients; most were minor and self-limiting. CONCLUSION An 8-month RMP-containing regimen was well tolerated and effective in the treatment of HIV-infected adults with initial episodes of pulmonary TB. Relapse rates were similar to those reported with 6-month short-course regimens in HIV-infected individuals. Decisions about the duration of anti-tuberculosis treatment for HIV-infected adults must balance programme resources and the likelihood of poor compliance with longer regimens with the potential for a modest decrease in relapses with longer treatment. PMID:11092715
Solan, M.J. )
A case is presented of a patient with four separate primary carcinomas (two breast, one thyroid, one multiple skin cancers) arising in areas of the body subject to repeated low-dose radiation exposure during artificial pneumothorax treatment of pulmonary tuberculosis. Evidence for ionizing radiation as the likely common etiologic agent for all four tumors is presented and substantiated by a review of the literature. 25 references.
Nebenzahl-Guimaraes, Hanna; Verhagen, Lilly M; Borgdorff, Martien W; van Soolingen, Dick
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.
Verhagen, Lilly M.; Borgdorff, Martien W.; van Soolingen, Dick
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. PMID:26224845
Adeyeye, Olufunke O.; Coker, Ayodele; Kuyinu, Yetunde; Bamisile, Raymond T.; Ekrikpo, Udeme; Onadeko, Babatunde
There is paucity of information on the quality of life of patients with pulmonary tuberculosis in Nigeria. This study assessed the factors influencing their quality of life and the independent predictors of low quality of life scores. Two hundred and sixty consecutive patients with pulmonary tuberculosis seen at the Lagos University Teaching Hospital were evaluated for health related quality of life using the World Health Organization Quality of life instrument (WHOQoL-BREF). Sociodemographic characteristics of the patients were related to the various domains of quality of life and a multivariate logistic regression analysis was performed to identify the independent predictors of low quality of life scores in the patients. The mean age of the patients was 36.7±12 years. Sex, age and marital status of patients were found to influence quality of life scores. The independent predictors of low quality of life scores were low monthly income, duration of the illness, concomitant illnesses, unemployment, advancing age and male gender. Several socio demographic and economic factors influenced the quality of life of patients with tuberculosis and are predictive of poor scores. It is important to consider these factors when treating patients with tuberculosis to optimise outcome of care. PMID:28299129
Lee, Hyun Woo; Lee, Jung Kyu; Kim, Eunyoung; Yim, Jae-Joon; Lee, Chang-Hoon
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
Griffin, Diane E
Due to the high infectivity of measles virus, achieving sufficient population immunity to interrupt transmission requires two doses of live attenuated measles virus vaccine. Subcutaneous delivery of vaccine by injection requires trained personnel, maintenance of a cold chain and safe disposal of used needles and syringes. Pulmonary vaccine delivery offers the opportunity for cost-savings and improved coverage, but requires re-licensure. Two aerosol vaccine formulations, nebulized liquid and dry powder, and multiple delivery devices have been evaluated in humans and macaques. Nebulized liquid vaccine is effective for a second dose of vaccine in older children, but less effective for primary vaccination of infants. Dry powder vaccine provides solid protection in macaques and boosts responses in immune adults, but has not yet been tested in infants.
TB incidence in our country is still quite high compared to the average of the European Union countries (1st place among EU countries and 3rd place among WHO European Region countries), which means that a national coordinated response against this disease needs to become the priority of the current health care policy. The multi-factorial conditioning, which includes the social and economic dimensions of TB spreading, requires a multi-disciplinary and inter-sectorial approach to this pathology, going beyond healthcare services. The National Tuberculosis Control Strategy is a part of Romania's Country Strategy based on the guidelines set out in WHO's 2006-2015 Global Plan to Stop Tuberculosis (MDGs 2015) and it provides the necessary framework for refining and harmonizing the national legislation and regulations with the European laws after Romania's integration in the EU.
Ruiz Del Olmo Izuzquiza, Ignacio; Orden Rueda, Claudia; Ochoa Gómez, Laura; Clavero Montañés, Nuria; Berdún Chéliz, Enrique; Guerrero Laleona, Carmelo
Paradoxical reaction to antituberculosis treatment is rare in paediatric population. We report a 9-year-old girl with high fever and productive cough for the last three weeks. Tuberculine test and Quantiferon were positive, erythrocyte sedimentation rate was 64 mm/h, culture and polymerase chain reaction for M. tuberculosis negative, and chest X ray showed a widened right mediastinum. Tuberculosis was diagnosed, therefore treatment with standard doses of rifampicin, isoniazid, pyrazinamide and ethambutol was started. Twenty-one days later she presented high fever with no other symptoms, worsening of radiological findings and normal blood tests, serologies and brain magnetic resonance imaging. The patient presented a paradoxical reaction and was given prednisone 1 mg/kg/day, fever disappeared in 24 hours. It is important to consider a paradoxical reaction when other causes of clinical and/or radiological worsening have been ruled out, to avoid unnecessary tests and treatment modifications.
Li, Jin; Pan, Yanyu; Zhang, Baohua; Chen, Qihuang
Although the association of tuberculosis (TB) and the development of lung carcinoma (LC) has been acknowledged, the underlying mechanism remains not clarified. Since sustained and repeated local inflammation and tissue remodeling have been suggested to be responsible for the high incidence of developing CL from TB, we hypothesize that macrophages may play a critical role in the process. To prove it, we induced TB in mice by injection of virulent Mycobacterium tuberculosis (MTB). Then the mice were allotted into two groups. One group received weekly tail vein injection of 20 μg saporin-conjugated antibody against the pan-macrophage surface marker CD11b to eliminate macrophages, while the other group received injection of control IgG in the same frequency. Six months later, the development of LC was determined by histology. We found that the occurrence of LC in TB mice that received macrophage depletion was significantly lower than those in control TB mice without macrophage intervention. These data suggest that macrophages may promote the progression of TB into LC.
Egelund, Eric F; Weiner, Marc; Singh, Rajendra P; Prihoda, Thomas J; Gelfond, Jonathon A L; Derendorf, Hartmut; Mac Kenzie, William R; Peloquin, Charles A
Rifapentine is highly protein bound in blood, but the free, unbound drug is the microbiologically active fraction. In this exploratory study, we characterized the free plasma fraction of rifapentine in 41 patients with tuberculosis. We found a lower total rifapentine concentration but significantly higher free rifapentine levels in African patients of black race compared to non-Africans. These data support larger pharmacokinetic/pharmacodynamic studies to confirm these findings and assess free rifapentine in relation to microbiological and clinical outcomes.
Egelund, Eric F.; Singh, Rajendra P.; Prihoda, Thomas J.; Gelfond, Jonathon A. L.; Derendorf, Hartmut; Mac Kenzie, William R.; Peloquin, Charles A.
Rifapentine is highly protein bound in blood, but the free, unbound drug is the microbiologically active fraction. In this exploratory study, we characterized the free plasma fraction of rifapentine in 41 patients with tuberculosis. We found a lower total rifapentine concentration but significantly higher free rifapentine levels in African patients of black race compared to non-Africans. These data support larger pharmacokinetic/pharmacodynamic studies to confirm these findings and assess free rifapentine in relation to microbiological and clinical outcomes. PMID:24841270
Hall, Ronald G.; Leff, Richard D.; Gumbo, Tawanda
Tuberculosis is a global pandemic, with 9 million new cases of the disease and approximately 2 million deaths each year. More than 98% of patients treated for tuberculosis in the United States between 1993 and 2007 had drug-susceptible strains. The standard treatment regimen for drug-susceptible tuberculosis has not changed in decades and was developed on the basis of empiric observations of different treatment regimens. Only recently has the veracity of the scientific basis for standard therapy been examined. The backbone of therapy is still isoniazid, rifampin, and pyrazinamide, although fluoroquinolones are being investigated as a replacement for isoniazid. Recent population pharmacokinetic studies have demonstrated the importance of individualized dosing of isoniazid, pyrazinamide, and rifampin. Isoniazid serum clearance differs depending on the patient’s number of N-acetyltransferase 2 gene *4 (NAT2*4) alleles. Pyrazinamide serum clearance has been shown to increase with increases in body weight. Rifampin’s volume of distribution, clearance, and absorption have wide between-patient and within-patient variability. Microbial pharmacokinetic-pharmacodynamic (PK-PD) indexes and targets to optimize microbial killing and minimize resistance have been identified for rifampin, isoniazid, pyrazinamide, and the fluoroquinolones. These PK-PD indexes suggest that different doses and dosing schedules than those currently recommended could optimize therapy and perhaps shorten duration of therapy. Efflux pump inhibition is also being investigated to enhance first-line antituberculosis drug therapy. Comorbid conditions such as diabetes mellitus and genetically determined iron overload syndromes have been associated with significantly worse patient outcomes. Therapy for these and other patient groups needs further improvement. These patient factors, the covariates for pharmacokinetic variability, and PK-PD factors suggest the need to individualize therapy for patients with
... Coccidioidomycosis Cystic fibrosis Histoplasmosis Lung abscess Lung cancer Sarcoidosis The most common species of fungus that causes ... fibrosis Histoplasmosis Lung cancer - small cell Pulmonary tuberculosis Sarcoidosis Review Date 7/31/2016 Updated by: Jatin ...
V, Dharma Rao; Rampure, Dilip; S, Rama Rao
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
After AIDS, tuberculosis (TB) is the leading killer worldwide due to a single infectious agent. Recently, drug-resistant strains of Mycobacterium tuberculosis elicited even more severe versions of TB. Bedaquiline inhibits mycobacterial ATP synthase. It shows potent and selective activity in vitro against M. tuberculosis, and in vivo against murine models of TB. Bedaquiline can be combined with antituberculosis and antiretroviral agents. The product displays good oral absorption, has a long terminal half-life and is metabolized mainly by cytochrome P450 3A4. In a phase II clinical trial in patients with multidrug-resistant TB, bedaquiline (combined with the standard five-drug, second-line TB regimen), showed a time to 50% culture negative conversion of 78 days, with 81.0% and 52.4% efficacy at weeks 24 and 104, respectively. Bedaquiline was generally safe and well tolerated. At the end of 2012, the U.S. Food and Drug Administration approved bedaquiline (Sirturo®) as part of a combination therapy to treat adults with multidrug-resistant TB.
Ding, Yan; Ma, Fei; Wang, Zhaohua
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
Singh, Amit; Kumar Gupta, Anil; Gopinath, Krishnamoorthy; Sharma, Pawan; Singh, Sarman
Improved methods are required for the early and accurate diagnosis of tuberculosis, especially in the patients with smear-negative disease. Several biomarkers have been tried but most have shown poor sensitivity or specificity. In present study we aimed to evaluate the diagnostic utility of five novel antigens identified earlier by us. This is an initial study conducted on 250 subjects. The five recombinant antigens, named as rSS1 (Rv2145c), rSS2 (Rv0164), rSS3 (Rv1437), rSS4 (Rv1827) and rSS5 (Rv2970c), were expressed in pQE-30 expression vector, purified and their sero-diagnostic efficacy was evaluated in an unblinded manner using dot-blot and ELISA methods. The sensitivity and specificity of these novel antigens were compared with commercially available standard esat6 and 38 kDa antigens. Bacteriologically confirmed TB patients, non-TB disease controls and healthy individuals were included. which are based on novel antigen or novel technology, Area under curve (AUC) of the selected antigens were 0.98 (0.98-0.99) for rSS1, 0.88 (0.84-0.92) for rSS2, 0.88 (0.84-0.92) for rSS3, 0.95 (0.93-0.98) for rSS4 and 0.99 (0.98-1.0) for rSS5. Receiver operative characteristic (ROC) curve showed highly significant difference between TB and healthy subjects (p = <0.001). These initial findings, show that the recombinant antigens rSS1, rSS4 and rSS5 could be used as highly potential biomarkers for the serological diagnosis of active TB.
Singh, Amit; Kumar Gupta, Anil; Gopinath, Krishnamoorthy; Sharma, Pawan; Singh, Sarman
Improved methods are required for the early and accurate diagnosis of tuberculosis, especially in the patients with smear-negative disease. Several biomarkers have been tried but most have shown poor sensitivity or specificity. In present study we aimed to evaluate the diagnostic utility of five novel antigens identified earlier by us. This is an initial study conducted on 250 subjects. The five recombinant antigens, named as rSS1 (Rv2145c), rSS2 (Rv0164), rSS3 (Rv1437), rSS4 (Rv1827) and rSS5 (Rv2970c), were expressed in pQE-30 expression vector, purified and their sero-diagnostic efficacy was evaluated in an unblinded manner using dot-blot and ELISA methods. The sensitivity and specificity of these novel antigens were compared with commercially available standard esat6 and 38 kDa antigens. Bacteriologically confirmed TB patients, non-TB disease controls and healthy individuals were included. which are based on novel antigen or novel technology, Area under curve (AUC) of the selected antigens were 0.98 (0.98–0.99) for rSS1, 0.88 (0.84–0.92) for rSS2, 0.88 (0.84–0.92) for rSS3, 0.95 (0.93–0.98) for rSS4 and 0.99 (0.98–1.0) for rSS5. Receiver operative characteristic (ROC) curve showed highly significant difference between TB and healthy subjects (p = <0.001). These initial findings, show that the recombinant antigens rSS1, rSS4 and rSS5 could be used as highly potential biomarkers for the serological diagnosis of active TB. PMID:28337993
Ebonyi, Augustine O.; Oguche, Stephen; Agbaji, Oche O.; Sagay, Atiene S.; Okonkwo, Prosper I.; Idoko, John A.; Kanki, Phyllis J.
Background Mortality data, including the risk factors for mortality in HIV-infected children with pulmonary TB (PTB) being treated for PTB and who are on antiretroviral therapy (ART), are scarce in Nigeria. We determined the mortality rate and risk factors for mortality among such children, at the pediatric HIV clinic of the Jos University Teaching Hospital (JUTH) in Jos, Nigeria. Methods We performed a retrospective cohort study on 260 PTB-HIV-1 co-infected children, aged 2 months to 13 years, being treated for PTB and on ART from July 2005 to March 2013. The mortality rate and associated risk factors were determined using multivariate Cox proportional hazards modelling. Results The mortality rate for the study cohort was 1.4 per 100 child-years of follow-up. Median follow-up time was 5.2 years (IQR, 3.5-6.0 years) with total study time being 1159 child-years. The median age of those who died was lower than that of survivors, 1.9 years (IQR, 0.6-3.6 years) versus 3.8 years (IQR, 1.8-6.0 years), p=0.005). The majority of the deaths occurred in males (13, 81.2%), those <5 years of age (14, 87.4%) and those who had severe immunosuppression (11, 68.8%). Risk factors for death were age (with the risk of dying decreasing by 25% for every 1 year increase in age, adjusted hazard ratio (AHR)=0.75 [0.58-0.98], p=0.032), male gender (AHR=3.80 [1.07-13.5], p=0.039) and severe immunosuppression (AHR=3.35 [1.16-9.66], p=0.025). Conclusion In our clinic setting, mortality among our PTB-HIV co-infected children being treated for PTB and on ART was low. However, those presenting with severe immunosuppression and who are males and very young, should be monitored more closely during follow-up in order to further reduce mortality. PMID:28053917
Smythe, Wynand; Merle, Corinne S.; Rustomjee, Roxana; Gninafon, Martin; Lo, Mame Bocar; Bah-Sow, Oumou; Olliaro, Piero L.; Lienhardt, Christian; Horton, John; Smith, Peter; Simonsson, Ulrika S. H.
A 4-month regimen of gatifloxacin with rifampin, isoniazid, and pyrazinamide is being evaluated for the treatment of tuberculosis in a phase 3 randomized controlled trial (OFLOTUB). A prior single-dose study found that gatifloxacin exposure increased by 14% in the combination. The aims of the study are to evaluate the initial and steady-state pharmacokinetics of gatifloxacin when daily doses are given to patients with newly diagnosed drug-sensitive pulmonary tuberculosis as part of a combination regimen and to evaluate the gatifloxacin dose with respect to the probability of attaining a pharmacokinetic/pharmacodynamic target. We describe the population pharmacokinetics of gatifloxacin from the first dose to a median of 28 days in 169 adults enrolled in the OFLOTUB trial in Benin, Guinea, Senegal, and South Africa. The probability of achieving a ratio of ≥125 for the area under the concentration time curve to infinity (AUC0–∞) for the free fraction of gatifloxacin over the MIC (fAUC/MIC) was investigated using Monte Carlo simulations. The median AUC0–∞ of 41.2 μg · h/ml decreased on average by 14.3% (90% confidence interval [CI], −90.5% to +61.5%) following multiple 400-mg daily doses. At steady state, 90% of patients achieved an fAUC/MIC of ≥125 only when the MIC was <0.125 μg/ml. We conclude that systemic exposure to gatifloxacin declines with repeated daily 400-mg doses when used together with rifampin, isoniazid, and pyrazinamide, thus compensating for any initial increase in gatifloxacin levels due to a drug interaction. (The OFLOTUB study has been registered at ClinicalTrials.gov under registration no. NCT00216385.) PMID:23774436
Hernández-Pando, R; Orozcoe, H; Sampieri, A; Pavón, L; Velasquillo, C; Larriva-Sahd, J; Alcocer, J M; Madrid, M V
T-helper 1 (Th1) Th2 kinetics were studied by immunohistochemistry and molecular biology techniques (reverse transcriptase polymerase chain reaction. RT PCR, Southern-blot) during the course of pulmonary tuberculosis induced in BALB/c mice by the intratracheal instillation of the live and virulent strain H-37Rv. The histopathological study clearly showed two phases of the disease. The first one was an acute phase which was characterized by inflammatory infiltrate in the alveolar capillary interstitium, blood vessel and bronchial wall with formation of granulomas. In this acute phase which lasted from 1 to 28 days, a clear predominance of Th1 cells was observed, manifested by a high percentage of interleukin-2 (IL-2) positive cells in the inflammatory infiltrate and granulomas demonstrated by immunohistology, as well as a gradual increment of interferon-gamma (INF-gamma) m-RNA. This was followed by a chronic or advanced phase characterized by pneumonia, focal necrosis and fibrosis, with a Th0 balance due to an equivalent proportion of IL-2 and IL-4 positive cells in the lung lesions, that coincided with the highest level of INF-gamma and IL-4 mRNA. The cytofluorometric analysis of bronchial lavage cells, showed a predominance of CD4 T cells during the acute phase and CD8 T lymphocytes in the chronic phase, gamma-delta T lymphocytes showed two peaks, at the beginning (3 days) and at the end (4 months) of the infection. These results suggest that T-lymphocyte subset kinetics and the pattern of cytokines produced in the lung during tuberculosis infection changed over time and correlate with the type and magnitude of tissue injury. Images Figure 1 Figure 3 Figure 5 PMID:8911136
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
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.
Radovic, Milan; Ristic, Lidija; Ciric, Zorica; Dinic-Radovic, Violeta; Stankovic, Ivana; Pejcic, Tatjana; Rancic, Milan; Bogdanovic, Dragan
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
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
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
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.
Chang, Ping-Chin; Wang, Pin-Hui; Chen, Kow-Tong
The value of QuantiFERON in the diagnosis of tuberculosis disease and in the monitoring of the response to anti-tuberculosis treatment is unclear. The aims of this study were to evaluate the accuracy of the QuantiFERON-TB Gold In-Tube (QFT-GIT) test in the diagnosis of tuberculosis and in the monitoring of the response to anti-tuberculosis treatment in patients with active pulmonary tuberculosis (PTB). Between January 2013 and December 2015, 133 cases with active PTB and 133 controls with no mycobacterial infection, matched by age (within 3 years) and by the week that they visited Tainan Chest Hospital, were enrolled in the study. Serial testing by QFT-GIT at baseline and after 2 and 6 months of treatment was performed. At these time points, a comparison of the performance of QFT-GIT with that of sputum culture status among study subjects was conducted. Compared to baseline, 116 (87.2%) cases showed a decreased response, whereas 17 (12.8%) showed persistent or stronger interferon-gamma (IFN-γ) responses at 2 months. PTB patients IFN-γ responses declined significantly from baseline to 2 months (median, 6.32 vs. 4.12; p < 0.005). The sensitivity values of the QFT-GIT test for the detection of pulmonary tuberculosis at cut-off points of 0.35 IU/mL, 0.20 IU/mL, and 0.10 IU/mL were 74.4%, 78.2%, and 80.5%, respectively. The specificity values at cut-off points of 0.35 IU/mL, 0.20 IU/mL, and 0.10 IU/mL were 66.2%, 63.9%, and 57.1%, respectively. Our results support the QFT-GIT assay as a potential tool for diagnosing tuberculosis and for monitoring the efficacy of anti-tuberculosis treatment. PMID:28264462
Selvakumar, N; Rahman, Fathima; Garg, Renu; Rajasekaran, S; Mohan, Nalini Sunder; Thyagarajan, K; Sundaram, V; Santha, T; Frieden, Thomas R; Narayanan, P R
We compared the sensitivity and specificity of the phenol ammonium sulfate (PhAS) sediment smear microscopy method for detection of acid-fast bacilli with those of direct smear microscopy, using culture results for Mycobacterium tuberculosis as the "gold standard." The sensitivities of the PhAS and direct smear methods were 85% (465 of 547) and 83% (454 of 547), respectively, and the specificity of each method was 97%. The PhAS method was better accepted by the laboratory technicians and safer but necessitates an overnight sedimentation, which delays reporting of results until 1 day after sputum collection.
Bertoni, Thâmara Aline; Perenha-Viana, Maysa Cláudia Zolin; Patussi, Eliana Valéria; Cardoso, Rosilene Fressatti
Sputum and sera from 134 patients screened for tuberculosis (TB) were analyzed to investigate TB and paracoccidioidomycosis (PCM). Of these patients, 11 (8.2%) were confirmed to have TB, but six (4.5%) were positive only for PCM. All patients with PCM presented anti-43-kDa-component antibodies in Western blotting (WB) assays, while in the TB-positive patients these antibodies did not appear. This preliminary study suggests WB as a potential tool for differential laboratory diagnosis between TB and PCM. PMID:22971781
Peck, Mogammad Thabit; Stephen, Lawrence X G; Marnewick, Johan; Majeed, Abdul
Tuberculosis (TB) is one of the leading casues of morbidity and death in a number of countries worldwide. A healthy 42-year-old patient presented with a chronic palatal ulcer that was not responsive to routine antibiotic treatment. A biopsy and further systemic investigation revealed a diagnosis of TB. An eight-month extended course of oral rifampin and isoniazid was instituted successfully resulting in complete resolution of symptoms. It is important that clinicians be aware that chronic oral ulcerations may be the first sign of systemic disease. A biopsy should therefore be mandatory for any chronic oral ulcer not responsive to conventional treatment.
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
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.
Rathee, Deepti; Arora, Piyush; Meena, Manoj; Sarin, Rohit; Chakraborty, Pitambar; Jaiswal, Anand; Goyal, Mukesh
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
Young, Bonnie N.; Rendón, Adrian; Rosas-Taraco, Adrian; Baker, Jack; Healy, Meghan; Gross, Jessica M.; Long, Jeffrey; Burgos, Marcos; Hunley, Keith L.
Diverse socioeconomic and clinical factors influence susceptibility to tuberculosis (TB) disease in Mexico. The role of genetic factors, particularly those that differ between the parental groups that admixed in Mexico, is unclear. The objectives of this study are to identify the socioeconomic and clinical predictors of the transition from latent TB infection (LTBI) to pulmonary TB disease in an urban population in northeastern Mexico, and to examine whether genetic ancestry plays an independent role in this transition. We recruited 97 pulmonary TB disease patients and 97 LTBI individuals from a public hospital in Monterrey, Nuevo León. Socioeconomic and clinical variables were collected from interviews and medical records, and genetic ancestry was estimated for a subset of 142 study participants from 291,917 single nucleotide polymorphisms (SNPs). We examined crude associations between the variables and TB disease status. Significant predictors from crude association tests were analyzed using multivariable logistic regression. We also compared genetic ancestry between LTBI individuals and TB disease patients at 1,314 SNPs in 273 genes from the TB biosystem in the NCBI BioSystems database. In crude association tests, 12 socioeconomic and clinical variables were associated with TB disease. Multivariable logistic regression analyses indicated that marital status, diabetes, and smoking were independently associated with TB status. Genetic ancestry was not associated with TB disease in either crude or multivariable analyses. Separate analyses showed that LTBI individuals recruited from hospital staff had significantly higher European genetic ancestry than LTBI individuals recruited from the clinics and waiting rooms. Genetic ancestry differed between individuals with LTBI and TB disease at SNPs located in two genes in the TB biosystem. These results indicate that Monterrey may be structured with respect to genetic ancestry, and that genetic differences in TB
Boum, Yap; Kim, Soyeon; Orikiriza, Patrick; Acuña-Villaorduña, Carlos; Vinhas, Solange; Bonnet, Maryline; Nyehangane, Dan; Mwanga-Amumpaire, Juliet; Fennelly, Kevin P.
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
Young, Bonnie N; Rendón, Adrian; Rosas-Taraco, Adrian; Baker, Jack; Healy, Meghan; Gross, Jessica M; Long, Jeffrey; Burgos, Marcos; Hunley, Keith L
Diverse socioeconomic and clinical factors influence susceptibility to tuberculosis (TB) disease in Mexico. The role of genetic factors, particularly those that differ between the parental groups that admixed in Mexico, is unclear. The objectives of this study are to identify the socioeconomic and clinical predictors of the transition from latent TB infection (LTBI) to pulmonary TB disease in an urban population in northeastern Mexico, and to examine whether genetic ancestry plays an independent role in this transition. We recruited 97 pulmonary TB disease patients and 97 LTBI individuals from a public hospital in Monterrey, Nuevo León. Socioeconomic and clinical variables were collected from interviews and medical records, and genetic ancestry was estimated for a subset of 142 study participants from 291,917 single nucleotide polymorphisms (SNPs). We examined crude associations between the variables and TB disease status. Significant predictors from crude association tests were analyzed using multivariable logistic regression. We also compared genetic ancestry between LTBI individuals and TB disease patients at 1,314 SNPs in 273 genes from the TB biosystem in the NCBI BioSystems database. In crude association tests, 12 socioeconomic and clinical variables were associated with TB disease. Multivariable logistic regression analyses indicated that marital status, diabetes, and smoking were independently associated with TB status. Genetic ancestry was not associated with TB disease in either crude or multivariable analyses. Separate analyses showed that LTBI individuals recruited from hospital staff had significantly higher European genetic ancestry than LTBI individuals recruited from the clinics and waiting rooms. Genetic ancestry differed between individuals with LTBI and TB disease at SNPs located in two genes in the TB biosystem. These results indicate that Monterrey may be structured with respect to genetic ancestry, and that genetic differences in TB
Sara, Chandy; Elsa, Heylen; Baijayanti, Mishra; Lennartsdotter, Ekstrand Maria
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
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
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
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
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.
Shin, Joong-Gon; Park, Byung Lae; Kim, Lyoung Hyo; Namgoong, Suhg; Kim, Ji On; Chang, Hun Soo; Park, Jong Sook; Jang, An Soo; Park, Sung Woo; Kim, Do Jin; Kim, Ki Up; Kim, Yang Gee; Uh, Soo-Taek; Seo, Ki Hyun; Kim, Young Hoon; Koh, Insong; Park, Choon Sik; Shin, Hyoung Doo
Tuberculosis (TB) is an infectious disease caused by mycobacterium, which most commonly affects the lungs. The adaptive immune response in Mycobacterium tuberculosis is predominantly mediated by the interferon-γ (IFN-γ) signaling pathway, which is regulated by IFN-γ receptors (IFNGR). IFN-γ activates the transcription of a number of genes that are important in immune responses, thus the appropriate function of IFNGR appears to be important in host defense against mycobacteria. In the present study, 22 genetic variants in IFNGR1 and IFNGR2 were genotyped in 673 patients and 592 normal controls to investigate the association between IFNGR1 and IFNGR2 polymorphisms and the risk of TB. Statistical analyses revealed that four genetic variants in IFNGR1, rs9376269, rs9376268, rs9376267 and rs56251346 were marginally associated with the risk of TB (P = 0.02-0.04), while other single nucleotide polymorphisms in IFNGR1 and IFNGR2 did not exhibit any associations. However, the significance of the four genetic variants rs9376269, rs9376268, rs9376267 and rs56251346 was eliminated following a multiple testing correction of the data (P>0.05). The present results revealed that certain genetic variants in IFNGR genes may be associated with TB development, which may be useful preliminary data for future investigation.
Moore, M; Valway, S E; Ihle, W; Onorato, I M
In January 1996, smear- and culture-positive tuberculosis (TB) was diagnosed for a 22-year-old black man after he had traveled on two U.S. passenger trains (29.1 hours) and a bus (5.5 hours) over 2 days. To determine if transmission had occurred, passengers and crew were notified of the potential exposure and instructed to undergo a tuberculin skin test (TST). Of the 240 persons who completed screening, 4 (2%) had a documented TST conversion (increase in induration of > or = 10 mm between successive TSTs), 11 (5%) had a single positive TST (> or = 10 mm), and 225 (94%) had a negative TST (< 10 mm). For two persons who underwent conversion, no other risk factors for a conversion were identified other than exposure to the ill passenger during train and/or bus travel. These findings support limited transmission of Mycobacterium tuberculosis from a potentially highly infectious passenger to other persons during extended train and bus travel.
Ali, Solomon; Haileamlak, Abraham; Wieser, Andreas; Pritsch, Michael; Heinrich, Norbert; Loscher, Thomas; Hoelscher, Michael; Rachow, Andrea
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
Liang, Yan; Wang, Ying; Li, Hang; Yang, Yourong; Liu, Jianyang; Yu, Ting; Wu, Xueqiong
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.
Feng, Danjun; Xu, Lingzhong
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.
Li, Xinxu; Jiang, Shiwen; Li, Xue; Mei, Jian; Zhong, Qiu; Xu, Weiguo; Li, Jun; Li, Weibin; Liu, Xiaoqiu; Zhang, Hui; Wang, Lixia
Objectives To determine the length of delay in initial health-seeking in new pulmonary tuberculosis (PTB) cases among migrant population in the eastern part of China, and factors associated with it. Methods A cross-sectional study was conducted using a structured questionnaire in six counties in Shanghai, Guangdong and Jiangsu from May to October, 2008, to estimate the extent and factors responsible for delayed initial health-seeking of the new PTB cases. The interval between self-reported onset of TB symptoms and date of first attendance at any medical institution was determined. More than the median duration was defined as delayed health-seeking. Results A total of 323 new migrant PTB patients participated in the study. Only 6.5% had medical insurance. The median and mean durations to initial health-seeking were respectively 10 and 31 days. There was no significant association between socio-demographic factors and delayed initial health-seeking. Average monthly working days >24 (AOR, 1.61; 95% CI, 1.03–2.51), and hemoptysis or bloody sputum (AOR, 0.48; 95% CI, 0.28–0.85) were significantly associated with delayed initial health-seeking. Conclusions Interventions to improve health seeking behavior among the migrant population in China must focus on strengthening their labor, medical security and health education. PMID:22384123
Ahidjo, Bintou A.; Maiga, Mariama C.; Ihms, Elizabeth A.; Maiga, Mamoudou; Ordonez, Alvaro A.; Cheung, Laurene S.; Beck, Sarah; Andrade, Bruno B.; Jain, Sanjay
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
Rusen, I. D.; Hinderaker, S. G.; Roldan, A.; Heldal, E.; Enarson, D. A.; Zhang, L-X.
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
Lin, Y; Chiang, C-Y; Rusen, I D; Hinderaker, S G; Roldan, A; Heldal, E; Enarson, D A; Zhang, L-X
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.
Mateveke, K.; Makamure, B.; Ferrand, R. A.; Gomo, E.
SUMMARY OBJECTIVE: To evaluate the diagnostic performance of Xpert® MTB/RIF on stool samples from children with clinical suspicion of pulmonary tuberculosis (PTB) at primary care clinics. DESIGN: A cross-sectional diagnostic evaluation enrolling 5–16 year olds from whom one induced sputum (IS) sample was tested for microbiological TB confirmation. Results of a single stool sample tested using Xpert were compared against microbiologically confirmed TB, defined as a positive result on sputum microscopy and/or culture and/or IS Xpert. RESULTS: Of 222 children enrolled, 218 had complete microbiological results. The median age was 10.6 years (interquartile range 8–13). TB was microbiologically confirmed in 19/218 (8.7%) children. Of these, respectively 5 (26%), 9 (47%) and 15 (79%) were smear-, culture- and IS Xpert-positive. Stool Xpert was positive in 13/19 (68%) microbiologically confirmed cases and 4/199 (2%) microbiologically negative cases. Stool Xpert detected 76.9% (10/13) of human immunodeficiency virus (HIV) infected and 50% (3/6) of non-HIV-infected children with microbiologically confirmed TB (P = 0.241). CONCLUSION: Stool Xpert is a potential alternative screening test for children with suspected TB if sputum is unavailable. Strategies to optimise the diagnostic yield of stool Xpert assay need further study. PMID:28234079
Ahmed, Tahmeed; Shahid, Abu S. M. S. B.; Shahunja, K. M.; Bardhan, Pradip Kumar; Faruque, Abu Syeed Golam; Das, Sumon Kumar; Salam, Mohammed Abdus
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
Naderi, Mohammad; Hashemi, Mohammad; Soroush, Navid; Amininia, Shadi; Taheri, Mohsen
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.
Kato, Yosuke; Iwase, Mitsunori; Kanazawa, Hiroaki; Kawata, Natsuki; Yoshimori, Yukie; Hashimoto, Katsunori; Yokoi, Toyoharu; Noda, Akiko; Takagi, Kenzo; Koike, Yasuo; Nishizawa, Takao; Nishimura, Masahiko; Yokota, Mitsuhiro
The present study aimed to evaluate the development of pulmonary hypertension by serial echocardiography, including measurements of pulmonary artery (PA) flow velocities, and correlate echocardiographic indices with pathological findings in rats administered monocrotaline (MCT). MCT (60 mg/kg body weight) or physiologic saline was administered to a total of 9 male Wistar rats at the age of 4 weeks (MCT group: n = 4, control group: n = 5, respectively). Echocardiography was performed serially until the age of 8 weeks. The ratio of right ventricular (RV) outflow tract dimensions to aortic dimensions increased progressively in the MCT group and became significantly greater than that of the control group after the age of 6 weeks. Peak PA velocity (Peak V) in the MCT group was significantly less than that of the control group at the ages of 7 and 8 weeks. The ratio of acceleration time to ejection time (AT/ET) in PA flow waveforms declined progressively and was significantly less than that of the control group after the age of 6 weeks. The ratio of RV weight to body weight (RVW/BW) in the MCT group was significantly greater than that of the control group. Both AT/ET ratio and Peak V were significantly inversely correlated with RVW/BW ratio. Furthermore, these echocardiographic findings were also significantly inversely correlated with the mean cross-sectional RV myocyte area. In conclusion, the progressive development of pulmonary hypertension leading to RV hypertrophy can be evaluated appropriately by echocardiography including PA flow Doppler indices in rats.
Pourfallah, F; Javadian, S; Zamani, Z; Saghiri, R; Sadeghi, S; Zarea, B; Mirkhani, F; Fatemi, N; Kordi, T
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.
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
Caner, S Sevkan; Köksal, Deniz; Ozkara, Seref; Berkoğlu, Mine; Aksaray, Sabahat; Tarhan, Dilek
Immunological events, not the bacilli, are responsible from the tissue damage of tuberculosis. Clarifying the immunological events may lead to the development of new approaches to treatment and defence against tuberculosis disease. In this study we aimed to determine the serum levels of interleukin-2 (IL-2) and C-reactive protein (CRP) in patients with tuberculosis and evaluate the relationship with clinical and radiological findings. The study included 60 patients (mean age: 37 +/- 12 years, all male) with newly diagnosed pulmonary tuberculosis and 23 healthy controls (mean age: 40 +/- 13 years, all male). Admission symptoms, clinical features, demographic data, laboratory investigations and radiological findings were all recorded into the study form. Serum samples which were obtained for determination of IL-2 and CRP levels were preserved at -80 degrees C. While serum IL-2 levels were similar in patients with tuberculosis and healthy controls, serum CRP levels were significantly higher in patients with tuberculosis (p< 0.001). There was a positive correlation between serum IL-2 level and the diameter of cavity (p= 0.012). CRP levels were significantly higher in patients who admitted with fever (p= 0.001) and weight loss (p= 0.024). Serum CRP levels were significantly higher in patients who had involvement of four or more zones (p= 0.029) and multiple cavitary disease (p= 0.001). There was a positive correlation between serum CRP level and the diameter of cavity (p= 0.004). In conclusion, apart from the diameter of cavity, serum IL-2 levels were not correlated with any clinical, laboratory or radiological parameter. Serum CRP levels were a good indicator of disease severity.
Guo, Chenglin; Liu, Chengwu; Pu, Qiang; Lin, Feng
Primary pulmonary synovial sarcoma (PPSS) is a relatively rare neoplasm with highly progressive potential. We present an extremely rare case of PPSS presenting as recurrent pneumothorax with bullous lesions. Bullectomy was performed at the local hospital. Unfortunately, the patient was initially misdiagnosed as atypical carcinoid. Although a negative resection margin was obtained during the first surgery and a remedial operation and chemotherapy followed, the patient developed severe disease progression and died soon after. This report demonstrates that PPSS can easily be misdiagnosed and should be seriously considered in the differential diagnosis of pneumothorax. PMID:27995774
A review of the pathology of human pulmonary TB cases at different stages of evolution in the pre-antibiotic era suggests that neutrophils play an instrumental role in the progression toward active TB. This progression is determined by the type of lesion generated. Thus, exudative lesions, in which neutrophils are the major cell type, are both triggered by and induce local high bacillary load, and tend to enlarge and progress toward liquefaction and cavitation. In contrast, proliferative lesions are triggered by low bacillary loads, mainly comprise epithelioid cells and fibroblasts and tend to fibrose, encapsulate and calcify, thus controlling the infection. Infection of the upper lobes is key to the progression toward active TB for two main reasons, namely poor breathing amplitude, which allows local bacillary accumulation, and the high mechanical stress to which the interlobular septae (which enclose secondary lobes) are submitted, which hampers their ability to encapsulate lesions. Overall, progressing factors can be defined as internal (exudative lesion, local bronchogenous dissemination, coalescence of lesions), with lympho-hematological dissemination playing a very limited role, or external (exogenous reinfection). Abrogating factors include control of the bacillary load and the local encapsulation process, as directed by interlobular septae. The age and extent of disease depend on the quality and speed with which lesions liquefy and disseminate bronchially, the volume of the slough, and the amount and distribution of the sloughing debris dispersed. PMID:26136741
Shafee, Muhammad; Abbas, Ferhat; Ashraf, Muhammad; Alam Mengal, Mohammad; Kakar, Niamatullah; Ahmad, Zafar; Ali, Fawad
Objectives: Tuberculosis (TB) is a chronic debilitating infectious disease affecting more than one third of the global population. This study was designed to investigate different peripheral blood parameters and risk factors in TB patients. Methods: A total of 600 (Male, 238 and Female, 362) aging 20-80 Years patients with clinical signs of prolonged cough, chest pain and fever, were evaluated for peripheral blood parameters using hematology analyzer. All the informations related to the disease were collected from the patients and recorded using predesigned questionnaire. Results: Erythrocytic Sedimentation Rate (ESR), Hemoglobin (Hb) and lymphocytes were markedly changed in both sexes. Hemoglobin was recorded lower than normal value in 55% and 53% of male and female population respectively. Total leukocyte count was also lower than normal values in 8% and 6% of male and female respectively. Similarly neutropenia was observed in 5% and 8% cases, while neutrophilia was recorded as 60% and 64% in male and female patients respectively. Lymphocytopenia was also observed in 59% and 43% patients in male and female respectively. Illiteracy, smoking habits, overcrowding and living in shared houses were the main associated risk factors contributing in the enhancement of the disease. Conclusion: The disease was present significantly more in females and was relatively higher in older patients. Different hematological parameters like Erythrocytic sedimentation Rate (ESR), platelets and leukocytes work as hallmark and help the clinicians in early diagnosis of the disease. Malnutrition, smoking tobacco, living in shared houses, illiteracy and poverty were the common risk factors contributing to the dissemination of the tuberculosis in the target area population. PMID:24639827
Roncoroni, A J; Barcat, J A; Quadrellis, A
A 36 year-old non-smoker woman was admitted because of a rapidly growing mass at the left hilum. Fiberoptic bronchoscopy did not show any abnormality. A percutaneous Rotex needle biopsy and a cutting needle biopsy showed atypical cells suggestive of an anaplastic tumor, possibly a sarcoma. A thoracotomy biopsy demonstrated nodal and pulmonary involvement by Hodgkin lymphoma (nodular-sclerosis form) and pulmonary TBC (granulomas with caseum and acid fast bacilli (AFB)). The patient started treatment with isoniazid, rifampin and pirazynamide and then she received chemotherapy and radiotherapy. One year later her chest and abdominal CT were normal. Twelve months after that she developed severe dyspnea with a chest x-ray film with interstitial infiltrates and a mass at the left-hilum. She worsened quickly and died. At autopsy no evidence of active TBC was found and extensive involvement by lymphoma was demonstrated. The diagnosis in this patient was not obtained by clinical-radiological signs or by non-invasive tests but only by surgical biopsy. The association between neoplasm and TBC is well known, but now is very rare. In Argentina TBC prevalence in lymphomas is 1.2% (higher than control population). TBC diagnosis can occasionally be difficult. In most of undiagnosed patients TBC is the main contributor to death. In this patient the mediastinopulmonary mass was adequately diagnosed only after an open biopsy which showed it to be caused by two coexistent diseases, previously unsuspected and both amenable of effective treatment. This case shows the heterogeneity of TBC presentation and stresses the need to consider it in each non-defined mediastino-pulmonary lesion in countries where TBC is highly prevalent.(ABSTRACT TRUNCATED AT 250 WORDS)
Masson, Muriel; Molnár, Erika; Donoghue, Helen D.; Besra, Gurdyal S.; Minnikin, David E.; Wu, Houdini H. T.; Lee, Oona Y-C.; Bull, Ian D.; Pálfi, György
Seventy-one individuals from the late Neolithic population of the 7000-year-old site of Hódmezővásárhely-Gorzsa were examined for their skeletal palaeopathology. This revealed numerous cases of infections and non-specific stress indicators in juveniles and adults, metabolic diseases in juveniles, and evidence of trauma and mechanical changes in adults. Several cases showed potential signs of tuberculosis, particularly the remains of the individual HGO-53. This is an important finding that has significant implications for our understanding of this community. The aim of the present study was to seek biomolecular evidence to confirm this diagnosis. HGO-53 was a young male with a striking case of hypertrophic pulmonary osteopathy (HPO), revealing rib changes and cavitations in the vertebral bodies. The initial macroscopic diagnosis of HPO secondary to tuberculosis was confirmed by analysis of Mycobacterium tuberculosis complex specific cell wall lipid biomarkers and corroborated by ancient DNA (aDNA) analysis. This case is the earliest known classical case of HPO on an adult human skeleton and is one of the oldest palaeopathological and palaeomicrobiological tuberculosis cases to date. PMID:24205173
Welsh, Michael D; Cunningham, Rodat T; Corbett, David M; Girvin, R Martyn; McNair, James; Skuce, Robin A; Bryson, David G; Pollock, John M
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
Zhao, Jiang-nan; Zhang, Xian-xin; He, Xiao-chun; Yang, Guo-ru; Zhang, Xiao-qi; Xin, Wen-gen; Li, Huai-chen
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
Lora, Wezzie; Khoo, Saye H.; Sloan, Derek J.; Mwandumba, Henry C.; Desmond, Nicola; Davies, Geraint R.
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
Han, Seung Jung; Kim, HongMin; Kwon, Kee Woong; Kim, So Jeong; Eum, Seok-Yong; Cho, Sang-Nae; Shin, Sung Jae
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
This report draws attention to the wide use of the controlled clinical trial in the study of tuberculosis in certain countries and centres and to the remarkable neglect of this method in the great majority of countries. Its versatility has been demonstrated by many studies: it has been used to study not only alternative combinations of drugs but also drug dosages, rhythms of administration, the duration of treatment with supplementary drugs or the total duration of treatment, and drug toxicity and its prevention. A particularly valuable use of the method is in the study of policies of therapy—e.g., treatment at home compared with treatment in a sanatorium; the inclusion of routine home visiting in the supervision of patients; the carrying out of pretreatment sensitivity tests as a basis for the selection of chemotherapeutic regimens; and treatment programmes based on short (6-month) intensive courses, as opposed to long-term (18-month) standard courses. It is concluded that well p