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.
... Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America clinical practice guidelines: treatment of drug-susceptible tuberculosis. Clin Infect Dis . 2016;63(7):e147-e195. PMID: 27516382 www.ncbi. ...
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.
Tirado, Yanely; Puig, Alina; Alvarez, Nadine; Borrero, Reinier; Aguilar, Alicia; Camacho, Frank; Reyes, Fatima; Fernandez, Sonsire; Perez, Jose Luis; Acevedo, Reynaldo; Mata Espinoza, Dulce; Payan, Jorge Alberto Barrios; Garcia, Maria de Los A; Kadir, Ramlah; Sarmiento, María E; Hernandez-Pando, Rogelio; Norazmi, Mohd-Nor; Acosta, Armando
Tuberculosis (TB) remains an important cause of mortality and morbidity. The TB vaccine, BCG, is not fully protective against the adult form of the disease and is unable to prevent its transmission although it is still useful against severe childhood TB. Hence, the search for new vaccines is of great interest. In a previous study, we have shown that proteoliposomes obtained from Mycobacterium smegmatis (PLMs) induced cross reactive humoral and cellular response against Mycobacterium tuberculosis (Mtb) antigens. With the objective to evaluate the protective capability of PLMs, a murine model of progressive pulmonary TB was used. Animals immunized with PLMs with and without alum (PLMs/PLMsAL respectively) showed protection compared to non-immunized animals. Mice immunized with PLMsAL induced similar protection as that of BCG. Animals immunized with BCG, PLMs and PLMsAL showed a significant decrease in tissue damage (percentage of pneumonic area/lung) compared to non-immunized animals, with a more prominent effect in BCG vaccinated mice. The protective effect of the administration of PLMs in mice supports its future evaluation as experimental vaccine candidate against Mtb. Copyright © 2016 Elsevier Ltd. All rights reserved.
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.
Niimi, S; Kato, T; Hayakawa, Y; Hirota, M; Kako, T
Nine patients with pulmonary tuberculosis underwent open chest surgery for pulmonary lesions of tuberculosis or other than tubercolosis. They were 1 case of lung cancer, 4 cases of pneumothorax, 1 case of multi drug resistant pulmonary tuberculosis and 3 cases of tuberculoma. Postoperative complications developed in 3 cases including 2 of pneumothorax and 1 of lung collapse.
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
Nakbanpot, Sudarat; Rattanawong, Pattara
We report the death of an infant due to severe sepsis caused by congenital tuberculosis following treatment with antituberculous drugs and antibiotics, who was born to a mother with misdiagnosed symptomatic pulmonary tuberculosis during pregnancy. Therefore, pregnant women with chronic cough and constitutional symptoms must be examined for pulmonary tuberculosis, particularly in tuberculosis endemic areas.
Srinivasaprasad, N D; Chandramohan, G; Praveen, V; Fernando, M E
Collapsing glomerulopathy (CG) usually presents with reduced glomerular filtration rate, heavy proteinuria and has unfavorable prognosis. Numerous associations with CG are found. We encountered a case of CG associated with pulmonary tuberculosis presenting with proteinuria and dialysis-requiring severe renal failure. Our patient made partial recovery of his renal function and became dialysis-independent after antituberculous therapy and oral steroids. Long-term follow-up is needed to assess the progression of the disease.
Sendrasoa, F. A.; Ranaivo, I. M.; Raharolahy, O.; Andrianarison, M.; Ramarozatovo, L. S.; Rapelanoro Rabenja, F.
Simultaneous occurrence of leprosy and pulmonary tuberculosis is reported infrequently in the modern era. We report a case of pulmonary tuberculosis diagnosed in patient being treated with glucocorticoids for complications of leprosy (type II reaction). Physicians should recognize that the leprosy patients treated with glucocorticoid may develop tuberculosis. PMID:26504603
Agrons, G A; Markowitz, R I; Kramer, S S
TB is no longer the scourge it once was, but it remains an important cause of morbidity and mortality worldwide. Fueled by increasing poverty, homelessness, immigration, drug abuse, declining prevention programs, and the HIV epidemic, its incidence in the United States has increased dramatically. The complex natural history of pulmonary TB in children is reflected in its varied radiographic manifestations. Strict distinction between "adult" and "childhood" patterns of TB should be avoided (Fig 16). In general, adenopathy is the footprint of childhood primary pulmonary TB, with or without a readily apparent primary parenchymal focus or pleural effusion. Infants and young children are more likely to present with adenopathy only than their older counterparts. The pediatric tracheobronchial tree is particularly susceptible to compression by surrounding nodes, producing segmental atelectasis, or less commonly, obstructive emphysema. Self-limited lymphohematogenous dissemination is the rule, but actual miliary disease is the exception. Pediatric postprimary TB, when it occurs, is usually observed in adolescents. It is characterized by parenchymal disease with an anatomic bias for the upper lung zones. Proper image interpretation is inextricably dependent on an understanding of the pathogenesis of this fascinating and often baffling illness whose appearance widely varies depending on host age and immunity as well as the virulence of the organism itself.
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)-γ by CD4+ T cells. Interleukin (IL)-12 is known to be a crucial cytokine in the differentiation of IFN-γ-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. PMID:18727633
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.
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
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
Sajid, Khan Mohammad; Parveen, Riffat; Sabih, Durr-e-; Mahmood, Rubaida
To evaluate the thyroid hormone economy in pulmonary tuberculosis (PTB). Cohort comparative study. Multan Institute of Radiotherapy and Nuclear Medicine (MINAR) from January 2003 to June 2005. The study included 266 confirmed cases of pulmonary tuberculosis (PTB), aged between 11 and 65 years, who had completed short course of chemotherapy. Two samples were collected from each patient, first after final diagnosis and second after completion of the treatment. Initial analysis of samples showed that 31 samples had both T3 (triiodothyronine) and T4 (thyroxine) in lower than normal range. One more sample in the middle of treatment was collected for these patients. Radioimmunoassays and immunoradiometeric assays were applied to estimate mean TT3, TT4 and TSH (thyroid stimulating hormone) levels. Students t-test was used to compare patient and normal values derived from 713 volunteers. The age had no effect on levels of T3, T4 and TSH in normal persons. Mean T3 and T4 values (0.74 nmol/l and 91.9 nmol/l) in PTB patients were significantly decreased (p < 0.001) with 50% and 11.6 % cases in lower than normal range respectively. Follow-up data on subgroup of 31 patients showed that both T3 and T4 levels improved after chemotherapy. TSH levels remained unaffected throughout. Both T3 and T4 levels were decreased in PTB but T4 levels were less affected. TSH was found unaffected by the disease. This confirms that PTB produces euthyroid sick syndrome (SES) i.e., decreased T3 and T4, and no change affected by 5'deiodinase (an enzyme that causes deiodination of T4). The levels improved after chemotherapy.
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.
Mata-Espinosa, Dulce; Molina-Salinas, Gloria María; Barrios-Payán, Jorge; Navarrete-Vázquez, Gabriel; Marquina, Brenda; Ramos-Espinosa, Octavio; Bini, Estela Isabel; Baeza, Isabel; Hernández-Pando, Rogelio
oxadiazole derivative contained in the same type of liposome showed significantly lower lung bacillary loads than control mice, producing 90% of bacilli burden reduction after 2 months of treatment. These results confirm and extend the reported highly efficient anti-mycobacterial activity of this lipophilic oxidazole derivative when it is carried by liposomes in mice suffering from late progressive pulmonary TB induced by drug-sensitive, and most prominently by, MDR strains. Copyright © 2015 Elsevier Ltd. All rights reserved.
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
Sarmiento, José Mauricio Hernández; Restrepo, Natalia Builes; Mejía, Gloria Isabel; Zapata, Elsa; Restrepo, Mary Alejandra; Robledo, Jaime
Introduction World Health Organization had estimated 9.4 million tuberculosis cases on 2009, with 1.7 million of deaths as consequence of treatment and diagnosis failures. Improving diagnostic methods for the rapid and timely detection of tuberculosis patients is critical to control the disease. The aim of this study was evaluating the accuracy of the cord factor detection on the solid medium Middlebrook 7H11 thin layer agar compared to the Lowenstein Jensen medium for the rapid tuberculosis diagnosis. Methods Patients with suspected tuberculosis were enrolled and their sputum samples were processed for direct smear and culture on Lowenstein Jensen and BACTEC MGIT 960, from which positive tubes were subcultured on Middlebrook 7H11 thin layer agar. Statistical analysis was performed comparing culture results from Lowenstein Jensen and the thin layer agar, and their corresponding average times for detecting Mycobacterium tuberculosis. The performance of cord factor detection was evaluated determining its sensitivity, specificity, positive and negative predictive value. Results 111 out of 260 patients were positive for M. tuberculosis by Lowenstein Jensen medium with an average time ± standard deviation for its detection of 22.3 ± 8.5 days. 115 patients were positive by the MGIT system identifying the cord factor by the Middlebrook 7H11 thin layer agar which average time ± standard deviation was 5.5 ± 2.6 days. Conclusion The cord factor detection by Middlebrook 7H11 thin layer agar allows early and accurate tuberculosis diagnosis during an average time of 5 days, making this rapid diagnosis particularly important in patients with negative sputum smear. PMID:25419279
Picciocchi, A; Granone, P; Margaritora, S; Cesario, A; Galetta, D
Surgery for pulmonary tubercolosis (PTB) is now the second place treatment. Among the surgical indications the most debated is the multi-drug resistance of a focal pulmonary tuberculous disease. Other indications are: bronchiectasis, hemoptysis and the presence of a broncho-pleural fistula. Pulmonary Aspergilloma is a frequent indication for surgery; it is commonly a PTB sequela and causes severe complications. The presence of an unknown pulmonary mass or nodule is a surgical criterion because it might signal a cancer. Surgery therefore now constitutes a valid option for the treatment of clinical patterns of PTB unresponsive to medical treatment in severe, potentially fatal clinical conditions.
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.
Isah, Muhammad Danasabe; Abbas, Aminu; Abba, Abdullahi A; Umar, Mohammed
Idiopathic pulmonary fibrosis (IPF), also known as cryptogenic fibrosing alveolitis, is one of a spectrum of idiopathic interstitial pneumonia. IPF is an increasingly common condition which poses many diagnostic and therapeutic challenges leading to misdiagnosis and mismanagement. We presented a 55-year-old male textile trader who was initially managed as sputum-negative pulmonary tuberculosis before histology report. He presented to our clinic with Breathlessness and cough of 3 years and 2.5 years, respectively. He had commenced anti-tuberculosis two months before presentation without significant relief. General Physical examination and vital signs were essentially normal. SPO2 was 96% on room air. Chest Examination revealed end-inspiratory bi-basal velcro-like crackles. Other systemic examinations were normal. Radiological examination by way of chest X- ray and chest CT showed features suggestive of IPF. The patient also had open Lung biopsy for histology and spirometry which demonstrated restrictive ventilatory function pattern. A diagnosis of Interstitial lung disease probably Idiopathic Pulmonary Fibrosis was entertained. He was commenced on Tab prednisolone, Tab Rabeprazole, with minimal improvement. IPF have often been misdiagnosed and treated as pulmonary tuberculosis with unfavorable outcome.
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.
Villar, I; Hernández, E; Cozzi, J; Paletta, C; Mathurín, S
A 32 year old man was admitted for dyspnea, hemoptysis, macroscopic hematuria, hypertension (140/100), peripheral edema and hemodynamic decompensation. Lung Xrays revealed pulmonary edema and a cavity in the left apex. Laboratory determinations revealed an altered renal function with increased creatinine and urea levels and nephrotic syndrome. There was leucocyturia, hematuria and cylindruria. The sputum showed a large number of acid-fast bacilli. The patient began anti-tuberculosis treatment with three drugs (isoniacid, rifampicin, pirazinamide). On ultrasonography, both kidneys revealed ecogenic lesions with size, shape and cortico-medular relationship preserved. The patient persisted with altered renal function, steady levels of urea nitrogen, creatinine and potassium, preserved diuresis and hypertension. Bidimensional echocardiogram: LVDD 55 mm, hypoquinetic septum, pericardic effusion, thickened pericardium, pleural effusion, shortening fraction decreased. He received treatment for this congestive cardiac failure and hypertension with enalapril, nifedipine and fursemide. A percutaneous renal biopsy was performed with anatomopathologic diagnosis of diffuse encocapillar proliferative glomerulonephritis with crescents (15%) and total glomerular sclerosis (33%). Immunofluorescence: positive, immune-complexes with IgM and C3. The patient gradually recovered his normal renal function, improved his pleural effusions and normalized his cardiac function. He was discharged in good clinical condition on the 69th day of anti-tuberculosis treatment. An association between pulmonary tuberculosis and glomerulonephritis is discussed. It is proposed that renal lesions might be the consequence of the tuberculosis due to the sedimentation of circulating immune-complexes.
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
De Siati, L; Paroli, M; Ferri, C; Muda, A O; Bruno, G; Barnaba, V
A 31-year-old man who presented with smear- and culture-negative pulmonary tuberculosis had associated macroscopic hematuria, elevation of serum creatinine and immunoglobulin A (IgA) levels, overt proteinuria, and peripheral edema. Renal biopsy revealed focal mesangial proliferation with IgA deposits, and a diagnosis of IgA nephropathy was made. The patient received treatment with isoniazide and rifampin. After 4 months, pulmonary lesions were almost completely healed, and a significant improvement of creatinine clearance with normalization of serum creatinine and IgA levels and disappearance of proteinuria were observed. Treatment with isoniazide and rifampin was discontinued after 6 months, without reappearance of either pulmonary or renal symptoms. Two years after the diagnosis of IgA nephropathy, the patient is in good general condition. Serum creatinine and IgA levels are normal, proteinuria is absent, and there is neither macrohematuria nor microhematuria. These findings suggest that IgA nephropathy may be a consequence of tuberculosis, possibly due to an abnormal IgA-mediated immune response against Mycobacterium tuberculosis with formation of nephrotoxic immune complexes.
Varik, Roma Subhash; Shubha, Attibele Mahadevaiah; Lewin, Maria; Alexander, Betty; Kini, Usha; Das, Kanishka
Infantile tuberculosis is common in developing countries and rarely presents as space occupying thoracic lesions mimicking congenital malformations. This case series reviews four such infants with varied presentations and their outcome. Four cases of infantile pulmonary/mediastinal tuberculosis that presented like congenital thoracic lesions are described. Details of demography, symptomatology, contact history, immunization status, provisional diagnosis, tuberculin testing, imaging, histopathology, final diagnosis, management and outcome were retrospectively collated and analyzed. They were 4-6-month males, term-born and immunized. They presented with pneumonia/hyperactive airway disease since 2-12 weeks. One had a suspect and another a close tuberculous contact. The provisional diagnosis after imaging were infected congenital lung cyst, posterior mediastinal cyst and bronchopulmonary malformation. Two were tuberculin positive; none had gastric acid-fast bacilli. One underwent a pulmonary lobectomy for necrotic lung cyst; the second had a biopsy and drainage of a posterior mediastinal cyst that contained caseating material and was densely adherent to the esophagus. Surgical biopsy showed necrotizing granulomatous inflammation in both; one with acid-fast bacilli. Both succumbed to postoperative complications. The other two with tuberculous contacts who were managed with early antituberculous therapy, responded well and recovered uneventfully. Infantile pulmonary/mediastinal tuberculosis may mimic congenital thoracic malformations. A review of contact history, investigations and imaging help to establish the tuberculous etiology, avoids surgical misadventures and prompts early antituberculous therapy to achieve a favorable outcome.
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.
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
Agostinis, Paolo; Copetti, Roberto; Lapini, Laura; Badona Monteiro, Geraldo; N'Deque, Augusto; Baritussio, Aldo
In resource-limited countries, the diagnosis of pulmonary tuberculosis (TB) is based on clinical findings, chest radiography and the demonstration of acid-fast bacilli in sputum. Few data are available on the use of ultrasound (US) to diagnose pulmonary TB. Chest US was performed in patients with lung TB from a rural African setting, to look for signs of the disease and to clarify the role US may have in the diagnosis of pulmonary TB. Sixty adult patients diagnosed with lung TB underwent chest US. All patients had abnormal findings. The most frequent was a subpleural nodule (SUN), which was mostly multiple and also found in radiologically normal areas. Other findings were lung consolidations, cavitations, miliary patterns made of miniature SUNs, and pleural and pericardial effusions. Chest US is a complementary tool in evaluating patients with suspected lung TB in resource-limited settings where the disease has high prevalence.
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
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
Firdessa, Rebuma; Berg, Stefan; Hailu, Elena; Schelling, Esther; Gumi, Balako; Erenso, Girume; Gadisa, Endalamaw; Kiros, Teklu; Habtamu, Meseret; Hussein, Jemal; Zinsstag, Jakob; Robertson, Brian D.; Ameni, Gobena; Lohan, Amanda J.; Loftus, Brendan; Comas, Iñaki; Gagneux, Sebastien; Tschopp, Rea; Yamuah, Lawrence; Hewinson, Glyn; Gordon, Stephen V.; Young, Douglas B.
Molecular typing of 964 specimens from patients in Ethiopia with lymph node or pulmonary tuberculosis showed a similar distribution of Mycobacterium tuberculosis strains between the 2 disease manifestations and a minimal role for M. bovis. We report a novel phylogenetic lineage of M. tuberculosis strongly associated with the Horn of Africa. PMID:23622814
Firdessa, Rebuma; Berg, Stefan; Hailu, Elena; Schelling, Esther; Gumi, Balako; Erenso, Girume; Gadisa, Endalamaw; Kiros, Teklu; Habtamu, Meseret; Hussein, Jemal; Zinsstag, Jakob; Robertson, Brian D; Ameni, Gobena; Lohan, Amanda J; Loftus, Brendan; Comas, Iñaki; Gagneux, Sebastien; Tschopp, Rea; Yamuah, Lawrence; Hewinson, Glyn; Gordon, Stephen V; Young, Douglas B; Aseffa, Abraham
Molecular typing of 964 specimens from patients in Ethiopia with lymph node or pulmonary tuberculosis showed a similar distribution of Mycobacterium tuberculosis strains between the 2 disease manifestations and a minimal role for M. bovis. We report a novel phylogenetic lineage of M. tuberculosis strongly associated with the Horn of Africa.
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.
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.
Rubleva, N V; Kolomiets, V M; Kochetkova, E Ya
The pulmonary tuberculosis process as dependent on the disease form and the therapy efficacy with the use of Cycloferon in the treatment scheme were investigated. The study had two stages. At the first stage the data concerning 358 patients with primary pulmonary tuberculosis and infiltration (93 patients) or degradation (89 patients) and 176 patients with pulmonary fibrocavernous tuberculosis were analysed. At the second stage the efficacy of the treatment schemes applied to the patients with pulmonary fibrocavernous tuberculosis was compared. The etiotropic therapy intensive phase was applied to all the patients. Moreover, 56 patients (group 1) under the therapy and rehabilitatinon were treated with Cycloferon in a dose of 0.25 administered intramuscularly twice a week (not less than 16 injections for the course), 60 patients (group 2) were treated with Omega 3, 30 patients (group 3) were given the standard complex (vitamins and tonics), 30 patients (group 4) were under the etiotropic therapy alone. The following additional factors promoting progression and aggravation of the tuberculosis process were confirmed: degradation at the time of the disease diagnosis, high resistance of the pathogen to antituberculosis drugs, low adherence to the treatment, social desadaptation and especially psychofunctional state of the patients. The use of Cycloferon in the schemes of the intensive phase treatment of the primary fibrocavernous tuberculosis resulted in reduction of the intoxication signs, bacteria isolation, positive dynamics of the cavity healing, lower lung infiltration and consequently high frequency of the treatment positive outcomes (94.1 ± 3.33%).
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.
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.
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.
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.
Marais, B J; Gie, R P; Obihara, C C; Hesseling, A C; Schaaf, H S; Beyers, N
The diagnosis of childhood pulmonary tuberculosis presents a major challenge as symptoms traditionally associated with tuberculosis are extremely common in children from endemic areas. The natural history of tuberculosis in children shows that progressive disease is associated with symptoms which have a persistent, non-remitting character. The aims of this study were to investigate whether improved symptom definition is possible in a clinical setting, and whether use of these well defined symptoms has improved value in the diagnosis of childhood pulmonary tuberculosis. A prospective, community based study was conducted in two suburbs of Cape Town, South Africa. All children (<13 years) presenting to the local community clinic with a cough of >2 weeks duration, were referred to the investigator. Parents completed a symptom based questionnaire, whereafter reported symptoms were characterised in a standard fashion. Of the 151 children enrolled, 21 (15.6%) reported symptoms with a persistent, non-remitting character. Tuberculosis was diagnosed in 16 (10.5%) children, all of whom reported these symptom characteristics. A persistent, non-remitting cough was reported in 15/16 (93.8%) children with tuberculosis and in 2/135 (1.5%) children without tuberculosis, indicating a specificity of 98.5% (135/137). Persistent fatigue of recent onset was also sensitive (13/16, 81.3%) and specific (134/135, 99.3%). Persistent fever and/or chest pain were exclusively reported in children with tuberculosis, but were present in only 4/16 (25.0%) children with tuberculosis. The use of well defined symptoms is feasible, even in resource limited settings, and may offer significantly improved value in the diagnosis of childhood pulmonary tuberculosis.
Namikawa, Hiroki; Takemoto, Yasuhiko; Kainuma, Shigeto; Umeda, Sakurako; Makuuchi, Ayako; Fukumoto, Kazuo; Kobayashi, Masanori; Kinuhata, Shigeki; Isaka, Yoshihiro; Toyoda, Hiromitsu; Kamata, Noriko; Tochino, Yoshihiro; Hiura, Yoshikazu; Morimura, Mina; Shuto, Taichi
We herein report a case of Addison's disease caused by tuberculosis characterized by atypical hyperpigmentation, noted as exacerbation of the pigmentation of freckles and the occurrence of new freckles, that was diagnosed in the presence of active pulmonary tuberculosis. The clinical condition of the patient was markedly ameliorated by the administration of hydrocortisone and anti-tuberculosis agents. When exacerbation of the pigmentation of the freckles and/or the occurrence of new freckles are noted, Addison's disease should be considered as part of the differential diagnosis. In addition, the presence of active tuberculosis needs to be assumed whenever we treat patients with Addison's disease caused by tuberculosis, despite its rarity.
Namikawa, Hiroki; Takemoto, Yasuhiko; Kainuma, Shigeto; Umeda, Sakurako; Makuuchi, Ayako; Fukumoto, Kazuo; Kobayashi, Masanori; Kinuhata, Shigeki; Isaka, Yoshihiro; Toyoda, Hiromitsu; Kamata, Noriko; Tochino, Yoshihiro; Hiura, Yoshikazu; Morimura, Mina; Shuto, Taichi
We herein report a case of Addison's disease caused by tuberculosis characterized by atypical hyperpigmentation, noted as exacerbation of the pigmentation of freckles and the occurrence of new freckles, that was diagnosed in the presence of active pulmonary tuberculosis. The clinical condition of the patient was markedly ameliorated by the administration of hydrocortisone and anti-tuberculosis agents. When exacerbation of the pigmentation of the freckles and/or the occurrence of new freckles are noted, Addison's disease should be considered as part of the differential diagnosis. In addition, the presence of active tuberculosis needs to be assumed whenever we treat patients with Addison's disease caused by tuberculosis, despite its rarity. PMID:28717080
Martín Sánchez, V; Alvarez-Guisasola, F; Caylá, J A; Alvarez, J L
Tuberculosis currently represents a serious problem in prison populations. With the aim of studying the predictive factors for, and the prevalence of, Mycobacterium tuberculosis infection and pulmonary tuberculosis in a Spanish prison, all those admitted during 1991 and 1992 were included (N = 1314). The tuberculin skin test, HIV serology, chest X-ray and bacteriological examination of sputum were carried out. Statistical analysis was done by univariant tests, stratified analysis and logistic regression. The prevalence of M. tuberculosis infection was 55.5% (95% confidence interval [CI] 52.5-58.5). An association was found with sex, imprisonment more than once, HIV infection and age. The co-infection rate (tuberculosis plus HIV) was 9.2%. Logistic regression showed a greater risk with age (4.4% per year), time spent in prison and for males. The prevalence of pulmonary tuberculosis was 1.26% and an association was found with M. tuberculosis infection, HIV infection (odds ratio [OR] = 13.7), intravenous drug users (OR = 17.2) and imprisonment more than once (OR = 7.3). Logistic regression showed an association with HIV co-infection (OR = 20.2). The prevalence of M. tuberculosis infection and pulmonary tuberculosis is high when compared with similar studies. The influence of age, time spent in prison and co-infection with HIV is relevant to recommendations for specific tuberculosis prevention programmes in correctional facilities.
Morehead, R S
A patient with fulminant pulmonary tuberculosis died after 41 days of intensive care despite pansensitive organisms and no known underlying immunosuppression. Two factors leading to death in this patient were a delay in seeking medical attention and a subtherapeutic serum level of rifampin, though no obvious evidence of malabsorption existed. Malabsorption of antitubercular drugs is under-recognized and of extreme importance in the treatment of critically ill patients with active pulmonary tuberculosis. Factors associated with mortality from tuberculosis and selected aspects of critical care management are discussed.
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
Salzer, Helmut J F; Wassilew, Nasstasja; Köhler, Niklas; Olaru, Ioana D; Günther, Gunar; Herzmann, Christian; Kalsdorf, Barbara; Sanchez-Carballo, Patricia; Terhalle, Elena; Rolling, Thierry; Lange, Christoph; Heyckendorf, Jan
Chronic respiratory infectious diseases are causing high rates of morbidity and mortality worldwide. Tuberculosis, a major cause of chronic pulmonary infection, is currently responsible for approximately 1.5 million deaths per year. Although important advances in the fight against tuberculosis have been made, the progress towards eradication of this disease is being challenged by the dramatic increase in multidrug-resistant bacilli. Nontuberculous mycobacteria causing pulmonary disease and chronic pulmonary aspergillosis are emerging infectious diseases. In contrast to other infectious diseases, chronic respiratory infections share the trait of having highly variable treatment outcomes despite longstanding antimicrobial therapy. Recent scientific progress indicates that medicine is presently at a transition stage from programmatic to personalized management. We explain current state-of-the-art management concepts of chronic pulmonary infectious diseases as well as the underlying methods for therapeutic decisions and their implications for personalized medicine. Furthermore, we describe promising biomarkers and techniques with the potential to serve future individual treatment concepts in this field of difficult-to-treat patients. These include candidate markers to improve individual risk assessment for disease development, the design of tailor-made drug therapy regimens, and individualized biomarker-guided therapy duration to achieve relapse-free cure. In addition, the use of therapeutic drug monitoring to reach optimal drug dosing with the smallest rate of adverse events as well as candidate agents for future host-directed therapies are described. Taken together, personalized medicine will provide opportunities to substantially improve the management and treatment outcome of difficult-to-treat patients with chronic respiratory infections. © 2016 S. Karger AG, Basel.
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.
Koyama, R; Nakanishi, F; Katoh, S
Recently we encountered a case of pulmonary tuberculosis with HIV infection. The patient was 54-years old male. His chief complaints were anemia, emaciation and severe diarrhea. He was admitted to our hospital on September 18, 1992. He had been diagnosed in another clinic as having pulmonary tuberculosis before the admission to our hospital. His chest films taken on admission revealed homogeneous infiltrates with cavitation in right upper lobe. Serial chest X-rays consisted with the findings of post-primary tuberculosis. Sputum smear for acid fast bacilli was positive. From his clinical manifestations and life-history, we had a suspicion that he had infected with HIV. Laboratory findings were as follows: serum albumin level was 1.9 g/dl, CRP was 10.2 mg/dl, serological tests for HIV were positive by EIA, IFA and western blott method, total lymphocyte count was 819/microliters, CD4+ T lymphocyte count was 120/microliter CD4+/CD8+ ratio was 0.2. He was treated with AZT, isoniazid, streptomycin and rifampicin. The disease progressed rapidly and interstitial pneumonia, jaundice and clouding of consciousness appeared at the terminal stage. He expired on October 14, 1992. In this paper, the authors reported a case of pulmonary tuberculosis with HIV infection and also reviewed 5 cases of pulmonary tuberculosis associated with HIV in Japan.
Morillon, Marc; Koeck, Jean-Louis; Varnerot, Anne; Briant, Jean-François; Nguyen, Gilbert; Verrot, Denis; Bonnet, Daniel; Vincent, Véronique
We identified an unusual strain of mycobacteria from two patients with pulmonary tuberculosis by its smooth, glossy morphotype and, primarily, its genotypic characteristics. Spoligotyping and restriction fragment length polymorphism typing were carried out with the insertion sequence IS6110 patterns. All known cases of tuberculosis caused by Mycobacterium canetti have been contracted in the Horn of Africa. PMID:12453369
Miltgen, Jean; Morillon, Marc; Koeck, Jean-Louis; Varnerot, Anne; Briant, Jean-François; Nguyen, Gilbert; Verrot, Denis; Bonnet, Daniel; Vincent, Véronique
We identified an unusual strain of mycobacteria from two patients with pulmonary tuberculosis by its smooth, glossy morphotype and, primarily, its genotypic characteristics. Spoligotyping and restriction fragment length polymorphism typing were carried out with the insertion sequence IS6110 patterns. All known cases of tuberculosis caused by Mycobacterium canetti have been contracted in the Horn of Africa.
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 2012-07-01 2012-07-01 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 and...
... 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 and...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 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 and...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 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 and...
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.
Fekih, L; Boussoffara, L; Fenniche, S; Hassene, H; Romdhane, K B; Abdelghaffar, H B; Belhabib, D; Ayadi, A; Zidi, A; Megdiche, M L
Amyloidosis is characterized by tissue deposits of amyloid material. Secondary amyloidosis can occur as a sequel to pulmonary tuberculosis over a relatively long period. However, this was not the case with our patient. Subsequently we conducted a literature review to try to explain the unusual course of AL amyloidosis in our patient. A 36- year-old patient was admitted to our department for investigation of haemoptysis. A diagnosis of primary pulmonary tuberculosis was made and antituberculous treatment was started. On the second day of treatment, a haematoma appeared on the sole of the right foot, which spread down to the toes during the following days. Renal investigations showed a 24h proteinuria of 9 g/L and serum protein electrophoresis revealed an albumin level of 11.8 g/L. A diagnosis of nephrotic syndrome was made. A renal biopsy was indicated but this was not possible on account of a marked worsening of the patient's condition after 14 days of treatment. The patient's level of consciousness deteriorated and he was transferred to the intensive care unit for ventilation. He died 48 hours later. Post-mortem histological examination of pulmonary and cutaneous tissue revealed AL amyloid deposits. In view of the association of active pulmonary tuberculosis and a pulmonary localisation of amyloidosis, a causal relationship is not definite. Coexistence of active pulmonary tuberculosis and primary amyloidosis must also be considered, particularly as the immunohistochemical characterisation revealed AL amyloidosis. Copyright © 2011 SPLF. Published by Elsevier Masson SAS. All rights reserved.
Pérez-Guzmán, Carlos; Vargas, Mario H
Although one-third of the world's population is infected by Mycobacterium tuberculosis, only approximately 10% will develop the overt clinical disease due to a yet undefined risk factor. We hypothesize that hypocholesterolemia might constitute such a factor, because: (a) cholesterol is an important molecule for the good functioning of an immune system, and is necessary for macrophages to uptake and engulf mycobacteria, (b) tuberculous patients often have hypocholesterolemia, in comparison with the general population and household contacts, (c) cholesterol has a beneficial effect against pulmonary tuberculosis, since a cholesterol-rich diet accelerates the bacteriological sterilization of sputum, and (d) many conditions traditionally considered major risk factors for tuberculosis are accompanied by hypocholesterolemia. If this hypothesis proves to be true, cholesterol might be given to hypocholesterolemic subjects who are at high risk for developing pulmonary tuberculosis.
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.
Kashif, Waqar; Yaqub, Sonia; Mahmood, Syed Faisal; Patel, Junaid
Anti-glomerular basement membrane (anti-GBM) disease usually presents as rapidly progressive glomerulonephritis, and, when accompanied with pulmonary hemorrhage, it is called Goodpasture's syndrome. Anti-neutrophilic cytoplasmic antibodies (ANCA) may co-exist with anti-GBM antibodies. In most of these "double positive" cases, ANCA is specific for myeloperoxidase (p-ANCA). We report a rare case of a critically ill patient c-ANCA-associated double-positive Goodpasture's syndrome with concomitant tuberculosis that was successfully treated with immunosuppression, plasmapheresis and anti-tuberculous therapy (ATT). A 32-year-old gentleman with a 15 pack-year smoking history presented with massive hemoptysis, respiratory failure and oliguria. Laboratory investigation revealed anemia, elevated creatinine and active urinary sediment. Chest X-ray revealed bilateral pulmonary infiltrates. Broad-spectrum antibiotics and intravenous corticosteroids were started. Bronchoscopy showed alveolar hemorrhage and smears from bronchial lavage from both lungs were positive for acid fast bacillus (AFB). Vasculitis work-up revealed high titers of c-ANCA and anti-GBM antibodies. Kidney biopsy revealed crescents in >50% glomeruli on light microscopy. Immunofluorescence showed linear deposition of IgG and C3. The patient received pulse methylprednisone for three days followed by oral prednisone and ATT. In addition, he also underwent nine sessions of plasmapheresis. Oral Cyclophosphamide was added on Day 10. The patient showed remarkable recovery as his lung fields cleared and his kidney function got stabilized. Cyclophosphamide was continued for three months and then switched to azathioprine. At six months, the creatinine is 1.2 mg/dL, with minimal proteinuria and a normal chest X-ray. To the best of our knowledge, this is the only reported case of double-positive Goodpasture's syndrome (c-ANCA and anti GBM) with active tuberculosis treated successfully.
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
Deĭkina, O N; Mishin, V Iu; Demikhova, O V
The purpose of this investigation was to enhance the efficiency of differential diagnosis of pneumonia and pulmonary tuberculosis. A hundred and fifty-nine adult patients were examined. These included 78 patients with pulmonary tuberculosis and 81 with community-acquired p neumonia. The clinical features of infiltrative pulmonary tuberculosis (n = 48) and mild community-acquired pneumonia (n = 51) were compared. The course of caseous pneumonia (n = 30) was compared with that of moderate and severe community-acquired pneumonia (n = 30). Significant differences in the manifestations of the intoxication and bronchopulmonary syndrome were not found in patients with community-acquired pneumonia and infiltrative pulmonary tuberculosis. Physical studies showed that in patients with community-acquired pneumonia, moist rale (54.9%) and crepitation (11.8%) were prevalent, but in those with infiltrative tuberculosis rale was absent in 60.4% of cases and the pattern of respiration was unchanged in 79.2%. Chest X-ray studies indicated that in patients with community-acquired pneumonia, lower lobar inflammatory changes were predominant in 62.8% of cases whereas in those with infiltrative pulmonary tuberculosis the process was mainly bilateral (43.8%) with the presence of destructive changes (83.3%) and bronchogenic dissemination (66.7%). In patients with caseous pneumonia, the intoxication syndrome was more significant than in those with severe community-acquired pneumonia. Chest X-ray studies demonstrated that in patients with caseous pneumonia, specific changes were bilateral with the involvement of 2 lobes or more, with destruction and bronchogenic dissemination while in those with community-acquired pneumonia, the pulmonary processes were predominantly bilateral (76.6%) at the lower lobar site (36.7%).
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.
Nagaraj, Vezhavendhan; Sashykumar, Shanthi; Viswanathan, Stalin; Kumar, Sathish
We report a 47 year old man who presented with painful non-healing tongue ulcers of 3 months duration. Examination revealed an additional buccal ulcer that he was unaware of. Histopathology of the ulcers showed caseation necrosis. Following this report, chest radiography and sputum microscopy performed revealed pulmonary tuberculosis. From this case-study, one should be aware of coexisting pulmonary tuberculosis in patients with chronic non-healing oral ulcers, both for diagnosis as well as prevention of transmission through respiratory droplets. PMID:24883035
Chiang, Chen-Yuan; Hsu, Chih-Jen; Hsu, Pi-Kung; Suo, Jen; Lin, Tao-Ping
Tuberculosis (TB) in prison is a serious public health problem that is fueled by overcrowding, poor nutrition and unsatisfactory medical services. To evaluate the magnitude of the TB epidemic in Taiwanese prisons, we analyzed the results of a screening program for TB among inmates. A mass radiography screening was performed in 24 prisons and five jails from July 1998 through June 1999. The National TB Register was notified and treatment with a rifampin-based short-course anti-TB regimen was given for all cases identified in the screening. The outcome of treatment of TB inmates was determined from records of the National TB Register. A total of 51,496 inmates were screened. Pulmonary TB was diagnosed in 107 (258.7 per 100,000 population) inmates. Among them, 88 (82.2%) were newly diagnosed TB patients, 12 (11.2%) had a history of anti-TB treatment and were re-treated after screening, and seven (6.6%) had previously diagnosed TB and were receiving treatment at the time of screening. Of the 107 inmates with TB, 86 (80.4%) completed treatment, 17 (15.9%) were lost to follow-up due to release from prison, and four (3.7%) died (three of TB). During a mean of 26.2 +/- 4.4 months (range, 19.7-39.0 mo) post-registration follow-up, three patients who had completed treatment relapsed. The high prevalence of TB in prisons indicates that prison administrators and the national TB program in Taiwan need to strengthen their activity to control this disease. The establishment of a surveillance section of the national TB program to systematically collect data on TB in prisons may facilitate efforts to monitor and control TB both in prisons and the general population. Our findings also indicate that TB control in prisons should give top priority to improving mycobacteriology laboratory services to ensure the quality of sputum examinations.
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
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.
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.
Meima, Abraham; Verver, Suzanne; Looman, Caspar W.N.; Bos, Vivian; Borgdorff, Martien W.; Habbema, J. Dik F.
Incidence rates of pulmonary tuberculosis among immigrants from high incidence countries remain high for at least a decade after immigration into the Netherlands. Possible explanations are reactivation of old infections and infection transmitted after immigration. Control policies should be determined on the basis of the as-yet unknown main causes of the persistent high incidence. PMID:15200873
Lantos, Ákos; Niemann, Stefan; Mezősi, László; Sós, Endre; Erdélyi, Károly; Dávid, Sándor; Parsons, Linda M.; Kubica, Tanja; Rüsch-Gerdes, Sabine
We report the first case of pulmonary tuberculosis caused by Mycobacterium bovis subsp. caprae in a captive Siberian tiger, an endangered feline. The pathogen was isolated from a tracheal aspirate obtained by bronchoscopy. This procedure provided a reliable in vivo diagnostic method in conjunction with conventional and molecular tests for the detection of mycobacteria. PMID:14718093
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.
Sasaki, Y; Yamagishi, F; Suzuki, K; Yagi, T; Miyazawa, H; Shirai, T; Satoh, N; Tougoh, N; Ihara, S
This study investigates 27 cases in which the patients left hospital care without permission for personal reasons. These patients were classified as "self-discharged patients". Each of the patients had been diagnosed as having pulmonary tuberculosis, and were receiving treatment at the National Chiba Higashi Hospital during the period from January 1988 to July 1991. Disease was in an advanced stage in each of the patients when admitted: all sputum examinations were positive and chest roentgenograms revealed cavities in 26 patients. In addition to pulmonary tuberculosis, the patients were also diagnosed has having a variety of other medical complications such as diabetes mellitus, gastric ulcers and liver disease. Many of them were unemployed or were day labors. Reasons attributed to patients self-discharge from the hospital included repetition of alcohol drinking and unauthorized outings. At the time patients chose to leave hospitalization 11 cases checked positive for sputum examinations, and 16 cases never returned to complete therapy. Many of them were rated as high risk patients for pulmonary tuberculosis because they had no immediate family, did not own a residence or have regular employment thus economic and psychological conditions were very low. There is a high possibility that these individuals will suffer pulmonary tuberculosis relapse and become infectious bacteria carriers. It is important that such patients be hospitalized long enough to receive adequate treatment to prevent then from becoming infectious carriers and spreading disease.
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...
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
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
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
Odell, John A
Thoracic surgical procedures evolved from surgical management of tuberculosis; lung resections, muscle flaps, and thoracoscopy all began with efforts to control the disease. The discovery of antituberculosis drugs in 1944 to 1946 made sanatorium therapy and collapse therapy in all its forms obsolete and changed thoracic surgery dramatically. Currently, management of tuberculosis is primarily medical, and surgery has a minimal role. Today surgery is usually only performed in patients with tuberculosis when the diagnosis is necessary, who have complications or sequelae of the disease, or who have active disease resistant to therapy. Copyright © 2012 Elsevier Inc. All rights reserved.
Marais, Ben J; Gie, Robert P; Hesseling, Anneke C; Schaaf, H Simon; Lombard, Carl; Enarson, Donald A; Beyers, Nulda
: 90.2%; positive predictive value: 82.3%) than in the high-risk group (< 3 years; sensitivity: 51.8%; specificity: 92.5%; positive predictive value: 90.1%). In children with an uncertain diagnosis at presentation, clinical follow-up was a valuable diagnostic tool that further improved diagnostic accuracy, particularly in the low-risk group. Symptom-based approaches offered little diagnostic value in HIV-infected children. Three (15%) of the 20 HIV-infected children diagnosed with pulmonary tuberculosis failed to report symptoms of sufficient duration to warrant study inclusion, whereas 25% reported persistent, nonremitting symptoms in the absence of tuberculosis. In addition, the tuberculin skin test was positive in < 20% of HIV-infected children diagnosed with pulmonary tuberculosis. The combined presence of 3 well-defined symptoms at presentation (persistent, nonremitting cough of > 2 weeks' duration; objective weight loss [documented failure to thrive] during the preceding 3 months; and reported fatigue) provided good diagnostic accuracy in HIV-uninfected children > or = 3 years of age, with clinical follow-up providing additional value. The approach performed less well in children < 3 years. However, the presence of a persistent, nonremitting cough together with documented failure to thrive still provided a fairly accurate diagnosis (sensitivity: 68.3%; specificity: 80.1%; positive predictive value: 82.1%), illustrating the importance of regular weight monitoring in young children. Clinical follow-up also offered additional diagnostic value, but caution is required, because very young children have an increased risk of rapid disease progression. The approach performed poorly in HIV-infected children. Recent household contact with an adult index case seemed to provide more diagnostic value than a positive tuberculin skin test, but novel T-cell-based assays may offer the only real improvement in sensitivity to diagnose M. tuberculosis infection in HIV
Silva, Denise Rossato; Valentini, Dirceu Felipe; Müller, Alice Mânica; de Almeida, Carlos Podalirio Borges; Dalcin, Paulo de Tarso Roth
OBJECTIVE: Lung cancer (LC) is the leading cause of cancer-related death and represents a major public health problem worldwide. Another major cause of morbidity and mortality, especially in developing countries, is tuberculosis. The simultaneous or sequential occurrence of pulmonary tuberculosis and LC in the same patient has been reported in various case series and case-control studies. The objective of this study was to describe the characteristics of patients developing tuberculosis and LC, either simultaneously or sequentially. METHODS: This was a cross-sectional study based on the review of medical charts. RESULTS: The study involved 24 patients diagnosed with tuberculosis and LC between 2009 and 2012. The diagnoses of tuberculosis and LC occurred simultaneously in 10 patients, whereas tuberculosis was diagnosed prior to LC in 14. The median time between the two diagnoses was 5 years (interquartile range: 1-30 years). Fourteen patients (58.3%) were male, 20 (83.3%) were White, and 22 (91.7%) were smokers or former smokers. The most common histological type was adenocarcinoma, identified in 14 cases (58.3%), followed by epidermoid carcinoma, identified in 6 (25.0%). Seven patients (29.2%) presented with distant metastases at diagnosis; of those 7 patients, 5 (71%) were diagnosed with LC and tuberculosis simultaneously. CONCLUSIONS: In the present study, most of the patients with tuberculosis and LC were smokers or former smokers, and tuberculosis was diagnosed either before or simultaneously with LC. Non-small cell lung cancer, especially adenocarcinoma, was the most common histological type. PMID:24068271
Prasad, Rajendra; Verma, Sanjay Kumar; Singh, Rajni; Hosmane, Giridhar
The concommitant occurrence of both tuberculosis and leprosy in a single individual are not an uncommon clinical condition but is being reported infrequently in literature. We report a case of leprosy, diagnosed previously and also diagnosed as pulmonary tuberculosis.
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.
Rojas, Christian Mauricio; Villegas, Sonia Lorena; Piñeros, Hildegard María; Chamorro, Ennid Margarita; Durán, Carlos Eduardo; Hernández, Edna Lorena; Pacheco, Robinson; Ferro, Beatriz Eugenia
The World Health Organization recommended strategy for global tuberculosis control is a short-course, clinically administered treatment, This approach has approximately 70% coverage in Colombia. The clinical, epidemiological and microbiological characteristics along with drug therapy outcomes were described in newly diagnosed, pulmonary tuberculosis patients. This was a descriptive study, conducted as part of a multicenter clinical trial of tuberculosis treatment. A cohort of 106 patients with pulmonary tuberculosis were recruited from several public health facilities in Cali between April 2005 and June 2006. Sputum smear microscopy, culture, drug susceptibility tests to first-line anti-tuberculosis drugs, chest X- ray and HIV-ELISA were performed. Clinical and epidemiological information was collected for each participant. Treatment was administered by the local tuberculosis health facility. Food and transportation incentives were provided during a 30 month follow-up period. The majority of patients were young males with a diagnostic delay longer than 9 weeks and a high sputum smear grade (2+ or 3+). The initial drug resistance was 7.5% for single drug treatment and 1.9% for multidrug treatments. The incidence of adverse events associated with treatment was 8.5%. HIV co-infection was present in 5.7% of the cases. Eighty-six percent of the patients completed the treatment and were considered cured. The radiographic presentation varied within a broad range and differed from the classic progression to cavity formation. Delay in tuberculosis diagnosis was identified as a risk factor for treatment compliance failure. The study population had similar baseline epidemiologic characteristics to those described in other cohort studies.
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
Background In the context of decreasing tuberculosis prevalence in China, we examined the effectiveness of screening household contacts of tuberculosis patients. Methods A tuberculosis survey was conducted in 2008. All 3,355 household contacts of notified tuberculosis cases were examined with a questionnaire interview, chest X-ray and three sputum smear tests. The effectiveness was examined by comparing the prevalence of pulmonary tuberculosis in household contacts with or without presenting clinical symptoms against the respective notification rates. Regression models were used to evaluate the factors associated with pulmonary tuberculosis. Results Of the 3,355 household contacts, 92 members (2.7%) had pulmonary tuberculosis, among which 46 cases were asymptomatic. The prevalence of pulmonary tuberculosis and smear positive cases in household contacts without symptoms were 20 and 7 times higher than the notification rates in 2008, while those in household contacts with symptoms were 247 and 108 times higher than notification rates, respectively. The patients detected were mainly Index Cases’ spouses, sisters/brothers and those who were in contact with female Index Cases. Conclusions The present study provides convincing evidence that household contacts of notified tuberculosis cases are at higher risk of developing tuberculosis. Routine screening for household contacts without any symptoms is recommended for sustained tuberculosis control in China as well as in the world. PMID:24502559
Jia, Zhongwei; Cheng, Shiming; Ma, Yan; Zhang, Tianhao; Bai, Liqiong; Xu, Weiguo; He, Xiaoxin; Zhang, Peiru; Zhao, Jinkou; Christiani, David C
In the context of decreasing tuberculosis prevalence in China, we examined the effectiveness of screening household contacts of tuberculosis patients. A tuberculosis survey was conducted in 2008. All 3,355 household contacts of notified tuberculosis cases were examined with a questionnaire interview, chest X-ray and three sputum smear tests. The effectiveness was examined by comparing the prevalence of pulmonary tuberculosis in household contacts with or without presenting clinical symptoms against the respective notification rates. Regression models were used to evaluate the factors associated with pulmonary tuberculosis. Of the 3,355 household contacts, 92 members (2.7%) had pulmonary tuberculosis, among which 46 cases were asymptomatic. The prevalence of pulmonary tuberculosis and smear positive cases in household contacts without symptoms were 20 and 7 times higher than the notification rates in 2008, while those in household contacts with symptoms were 247 and 108 times higher than notification rates, respectively. The patients detected were mainly Index Cases' spouses, sisters/brothers and those who were in contact with female Index Cases. The present study provides convincing evidence that household contacts of notified tuberculosis cases are at higher risk of developing tuberculosis. Routine screening for household contacts without any symptoms is recommended for sustained tuberculosis control in China as well as in the world.
Fry, Donald E
Tuberculous infection has declined in the United States but remains a major infectious disease with morbidity and death for millions of people. Although the primary therapy is drugs, complications of the disease require surgical interventions. The published literature on tuberculosis was reviewed to provide a current understanding of the medical treatment of the disease and to define those areas where surgical intervention continues to be necessary. Multi-drug therapy for tuberculosis has become the standard and has reduced the complications of the disease necessitating surgical intervention. However, multi-drug resistance and extensively drug-resistant tuberculosis continue to be major problems and require effective initial therapy with surveillance to define resistant infections. The roles of surgery in tuberculosis are in establishing the diagnosis in extra-pulmonary infection and in the management of complications of disseminated disease. Tuberculosis remains an occupational risk for surgeons and surgical personnel. Tuberculosis is still a global problem, mandating recognition and treatment. Surgeons should have an understanding of the diverse presentation and complications of the disease.
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
Phelippeau, M; Petureau, F
Pulmonary tuberculosis can rarely lead to acute respiratory distress syndrome and anti-tuberculous therapy initiation depends on this difficult diagnosis in ICU. A 50-year-old man presented a septic shock and acute respiratory distress syndrome with bilateral infiltrates mainly in the upper lobes on chest radiography. Diagnosis of pulmonary tuberculosis was made 10days after admission on examination of cavitary and diffuse infiltrates on a second CT scan, in addition to presence of acid-fast bacilli on smear examination of bronchial aspirates. Amikacin, with four first-line anti-tuberculous drugs, was started in the case of a resistant strain and seriousness of the illness. After 14weeks, he left on rifampicin and isoniazid treatment. There are no specific recommendations concerning pulmonary tuberculosis in ICU but a delay in initiation of anti-tuberculous therapy is a factor of poor prognosis. Using a second-line anti-tuberculous drug, like amikacin or/and fluoroquinolones, within initial treatment may accelerate improvement of sepsis and immediately treat resistant strains, when genomic methods for detection of resistance are not available in routine. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
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.
Zenebe, Yohannes; Anagaw, Belay; Tesfay, Wogahta; Debebe, Tewodros; Gelaw, Baye
While pulmonary tuberculosis is the most common presentation, extra pulmonary tuberculosis is also an important clinical problem. However, no adequate information had been made available on the prevalence of smear positive extra pulmonary tuberculosis in Gondar. The aim of this study was to assess the prevalence and possible risk factors of smear positive extra pulmonary tuberculosis among suspected patients at University of Gondar Hospital. A cross-sectional study on extra pulmonary tuberculosis suspected patients was conducted at University of Gondar Hospital from January 2012 to April, 2012. Specimens of patients suspected of extra pulmonary tuberculosis were obtained from fine needle aspiration and body fluid samples collected by pathologist. Demographic characteristics and other variables were collected using a pretested semi-structured questionnaire. Smears were prepared from each sample and stained by Ziehel Neelson and Wright stain. The result of the study was analyzed with bivariate and multivariate logistic regression. A total of 344 extra pulmonary tuberculosis suspected clients were included in the study and specimens were taken from lymph node aspirates and body fluids. The overall prevalence of smear positive extra pulmonary tuberculosis was 34 (9.9%). Of these cases of extra pulmonary tuberculosis, lymph node tuberculosis constituted the largest proportion (82.4%). Among the 34 extra pulmonary tuberculosis patients, over half of them (52.9%) were positive for human immunodeficiency virus. The largest proportion of tuberculosis and human immunodeficiency virus cases occurred among persons with in the age group of 31-40 years. Previous history of tuberculosis (OR = 4.77, 95% CI 1.86-12.24), contact to a known tuberculosis cases (OR = 6.67 95% CI 2.78-16.90), history of underlying diseases (OR = 2.79 95% CI 1.15-6.78) and income (OR = 12.9 95% CI 2.25-68.02) were significantly associated with extra pulmonary tuberculosis infection. The prevalence of
Sharma, Surendra K.; Kumar, Sanjeev; Saha, P.K.; George, Ninoo; Arora, S.K.; Gupta, Deepak; Singh, Urvashi; Hanif, M.; Vashisht, R.P.
Background & objectives: Multidrug-resistant tuberculosis (MDR-TB) has emerged as a significant global health concern. The most important risk factor for the development of MDR-TB is previous anti-tuberculosis therapy. Category II pulmonary TB includes those patients who had failed previous TB treatment, relapsed after treatment, or defaulted during previous treatment. We carried out this study to ascertain the prevalence of MDR-TB among category II pulmonary TB patients. Methods: This was a cross-sectional, descriptive study involving category II pulmonary TB patients diagnosed between 2005 and 2008. All sputum-positive category II TB cases were subjected to mycobacterial culture and drug-susceptibility testing (DST). MDR-TB was defined as TB caused by bacilli showing resistance to at least isoniazid and rifampicin. Results: A total of 196 cases of sputum-positive category II pulmonary tuberculosis patients were included. Of these, 40 patients (20.4%) had MDR-TB. The mean age of MDR-TB patients was 33.25 ± 12.04 yr; 9 patients (22.5%) were female. Thirty six patients showed resistance to rifampicin and isoniazid; while 4 patients showed resistance to rifampicin, isoniazid and streptomycin. The prevalence of MDR-TB among category-II pulmonary tuberculosis patients was 20.4 per cent. Interpretation & conclusions : The prevalence of MDR-TB in category II TB patients was significant. However, nation-wide and State-wide representative data on prevalence of MDR-TB are lacking. We stress the importance of continuous monitoring of drug resistance trends, in order to assess the efficacy of current interventions and their impact on the TB epidemic. PMID:21441686
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.
Background Delays seeking care worsen the burden of tuberculosis and cost of care for patients, families and the public health system. This study investigates costs of tuberculosis diagnosis incurred by patients, escorts and the public health system in 10 districts of Ethiopia. Methods New pulmonary tuberculosis patients ≥ 15 years old were interviewed regarding their health care seeking behaviour at the time of diagnosis. Using a structured questionnaire patients were interviewed about the duration of delay at alternative care providers and the public health system prior to diagnosis. Costs incurred by patients, escorts and the public health system were quantified through patient interview and review of medical records. Results Interviews were held with 537 (58%) smear positive patients and 387 (42%) smear negative pulmonary patients. Of these, 413 (45%) were female; 451 (49%) were rural residents; and the median age was 34 years. The mean (median) days elapsed for consultation at alternative care providers and public health facilities prior to tuberculosis diagnosis was 5 days (0 days) and 3 (3 days) respectively. The total median cost incurred from first consultation to diagnosis was $27 per patient (mean = $59). The median costs per patient incurred by patient, escort and the public health system were $16 (mean = $29), $3 (mean = $23) and $3 (mean = $7) respectively. The total cost per patient diagnosed was higher for women, rural residents; those who received government food for work support, patients with smear negative pulmonary tuberculosis and patients who were not screened for TB in at least one district diagnostic centers. Conclusions The costs of tuberculosis diagnosis incurred by patients and escorts represent a significant portion of their monthly income. The costs arising from time lost in seeking care comprised a major portion of the total cost of diagnosis, and may worsen the economic position of patients and their families. Getting treatment
Rey, Adriana Del; Mahuad, Carolina V; Bozza, Verónica V; Bogue, Cristina; Farroni, Miguel A; Bay, María Luisa; Bottasso, Oscar A; Besedovsky, Hugo O
Endocrine responses during chronic infections such as lung tuberculosis are poorly characterized. Hormonal changes are likely to occur since some of the cytokines produced during this disease could affect endocrine mechanisms that, in turn, influence the course of infectious/inflammatory processes. A main purpose of this work was to study endocrine responses involving pituitary, adrenal, gonadal, and thyroid hormones in parallel to IFN-gamma, IL-10, and IL-6 levels in tuberculosis patients with different degree of pulmonary involvement. We have also studied whether products derived from peripheral immune cells obtained from the patients can affect the in vitro production of adrenal steroids. The population studied comprised HIV-negative newly diagnosed, untreated male patients with mild, moderate, and advanced lung tuberculosis, and matched, healthy controls. IFN-gamma, IL-10, and IL-6 levels were elevated in patients with tuberculosis. Dehydroepiandrosterone and testosterone levels were profoundly decreased and growth hormone levels were markedly elevated in patients, in parallel to modest increases in cortisol, estradiol, prolactin, and thyroid hormone concentrations. Supernatants of peripheral blood mononuclear cells obtained from the patients and stimulated in vitro with Mycobacterium tuberculosis antigens significantly inhibited dehydroepiandrosterone secretion by the human adrenal cell line NCI-H295-R. These results support the hypothesis that at least some of the endocrine changes observed in the patients may be mediated by endogenous cytokines. The endocrine profile of tuberculosis patients would favor a reduction of protective cell-mediated immunity and an exacerbation of inflammation leading to perpetuation of the lung injury and to the hypercatabolic condition that characterizes this disease.
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
Swaminathan, Soumya; Datta, Manjula; Radhamani, M P; Mathew, Sara; Reetha, A M; Rajajee, Sarala; Mathew, Rema; Radhakrishnan, A; Raghu, M B
To describe the clinical profile of children with bacteriologically confirmed tuberculosis. A multicentric study was conducted in three hospitals in Chennai city between July 1995 and December 1997. Children aged 6 months to 12 years with signs and symptoms suggestive of tuberculosis were investigated further. Clinical examination, chest radiograph, tuberculin skin test with 1 TU PPD and, sputum or gastric lavage for mycobacterial smear and culture were done for all and, lymph node biopsy when necessary. A total of 2652 children were registered and tuberculosis was bacteriologically confirmed in 201. Predominant symptoms were history of an insidious illness (49%), fever and cough (47%), loss of weight (41%) and a visible glandular swelling (49%). Respiratory signs were few and 62% were undernourished. Over half the patients with confirmed TB had normal chest X-ray. Abnormal X-ray findings included parenchymal opacities in 47% and hilar or mediastinal lymphadenopathy in 26%. The prevalence of isoniazid resistance was 12.6% and MDR TB 4%. Children with tuberculosis present with fever and cough of insidious onset. Lymphadenopathy is a common feature even in children with pulmonary TB. A significant proportion of children have normal chest X-rays despite positive gastric aspirate cultures. Drug resistance rates in children mirror the pattern seen in adults in this geographic area.
Amorim Pellicioli, Ana Carolina; Neves-Silva, Rodrigo; Santos-Silva, Alan Roger; Vargas, Pablo Agustin; Lopes, Márcio Ajudarte
Paracoccidioidomycosis (PCM) and tuberculosis (TB) are chronic granulomatous infectious diseases, in which the main form of contraction is through inhalation of the microorganism-Paracoccidioides brasiliensis and Mycobacterium tuberculosis. Oral involvement of PCM is observed in up to 70 % of the cases and usually presents clinically as ulcerations with granular surface showing tiny hemorrhagic areas. Oral presentation of TB is rare with prevalence smaller than 0.5 % of all cases. Clinical presentation of oral TB mainly consists of single ulcers with irregular limits and necrotic base. A 70-year-old immunocompetent man presented simultaneously oral PCM and pulmonary TB. Medical history revealed a previous diagnosis of pulmonary TB; however, even under treatment for TB, the patient remained with oral lesions and intense pulmonary fibrosis. The physician requested P. brasiliensis serological analysis, which resulted positive. Although the combination of PCM and TB has been reported in the literature, it is still considered an uncommon condition and their diagnosis may represent a challenge to healthcare professionals because of the similarity between their clinical and radiological presentations.
Background The diagnosis of pulmonary tuberculosis in patients with Human Immunodeficiency Virus (HIV) is complicated by the increased presence of sputum smear negative tuberculosis. Diagnosis of smear negative pulmonary tuberculosis is made by an algorithm recommended by the National Tuberculosis and Leprosy Programme that uses symptoms, signs and laboratory results. The objective of this study is to determine the sensitivity and specificity of the tuberculosis treatment algorithm used for the diagnosis of sputum smear negative pulmonary tuberculosis. Methods A cross-section study with prospective enrollment of patients was conducted in Dar-es-Salaam Tanzania. For patients with sputum smear negative, sputum was sent for culture. All consenting recruited patients were counseled and tested for HIV. Patients were evaluated using the National Tuberculosis and Leprosy Programme guidelines and those fulfilling the criteria of having active pulmonary tuberculosis were started on anti tuberculosis therapy. Remaining patients were provided appropriate therapy. A chest X-ray, mantoux test, and Full Blood Picture were done for each patient. The sensitivity and specificity of the recommended algorithm was calculated. Predictors of sputum culture positive were determined using multivariate analysis. Results During the study, 467 subjects were enrolled. Of those, 318 (68.1%) were HIV positive, 127 (27.2%) had sputum culture positive for Mycobacteria Tuberculosis, of whom 66 (51.9%) were correctly treated with anti-Tuberculosis drugs and 61 (48.1%) were missed and did not get anti-Tuberculosis drugs. Of the 286 subjects with sputum culture negative, 107 (37.4%) were incorrectly treated with anti-Tuberculosis drugs. The diagnostic algorithm for smear negative pulmonary tuberculosis had a sensitivity and specificity of 38.1% and 74.5% respectively. The presence of a dry cough, a high respiratory rate, a low eosinophil count, a mixed type of anaemia and presence of a cavity were
Swai, Hedwiga F; Mugusi, Ferdinand M; Mbwambo, Jessie K
The diagnosis of pulmonary tuberculosis in patients with Human Immunodeficiency Virus (HIV) is complicated by the increased presence of sputum smear negative tuberculosis. Diagnosis of smear negative pulmonary tuberculosis is made by an algorithm recommended by the National Tuberculosis and Leprosy Programme that uses symptoms, signs and laboratory results.The objective of this study is to determine the sensitivity and specificity of the tuberculosis treatment algorithm used for the diagnosis of sputum smear negative pulmonary tuberculosis. A cross-section study with prospective enrollment of patients was conducted in Dar-es-Salaam Tanzania. For patients with sputum smear negative, sputum was sent for culture. All consenting recruited patients were counseled and tested for HIV. Patients were evaluated using the National Tuberculosis and Leprosy Programme guidelines and those fulfilling the criteria of having active pulmonary tuberculosis were started on anti tuberculosis therapy. Remaining patients were provided appropriate therapy. A chest X-ray, mantoux test, and Full Blood Picture were done for each patient. The sensitivity and specificity of the recommended algorithm was calculated. Predictors of sputum culture positive were determined using multivariate analysis. During the study, 467 subjects were enrolled. Of those, 318 (68.1%) were HIV positive, 127 (27.2%) had sputum culture positive for Mycobacteria Tuberculosis, of whom 66 (51.9%) were correctly treated with anti-Tuberculosis drugs and 61 (48.1%) were missed and did not get anti-Tuberculosis drugs. Of the 286 subjects with sputum culture negative, 107 (37.4%) were incorrectly treated with anti-Tuberculosis drugs. The diagnostic algorithm for smear negative pulmonary tuberculosis had a sensitivity and specificity of 38.1% and 74.5% respectively. The presence of a dry cough, a high respiratory rate, a low eosinophil count, a mixed type of anaemia and presence of a cavity were found to be predictive of
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.
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.
Srilohasin, Prapaporn; 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. PMID:25297330
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.
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.
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).
Liang, L; Shi, R; Liu, X; Yuan, X; Zheng, S; Zhang, G; Wang, W; Wang, J; England, K; Via, L E; Cai, Y; Goldfeder, L C; Dodd, L E; Barry, C E; Chen, R Y
Interferon-gamma (IFN-γ) release assays (IGRAs) are used to diagnose tuberculosis (TB) but not to measure treatment response. To measure IFN-γ response to active anti-tuberculosis treatment. Patients from the Henan Provincial Chest Hospital, Henan, China, with TB symptoms and/or signs were enrolled into this prospective, observational cohort study and followed for 6 months of treatment, with blood and sputum samples collected at 0, 2, 4, 6, 8, 16 and 24 weeks. The QuantiFERON® TB-Gold assay was run on collected blood samples. Participants received a follow-up telephone call at 24 months to determine relapse status. Of the 152 TB patients enrolled, 135 were eligible for this analysis: 118 pulmonary (PTB) and 17 extra-pulmonary TB (EPTB) patients. IFN-γ levels declined significantly over time among all patients (P = 0.002), with this decline driven by PTB patients (P = 0.001), largely during the initial 8 weeks of treatment (P = 0.019). IFN-γ levels did not change among EPTB patients over time or against baseline culture or drug resistance status. After 6 months of effective anti-tuberculosis treatment, IFN-γ levels decreased significantly in PTB patients, largely over the initial 8 weeks of treatment. IFN-γ concentrations may offer some value for monitoring anti-tuberculosis treatment response among PTB patients.
Londero, A T; Severo, L C
Paracoccidioidomycosis is an important Latin American endemy. The lung is the portal of entrance of the infection and the lesions are confined to this organ in, at least, 30 per cent of the progressive cases. Twelve case histories of patients with the progressive pulmonary form are presented in order to illustrate the repetitious clinical manifestations but the large variety of radiological presentations. The mycologic diagnosis is also emphasized.
Realpe, Teresa; Correa, Nidia; Rozo, Juan Carlos; Ferro, Beatriz Eugenia; 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
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. 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). 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 sublineage.
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
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.
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.
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
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.
Bedewi, Zufan; Worku, Adane; Mekonnen, Yalemtsehay; Yimer, Getnet; Medhin, Girmay; Mamo, Gezahegne; Pieper, Rembert; Ameni, Gobena
Identification of the types of strains of Mycobacterium tuberculosis (M. tuberculosis) complex causing tuberculosis (TB) could contribute to TB control program of specific geographic region as well as it could add knowledge onto the existing literature on TB worldwide. The objective of the present study was to identify the species and strains of M. tuberculosis complex causing pulmonary tuberculosis in central Ethiopia. A health institution- based cross-sectional study was conducted on 338 smear positive TB cases visiting three hospitals between October 2012 and September 2013. Morning and spot sputum samples were collected before the starting of treatment regimens. Thus, a total of 338 pooled sputum samples collected from these cases. Samples were cultured on Löwenstein Jensen media and the isolates were identified by the region of difference (RD) 9 based polymerase chain reaction (PCR) and spoligotyping. Of the total isolates 98.6% of the isolates were identified to be M. tuberculosis while the remaining 1.4% were identified as M. africanum. Further, typing of M. tuberculosis using spoligotyping lead to the identification of 90 different strains of M. tuberculosis. Of these strains, 32 were clustered consisting of more than one isolate while the remaining 58 strains were unique consisting of single isolate. Thus, 79.3% (223/281) of the isolates were found in the clustered while only 20.6% (58/281) of the strains were unique. Forty-five of the spolgotyping patterns were registeredin the SITVIT2 or SpolDB4 database in while the remaining 45 were notfound in the database and hence were orphan strains. The dominant strains were SIT53, SIT149, and SIT54, consisting of 43, 37 and 34 isolates, respectively. Classification of the spoligotype patterns using TB-insight RUN TB-Lineage showed that 86.8, 6.4, 5, 1.4% ofthe isolatesbelonged to the Euro-American lineage, East-African-Indian, Indo-oceanic and M. africanum, respectively. The identification of clustered and new
Huard, Richard C.; Chitale, Sadhana; Leung, Mary; Lazzarini, Luiz Claudio Oliveira; Zhu, Hongxia; Shashkina, Elena; Laal, Suman; Conde, Marcus B.; Kritski, AfrÂnio L.; Belisle, John T.; Kreiswirth, Barry N.; Lapa e Silva, José Roberto; Ho, John L.
Human tuberculosis (TB) is caused by the bacillus Mycobacterium tuberculosis, a subspecies of the M. tuberculosis complex (MTC) of mycobacteria. Postgenomic dissection of the M. tuberculosis proteome is ongoing and critical to furthering our understanding of factors mediating M. tuberculosis pathobiology. Towards this end, a 32-kDa putative glyoxalase in the culture filtrate (CF) of growing M. tuberculosis (originally annotated as Rv0577 and hereafter designated CFP32) was identified, cloned, and characterized. The cfp32 gene is MTC restricted, and the gene product is expressed ex vivo as determined by the respective Southern and Western blot testing of an assortment of mycobacteria. Moreover, the cfp32 gene sequence is conserved within the MTC, as no polymorphisms were found in the tested cfp32 PCR products upon sequence analysis. Western blotting of M. tuberculosis subcellular fractions localized CFP32 predominantly to the CF and cytosolic compartments. Data to support the in vivo expression of CFP32 were provided by the serum recognition of recombinant CFP32 in 32% of TB patients by enzyme-linked immunosorbent assay (ELISA) as well as the direct detection of CFP32 by ELISA in the induced sputum samples from 56% of pulmonary TB patients. Of greatest interest was the observation that, per sample, sputum CFP32 levels (a potential indicator of increasing bacterial burden) correlated with levels of expression in sputum of interleukin-10 (an immunosuppressive cytokine and a putative contributing factor to disease progression) but not levels of gamma interferon (a key cytokine in the protective immune response in TB), as measured by ELISA. Combined, these data suggest that CFP32 serves a necessary biological function(s) in tubercle bacilli and may contribute to the M. tuberculosis pathogenic mechanism. Overall, CFP32 is an attractive target for drug and vaccine design as well as new diagnostic strategies. PMID:14638775
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
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.
Keflie, Tibebe Seyoum; Ameni, Gobena
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. 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. 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). 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.
Bini, Estela Isabel; Mata Espinosa, Dulce; Marquina Castillo, Brenda; Barrios Payán, Jorge; Colucci, Darío; Cruz, Alejandro Francisco; Zatarain, Zyanya Lucía; Alfonseca, Edgar; Pardo, Marta Romano; Bottasso, Oscar; Hernández Pando, Rogelio
The relation between men and women suffering pulmonary tuberculosis is 7/3 in favor to males. Sex hormones could be a significant factor for this difference, considering that testosterone impairs macrophage activation and pro-inflammatory cytokines production, while estrogens are proinflammatory mediator's inducer. The aim of this work was to compare the evolution of tuberculosis in male and female mice using a model of progressive disease. BALB/c mice, male and female were randomized into two groups: castrated or sham-operated, and infected by the intratracheal route with a high dose of Mycobacterium tuberculosis strain H37Rv. Mice were euthanized at different time points and in their lungs were determined bacilli loads, inflammation, cytokines expression, survival and testosterone levels in serum. Non-castrated male mice showed significant higher mortality and bacilli burdens during late disease than female and castrated male animals. Compared to males, females and castrated males exhibited significant higher inflammation in all lung compartments, earlier formation of granulomas and pneumonia, while between castrated and non-castrated females there were not significant differences. Females and castrated males expressed significant higher TNF-α, IFN γ, IL12, iNOS and IL17 than non-castrated males during the first month of infection. Serum Testosterone of males showed higher concentration during late infection. Orchidectomy at day 60 post-infection produced a significant decrease of bacilli burdens in coexistence with higher expression of TNFα, IL-12 and IFNγ. Thus, male mice are more susceptible to tuberculosis than females and this was prevented by castration suggesting that testosterone could be a tuberculosis susceptibility factor.
Derseh, Dejene; Moges, Feleke; Tessema, Belay
Tuberculosis (TB) remains one of the world's deadliest communicable diseases. In Ethiopia, tuberculosis patients have different pattern of health care seeking behavior. They usually adopt other approaches like traditional healers and spiritual holy water sites before consulting public health facilities. This study was aimed to assess the prevalence of smear positive pulmonary tuberculosis and associated risk factors among tuberculosis suspects attending spiritual holy water sites. A cross-sectional study was conducted from February 01, 2015 to March 30, 2015 in seven selected holy water sites in Northwest Ethiopia. During the study period, a total of 1384 adult holy water users were screened for PTB symptoms. A total of 382 pulmonary tuberculosis suspects participated in the study. Socio-demographic data were collected using a semi-structured questionnaire. Spot-morning-spot sputum specimens were collected and examined for acid fast bacilli using Auramine O fluorescence staining technique. Smear positive sputum samples were tested by GeneXpert MTB/RIF assay for rifampicin resistance. Descriptive statistics, binary and multivariate logistic regression analysis were employed using SPSS-16 software. The prevalence of smear positive pulmonary tuberculosis was 2.9% with point prevalence of 795/100, 000 holy water users. History of contact with tuberculosis patient (AOR = 9.174, 95% C.I = 2.195-38.34) and the number of family members > 5 per household (AOR = 9.258, 95% C.I = 1.14-74.97) were significantly associated with smear positive pulmonary tuberculosis. Rifampicin resistance was not detected from all smear positives by GeneXpert MTB/RIF assay. The prevalence of smear positive pulmonary tuberculosis in spiritual holy water sites was 7.4 fold higher than the general population. History of contact with active tuberculosis patients and increased family size were significantly associated with smear positive pulmonary TB. The national tuberculosis
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
Shinohara, Tsutomu; Kagawa, Kozo; Okano, Yoshio; Sawada, Toru; Kobayashi, Tooru; Takikawa, Masaya; Iwahara, Yoshihito; Ogushi, Fumitaka
Early postpartum women are more likely to develop tuberculosis than nonpregnant women mainly due to immune reconstitution after delivery. Paradoxical response (PR) during antituberculosis treatment also arises via recovery from immunosuppression. However, no study focused on PR during antituberculosis treatment in a postpartum patient has been reported. We present two sequential cases (Patient 1: 26-year-old; Patient 2: 29-year-old) of postpartum tuberculosis with pulmonary and extrapulmonary lesions (Patient 1: peritonitis; Patient 2: psoas abscess secondary to spondylitis). Both cases progressed to PR (worsening of pre-existing lung infiltrations (Patients 1, 2) and new contralateral effusion (Patient 2)) in a relatively short time after initiation of treatment (Patient 1: 1 week; Patient 2: 3 weeks), suggesting that immune modulations during pregnancy and delivery may contribute to the pathogenesis of both disseminated tuberculosis and its PR. The pulmonary lesions and effusion of both cases gradually improved without change of chemotherapy regimen. Physicians should recognize PR in tuberculosis patients with postpartum and then evaluate treatment efficacy.
Devrim, Ilker; Aktürk, Hüseyin; Bayram, Nuri; Apa, Hurşit; Tulumoğlu, Sener; Devrim, Fatma; Erdem, Tülin; Gulfidan, Gamze; Ayhan, Yüce; Tamsel, Ipek; Can, Demet; Alper, Hüdaver
Tuberculosis (TB) remains a major global health problem. The childhood tuberculosis has some unique features different which makes the diagnosis more complicated. Here we described the epidemiologic, clinical and microbiologic features of children with extra pulmonary and pulmonary TB. The data of the patients <14 years with active TB were collected and compared in pulmonary (PTB) and extrapulmonary TB (EXPTB) patients. A total of 128 cases was included. Forty-two cases occurred in children were < 5 years of age; 41 cases between 6-10 years and 45 cases > 10 years. PTB was present in 75,0% of the cases, and EXPTB was present in 25% of cases. There was no significant difference between the EXPTB and PTB by means of distribution of age groups (p=0,201). The rate of patients free of constitutional symptoms were significantly higher in EXPTB compared to PTB(p=0,000). There was no significant difference between EXPTB and PTB by means of sources detection(p=0,069). TB is still a major public health problem. EXPTB has an insidious and silent onset without any constitutional symptoms, and both microbiological confirmation and the source by an adult are not frequently found. Moreover, detection of the adult source is mandatory for controlling the TB disease in children.
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.
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.
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.
Bertholet, Sylvie; Horne, David J; Laughlin, Elsa M; Savlov, Margery; Tucakovic, Ines; Coler, Rhea N; Narita, Masahiro; Reed, Steven G
The development of genomic and proteomic tools has enabled studies that begin to characterize the molecular targets of an effective host immune response to Mycobacterium tuberculosis, including understanding the specific immune responses associated with tuberculosis (TB) disease progression, disease resolution, and the development of latency. One application of such tools is the development of diagnostic reagents and assays useful as a test of cure. Such a test could be of considerable importance for the evaluation of new therapeutics. We and others have previously described immunodominant proteins of M. tuberculosis, including both vaccine and diagnostic candidates. In the present study, we describe the changes in immune responses to a panel of 71 M. tuberculosis antigens in six patients during the course of therapy. The levels of six cytokines were measured in 24-h whole-blood assays with these antigens, revealing that gamma interferon (IFN-γ), tumor necrosis factor (TNF), and interleukin-10 (IL-10) were differentially regulated in response to a subset of antigens. Therefore, measuring the production of these three cytokines in response to a panel of carefully selected M. tuberculosis proteins during the course of TB therapy might be a promising path toward the development of a test of cure and warrants further validation in larger cohorts of pulmonary TB patients.
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
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.
... 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 not...
... 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 not...
... 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 not...
... 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 not...
... 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 not...
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.
Bras, A L; Gomes, D; Filipe, P A; de Sousa, B; Nunes, C
Tuberculosis (TB) is a global public health concern. Surveillance programmes present invaluable epidemiological information regarding its temporal evolution, particularly for pulmonary tuberculosis (PTB), the most common form of TB and the one that presents the greatest challenge in public health. To characterise, model and predict monthly incidence rates for PTB in Portugal disaggregated by high/low-incidence areas, sex and age groups. PTB monthly incidence rates were estimated based on PTB cases diagnosed in 2000-2010, disaggregated by population and geographic characteristics. Seasonal-trend LOESS (STL) decomposition was employed to model trend and seasonality. Seasonal autoregressive integrated moving average (SARIMA) models were fit to characterise series behaviour and forecast PTB monthly incidence rates. Overall, the time series showed a downward trend in and seasonality of PTB diagnosis, with a peak in March and a trough in December. The mean seasonal amplitude was consistently higher in high-incidence areas, in males and in adults aged 25-54 years. SARIMA models were found to adequately fit and forecast the time series, thus predicting trend and seasonal persistence. STL and SARIMA findings concurred and were accurate. Endemic PTB seems to be slowly declining and case diagnosis is likely seasonal, which can be expected to persist if past conditions continue.
Skowroński, Marcin; Iwanik, Katarzyna; Halicka, Anna; Barinow-Wojewódzki, Aleksander
Lung cancer and pulmonary tuberculosis (TB) are highly prevalent and representing major public health issues. They share common risk factors and clinical manifestations. It is also suggested that TB predicts raised lung cancer risk likely related to chronic inflammation in the lungs. However, it does not seem to influence the clinical course of lung cancer provided that it is properly treated. We present a case report of a 57-year old male with concurrent TB and lung cancer. He was diagnosed with positive sputum smear for acid fast bacilli (AFB) and subsequent culture of Mycobacterium tuberculosis. Besides, his comorbid conditions were chronic hepatitis C virus (HCV) infection and peripheral artery disease (PAD). Later while on anti-tuberculous treatment (ATT) squamous cell lung cancer (SCC) was confirmed with computed tomography (CT) guided biopsy. Due to poor general condition the patient was not fit for either surgery or radical chemo- and radiotherapy. He was transferred to hospice for palliative therapy. We want to emphasize that both TB and lung cancer should be actively sought for in patients with either disorder. In addition, there is no doubt that these patients with lung cancer and with good response to TB treatment should be promptly considered for appropriate anticancer therapy.
Tiemersma, Edine W.; van der Werf, Marieke J.; Borgdorff, Martien W.; Williams, Brian G.; Nagelkerke, Nico J. D.
Background The prognosis, specifically the case fatality and duration, of untreated tuberculosis is important as many patients are not correctly diagnosed and therefore receive inadequate or no treatment. Furthermore, duration and case fatality of tuberculosis are key parameters in interpreting epidemiological data. Methodology and Principal Findings To estimate the duration and case fatality of untreated pulmonary tuberculosis in HIV negative patients we reviewed studies from the pre-chemotherapy era. Untreated smear-positive tuberculosis among HIV negative individuals has a 10-year case fatality variously reported between 53% and 86%, with a weighted mean of 70%. Ten-year case fatality of culture-positive smear-negative tuberculosis was nowhere reported directly but can be indirectly estimated to be approximately 20%. The duration of tuberculosis from onset to cure or death is approximately 3 years and appears to be similar for smear-positive and smear-negative tuberculosis. Conclusions Current models of untreated tuberculosis that assume a total duration of 2 years until self-cure or death underestimate the duration of disease by about one year, but their case fatality estimates of 70% for smear-positive and 20% for culture-positive smear-negative tuberculosis appear to be satisfactory. PMID:21483732
Hsieh, Yao-Peng; Wen, Yao-Ko
A 66-year-old man with uremia and on hemodialysis was referred to our hospital because of hemoptysis. A chest radiograph showed diffuse infiltration in the right lung field. Laboratory data were remarkable for renal failure accompanied by hematuria and proteinuria. A kidney biopsy revealed diffuse crescentic glomerulonephritis with linear staining of IgG along the glomerular basement membrane (GBM). Circulating IgG anti-GBM antibody was not detected. Because the findings of renal biopsy suggested anti-GBM disease, the patient was treated with plasmapheresis and pulse steroid therapy, which resulted in a rapid resolution of his pulmonary symptoms and chest radiograph abnormalities. However, sputum culture submitted on admission yielded Mycobacterium tuberculosis 3 weeks later. Therefore, immunosuppressive agents were discontinued and antituberculous agents were administrated. No relapse of pulmonary hemorrhage occurred during the next 1-year period of follow-up, but the patient did not regain renal function and remained on hemodialysis.
Wen, Yao-Ko; Wen, Kai-I
A 72-year-old man with ESRD on hemodialysis was referred to the hospital because of hemoptysis. A chest radiograph showed diffuse infiltration in the right lung field. Laboratory data showed hematuria and proteinuria. A kidney biopsy revealed diffuse crescentic glomerulonephritis with linear staining of IgG along the glomerular basement membrane (GBM). However, circulating IgG anti-GBM antibodies were not detected. Because the findings of renal biopsy suggested Goodpasture's disease, the patient was treated with plasmapheresis and pulse steroid therapy, which resulted in a rapid resolution of his pulmonary symptoms and chest radiograph abnormalities. However, sputum culture on admission yielded Mycobacterium tuberculosis 3 weeks later. Therefore, immuosuppressive agents were discontinued and antituberculous agents were administered. There was no relapse of pulmonary hemorrhage during the next 1-year period of follow-up, but the patient did not regain renal function and remained on hemodialysis.
Dross, V P
A critical retrospective analysis of 14 cases of bilateral staged pulmonary resections for the treatment of pulmonary tuberculosis is described. Lobectomies with or without segmentectomies were the preferred procedures. The four positive cases had mostly cavitary disease (85%) with positive bacteriologic culture from the specimens (75%). The ten negative cases had less cavitary disease (65%) with negative bacteriologic culture of the specimens (90%). Positive residual bacteriologic specimen activity (10%) of the negative group favors the surgical removal of residual disease, despite the fact that 45% have no culture or bacterial stain obtained. Negative residual bacteriologic specimen activity (25%) of the positive group indicates the limitations of inadequate surgery. Thus the indications of surgery may gradually reestablish their own crieteria in this era of massive chemotherapy.
Dixit, Ramakant; Gupta, Rakesh; Dave, Lokendra; Prasad, Nishi; Sharma, Sidharth
This study was planned to define the clinical profile of pulmonary tuberculosis (PTB) patients having renal amyloidosis, to identify the factors responsible for development of amyloidosis, to detect the time period between onset of amyloidosis and PTB, and analyze clinical features of amyloidosis in PTB patients for early diagnosis and timely assessment. Patients of PTB having pedal edema, proteinuria, and grossly diseased kidneys on ultrasound abdomen were subjected to renal biopsy and appropriate biochemical investigations. Clinical profile of biopsy proven amyloidosis cases was analyzed. There were 43 patients (32 males, 11 females, age range 20-65 years) having PTB with pedal edema, proteinuria, and renal medical disease on abdominal ultrasound where amyloidosis was confirmed by renal biopsy. The total duration of illness ranged from two months to seven years (mean 2.25 years) and was less than five years in 93% patients. All patients had significant proteinuria. Nephrotic syndrome was seen in 23, hypertension in 19, hypoalbuminemia in 33, hypercholesterolemia in 29, and deranged renal functions in 32 patients. Ninety percent patients had moderate to far advanced pulmonary lesions on chest radiography with smear positivity in 21 patients. Renal amyloidosis is an important complication of PTB and should be suspected clinically in patients presenting with a triad of pedal edema, proteinuria, and medical renal disease on ultrasound. Contrary to general belief, renal amyloidosis may occur in PTB patients having disease for relatively shorter duration, and even if adequately treated.
Dixit, Ramakant; Gupta, Rakesh; Dave, Lokendra; Prasad, Nishi; Sharma, Sidharth
Objectives: This study was planned to define the clinical profile of pulmonary tuberculosis (PTB) patients having renal amyloidosis, to identify the factors responsible for development of amyloidosis, to detect the time period between onset of amyloidosis and PTB, and analyze clinical features of amyloidosis in PTB patients for early diagnosis and timely assessment. Materials and Methods: Patients of PTB having pedal edema, proteinuria, and grossly diseased kidneys on ultrasound abdomen were subjected to renal biopsy and appropriate biochemical investigations. Clinical profile of biopsy proven amyloidosis cases was analyzed. Results: There were 43 patients (32 males, 11 females, age range 20–65 years) having PTB with pedal edema, proteinuria, and renal medical disease on abdominal ultrasound where amyloidosis was confirmed by renal biopsy. The total duration of illness ranged from two months to seven years (mean 2.25 years) and was less than five years in 93% patients. All patients had significant proteinuria. Nephrotic syndrome was seen in 23, hypertension in 19, hypoalbuminemia in 33, hypercholesterolemia in 29, and deranged renal functions in 32 patients. Ninety percent patients had moderate to far advanced pulmonary lesions on chest radiography with smear positivity in 21 patients. Conclusions: Renal amyloidosis is an important complication of PTB and should be suspected clinically in patients presenting with a triad of pedal edema, proteinuria, and medical renal disease on ultrasound. Contrary to general belief, renal amyloidosis may occur in PTB patients having disease for relatively shorter duration, and even if adequately treated. PMID:20440393
Kim, Ji Hae; Lee, Choon-Taek; Yoon, Ho Il; Song, Junghan; Shin, Wan Gyoon; Lee, Jae Ho
Malnutrition is a prominent feature of tuberculosis. Little is known about the role of the appetite-related hormones, ghrelin and leptin, in malnutrition in tuberculosis. This study was undertaken to determine whether ghrelin and leptin contribute to malnutrition in active pulmonary tuberculosis. Nutritional parameters and plasma levels of ghrelin, leptin, and inflammatory cytokines were measured before treatment and after clinical improvement following anti-tuberculosis chemotherapy in 23 tuberculosis subjects and 23 healthy controls prospectively. Patients were divided into well-nourished (n=15) and malnourished (n=8) groups. Ghrelin but not leptin levels were significantly lower in the malnourished tuberculosis group than in the well-nourished tuberculosis group [44.0 (43.0-54.0) vs. 122 (108-158)pg/mL; p<0.05]. Malnutrition score was negatively correlated to ghrelin (rho=-0.76, p<0.01) but not to leptin levels. TNF-alpha and IL-6 levels were significantly higher in the malnourished tuberculosis group than in the well-nourished tuberculosis group and controls. Plasma levels of ghrelin tended to decrease as inflammatory cytokines increased before treatment. Decreased plasma ghrelin levels, in addition to increased plasma inflammatory cytokine levels, may be associated with malnutrition in active pulmonary tuberculosis. Copyright 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
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.
Fung, W. P.; Tan, K. K.; Yu, S. F.; Kho, K. M.
A case of malabsorption and subtotal villous atrophy secondary to pulmonary and intestinal tuberculosis is reported. The patient was a 21-year-old Chinese girl who had active pulmonary tuberculosis, malabsorption, subtotal villous atrophy, atrophic gastritis with hypochlorhydria, ileal stricture, and a severe non-specific anaemia. There was also evidence to suggest protein-losing enteropathy. The association of subtotal villous atrophy and atrophic gastritis with tuberculosis is discussed. When antituberuclous therapy was instituted, improvement was marked not only clinically but also in the tests for intestinal absorption and in the jejunal mucosa. ImagesFig. 1Fig. 2Fig. 3Fig. 4 PMID:5423899
Urazova, O I; Novitskii, V V; Kolobovnikova, Yu V; Churina, E G
We studied possible mechanisms of immunosuppression mediated by regulatory T cells that promotes suppression of antigen-specific immune response to Mycobacterium tuberculosis in patients with pulmonary tuberculosis and eosinophilia. It was shown that the number of CD4(+)CD25(+)Foxp3(+) regulatory T cells with immunosuppressive activity (Treg) increased in the peripheral blood of patients with disseminated destructive forms of pulmonary tuberculosis with multiple resistance of the causative agent to antituberculosis substances and eosinophilia. These changes were accompanied by imbalance in secretion of Treg-associated cytokines (in vitro) manifested in hyperproduction of TGFβ and IL-10 and decreased production of IL-2.
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
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
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.
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
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).
Moreno, Javier Rangel; García, Iris Estrada; de la Luz García Hernández, María; Leon, Diana Aguilar; Marquez, Ricardo; Pando, Rogelio Hernández
Prostaglandins (PG) are potent mediators of intercellular communication, and PGE2 at high concentration is immunosuppressive for T-cell-mediated immunity. We studied the kinetics of PGE2 production and the expression of the enzymes related to its synthesis during the course of experimental pulmonary tuberculosis. Secondly, we analysed the pathological and immunological changes produced by the pharmacological suppression of PG production. In BALB/c mice infected via the trachea with Mycobacterium tuberculosis H37Rv there is an initial phase of partial resistance, dominated by type 1 cytokines plus tumour necrosis factor-α (TNF-α) and expression of the inducible form of nitric oxide synthase (iNOS), followed by a phase of progressive disease. During the early phase of the infection some activated macrophages located in the alveolar-capillary interstitium and in granulomas showed strong PGE2 immunostaining. However, PGE2 concentrations were relatively low and stable. Animals in this early phase of infection were treated with niflumic acid, a potent and specific blocker of cyclo-oxygenase 2, the rate-limiting enzyme of PG production. In comparison with control animals, the suppression of PG synthesis produced higher inflammation and expression of TNF-α, interleukin-1α and interferon-γ (IFN-γ), but almost complete disappearance of iNOS expression, which coexisted with a significant increment of bacterial load. The late progressive phase in this experimental model is characterized by progressive pneumonia, small granulomas and diminished expression of IFN-γ, TNF-α and iNOS in coexistence with high expression of IL-4. Strong PGE2 immunostaining was seen in foamy macrophages localized in the pneumonic areas, and the PGE2 concentration was four-fold higher in this late phase of infection than during the early phase. When PG production was suppressed in animals suffering advanced phase infection, a significant reduction of pneumonia and bacillus load with striking
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
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
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
Wexler, Isaiah D; Johannesson, Marie; Edenborough, Frank P; Sufian, Beth S; Kerem, Eitan
Progressive pulmonary disease may preclude the option of pregnancy for a number of women in their child-bearing years due to the severity of the disease. For a subset of women with chronic lung disease including cystic fibrosis, pregnancy is possible, but can have a devastating effect both on the prospective mother and fetus. The potential hazards of pregnancy in cystic fibrosis or other progressive pulmonary diseases may trigger a moral conflict between physician and patient. The female patient may argue that her autonomy cannot be circumscribed and that the physician is obliged to assist her reproductive efforts. The physician can counter that his/her participation in potentially harmful interventions is not consistent with professional norms requiring adherence to the principles of beneficence and nonmaleficence. Whenever possible, the ethical conflict between physician and patient should be resolved before initiation of pregnancy. We propose that this best be done through structured negotiations between physician and patient with the goal of constructing an ethical framework for reducing the moral tension between the two. Steps in the negotiating process include defining the therapeutic alliance, information exchange, dialog, and deliberation. As part of the information exchange, it is important to discuss alternatives to pregnancy such as adoption and surrogacy, especially when there are strong contraindications to pregnancy. If negotiations reach a satisfactory conclusion for both sides, there should be a well-delineated consensual agreement to commence the pregnancy with the full support of the medical team.
Zheng, Ruijuan; Zhu, Changtai; Guo, Qi; Qin, Lianhua; Wang, Jie; Lu, Junmei; Cui, Haiyan; Cui, Zhenling; Ge, Baoxue; Liu, Jinming; Hu, Zhongyi
Multidrug-resistant tuberculosis (MDR-TB) is a major public health problem. Early diagnosis of MDR-TB patients is essential for minimizing the risk of Mycobacterium tuberculosis (MTB) transmission. The conventional drug susceptibility testing (DST) methods for detection of drug-resistant M. tuberculosis are laborious and cannot provide the rapid detection for clinical practice. The aim of this study was to develop a pyrosequencing approach for the simultaneous detection of resistance to rifampin (RIF), isoniazid (INH), ethambutol (EMB), streptomycin (SM), ofloxacin (OFL) and amikacin (AMK) in M. tuberculosis clinical isolates and sputum samples from re-treatment pulmonary tuberculosis (PTB) patients. We identified the optimum conditions for detection mutation of rpoB, katG, rpsl, embB, gyrA and rrs gene by pyrosequencing. Then this approach was applied to detect 205 clinical isolates and 24 sputum samples of M. tuberculosis from re-treatment PTB patients. The mutations of rpoB and gyrA gene were detected by pyrosequencig with the SQA mode, and the mutations of katG, rpsl, embB, gyrA and rrs gene were detected by pyrosequencing with SNP mode. Compared with the Bactec MGIT 960 mycobacterial detection system, the accuracy of pyrosequencing for the detection of RIF, INH, EMB, SM, AMK and OFL resistance in clinical isolates was 95.0%, 79.2%, 70.3%, 84.5%, 96.5% and 91.1%, respectively. In sputum samples the accuracy was 83.3%, 83.3%, 60.9%, 83.3%, 87.5% and 91.7%, respectively. The newly established pyrosequencing assay is a rapid and high-throughput method for the detection of resistance to RIF, INH, SM, EMB, OFL and AMK in M. tuberculosis. Pyrosequencing can be used as a practical molecular diagnostic tool for screening and predicting the resistance of re-treatment pulmonary tuberculosis patients.
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
Zhang, Shao-Ru; Yan, Hong; Zhang, Jin-Jing; Zhang, Tian-Hua; Li, Xiao-Hong; Zhang, Yin-Ping
The prevalence of pulmonary tuberculosis among college students in Shaanxi is high. Although tuberculosis leaves much psychological and social impact on patients, little is known about its impact on college students. The objective of this study is to explore the experiences and psychological process of college students with pulmonary tuberculosis in Shaanxi, China. 17 college students with pulmonary tuberculosis were recruited purposively from 9 colleges in Shaanxi. In-depth interviews were conducted to collect data and a thematic framework analysis was used. The participants reported that pulmonary tuberculosis deeply influenced their mental health. They were fearful to the nature of pulmonary tuberculosis at the stage of diagnosis, anxious about the illness before the period of diagnosis and the early week of the treatment, excessive worry immediately before the first recheck. They expected an early full recovery, bored on tedious treatment life and worried about future heath and prospects during the whole treatment phase. Their daily life was also influenced, namely discontinued studies, isolation and increased financial burden. They also reported that they could get strong supports from family members, while little supports from healthcare workers and their friends. The participants' psychological pressure was significant during the treatment. In addition, there was serious conflict between treatment and study; social support provided for them was insufficient. Healthcare workers should provide psychological support for college students with pulmonary tuberculosis according to the psychological characteristics and offer social support through strengthening communication with them. Colleges should follow governmental policies on TB exactly and provide opportunities for the patients to continue their studies.
Masala, C; Amendolea, M A; Bonini, S
An indirect immunofluorescence technique and an indirect immunoperoxidase technique were used on cryostat sections of human group-O submaxillary salivary gland and rat stomach. Circulating antibodies reacting with mucus antigen(s) were found in sera from 52-7% of patients with active pulmonary tuberculosis and in 21-8% of patients with chronic obstructive lung disease. Among hospital patients with other diseases and healthy controls, mucus antibodies were found in 7-2 and 5.4% respectively. The mucus antibodies were not absorbed by an excess of red blood-cells derived from group AD+ healthy subjects or from the rat donor of the stomach, while the fluorescence and the immunoperoxidase reactions were almost completely abolished after the absorption of positive sera with human dried bronchial secretion. It is postulated that mucus antibody may be a new and important serological marker of disorders accompanied by mucus accumulation in the lung and possibly other organs and/or by severe changes of the anatomical structures which act as a barrier to the reabsorption of abnormal amounts of mucus.
Salinas, J; Calvillo, S; Caylà, J; Nedel, F B; Martín, M; Navarro, A
To determine diagnostic delay in pulmonary tuberculosis (PTB) cases and analyse associated factors. New PTB cases were studied in Coahuila, Northern Mexico, between 2008 and 2009. We obtained census data and data on residential address, symptoms and diagnosis from the national patient database; sociodemographic variables were obtained during home visits. Bivariate analyses used the Kaplan-Meier method; multivariate analysis consisted of modelling survival. We studied 458 subjects (median age 48 years), who were predominantly males (56.1%); the median years of schooling was 6.0 years, 83.4% were urban residents, 50.3% were unemployed, and 87.7% suffered from food poverty. The median delay between the onset of symptoms and the first medical consultation was 53.5 days. Lack of formal education (P = 0.050) and living ≥5 km from a health unit (P = 0.034) were associated with longer delays and consequently with severe symptoms (cough ≥2 weeks, P = 0.001; chest pain, P = 0.032; malnutrition, P = 0.003). Mean health system delay (between first consultation and smear test result) was 18.5 days, and was significantly longer when the first consultation was with a private physician (P < 0.001) and when patient age was ≥46 years (P = 0.001). In Coahuila, lack of formal education, living ≥5 km from a health unit, first consultation with a private physician, and being aged ≥46 years contributed to delays in PTB diagnosis.
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
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. 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). 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. 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.
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
Suganthi, P; Chadha, V K; Ahmed, J; Umadevi, G; Kumar, P; Srivastava, R; Magesh, V; Gupta, J; Sharda, M A
Bangalore city slums, India. To ascertain 1) health-seeking behaviour patterns in persons with pulmonary symptoms; 2) pathways followed by pulmonary tuberculosis (PTB) cases until diagnosis and treatment; and 3) their knowledge about TB-symptoms, cause, mode of transmission, diagnosis and treatment. In selected slums, persons with pulmonary symptoms identified during house visits and residents with PTB were interviewed using pre-tested, semi-structured questionnaires. Visits to relevant health centres were made to obtain information regarding their treatment. About 50% of the 124 persons with pulmonary symptoms interviewed had taken action for relief; of these, three quarters had first approached private health facilities. About 19% had undergone sputum microscopy and 27% chest X-ray. Of 47 PTB cases interviewed, 72% first approached private health facilities; about 50% visited two health facilities before diagnosis and 87% visited two or more facilities before initiating treatment; 42 initiated treatment at government health facilities and five who initiated treatment at private health facilities were later referred to government health facilities. The majority of persons with pulmonary symptoms and PTB cases had poor knowledge about TB, and most of those with pulmonary symptoms were not aware of the availability of free anti-tuberculosis services at government health facilities. Educational interventions targeted at slum dwellers and their health providers are needed.
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
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
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.
Ugalde, Israel; Pirela, Daniela; Lo Presti, Saberio; Bilderback, Molly; Pirela, Andrés; Chan, Joseph
In developed countries, tuberculosis remains a health care challenge due to human immunodeficiency virus (HIV) and immigration from endemic regions. The Centers for Disease Control and Prevention reported 9557 new cases in 2015, with extrapulmonary involvement in 20.2% of the cases. We present a 33-year-old woman from Cape Town, South Africa, who developed abdominal pain and fever while working on a cruise ship. She sought medical where she underwent computed tomography of her chest, abdomen, and pelvis with findings suggestive of pulmonary tuberculosis and an 8.9-cm pelvic mass. HIV testing was positive and the patient was started on antiretroviral therapy. Bronchoscopy confirmed the presence of acid-fast bacilli, and she was started on rifampin, isoniazid, pyrazinamide, and ethambutol. She remained persistently febrile, raising suspicion for immune reconstitution inflammatory syndrome. However, despite empiric antibiotics, the patient remained persistently febrile, tachycardic, and on day 10 of admission she went into ventricular fibrillation and expired. Autopsy revealed an occlusive thrombus in the left main pulmonary artery in addition to necrotizing granulomata in multiple organs and bilateral tubo-ovarian abscesses. Postmortem cultures for were positive for Mycobacterium tuberculosis, all consistent with disseminated Mycobacterium tuberculosis. Although previous reports underscore the association between tuberculosis and hypercoagulability, the exact mechanism remains unknown. In this article, we report a case of disseminated tuberculosis complicated by bilateral tubo-ovarian abscesses with fatal pulmonary thrombus formation.
Schuhmacher Neto, R; Giacomelli, I L; Schuller Nin, C; da Silva Moreira, J; Comaru Pasqualotto, A; Marchiori, E; Loureiro Irion, K; Hochhegger, B
To assess the high-resolution computed tomography (HRCT) findings in liver transplant patients diagnosed with pulmonary Mycobacterium tuberculosis infection. The HRCT findings from 19 patients diagnosed with pulmonary tuberculosis infection after liver transplantation were reviewed. The patients included were 12 men and seven women, age range 23-65 years; mean age 57 years. The diagnosis was established with Mycobacterium tuberculosis detection in bronchoalveolar lavage, sputum, or biopsy. HRCT images were reviewed independently by two observers who reached a consensus decision. The HRCT findings were classified as (1) miliary nodules; (2) cavitation and centrilobular tree-in-bud nodules; (3) ground-glass attenuation and consolidation; and (4) mediastinal lymph node enlargement. The time between the transplantation and the diagnosis of pulmonary tuberculosis ranged from 7 to 153 days with an average of 79 days. The main HRCT pattern was cavitation and centrilobular tree-in-bud nodules (79%) followed by mediastinal lymph node enlargement (10.4%), ground-glass attenuation or consolidation (5.2%) and miliary nodules (5.2%). None of the patients presented pleural effusion. The cavitation and centrilobular tree-in-bud nodules pattern had upper lobe predominance, and ground-glass attenuation and consolidation pattern had middle lobe/lingular segment predominance. The main HRCT pattern of pulmonary tuberculosis in liver transplant patients was cavitation and centrilobular tree-in-bud nodules. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
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
Zar, Heather J; Workman, Lesley J; Little, Francesca; Nicol, Mark P
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. 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. 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%]). Entry criteria for diagnostic studies should not be restrictive. Data from this analysis have informed revision of the NIH definitions. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.
Ozden, Kemalettin; Araz, Omer; Ucar, Elif Yilmazel; Alper, Fatih; Akgun, Metin
Silicosis is a well-known occupational lung disease that was discovered by the ancient Greeks and Romans. In 2001, it has emerged again in an unexpected occupation: denim sandblasting. Exposure to crystalline silica, with or without clinical disease, is one of the most important predisposing factors for the development of tuberculosis; however, there has been no previous report of tuberculosis among cases of silicosis due to denim sandblasting. Herein, we report the first case of a denim sandblaster with silicosis who developed both pulmonary tuberculosis and tuberculous meningitis. PMID:25610207
Ozden, Kemalettin; Araz, Omer; Ucar, Elif Yilmazel; Alper, Fatih; Akgun, Metin
Silicosis is a well-known occupational lung disease that was discovered by the ancient Greeks and Romans. In 2001, it has emerged again in an unexpected occupation: denim sandblasting. Exposure to crystalline silica, with or without clinical disease, is one of the most important predisposing factors for the development of tuberculosis; however, there has been no previous report of tuberculosis among cases of silicosis due to denim sandblasting. Herein, we report the first case of a denim sandblaster with silicosis who developed both pulmonary tuberculosis and tuberculous meningitis.
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
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.
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
Proaño, Alvaro; 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
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. 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. 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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
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.
Nihues, Simone de Sousa Elias; Mancuzo, Eliane Viana; Sulmonetti, Nara; Sacchi, Flávia Patussi Correia; Viana, Vanessa de Souza; Netto, Eduardo Martins; Miranda, Silvana Spindola; Croda, Julio
Questionnaire and spirometry were applied to post-tuberculosis indigenous and non-indigenous individuals from Dourados, Brazil, to investigate the prevalence of chronic respiratory symptoms and pulmonary dysfunction. This was a cross-sectional study in cured tuberculosis individuals as reported in the National System on Reportable Diseases (SINAN) from 2002 to 2012. One hundred and twenty individuals were included in the study and the prevalence of chronic respiratory symptoms was 45% (95% CI, 34-59%). Respiratory symptoms included cough (28%), sputum (23%), wheezing (22%) and dyspnea (8%). These symptoms were associated with alcoholism, AOR: 3.1 (1.2-8.4); less than 4 years of schooling, AOR: 5.0 (1.4-17.7); and previous pulmonary diseases, AOR: 5.4 (1.7-17.3). Forty-one percent (95% CI, 29-56) had pulmonary disorders, of which the most prevalent were obstructive disorders (49%), followed by obstructive disorder with reduced forced vital capacity disorders (46%) and restrictive disorders (5%). The lifestyle difference could not explain differences in chronic symptoms and/or the prevalence of pulmonary dysfunction. The high prevalence of chronic respiratory symptoms and pulmonary dysfunction in post-tuberculosis patients indicates a need for further interventions to reduce social vulnerability of patients successfully treated for tuberculosis. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.
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
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
Tuberculosis (TB) remains a public health problem in Mexico while the incidence of diabetes mellitus type 2 (DM) has increased rapidly in recent years. 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. 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. 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. 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.
Fox, Gregory J.; Sy, Dinh Ngoc; Nhung, Nguyen Viet; Yu, Bing; Ellis, Magda K.; Van Hung, Nguyen; Cuong, Nguyen Kim; Thi Lien, Luu; Marks, Guy B.; Saunders, Bernadette M.; Britton, Warwick J.
Background Tuberculosis (TB) is an infectious disease that remains a major cause of morbidity and mortality worldwide, yet the reasons why only 10% of people infected with Mycobacterium tuberculosis go on to develop clinical disease are poorly understood. Genetically determined variation in the host immune response is one factor influencing the response to M. tuberculosis. SP110 is an interferon-responsive nuclear body protein with critical roles in cell cycling, apoptosis and immunity to infection. However association studies of the gene with clinical TB in different populations have produced conflicting results. Methods To examine the importance of the SP110 gene in immunity to TB in the Vietnamese we conducted a case-control genetic association study of 24 SP110 variants, in 663 patients with microbiologically proven TB and 566 unaffected control subjects from three tertiary hospitals in northern Vietnam. Results Five SNPs within SP110 were associated with all forms of TB, including four SNPs at the C terminus (rs10208770, rs10498244, rs16826860, rs11678451) under a dominant model and one SNP under a recessive model, rs7601176. Two of these SNPs were associated with pulmonary TB (rs10208770 and rs16826860) and one with extra-pulmonary TB (rs10498244). Conclusion SP110 variants were associated with increased susceptibility to both pulmonary and extra-pulmonary TB in the Vietnamese. Genetic variants in SP110 may influence macrophage signaling responses and apoptosis during M. tuberculosis infection, however further research is required to establish the mechanism by which SP110 influences immunity to tuberculosis infection. PMID:25006821
Honarvar, B; Odoomi, N; Rezaei, A; Haghighi, H B; Karimi, M; Hosseini, A; Mazarei, S; Panahi, M; Jamshidi, F; Moghadami, M; Lankarani, K B
To detect pulmonary tuberculosis (PTB) in migratory nomadic populations in Fars Province, southern Iran. Cross-sectional study. In this study, 5506 (82.8%) of a total nomad population of 6650 from 1337 tents were screened for PTB. The mean age was 27.4 ± 18.2 years (range 1-109). Based on clinical symptoms, 141/5506 (2.6%) were identified as TB suspects. One male and three female adult new smear-positive PTB cases were detected, giving an incidence rate of 0.7/1000 population compared to 0.08/1000 in the general population of the region, and 28.4/1000 TB suspects. The median time to onset of symptoms in detected cases was 82.5 days. Tribal stigma against female TB patients was one of the main barriers to appropriate health-seeking behaviour. The incidence of smear-positive PTB among migratory nomads is approximately nine-fold higher than in the general population. Active screening of TB in migratory nomads should be integrated into Iran's national TB control programme. The issue of destigmatisation, particularly among female TB patients, should also be addressed.
Zenebe, Tizazu; Tefera, Ermias
Evaluating the outcomes of tuberculosis treatment and understanding the specific reasons for unfavorable treatment outcome are important in evaluating the effectiveness of tuberculosis control program. A retrospective study was conducted to assess tuberculosis treatment outcomes and associated factors among smear positive pulmonary tuberculosis patients in zone-one health facilities of Afar regional state, Ethiopia. A total of 380 smear positive pulmonary tuberculosis patients' registration book recorded with complete information from Jan 2011 to Dec 2013 were analyzed. Of 380 patients included in the analysis, 238 were male and 142 female with mean age of 30.7. Overall treatment outcome were 128 (33.7%) cured, 192 (50.2%) completed, 17 (4.5%) died, 1 (0.3%) treatment failure, 34 (8.9%) default and 8 (2.1%) transfer out. Treatment success rate was 81.8%. There was statistically significance association between age (p-value=0.000), sex (p-value=0.018), HIV status (p-value=0.000), four week attendance (p-value=0.000), sputum follow up test (p-value=0.000), and treatment outcome year (p-value=0.000), and treatment success (p-value=0.000). Treatment success rate almost reached to the WHO targets although yet need to work a lot for fulfillment of global targets. Regular four week attendance in continuation phase and doing follow up sputum test with unsuccessful outcome for smear positive tuberculosis patient were vital. Copyright © 2016 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.
Abashev, I M; Kozlova, A I; Ivanova, L N
Treatment of 63 patients having infiltrative and disseminated pulmonary tuberculosis attended by decay and bacterial excretion with 4 essential drugs (isoniazid, rifadine, pyrazinamide, ethambutol) and, in disseminated processes, additionally with streptomycin without determining their drug sensitivity contributed to the cessation of sputum acid-resistant mycobacteria in 96.8% and to cavity cicatrisation in 77.8%. Irregular use of izoniazid and rifadine during continued treatment is one of the reasons for the low rates of cavity resolution.
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
Rangel-Santiago, Jesus F; Baay-Guzman, Guillermina J; Duran-Padilla, Marco A; Lopez-Bochm, Karla A; Garcia-Romero, Beatriz L; Hernandez-Cueto, Daniel D; Pantoja-Escobar, Gerardo; Vega, Mario I; Hernandez-Pando, Rogelio; Huerta-Yepez, Sara
Mycobacterium tuberculosis (M. tb) is the etiological agent of pulmonary tuberculosis (TB); this disease remains a worldwide health problem. Yin-Yang-1 (YY1) plays a major role in the maintenance and progression of some pulmonary diseases, including pulmonary fibrosis. However, the role of YY1 in TB remains unknown. The aim of this study was to elucidate the role of YY1 in the regulation of CCL4 and its implication in TB. We determined whether YY1 regulates CCL4 using reporter plasmids, ChIP and siRNA assays. Immunohistochemistry and digital pathology were used to measure the expression of YY1 and CCL4 in a mouse model of TB. A retrospective comparison of patients with TB and control subjects was used to measure the expression of YY1 and CCL4 using tissue microarrays. Our results showed that YY1 regulates the transcription of CCL4; moreover, YY1, CCL4 and TGF-β were overexpressed in the lung tissues of mice with TB during the late stages of the disease and the tissues of TB patients. The expression of CCL4 and TGF-β correlated with YY1 expression. In conclusion, YY1 regulates CCL4 transcription; moreover, YY1 is overexpressed in experimental and human TB and is positively correlated with CCL4 and TGF-β expression. Therefore, treatments that decrease YY1 expression may be a new therapeutic strategy against TB. Copyright © 2015 Elsevier Ltd. All rights reserved.
Pai, Madhukar; Behr, Marcel A; Dowdy, David; Dheda, Keertan; Divangahi, Maziar; Boehme, Catharina C; Ginsberg, Ann; Swaminathan, Soumya; Spigelman, Melvin; Getahun, Haileyesus; Menzies, Dick; Raviglione, Mario
Tuberculosis (TB) is an airborne infectious disease caused by organisms of the Mycobacterium tuberculosis complex. Although primarily a pulmonary pathogen, M. tuberculosis can cause disease in almost any part of the body. Infection with M. tuberculosis can evolve from containment in the host, in which the bacteria are isolated within granulomas (latent TB infection), to a contagious state, in which the patient will show symptoms that can include cough, fever, night sweats and weight loss. Only active pulmonary TB is contagious. In many low-income and middle-income countries, TB continues to be a major cause of morbidity and mortality, and drug-resistant TB is a major concern in many settings. Although several new TB diagnostics have been developed, including rapid molecular tests, there is a need for simpler point-of-care tests. Treatment usually requires a prolonged course of multiple antimicrobials, stimulating efforts to develop shorter drug regimens. Although the Bacillus Calmette-Guérin (BCG) vaccine is used worldwide, mainly to prevent life-threatening TB in infants and young children, it has been ineffective in controlling the global TB epidemic. Thus, efforts are underway to develop newer vaccines with improved efficacy. New tools as well as improved programme implementation and financing are necessary to end the global TB epidemic by 2035.
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.
Öngen, Gül; Börekçi, Şermin; İçmeli, Özlem Saniye; Birgen, Nur; Karagül, Gülsüm; Akgün, Salih; Kılıçaslan, Zeki; Umut, Sema
The purpose of this study was to evaluate the burden of pulmonary tuberculosis in 10 prisons mostly located in the Marmara Region of Turkey, and to compare them with the country incidence. All the inmates in ten prisons mostly located in the four cities in the Marmara Region of Turkey were enrolled in this study. Tuberculosis screening was done between January 2006-January 2007. Radiological screening for tuberculosis was performed by the mobile X-ray system and it was followed by bacteriological analysis of sputum for tuberculosis suspects. Four physicians evaluated the X-rays independently. Four thousand six hundred and fifteen prisoners were detected by radiological screening. Three hundred and one (7%) of them were female and 4314 (93%) were male, age range was between 14-72 years. Age ranges of female and male prisoners were 16-59 and 14-72 respectively. 398/4615 (8.6%) were young adults inmates with an age range of 14-18. Radiological abnormalities consistent with tuberculosis were found in 130 chest X-rays and followed by sputum bacteriology. Smear and culture positive pulmonary tuberculosis diagnosed in five out of 130, were all male with mean age 33 ± 10 years. Tuberculosis prevalence in the prisons was found to be 108/100.000 which was four times higher than the overall incidence of tuberculosis in Turkey in the year which the present study was conducted. Prisoners are one of the most important risk groups with high burden of tuberculosis in Turkey. This result highlights the need for adequate case- finding strategies in prisons.
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.
Behar, Samuel M.; Carpenter, Stephen M.; Booty, Matthew G.; Barber, Daniel L.; Jayaraman, Pushpa
Despite the introduction almost a century ago of Mycobacterium bovis BCG (BCG), an attenuated form of M. bovis that is used as a vaccine against Mycobacterium tuberculosis, tuberculosis remains a global health threat and kills more than 1.5 million people each year. This is mostly because BCG fails to prevent pulmonary disease – the contagious form of tuberculosis. Although there have been significant advances in understanding how the immune system responds to infection, the qualities that define protective immunity against M. tuberculosis remain poorly characterized. The ability to predict who will maintain control over the infection and who will succumb to clinical disease would revolutionize our approach to surveillance, control, and treatment. Here we review the current understanding of pulmonary T cell responses following M. tuberculosis infection. While infection elicits a strong immune response that contains infection, M. tuberculosis evades eradication. Traditionally, its intracellular lifestyle and alteration of macrophage function are viewed as the dominant mechanisms of evasion. Now we appreciate that chronic inflammation leads to T cell dysfunction. While this may arise as the host balances the goals of bacterial sterilization and avoidance of tissue damage, it is becoming clear that T cell dysfunction impairs host resistance. Defining the mechanisms that lead to T cell dysfunction is crucial as memory T cell responses are likely to be subject to the same subject to the same pressures. Thus, success of T cell based vaccines is predicated on memory T cells avoiding exhaustion while at the same time not promoting overt tissue damage. PMID:25311810
... shown by X-ray in active service. 3.370 Section 3.370 Pensions, Bonuses, and Veterans' Relief DEPARTMENT... Rating Considerations Relative to Specific Diseases § 3.370 Pulmonary tuberculosis shown by X-ray in active service. (a) Active disease. X-ray evidence alone may be adequate for grant of direct service...
Lantos, Akos; Niemann, Stefan; Mezõsi, Lásló; Sós, Endre; Erdélyi, Károly; Dávid, Sándor; Parsons, Linda M; Kubica, Tanja; Rüsch-Gerdes, Sabine; Somoskövi, Akos
We report the first case of pulmonary tuberculosis caused by Mycobacterium bovis subsp. caprae in a captive Siberian tiger, an endangered feline. The pathogen was isolated from a tracheal aspirate obtained by bronchoscopy. This procedure provided a reliable in vivo diagnostic method in conjunction with conventional and molecular tests for the detection of mycobacteria.
Abashev, I M; Kozlova, A I
Patients with destructive pulmonary tuberculosis were examined. Comparing those receiving chemopathogenetic, epicutaneous laser and ultrasound therapies showed an increase in the incidence of cavitary scarring in those taking successive epicutaneous laser and ultrasound therapies and exposed to biologically active points. Epicutaneous laser therapy promoted cicatrization of large cavities.
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
Curley, Catherine Anne
In the article "Rule out pulmonary tuberculosis: Clinical and radiographic clues for the internist" (Curley CA. Cleve Clin J Med 2015; 82:32-38), on page 33, "Bacillus Calmette-Guérin vaccine" has been corrected to "BCG vaccine."
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.
Magazine, Rahul; Pal, Mahuya; Chogtu, Bharti; Nayak, Veena
A patient of multidrug-resistant pulmonary tuberculosis was prescribed an anti-tubercular regimen containing capreomycin. Patient developed optic neuritis 3 months after starting treatment. Investigations did not reveal any specific cause for this ocular condition and on discontinuing capreomycin his vision recovered. We conclude that capreomycin is the cause of reversible optic neuritis in our case. PMID:20927254
Isobe, Zen; Suga, Tatsuo; Aoki, Yasuhiro; Aoki, Fumiaki; Ikeda, Kana; Ueno, Manabu; Maeno, Toshitaka; Kurabayashi, Masahiko
A 54-year old man was admitted to our hospital because of high fever, productive cough and purpura in both legs in June 2005. Urinalysis showed microscopic hematuria and proteinuria. Chest radiograph showed consolidation of right upper field. Because acid-fast bacilli and polymerase chain reaction test for Mycobacterium tuberculosis were positive in bronchial lavage fluid, we made a diagnosis of pulmonary tuberculosis, and prescribed antituberculosis therapy with isoniazid, rifampicin, ethambutol and pyrazinamide. In addition, anaphylactoid purpura was diagnosed by skin biopsy. In July 2005, renal function was deteriorated and nephrosis appeared. We treated with corticosteroid in addition to antituberculosis therapy. His symptoms and renal dysfunction improved. We report a rare case of an anaphylactoid purpura following occurence of pulmonary tuberculosis.
Tsubota, Noriyuki; Tanimukai, Shigeatsu
The usefulness of a rifampicin (RFP) suppository for treatment of pulmonary tuberculosis was examined in patients who had difficulty with oral consumption of medication. Among inpatients receiving first-time treatment for pulmonary tuberculosis susceptible to both isoniazid (INH) and RFP, and who underwent standard 3- or 4-drug treatments including INH and RFP, we compared the number of days required for obtaining two and three consecutive negative sputum smears and cultures, respectively, in patients who received hospital-made suppositories or standard oral RFP administration. There was no significant difference between groups in the number of days required for negative cultures and smears; although the times were equivalent, there were more number of elderly patients and those in generally poor condition in the RFP suppository group than the oral intake group. RFP suppositories may be one method for administration of standard tuberculosis treatment in patients with difficulty in oral consumption of medication.
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.
Becerra, Mercedes C; Appleton, Sasha C; Franke, Molly F; Chalco, Katiuska; Bayona, Jaime; Murray, Megan B; Mitnick, Carole D
We estimated the proportion of recurrence within 2 years among adults cured by individualized multidrug-resistant tuberculosis regimens in Peru. Among 310 individuals with at least 24 months of follow-up, 16 experienced an episode of recurrent tuberculosis. If we assume the worst for treatment effectiveness-that all 16 episodes were caused by the original tuberculosis strain-then 5.2% (95% confidence interval, 3.0%-8.2%) experienced true relapse. This is an upper-bound estimate of relapse on which new regimens must improve.
Vargas, Daniel; García, Luis; Gilman, Robert H; Evans, Carlton; Ticona, Eduardo; Ñavincopa, Marcos; Luo, Robert F; Caviedes, Luz; Hong, Clemens; Escombe, Rod; Moore, David A J
Sputum induction, bronchoalveolar lavage, or gastric aspiration are often needed to produce adequate diagnostic respiratory samples from people with HIV in whom tuberculosis is suspected. Since these procedures are rarely appropriate in less-developed countries, we compared the performances of a simple string test and the gold-standard sputum induction. 160 HIV-positive adults under investigation for tuberculosis, and 52 asymptomatic HIV-positive control patients underwent the string test followed by sputum induction. The string test detected tuberculosis in 14 patients in whom this disease was suspected; sputum induction detected only eight of them (McNemar's test, p=0·03). These preliminary data suggest that the string test is safe and effective for retrieval of useful clinical specimens for diagnosis of pulmonary tuberculosis, and is at least as sensitive as sputum induction. PMID:15639297
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.
Marchiori, Edson; Zanetti, Gláucia; Irion, Klaus Loureiro; Nobre, Luiz Felipe; Hochhegger, Bruno; Mançano, Alexandre Dias; Escuissato, Dante Luiz
The purpose of this study was to compare the morphologic characteristics of the "reversed halo" sign caused by tuberculosis with those caused by cryptogenic organizing pneumonia (COP) and to determine whether high-resolution CT (HRCT) can differentiate between these two conditions. We retrospectively reviewed the HRCT scans of patients with the reversed halo sign caused by active tuberculosis and HRCT scans of patients with the reversed halo sign caused by COP. The study included 12 patients with active pulmonary tuberculosis (10 women and two men) and 10 patients with biopsy-proven COP (five women and five men). Tuberculosis was diagnosed by culture of sputum, bronchoalveolar lavage, or biopsy specimen. All patients underwent HRCT, and the images were reviewed by two chest radiologists who reached decisions by consensus. HRCT scans of all patients with active tuberculosis showed reversed halos with nodular walls; in most cases (10/12), we also observed nodules inside the halos. None of the HRCT scans of the COP cases reviewed had halos with nodular walls or nodules inside them. We also observed parenchymal abnormalities, such as consolidation, ground-glass, and linear opacities, associated with the reversed halo sign. Neither the number of reversed halo sign lesions nor the associated parenchymal lesions discriminated between tuberculosis and COP. Nevertheless, the association of the reversed halo sign with nodular walls or nodules inside the halo was seen only in tuberculosis patients. Although COP is considered the most frequent cause of the reversed halo sign, the presence of nodular walls or nodules inside the reversed halo strongly favors a diagnosis of active pulmonary tuberculosis rather than COP.
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.
Chushkin, Mikhail Ivanovich; Ots, Oleg Nikolayevich
To evaluate the prevalence of pulmonary function abnormalities and to investigate the factors affecting lung function in patients treated for pulmonary tuberculosis. A total of 214 consecutive patients (132 men and 82 women; 20-82 years of age), treated for pulmonary tuberculosis and followed at a local dispensary, underwent spirometry and plethysmography at least one year after treatment. Pulmonary impairment was present in 102 (47.7%) of the 214 patients evaluated. The most common functional alteration was obstructive lung disease (seen in 34.6%). Of the 214 patients, 60 (28.0%) showed reduced pulmonary function (FEV1 below the lower limit of normal). Risk factors for reduced pulmonary function were having had culture-positive pulmonary tuberculosis in the past, being over 50 years of age, having recurrent tuberculosis, and having a lower level of education. Nearly half of all tuberculosis patients evolve to impaired pulmonary function. That underscores the need for pulmonary function testing after the end of treatment. Avaliar a prevalência de alterações da função pulmonar e investigar os fatores que afetam a função pulmonar em pacientes tratados para tuberculose pulmonar. Um total de 214 pacientes consecutivos (132 homens e 82 mulheres; 20-82 anos de idade), tratados para tuberculose pulmonar e acompanhados em um dispensário local, foi submetido a espirometria e pletismografia pelo menos um ano após o tratamento. O comprometimento pulmonar estava presente em 102 (47,7%) dos 214 pacientes avaliados. A alteração funcional mais comum foi o distúrbio ventilatório obstrutivo (observado em 34,6%). Dos 214 pacientes, 60 (28,0%) apresentaram função pulmonar reduzida (VEF1 abaixo do limite inferior de normalidade). Os fatores de risco para função pulmonar reduzida foram tuberculose pulmonar com cultura positiva no passado, idade acima de 50 anos, recidiva de tuberculose e menor nível de escolaridade. Quase metade de todos os pacientes com tuberculose
Li, Jiong; Zhou, Ying; Zhang, Hongqi; He, Dan; Zhang, Rongmou; Li, Yanbing; Guo, Chaofeng; Guo, Qiang; Wang, Longjie; Yang, Guanteng; Gao, Qile
Spinal tuberculosis (STB) is an extrapulmonary form of tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb), which accounts for around 2% of all TB cases and can lead to spine degeneration. It is widely accepted that host genetic factors participate in the pathogenesis of active TB, but the factors controlling which TB form will manifest after Mtb infection remain unknown. We hypothesized that a genetic difference may exist between the development of STB and pulmonary tuberculosis (PTB). Here, three single nucleotide polymorphisms (SNPs) in the IFNG gene (rs2069718), IRGM gene (rs10065172), and MBL2 gene (rs11003125) were genotyped among 183 PTB patients, 177 STB patients, and 360 healthy controls from the Chinese Han population. We found that rs2069718 genotypes were significantly associated with PTB (TT, p = 0.007; CT, p = 0.008) but not STB, and the TT genotype (p = 0.046) of rs2069718 were less common in PTB than in STB. In contrast, neither PTB nor STB were found to be associated with rs10065172 and rs11003125. Overall, we found a difference in the rs2069718 genetic distribution between the STB and PTB patients in a Chinese Han population. The rs2069718 TT genotype was associated with a protective role in PTB but not STB development during active Mtb infection. Copyright © 2017. Published by Elsevier Ltd.
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.
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
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
Francisco-Cruz, A.; Mata-Espinosa, D.; Estrada-Parra, S.; Xing, Z.; Hernández-Pando, R.
Summary BALB/c mice with pulmonary tuberculosis (TB) develop a T helper cell type 1 that temporarily controls bacterial growth. Bacterial proliferation increases, accompanied by decreasing expression of interferon (IFN)-γ, tumour necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS). Activation of dendritic cells (DCs) is delayed. Intratracheal administration of only one dose of recombinant adenoviruses encoding granulocyte–macrophage colony-stimulating factor (AdGM-CSF) 1 day before Mycobacterium tuberculosis (Mtb) infection produced a significant decrease of pulmonary bacterial loads, higher activated DCs and increased expression of TNF-α, IFN-γ and iNOS. When AdGM-CSF was given in female mice B6D2F1 (C57BL/6J X DBA/2J) infected with a low Mtb dose to induce chronic infection similar to latent infection and corticosterone was used to induce reactivation, a very low bacilli burden in lungs was detected, and the same effect was observed in healthy mice co-housed with mice infected with mild and highly virulent bacteria in a model of transmissibility. Thus, GM-CSF is a significant cytokine in the immune protection against Mtb and gene therapy with AdGM-CSF increased protective immunity when administered in a single dose 1 day before Mtb infection in a model of progressive disease, and when used to prevent reactivation of latent infection or transmission. PMID:23379435
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
Atif, Muhammad; Sulaiman, Syed Azhar Syed; Shafie, Asrul Akmal; Ali, Irfhan; Asif, Muhammad; Babar, Zaheer-Ud-Din
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). 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). 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 included high-grade sputum and presence
Wu, Zheyuan; Guo, Juntao; Huang, Ying; Cai, Enmao; Zhang, Xia; Pan, Qichao; Yuan, Zheng'an; Shen, Xin
To determine the prevalence of diabetes mellitus among pulmonary tuberculosis patients and the difference of clinical characteristics and outcomes between pulmonary tuberculosis patients with and without diabetes mellitus in an aging population in Shanghai, China. This is a retrospective population-based study. 201 newly diagnosed pulmonary tuberculosis patients in Changning District, Shanghai during 2007-2008 were included. Clinical characteristics and outcomes were collected. Determination of diabetes mellitus was based on the medical records before pulmonary tuberculosis was diagnosed. The prevalence of diabetes mellitus among pulmonary tuberculosis patients was 19.9% (40/201). Pulmonary tuberculosis patients with diabetes mellitus were more likely to be old (≥50, OR=5.23, 95% CI=2.07-13.25), to have pulmonary cavities (OR=3.02, 95% CI=1.31-6.98), to be sputum smear positive (OR=2.90, 95% CI=1.12-7.51), and to have extension of anti-tuberculosis treatment duration (OR=2.68, 95% CI 1.17-6.14). Besides, they had a higher 2nd month sputum smear positive proportion (OR=2.97, 95% CI 1.22-7.22) and a higher 5-year recurrence rate (OR=5.87, 95% CI 1.26-27.40). High prevalence, severe clinical characteristics and poor outcomes of pulmonary tuberculosis patients with diabetes mellitus highlight the necessity of early bi-directional screening and co-management of these two diseases in Shanghai, China. Copyright © 2016 Elsevier Inc. All rights reserved.
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.
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
Gorospe Sarasúa, Luis; Ureña-Vacas, Almudena; Arrieta, Paola; Santos-Carreño, Astrid Lucía; Navas-Elorza, Enrique; de la Puente-Bujidos, Carlos
Sarcoidosis and tuberculosis are two common granulomatous conditions that may share clinical and radiological presentations. The galaxy sign (sarcoid galaxy sign) is a characteristic radiological sign of pulmonary sarcoidosis on thoracic computed tomography (CT). We present the case of a patient with sarcoidosis that was initially misdiagnosed as tuberculosis, in whom the galaxy sign on CT was useful as it suggested the correct diagnosis. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.
Chakrabarti, Biswajit; Calverley, Peter MA; Davies, Peter DO
Tuberculosis (TB) and chronic obstructive pulmonary disease (COPD) carry a significant burden in terms of morbidity and mortality worldwide. This review article focuses on different aspects of Tuberculosis in terms of the relationship with COPD such as in the development of chronic airflow obstruction as a sequel to active TB and reviewing the key role of cigarette smoking in the pathogenesis of both conditions. Patients diagnosed with TB may often have extensive co-morbidity such as COPD and the effect of an underlying diagnosis of COPD on outcomes in TB is also reviewed. PMID:18229564
Lancioni, Christina; LaBeaud, A Desiree; Esper, Frank; Abughali, Nazha; Auletta, Jeffery
Children who undergo treatment for malignancies are at high for infection with both typical and opportunistic pathogens. Fever in these children prompts extensive evaluation and empiric treatment with broad-spectrum antimicrobials. In the United States (US), tuberculosis is an infrequently reported cause of fever in the pediatric cancer patient and has not been well described. In this report we describe a case of primary pulmonary tuberculosis (TB) in a boy with precursor B-cell acute lymphoblastic leukemia (ALL) and review the pertinent literature. (c) 2009 Wiley-Liss, Inc.
Azam, Fahad; Shaheen, Abida; Arshad, Rabia
Objective: To find out the frequency of hypovitaminosis D and its associated risk factors in newly diagnosed pulmonary tuberculosis patients prior to administration of standard anti tuberculosis therapy. Methods: This cross-sectional study was carried out in Ojha Institute of Chest Diseases-DUHS. After approval from BASR and following written informed consent eighty newly diagnosed, as per WHO criteria, tuberculosis patients were enrolled. Prior to the initiation of anti tuberculosis therapy, the serum vitamin D level was determined by 25-OH Vitamin D kit using the chemiluminescent immunoassay (CLIA) method. A cut off value of >30 ng/mL of serum vitamin D was taken as normal whereas a range between 10-30 ng/mL and <10 ng/mL were considered insufficient and deficient respectively. Frequency of socio-demographic associated risk factors of hypovitaminosis D was also determined. Results: Out of eighty newly diagnosed tuberculosis patients 33 (41.25%) were males and 47(58.75%) were females with their ages ranging from 18-50 years. 54 patients (26 male and 28 female patients) were smokers. BMI of all the patients was found to be less than the normal ranges. Hypovitaminosis was present in all the cases. Vitamin D insufficiency was found in 49 participants (20 male and 29 female) whereas 31 patients (13 male and 18 female) were found to be vitamin D deficient. Conclusion: Prevalence of serum vitamin D level derangement is very high in newly diagnosed patients with pulmonary tuberculosis in our local setting which necessitates administration of adjuvant vitamin D along with standard anti tuberculosis therapy. PMID:27182266
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.
Cordova, Julianna; Shiloh, Ron; Gilman, Robert H; Sheen, Patricia; Martin, Laura; Arenas, Fanny; Caviedes, Luz; Kawai, Vivian; Soto, Giselle; Williams, Diana L; Zimic, Mirko; Escombe, A Roderick; Evans, Carlton A
Pulmonary tuberculosis diagnosis is difficult when patients cannot produce sputum. Most sputum is swallowed, and tuberculosis DNA can survive intestinal transit. We therefore evaluated molecular testing of stool specimens for detecting tuberculosis originating from the lungs. Paired stool and sputum samples (n=159) were collected from 89 patients with pulmonary tuberculosis. Control stool samples (n=47) were collected from patients without tuberculosis symptoms. Two techniques for DNA extraction from stool samples were compared, and the diagnostic accuracy of the PCR in stool was compared with the accuracy of sputum testing by PCR, microscopy, and culture. A heminested IS6110-PCR was used for tuberculosis detection, and IS6110-PCR-positive stool samples then underwent rifampin sensitivity testing by universal heteroduplex generator PCR (heteroduplex-PCR) assay. For newly diagnosed pulmonary tuberculosis patients, stool IS6110-PCR had 86% sensitivity and 100% specificity compared with results obtained by sputum culture, and stool PCR had similar sensitivities for HIV-positive and HIV-negative patients (P=0.3). DNA extraction with commercially available spin columns yielded greater stool PCR sensitivity than DNA extraction with the in-house Chelex technique (P=0.007). Stool heteroduplex-PCR had 98% agreement with the sputum culture determinations of rifampin resistance and multidrug resistance. Tuberculosis detection and drug susceptibility testing by stool PCR took 1 to 2 days compared with an average of 9 weeks to obain those results by traditional culture-based testing. Stool PCR was more sensitive than sputum microscopy and remained positive for most patients for more than 1 week of treatment. In conclusion, stool PCR is a sensitive, specific, and rapid technique for the diagnosis and drug susceptibility testing of pulmonary tuberculosis and should be considered when sputum samples are unavailable.
Cordova, Julianna; Shiloh, Ron; Gilman, Robert H.; Sheen, Patricia; Martin, Laura; Arenas, Fanny; Caviedes, Luz; Kawai, Vivian; Soto, Giselle; Williams, Diana L.; Zimic, Mirko; Escombe, A. Roderick; Evans, Carlton A.
Pulmonary tuberculosis diagnosis is difficult when patients cannot produce sputum. Most sputum is swallowed, and tuberculosis DNA can survive intestinal transit. We therefore evaluated molecular testing of stool specimens for detecting tuberculosis originating from the lungs. Paired stool and sputum samples (n = 159) were collected from 89 patients with pulmonary tuberculosis. Control stool samples (n = 47) were collected from patients without tuberculosis symptoms. Two techniques for DNA extraction from stool samples were compared, and the diagnostic accuracy of the PCR in stool was compared with the accuracy of sputum testing by PCR, microscopy, and culture. A heminested IS6110-PCR was used for tuberculosis detection, and IS6110-PCR-positive stool samples then underwent rifampin sensitivity testing by universal heteroduplex generator PCR (heteroduplex-PCR) assay. For newly diagnosed pulmonary tuberculosis patients, stool IS6110-PCR had 86% sensitivity and 100% specificity compared with results obtained by sputum culture, and stool PCR had similar sensitivities for HIV-positive and HIV-negative patients (P = 0.3). DNA extraction with commercially available spin columns yielded greater stool PCR sensitivity than DNA extraction with the in-house Chelex technique (P = 0.007). Stool heteroduplex-PCR had 98% agreement with the sputum culture determinations of rifampin resistance and multidrug resistance. Tuberculosis detection and drug susceptibility testing by stool PCR took 1 to 2 days compared with an average of 9 weeks to obain those results by traditional culture-based testing. Stool PCR was more sensitive than sputum microscopy and remained positive for most patients for more than 1 week of treatment. In conclusion, stool PCR is a sensitive, specific, and rapid technique for the diagnosis and drug susceptibility testing of pulmonary tuberculosis and should be considered when sputum samples are unavailable. PMID:20200293
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.
Weijer, Sebastiaan; Leemans, Jaklien C; Florquin, Sandrine; Shimizu, Takao; Ishii, Satoshi; van der Poll, Tom
Platelet-activating factor (PAF) is a phospholipid with potent, diverse actions, which has been implicated as an important mediator in host defence against several intracellular pathogens. To determine the role of PAF in host defence in pulmonary tuberculosis, PAF receptor-deficient (PAFR−/−) and wild-type (PAFR+/+) mice were infected intranasally with a virulent strain of Mycobacterium tuberculosis. Mycobacterial outgrowth in lungs and liver did not differ significantly between PAFR−/− and PAFR+/+ mice at 2 or 6 weeks postinfection. After 28 weeks, 86% of PAFR−/− mice and 79% of PAFR+/+ mice had died (non-significant). In addition, both mouse strains were indistinguishable with respect to histopathology, the recruitment and activation of lymphocytes, and cytokine concentrations in the lung. These data suggest that PAF is not involved in the protective immune response to tuberculosis. PMID:12871222
Argemi, X; Albrecht, M; Hansmann, Y; Jaulhac, B; Koebel, C; Schramm, F
Our aim was to evaluate the criteria required to discontinue airborne precautions for patients presenting with sputum smear-positive pulmonary tuberculosis as the need for sputum smear examinations is still a matter of debate. We conducted a retrospective study in the University Hospitals of Strasbourg (France) from July 2011 to July 2013. Our aim was to describe the results of sputum smear examinations and cultures obtained from treated patients presenting with drug-sensitive pulmonary tuberculosis. We included 97 patients in the study. Nearly half of patients for whom a sputum smear examination was performed had a negative sputum direct examination but a positive culture. According to the literature, those patients are still likely to be contagious. This questions the safety of discontinuing airborne precautions in this situation. We also observed a great disparity in physicians' behaviors. Only half of them waited to get a negative sputum direct examination before discontinuing airborne precautions. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
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.
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.
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
Lala, Sanjay; Dheda, Keertan; Chang, Jung-Su; Huggett, Jim F; Kim, Louise U; Johnson, Margaret A; Rook, Graham AW; Keshav, Satish; Zumla, Alimuddin
Background NOD2, an intracellular pathogen recognition sensor, modulates innate defences to muropeptides derived from various bacterial species, including Mycobacterium tuberculosis (MTB). Experimentally, NOD2 attenuates two key putative mycobactericidal mechanisms. TNF-α synthesis is markedly reduced in MTB-antigen stimulated-mononuclear cells expressing mutant NOD2 proteins. NOD2 agonists also induce resistance to apoptosis, and may thus facilitate the survival of MTB in infected macrophages. To further define a role for NOD2 in disease pathogenesis, we analysed NOD2 transcriptional responses in pulmonary leucocytes and mononuclear cells harvested from patients with pulmonary tuberculosis (PTB). Methods We analysed NOD2 mRNA expression by real-time polymerase chain-reaction in alveolar lavage cells obtained from 15 patients with pulmonary tuberculosis and their matched controls. We compared NOD2 transcriptional responses, in peripheral leucocytes, before and after anti-tuberculous treatment in 10 patients. In vitro, we measured NOD2 mRNA levels in MTB-antigen stimulated-mononuclear cells. Results No significant differences in NOD2 transcriptional responses were detected in patients and controls. In some patients, however, NOD2 expression was markedly increased and correlated with toll-like-receptor 2 and 4 expression. In whole blood, NOD2 mRNA levels increased significantly after completion of anti-tuberculosis treatment. NOD2 expression levels did not change significantly in mononuclear cells stimulated with mycobacterial antigens in vitro. Conclusion There are no characteristic NOD2 transcriptional responses in PTB. Nonetheless, the increased levels of NOD2 expression in some patients with severe tuberculosis, and the increases in expression levels within peripheral leucocytes following treatment merit further studies in selected patient and control populations. PMID:17705850
Lala, Sanjay; Dheda, Keertan; Chang, Jung-Su; Huggett, Jim F; Kim, Louise U; Johnson, Margaret A; Rook, Graham A W; Keshav, Satish; Zumla, Alimuddin
NOD2, an intracellular pathogen recognition sensor, modulates innate defences to muropeptides derived from various bacterial species, including Mycobacterium tuberculosis (MTB). Experimentally, NOD2 attenuates two key putative mycobactericidal mechanisms. TNF-alpha synthesis is markedly reduced in MTB-antigen stimulated-mononuclear cells expressing mutant NOD2 proteins. NOD2 agonists also induce resistance to apoptosis, and may thus facilitate the survival of MTB in infected macrophages. To further define a role for NOD2 in disease pathogenesis, we analysed NOD2 transcriptional responses in pulmonary leucocytes and mononuclear cells harvested from patients with pulmonary tuberculosis (PTB). We analysed NOD2 mRNA expression by real-time polymerase chain-reaction in alveolar lavage cells obtained from 15 patients with pulmonary tuberculosis and their matched controls. We compared NOD2 transcriptional responses, in peripheral leucocytes, before and after anti-tuberculous treatment in 10 patients. In vitro, we measured NOD2 mRNA levels in MTB-antigen stimulated-mononuclear cells. No significant differences in NOD2 transcriptional responses were detected in patients and controls. In some patients, however, NOD2 expression was markedly increased and correlated with toll-like-receptor 2 and 4 expression. In whole blood, NOD2 mRNA levels increased significantly after completion of anti-tuberculosis treatment. NOD2 expression levels did not change significantly in mononuclear cells stimulated with mycobacterial antigens in vitro. There are no characteristic NOD2 transcriptional responses in PTB. Nonetheless, the increased levels of NOD2 expression in some patients with severe tuberculosis, and the increases in expression levels within peripheral leucocytes following treatment merit further studies in selected patient and control populations.
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
Mzinza, David T; Sloan, Derek J; Jambo, Kondwani C; Shani, Doris; Kamdolozi, Mercy; Wilkinson, Katalin A; Wilkinson, Robert J; Davies, Geraint R; Heyderman, Robert S; Mwandumba, Henry C
In HIV-uninfected adults with pulmonary tuberculosis (TB), anti-TB treatment is associated with changes in Mycobacterium tuberculosis (Mtb)-specific immune responses, which correlate with sputum bacillary load. It is unclear if this occurs in HIV-infected TB patients. We investigated changes in Mtb-specific immune responses and sputum bacillary clearance during anti-TB treatment in HIV-infected and HIV-uninfected adults with pulmonary TB. Sputum bacillary load was assessed by smear microscopy and culture. Mtb-specific IFN-γ secreting peripheral blood mononuclear cells were enumerated using an ELISPOT assay following stimulation with PPD, ESAT-6 and CFP-10. The baseline frequency of Mtb-specific IFN-γ secreting cells was lower in HIV-infected than HIV-uninfected patients (median PPD 32 vs. 104 Spot Forming Units (SFU), p = 0.05; CFP-10 19 vs. 74 SFU, p = 0.01). ESAT-6-specific IFN-γ secreting cells and sputum bacillary load declined progressively during treatment in both HIV-infected and HIV-uninfected patients. HIV infection did not influence the 2-month sputum culture conversion rate (Odds Ratio 0.89, p = 0.95). These findings suggest that changes in ESAT-6-specific immune responses during anti-TB treatment correspond with changes in sputum bacillary load irrespective of host HIV infection status. The utility of Mtb-specific IFN-γ responses as a proxy measure of treatment response in HIV-infected TB patients warrants further evaluation in other settings.
Valdés Díaz, Solangel; García Silvera, Eberto; Rosas Valladares, Carmen; Cayon Escobar, Isis G; Valladares Baena, Aleida; Crespo Díaz, Tatiana T
the diagnosis of pulmonary tuberculosis in sputum smears-negative patients is a challenge for today's medical practice, mostly supported on clinical and radiographic elements. In Hospital Neumológico Benéfico Jurídico of Havana, there is an expert commission for the sputum smear-negative diagnosis of tuberculosis called CODIBAARNE. to identify the radiological patterns and the final diagnosis of patients submitted to this committee from October 2002 to December 2003. a descriptive study was conducted in a sample of patients within the above-mentioned period, who had been studied and followed-up in Hospital Neumológico Benéfico Jurídico in order to define their final diagnoses under the CODIBAARNE commission recommendation. Data were gathered from the register of patients and from the individual medical histories. the average age of these patients was 68.2 years and 57 % were males. The most frequent symptoms were cough (76 %), general syndrome (70 %) and expectoration (61 %). The mostly seen radiographic patterns were infiltrates, with or without cavitation (44 %) and fibrotic lesions (34 %). The most common diagnoses showed bronchiectasia (26 %), followed by sputum smears-negative pulmonary tuberculosis (24 %). the results of this research work evinced the importance of the work by the group of experts in CODIBAARNE regarding the sputum smears-negative diagnosis of tuberculosis cases.
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.
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
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
Asmar, Shady; Drancourt, Michel
Culturing Mycobacterium tuberculosis remains the gold standard for the laboratory diagnosis of pulmonary tuberculosis, with 9 million new cases and 1.5 million deaths mainly in developing countries. Reviewing data reported over 20 years yields a state-of-the-art procedure for the routine culture of M. tuberculosis in both developed and developing countries. Useful specimens include sputum, induced sputum, and stools collected in quaternary ammonium preservative-containing sterile cans. The usefulness of other non-invasive specimens remains to be evaluated. Specimens can be collected in a diagnosis kit also containing sampling materials, instructions, laboratory requests, and informed consent. Automated direct LED fluorescence microscopy after auramine staining precedes inoculation of an egg-lecithin-containing culture solid medium under microaerophilic atmosphere, inverted microscope reading or scanning video-imaging detection of colonies and colonies identification by recent molecular methods. This procedure should result in a diagnosis of pulmonary tuberculosis as fast as 5 days. It may be implemented in both developed and developing countries with automated steps replaceable by manual steps depending on local resources. PMID:26579092
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
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
Singh, Urvashi B.; Pandey, Pooja; Mehta, Girija; Bhatnagar, Anuj K.; Mohan, Anant; Goyal, Vinay; Ahuja, Vineet; Ramachandran, Ranjani; Sachdeva, Kuldeep S.; Samantaray, Jyotish C.
Background Newer molecular diagnostics have brought paradigm shift in early diagnosis of tuberculosis [TB]. WHO recommended use of GeneXpert MTB/RIF [Xpert] for Extra-pulmonary [EP] TB; critics have since questioned its efficiency. Methods The present study was designed to assess the performance of GeneXpert in 761 extra-pulmonary and 384 pulmonary specimens from patients clinically suspected of TB and compare with Phenotypic, Genotypic and Composite reference standards [CRS]. Results Comparison of GeneXpert results to CRS, demonstrated sensitivity of 100% and 90.68%, specificity of 100% and 99.62% for pulmonary and extra-pulmonary samples. On comparison with culture, sensitivity for Rifampicin [Rif] resistance detection was 87.5% and 81.82% respectively, while specificity was 100% for both pulmonary and extra-pulmonary TB. On comparison to sequencing of rpoB gene [Rif resistance determining region, RRDR], sensitivity was respectively 93.33% and 90% while specificity was 100% in both pulmonary and extra-pulmonary TB. GeneXpert assay missed 533CCG mutation in one sputum and dual mutation [517 & 519] in one pus sample, detected by sequencing. Sequencing picked dual mutation [529, 530] in a sputum sample sensitive to Rif, demonstrating, not all RRDR mutations lead to resistance. Conclusions Current study reports observations in a patient care setting in a high burden region, from a large collection of pulmonary and extra-pulmonary samples and puts to rest questions regarding sensitivity, specificity, detection of infrequent mutations and mutations responsible for low-level Rif resistance by GeneXpert. Improvements in the assay could offer further improvement in sensitivity of detection in different patient samples; nevertheless it may be difficult to improve sensitivity of Rif resistance detection if only one gene is targeted. Assay specificity was high both for TB detection and Rif resistance detection. Despite a few misses, the assay offers major boost to early
Dorman, Susan E; Goldberg, Stefan; Stout, Jason E; Muzanyi, Grace; Johnson, John L; Weiner, Marc; Bozeman, Lorna; Heilig, Charles M; Feng, Pei-Jean; Moro, Ruth; Narita, Masahiro; Nahid, Payam; Ray, Susan; Bates, Edward; Haile, Betial; Nuermberger, Eric L; Vernon, Andrew; Schluger, Neil W
Rifapentine administered 5 days per week has potent activity in mouse models of antituberculosis chemotherapy, but efficacy and safety data are limited in humans. We compared the antimicrobial activity and safety of rifapentine vs rifampin during the first 8 weeks of pulmonary tuberculosis treatment. In total, 531 adults with sputum smear-positive pulmonary tuberculosis were randomized to rifapentine 10 mg/kg/dose or rifampin 10 mg/kg/dose, administered 5 days per week for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. Coprimary outcomes were negative sputum culture on liquid and on solid media at completion of intensive phase. Negative cultures on solid media occurred in 145 of 174 participants (83.3%) in the rifampin group and 171 of 198 participants (86.4%) in the rifapentine group (difference, 3.0%; 95% confidence interval [CI]: -4.3, 10.5); negative cultures in liquid media occurred in 110 of 169 (65.1%) in the rifampin group and 133 of 196 (67.9%) in the rifapentine group (difference, 2.8%; 95% CI: -6.9, 12.4). Among 529 participants who received study therapy, 40 of 254 participants (15.7%) in the rifampin group and 40 of 275 participants (14.5%) in the rifapentine group prematurely discontinued treatment (P=.79). The rifapentine regimen was safe but not significantly more active than a standard rifampin regimen, by the surrogate endpoint of culture status at completion of intensive phase. Assessment of higher exposures to rifapentine for tuberculosis treatment is warranted. NCT00694629.
Srikanth, Padma; Kamesh, S; Daley, Peter
The Revised National Tuberculosis Control Programme (RNTCP) aims to improve case detection rates of tuberculosis to facilitate prompt recognition and treatment. The low case detection rates in the programme can be directly attributed to failure to screen patients with suspected tuberculosis and the low sensitivity of the direct smear microscopy method to detect cases among the fraction of patients that are screened. Apart from low sensitivity, this method also has other disadvantages including the increased risk of infection transmission to technicians. There are several methods that can be used to improve sensitivity, but their applicability in a national programme and in resource limited settings are limited. Bleach processing of sputum smears prior to microscopy may be a cheap and effective way to improve on the sensitivity of the direct smear. Four distinctive techniques of sputum smear processing using bleach are described in the review, with the variations in each technique, along with the sensitivity. An analysis of reports published earlier on the bleach method is also presented including a discussion on when and why the bleach method works.
Chen, Z F; Lao, H L; Li, X H; Wang, J; Chen, Q; Wang, Z X; Wang, D C
To explore the application value of GeneXpert MTB/RIF for detection of extra-pulmonary tuberculosis and resistance to rifampin. A total of 150 samples were collected, including 33 needle aspirates from lymphoid tuberculosis, 23 needle aspirates from spinal tuberculosis, 49 from tuberculous pleural effusions, 24 from cerebrospinal fluid of tuberculous cephalomeningitis, and 21 urinary sediment samples from renal tuberculosis. Smear microscopy, mycobacterium tuberculosis culture and the MTB/RIF method were used to examine these samples and their positive rates were compared. Rifampin susceptibility tests was performed for culture-positive strains using proportion method, which was compared with the result from GeneXpert MTB/RIF method. Of the 150 cases of extra-pulmonary tuberculosis, 17 samples were smear-positive, with a sensitivity of 11.3% (17/150); 30 were culture-positive with a sensitivity of 20.0% (30/150); and 96 were positive by MTB/RIF method with a sensitivity of 64.0% (96/150). There was a significant difference between MTB/RIF method and the culture method (χ(2)=59.61, P<0.01). The differences were also significant when the MTB/RIF method was compared with the smear method (χ(2)=88.60, P<0.01) or compared with culture plus smear methods (χ(2)=4.26, P<0.05). Separately, the differences were statistically significant between GeneXpert MTB/RIF method and other 2 methods for diagnosis of lymphoid tuberculosis (n=33, χ(2)=20.56, P<0.01 vs. culture method; χ(2)=27.13, P<0.01 vs. smear results) while no difference was found between culture and smear method (χ(2)=0.67, P>0.05), spinal tuberculosis (n=23, χ(2)=12.74, P<0.01 vs. culture method; χ(2)=14.81, P< 0.01 vs. smear method), tuberculous pleurisy (n=49, χ(2)=32.34, P<0.01 vs.culture method; χ(2)=49.69, P<0.01 vs. smear method) and renal tuberculosis (n=21, χ(2)=4.20, P<0.05 vs. culture method; χ(2) =8.40, P<0.01 vs. smear results). The sensitivity for tuberculous meningitis had no difference
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.
Bertholet, Sylvie; Horne, David J.; Laughlin, Elsa M.; Savlov, Margery; Tucakovic, Ines; Coler, Rhea N.; Narita, Masahiro; Reed, Steven G.
The development of genomic and proteomic tools has enabled studies that begin to characterize the molecular targets of an effective host immune response to Mycobacterium tuberculosis, including understanding the specific immune responses associated with tuberculosis (TB) disease progression, disease resolution, and the development of latency. One application of such tools is the development of diagnostic reagents and assays useful as a test of cure. Such a test could be of considerable importance for the evaluation of new therapeutics. We and others have previously described immunodominant proteins of M. tuberculosis, including both vaccine and diagnostic candidates. In the present study, we describe the changes in immune responses to a panel of 71 M. tuberculosis antigens in six patients during the course of therapy. The levels of six cytokines were measured in 24-h whole-blood assays with these antigens, revealing that gamma interferon (IFN-γ), tumor necrosis factor (TNF), and interleukin-10 (IL-10) were differentially regulated in response to a subset of antigens. Therefore, measuring the production of these three cytokines in response to a panel of carefully selected M. tuberculosis proteins during the course of TB therapy might be a promising path toward the development of a test of cure and warrants further validation in larger cohorts of pulmonary TB patients. PMID:21715581
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.
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.
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.
Balwani, Manish R; Kute, Vivek B; Shah, Pankaj R; Wakhare, Pawan; Trivedi, Hargovind L
Common variable immunodeficiency (CVID) usually manifests in the second or third decade of life with recurrent bacterial infections and hypoglobulinemia. Secondary renal amyloidosis with history of pulmonary tuberculosis is rare in CVID, although T cell dysfunction has been reported in few CVID patients. A 40-year-old male was admitted to our hospital with a 3-month history of recurrent respiratory infections and persistent pitting pedal edema. His past history revealed 3 to 5 episodes of recurrent respiratory tract infections and diarrhoea each year since last 20 years. He had been successfully treated for sputum positive pulmonary tuberculosis 8 years back. Laboratory studies disclosed high erythrocyte sedimentation rate (ESR), hypoalbuminemia and nephrotic range proteinuria. Serum immunoglobulin levels were low. CD4/CD8 ratio and CD3 level was normal. C3 and C4 complement levels were normal. Biopsy revealed amyloid A (AA) positive secondary renal amyloidosis. Glomeruli showed variable widening of mesangial regions with deposition of periodic schiff stain (PAS) pale positive of pink matrix showing apple green birefringence on Congo-red staining. Immunohistochemistry was AA stain positive. Immunofluorescence microscopy revealed no staining with anti-human IgG, IgM, IgA, C3, C1q, kappa and lambda light chains antisera. Patient was treated symptomatically for respiratory tract infection and was discharged with low dose angiotensin receptor blocker. An old treated tuberculosis and chronic inflammation due to recurrent respiratory tract infections were thought to be responsible for AA amyloidosis. Thus pulmonary tuberculosis should be considered in differential diagnosis of secondary causes of AA renal amyloidosis in patients of CVID especially in endemic settings.
Hoque, M R; Chakraborty, P K; Paul, U K; Sarkar, S; Akhter, S; Shahidullah, S M; Gautam, B; Sultana, S; Ferdous, N; Samsunnahar, M
This case control study was carried out in the Department of Biochemistry, Mymensingh Medical College in cooperation with the Outpatient Department and Medicine Units of Mymensingh Medical College Hospital, Fulbaria Upazilla Health Complex, Mymensingh and some DOTS centers of BRAC, a non-government organization during the period of July 2006 to June 2007. The aim of the study was to explore the status of serum albumin & creatinine clearance levels in smear positive Bangladeshi pulmonary tuberculosis patients as a means to monitor the possibility of management of these patients as these levels decrease significantly. Serum albumin level was investigated in TB patients for monitoring the nutritional status of TB patients and also for the adjustment of serum calcium level. Creatinine clearance rate was investigated in TB patients for monitoring the impairment of renal function and nutritional depletion in tuberculosis patients. A total of 120 people of different age groups were included in this study. Subjects were divided into two groups- Group I (Control; n=60) - apparently healthy people selected matching by age, sex and socioeconomic status with the cases and Group II (Case; n=60) - people with smear positive pulmonary tuberculosis. Serum albumin was estimated by colorimetric principle. Serum creatinine was also estimated by colorimetric principle & creatinine clearance rate was estimated from serum creatinine by Cockcroft- Gault equation. Statistical analysis was done by using SPSS windows package. Among the groups, mean±SD of serum albumin in Group II (3.74±0.44gm/dl) was significantly lower (p<0.001) than that in Group I (4.85±0.31gm/dl). Mean±SD of creatinine clearance rate in Group II (35.36±8.29ml/min) was also significantly lower than that in Group I (84.16±20.20ml/min). It is evident from the study that serum albumin & creatinine clearance rate levels significantly decrease in smear positive Bangladeshi pulmonary tuberculosis patients.
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
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
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.
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.
Brhane, Mussie; Kebede, Ameha; Petros, Yohannes
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. 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. 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. 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.
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
Martín, V; Domínguez, A; Alcaide, J
In spanish prisons, tuberculosis is a serious problem of public health and health authorities don't take it seriously. To prove the efficiency of pulmonary tuberculosis case-finding on arrival at prison in order to get location resources in this activity. Cost-benefit analysis of a case-finding program compared with to wait for diagnostic to illness. The sensitivity of test was fixed in 80% and the specificity in 99.99%. The cost was based on market prices. Sensitivity analysis was done in every variables as well as tridimensional analysis in those one of more influence. The case-finding was efficient on prevalences of tuberculosis over 5 per mil. Its efficiency was hardly affected by discount social rates or the sensitivity of diagnostic tests. The prevalence of illness, the cost of diagnostic activities as well as the success of treatment and the specificity of diagnostic tests used had as influence on the efficiency model. The tridimensional analysis proved that the case-finding of pulmonary tuberculosis has efficiency on low prevalences (1 per thousand), provided the number of people cured is a 5% higher than the alternative one and the costs of case-finding less than 1,000 pesetas per subject. The case-finding pulmonary tuberculosis on arrival at prisons is of high efficiency. In a cost-opportunity situation (location of available resources, penitentiary and extrapenitentiary) the program is very efficacious taking into account the fact of higher prevalence of pulmonary tuberculosis in this people.
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
Méchaï, F; Figoni, J; Leblanc, C; Gousseff, M; Vignier, N; Bouchaud, O
To evaluate the efficacy of amikacin on sputum conversion during initial sputum smear positive tuberculosis treatment. Single-center observational cohort study (2012-2013) evaluating time to sputum smear conversion with standard treatment (ST) versus standard treatment+amikacin (IV 15mg/kg/day) for seven days (STamK). Forty-five patients were included. Median time to smear negative samples was 26.5 days (14-56) for the 30 (66.7%) patients included in the ST group and 48 days (19.5-69.5) for the 15 patients (33.3%) included in the STamK group (P=0.76). Time to negative culture was only known for 27 patients (61.4%): 47.5 days (26-58) for 18 patients in the ST group and 40 days (14-77) for nine patients in the STamK group. Despite our small sample size, the addition of amikacin in active tuberculosis treatment did not seem to impact time to smear conversion or period of contagiousness. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
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.
Miyata, Shigeru; Tanaka, Mikio; Ihaku, Daizo
Malnutrition is frequently observed in patients with pulmonary tuberculosis (TB). The present study aimed to examine the relationship between nutritional status using Malnutrition Universal Screening Tool (MUST) and the mortality of patients with pulmonary TB. Fifty-seven patients with pulmonary TB were analyzed. Nutrition assessment was carried out using MUST. The Cox proportional hazard model was applied to assess the ability of MUST to predict prognosis. Receiver operating characteristic curve analysis was used to assess MUST score as a prognostic indicator in pulmonary TB patients. To obtain optimal cut-off values for MUST score for prognostic assessment in TB patients, we used the maximum Youden Index. For predicting the risk of mortality, the optimal cut-off value for MUST score was 3.5. Univariate and multivariate analyses identified age and MUST score ≥ 4 as significant independent prognostic factors for survival. The patients with MUST score ≤ 3 had a median survival of 481 days (95% CI: 453 to 510) and that for the patients with MUST score ≥ 4 was 304 days (95% CI: 214 to 394); the difference was statistically significant (P = 0.001). MUST appears to be a reliable tool for nutritional risk assessment of patients with pulmonary TB. In addition, MUST may be a useful prognostic indicator of survival in patients with pulmonary TB.
Reither, Klaus; Saathoff, Elmar; Jung, Jutta; Minja, Lilian T; Kroidl, Inge; Saad, Eiman; Huggett, Jim F; Ntinginya, Elias N; Maganga, Lucas; Maboko, Leonard; Hoelscher, Michael
The development and evaluation of rapid and accurate new diagnostic tools is essential to improve tuberculosis (TB) control in developing countries. In a previous study, the first release of a urine LAM-ELISA by Chemogen (Portland, USA) has been evaluated with a promising sensitivity and specificity for the diagnosis of pulmonary TB. In the present study, the now commercially available assay has been clinically assessed regarding its diagnostic value alone and in combination with clinical co-factors. The test was applied to two urine samples from 291 consecutively enrolled Tanzanian patients with suspected pulmonary tuberculosis. The participants were subsequently assigned to classification groups according to microbiological, clinical and radiological findings at recruitment and during a maximum follow up period of 56 days. Only 35 out of 69 pulmonary TB cases -confirmed by smear microscopy and/or solid culture and/or liquid culture- showed at least one positive LAM-ELISA result (sensitivity 50.7%). The sensitivity was noticeably higher in females (66.7%) and in HIV positive participants (62.0%). The specificity amounted to 87.8% and was determined in participants with negative results in all microbiological tests and with sustained recovery under antibiotic treatment at day 56. Correlation with urinalysis revealed that proteinuria was significantly and positively associated with LAM-positivity (P = 0.026). This commercially available generation of LAM-ELISA does not appear to be useful as an independent diagnostic test for pulmonary tuberculosis. The question whether the assay is suitable as a supplemental device in the diagnosis of HIV-associated TB, requires further investigations.
Background The development and evaluation of rapid and accurate new diagnostic tools is essential to improve tuberculosis (TB) control in developing countries. In a previous study, the first release of a urine LAM-ELISA by Chemogen (Portland, USA) has been evaluated with a promising sensitivity and specificity for the diagnosis of pulmonary TB. In the present study, the now commercially available assay has been clinically assessed regarding its diagnostic value alone and in combination with clinical co-factors. Methods The test was applied to two urine samples from 291 consecutively enrolled Tanzanian patients with suspected pulmonary tuberculosis. The participants were subsequently assigned to classification groups according to microbiological, clinical and radiological findings at recruitment and during a maximum follow up period of 56 days. Results Only 35 out of 69 pulmonary TB cases -confirmed by smear microscopy and/or solid culture and/or liquid culture- showed at least one positive LAM-ELISA result (sensitivity 50.7%). The sensitivity was noticeably higher in females (66.7%) and in HIV positive participants (62.0%). The specificity amounted to 87.8% and was determined in participants with negative results in all microbiological tests and with sustained recovery under antibiotic treatment at day 56. Correlation with urinalysis revealed that proteinuria was significantly and positively associated with LAM-positivity (P = 0.026). Conclusion This commercially available generation of LAM-ELISA does not appear to be useful as an independent diagnostic test for pulmonary tuberculosis. The question whether the assay is suitable as a supplemental device in the diagnosis of HIV-associated TB, requires further investigations. PMID:19715562
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.
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. BTLA(high) 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.
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
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
Mello, Fernanda Carvalho de Queiroz; Bastos, Luiz Gustavo do Valle; Soares, Sérgio Luiz Machado; Rezende, Valéria MC; Conde, Marcus Barreto; Chaisson, Richard E; Kritski, Afrânio Lineu; Ruffino-Netto, Antonio; Werneck, Guilherme Loureiro
Background Smear negative pulmonary tuberculosis (SNPT) accounts for 30% of pulmonary tuberculosis cases reported yearly in Brazil. This study aimed to develop a prediction model for SNPT for outpatients in areas with scarce resources. Methods The study enrolled 551 patients with clinical-radiological suspicion of SNPT, in Rio de Janeiro, Brazil. The original data was divided into two equivalent samples for generation and validation of the prediction models. Symptoms, physical signs and chest X-rays were used for constructing logistic regression and classification and regression tree models. From the logistic regression, we generated a clinical and radiological prediction score. The area under the receiver operator characteristic curve, sensitivity, and specificity were used to evaluate the model's performance in both generation and validation samples. Results It was possible to generate predictive models for SNPT with sensitivity ranging from 64% to 71% and specificity ranging from 58% to 76%. Conclusion The results suggest that those models might be useful as screening tools for estimating the risk of SNPT, optimizing the utilization of more expensive tests, and avoiding costs of unnecessary anti-tuberculosis treatment. Those models might be cost-effective tools in a health care network with hierarchical distribution of scarce resources. PMID:16504086
Doğru, Sibel; Döner, Pınar
It is known that tuberculosis is frequently seen among refugees. Hatay province is one of the cities that substantially expose to migration of refugees after Syrian civil war. In this study, it was aimed to compare frequency of new pulmonary tuberculosis (PTB) cases and treatment success/cure rates between Turkish and Syrian patients. The study included 211 patients with PTB (178 Turkish and 33 Syrian patients) registered to Hatay Tuberculosis Outpatient Clinic between 2010 and 2013. On the basis of years, number of PTB patients registered was 53 (Turkish/Syrian: 52/1) in 2010, 44 (44/0) in 2011, 41 (39/2) in 2012, and 73 (43/30) in 2013. There were no significant differences between Turkish and Syrian patients regarding age groups, gender, marital status, contact history, smear result, and drug sensitivity assays when treatment success was considered (p>0.05). Directly observed therapy (DOT) rate was higher in patients who achieved successful treatment (97.6% vs. 2.4%; p<0.001). Number of patients successfully treated was smaller among Syrian patients (63.6% vs. 88.8%; p<0.001). Leaving the treatment and/or transfer rates were higher among Syrian patients (30.3% vs. 3.9%; p<0.001). During the study period, drug-resistant tuberculosis was detected in one Syrian and 3 Turkish patients. Although PTB frequency has increased in Hatay province within prior 4 years, treatment success among local population is still within limits established by World Health Organization (WHO). However, the treatment goal could not be achieved when considered together with refugees. To improve treatment success in refugees, implementation of a new national tuberculosis is needed control program in this population. Copyright © 2016 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.
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.
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.
Zümrütdal, Ayşegül; Yıldız, Ismail; Ozelsancak, Rüya; Canpolat, Tuba
Tuberculosis-related chronic granulomatous tubulointerstitial nephritis (GTN) and chronic renal dysfunction as a consequence of GTN is a rarely seen clinical condition, with a few case reports in the literature. In this report, a case with end stage renal failure as an unexpected late extrapulmonary sequela of tuberculosis has been presented. A 60 years old female patient was admitted to hospital with the complaints of fever, malaise and nausea. Her history revealed that she had pulmonary tuberculosis 30 years ago and received antituberculosis therapy for nine months. The laboratory results on admission were as follows: blood urea nitrogen 90 mg/dl, serum creatinine 9 mg/dl, sodium 116 mEq/L, potassium 6.6 mEq/L, albumine 2.9 g/dl, hemoglobin, 8.4 g/dl, white blood cell count 10.800/mm3, C-reactive protein 187 mg/L and erythrocyte sedimentation rate 110 mm/hour. Urinalysis showed 8.1 g/L protein, 10-12 leukocytes, 1-2 erythrocytes, while 24-hours urinalysis yielded proteinuria with 8 ml/minutes creatinine clearance value. Urine and blood cultures of the patient revealed neither bacteria or mycobacteria. PPD skin test was negative. Acid-resistant bacilli (ARB) were not detected in sequential urine samples obtained on three consecutive days. Since sputum samples could not be obtained, diagnostic procedures for sputum were not performed. Abdomen ultrasonography yielded bilateral edema and grade II echogenity in kidneys. Computed tomography of the chest showed bilateral pulmonary nodules, chronic sequela lesions, pleural scarring and calcifications, as well as minimal interstitial infiltrate. Transthoracic lung biopsy showed chronic inflammation and fibrosis, while amyloid was negative. Renal biopsy showed GTN with central caseified necrosis and granulomas, multinuclear giant cells, tubular atrophy and interstitial fibrosis. Amyloid was negative and ARB were not detected in renal biopsy sample. Definitive diagnosis was achieved by the demonstration of Mycobacterium
Last, J.A.; Gelzleichter, T.R.; Pinkerton, K.E.; Walker, R.M.; Witschi, H. )
Sprague-Dawley rats were exposed for 6 h daily to 0.8 ppm of ozone and 14.4 ppm of nitrogen dioxide. Approximately 7 to 10 wk after the initiation of exposure, animals began to demonstrate respiratory insufficiency and severe weight loss. About half of the rats died between Days 55 and 78 of exposure; no overt ill effects were observed in animals exposed to filtered air, to ozone alone, or to nitrogen dioxide. Biochemical findings in animals exposed to ozone and nitrogen dioxide included increased lung content of DNA, protein, collagen, and elastin, which was about 300% higher than the control values. The collagen-specific crosslink hydroxy-pyridinium, a biomarker for mature collagen in the lung, was decreased by about 40%. These results are consistent with extensive breakdown and remodeling of the lung parenchyma and its associated vasculature. Histopathologic evaluation showed severe fibrosis, alveolar collapse, honeycombing, macrophage and mast cell accumulation, vascular smooth muscle hypertrophy, and other indications of severe progressive interstitial pulmonary fibrosis and end-stage lung disease. This unique animal model of progressive pulmonary fibrosis resembles the final stages of human idiopathic pulmonary fibrosis and should facilitate studying underlying mechanisms and potential therapy of progressive pulmonary fibrosis.
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
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
Yang, LiKun; Cao, Yan; Dan, Zijun; Wang, Zhongyuan; Wang, Xinjing
This report describes a case of Tsukamurella pneumonia in a 24-year-old immunocompetent woman. The patient was diagnosed as having pulmonary tuberculosis and was treated for nearly 9 months. The correct diagnosis was suspected only when the results of mycobacteria nucleic acid amplification tests on cultural colonies were negative. Tsukamurella was identified from the patient's sputum and bronchoalveolar lavage fluid by using 16S rRNA sequence analysis. Here, the clinical presentation, diagnosis, and treatment strategies of Tsukamurella pneumonia are discussed, along with a literature review. Tsukamurella pneumonia may be highly underdiagnosed owing to its similarity with pulmonary tuberculosis and the habitual thinking of doctors in countries with a high tuberculosis burden. Tsukamurella should be carefully considered in the etiology of tuberculosis-like lung diseases.
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. Copyright © 2015 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.
Karagoz, T; Pazarli, P; Mocin, O Y; Duman, D; Duman, G; Salturk, C; Unal, O
Sureyyapasa Chest Diseases and Thoracic Surgery Training Hospital, Istanbul, Turkey. To determine levels of Mycobacterium tuberculosis resistance to first-line drugs in patients with pulmonary tuberculosis (PTB). Between 1 January and 31 December 2005, all hospitalised PTB patients with culture-positive M. tuberculosis specimens and corresponding drug susceptibility tests (DST) for isoniazid (INH), rifampicin (RMP), streptomycin (SM) and ethambutol, routinely performed for every tuberculosis (TB) case at our centre, were included. Of a total of 1513 cases, 1277 (84.4%) were new and 236 (15.6%) were previously treated cases. Of the 1513 isolates, 290 (19%) isolates were resistant to at least one of the drugs tested. Resistance among new and previously treated cases was respectively 16.3% (209 of 1277) and 34.3% (81/236). Any SM resistance and any INH resistance were the most common drug resistance in new cases, while any RMP resistance was the most common drug resistance in previously treated cases. Multidrug resistance was detected in 3.2% (n = 41) of new cases and in 13.5% (n = 32) of previously treated cases. Planning for TB control requires an assessment of the number and distribution of drug-resistant cases, with laboratories providing accurate and reliable results.
In India, as in most under-development countries, the tuberculosis problem is aggravated by an acute shortage of sanatorium beds. The number of active cases of tuberculosis in the country has been estimated at 2 ½ million, but only 23 000 tuberculosis beds are available. In these circumstances great importance attaches to the possibility of applying mass domiciliary chemotherapy as a substitute for sanatorium treatment in cases of pulmonary tuberculosis. The findings of the present study, based on a comparison of the two types of treatment over a period of 12 months, show that despite the manifest advantages of sanatorium care—rest, adequate diet, nursing and supervised medicine-taking—the merits of domiciliary chemotherapy are comparable to those of sanatorium treatment, and that it would therefore be appropriate to treat the majority of patients at home, provided an adequate service were established. Imagesp135-ap136-ap137-ap138-ap139-ap140-ap141-ap142-ap143-ap144-a PMID:20604054
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
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
Zhang, Junai; Liu, Ganbin; Zeng, Jincheng; Wang, Wandang; Xiang, Wenyu; Kong, Bin; Yi, Lailong; Xu, Junfa
To investigate the level of plasma interleukin 37 (IL-37) and explore the clinical significance of IL-37 in patients with active pulmonary tuberculosis (ATB). ELISA was used to detect the level of plasma IL-37 from 30 patients with ATB, 15 patients who had been treated for ATB, and 21 healthy volunteers as controls. The level of plasma IL-37 in patients with ATB was significantly higher than that in healthy controls. The monitoring on the 15 patients showed that plasma IL-37 was reduced after treatment for ATB. The level of plasma IL-37 in patients with anti-Mycobecterium tuberculosis antibody positive or sputum smear positive were higher than that in patients with anti-Mycobecterium tuberculosis antibody negative or sputum smear negative for Mycobecterium tuberculosis, and the level was negatively correlated with the number of white blood cells in peripheral blood. The patients with ATB present with significantly increased level of plasma IL-37, which might be an indicator of curative effect in ATB.
Thammavong, C; Paboriboune, P; Bouchard, B; Harimanana, A; Babin, F-X; Phimmasone, P; Berland, J-L; Buisson, Y
Laos has a high prevalence of tuberculosis (TB) and a slowly increasing prevalence of human immunodeficiency virus/acquired immunedeficiency syndrome (HIV/AIDS). Sputum smear microscopy is the only method currently available for routine screening of pulmonary TB, although it only detects one in three cases among persons living with HIV (PLWH). Bleach treatment of sputum samples (bleach method) has been shown to significantly improve the sensitivity of the test; however, its effectiveness in PLWH remains to be determined in Laos. To determine the performance of the bleach method as a diagnostic tool for pulmonary TB in PLWH and to assess its cost-effectiveness in Laos. Of 174 sputum samples collected from 92 patients, 29 were culture-positive for Mycobacterium tuberculosis in 17 patients. The sensitivity of the direct method and the bleach method was respectively 59% and 93%, and specificity was 100% for both methods. The incremental cost-effectiveness ratio for screening an additional case was US$17.40. The bleach method is simple, cheap, easy to perform and cost-effective in PLWH. Its implementation in laboratories involved in routine screening of pulmonary TB among PLWH would allow practitioners to start the treatment of this life-threatening co-infection earlier.
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
Roth, Daniel E; Soto, Giselle; Arenas, Fanny; Bautista, Christian T; Ortiz, Jaime; Rodriguez, Richard; Cabrera, Lilia; Gilman, Robert H
Polymorphisms in the gene that encodes the vitamin D receptor (VDR) may influence the host response to Mycobacterium tuberculosis infection. In a Peruvian community with a high incidence of tuberculosis (TB), VDR TaqI and FokI polymorphisms were compared among 103 patients with pulmonary TB and 206 matched healthy control subjects. Associations of VDR polymorphisms with treatment outcome were analyzed among 78 patients undergoing treatment of pulmonary TB. Sputum mycobacterial culture and auramine stain conversions were significantly faster among participants with the FokI FF genotype, compared with participants with the non-FF genotypes. Sputum culture conversion was faster among participants with the TaqI Tt genotype, compared with those with the TT genotype. Increased probability of culture conversion during TB treatment was independently associated with the TaqI Tt genotype (age- and sex-adjusted relative risk, 4.28; 95% confidence interval, 1.88-9.75; P = .001). VDR polymorphisms were not significantly associated with susceptibility to TB in the case-control study. VDR gene polymorphisms are associated with the time to sputum culture and auramine stain conversion during TB treatment. To our knowledge, the present study is the first report of a specific host gene influence on the outcome of TB treatment. These findings demonstrate the potential clinical relevance of immunomodulatory functions of vitamin D metabolites acting via the VDR in the host response against pulmonary TB.
Dalar, L; Karasulu, L; Sökücü, S; Düger, M; Altın, S
Pulmonary tuberculosis and lung cancer are still important public health problems and can occur simultaneously. In this article, we present the case of a 38-year-old patient treated for smear positive pulmonary tuberculosis. During the third month of treatment, the patient developed respiratory distress and was found to have total atelectasis of the left lung. At rigid bronchoscopy, a lesion obstructing the left main bronchus was removed with a diode laser. Oncological treatment was started following the histological diagnosis of small cell bronchial carcinoma. Pulmonary tuberculosis and bronchial carcinoma can occur at the same time and cause diagnostic confusion. The possibility should be considered in situations where both diseases are endemic. Copyright © 2011. Published by Elsevier Masson SAS.
Wang, Jun; Dai, Yaping; Liu, Jun; Yin, Yongmei; Pei, Hao
Tuberculosis (TB), an infectious disease caused by the bacillus Mycobacterium tuberculosis (MTB), is a global health problem. Because the failing immune response in the lung can lead to formation of a pulmonary cavity, this study was designed to clarify MTB-specific lymphocyte responses in TB patients with pulmonary cavities. We utilized culture filtrate protein 10 (CFP-10) and early secretory antigenic target 6 (ESAT-6) as immunogenic MTB antigens following overnight stimulation of peripheral blood mononuclear cells (PBMCs). By flow cytometry, we then dissected CD4+ and CD8+ T lymphocytes secreting intracellular cytokines of IFN-γ and TNF-α to assess the local immune response of TB patients with pulmonary cavities compared with those having other radiological infiltrates. As expected, after 16 h of ex vivo activation using both ESAT-6 and CFP-10, the proportions of CD4+IFN-γ, CD4+TNF-α, CD8+TNF-α, and CD8+IFN-γ cells were all markedly increased in 46 patients with TB when compared with 23 household contacts. However, the IFN-γ and TNF-α responses of both CD4+ and CD8+ T lymphocytes were found to be relatively lower in 18 patients who had pulmonary cavities when compared with 28 patients who had radiological infiltrates. Moreover, patients with cavities had higher absolute numbers of neutrophils than patients with infiltrates. Further analysis indicated an inverse correlation between neutrophil counts and the proportions of IFN-γ-secreting T cells. MTB-specific lymphocyte responses are impaired in TB patients with pulmonary cavities that are likely to play an important role in the pathogenesis of cavitary TB.
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.
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.
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. 2017 BMJ Publishing Group Ltd.
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.
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
Sabri, Ayoub; Grant, Audrey V.; Cosker, Kristel; El Azbaoui, Safa; Abid, Ahmed; Abderrahmani Rhorfi, Ismail; Souhi, Hicham; Janah, Hicham; Alaoui-Tahiri, Kebir; Gharbaoui, Yasser; Benkirane, Majid; Orlova, Marianna; Boland, Anne; Deswarte, Caroline; Migaud, Melanie; Bustamante, Jacinta; Schurr, Erwin; Boisson-Dupuis, Stephanie; Casanova, Jean-Laurent; Abel, Laurent; El Baghdadi, Jamila
Background. Only a minority of individuals infected with Mycobacterium tuberculosis develop clinical tuberculosis. Genetic epidemiological evidence suggests that pulmonary tuberculosis has a strong human genetic component. Previous genetic findings in Mendelian predisposition to more severe mycobacterial infections, including by M. tuberculosis, underlined the importance of the interleukin 12 (IL-12)/interferon γ (IFN-γ) circuit in antimycobacterial immunity. Methods. We conducted an association study in Morocco between pulmonary tuberculosis and a panel of single-nucleotide polymorphisms (SNPs) covering 14 core IL-12/IFN-γ circuit genes. The analyses were performed in a discovery family-based sample followed by replication in a case-control population. Results. Out of 228 SNPs tested in the family-based sample, 6 STAT4 SNPs were associated with pulmonary tuberculosis (P = .0013–.01). We replicated the same direction of association for 1 cluster of 3 SNPs encompassing the promoter region of STAT4. In the combined sample, the association was stronger among younger subjects (pulmonary tuberculosis onset <25 years) with an odds ratio of developing pulmonary tuberculosis at rs897200 for GG vs AG/AA subjects of 1.47 (1.06–2.04). Previous functional experiments showed that the G allele of rs897200 was associated with lower STAT4 expression. Conclusions. Our present findings in a Moroccan population support an association of pulmonary tuberculosis with STAT4 promoter-region polymorphisms that may impact STAT4 expression. PMID:24610875
Dair, Roberto; Torres, Etelivar; Rodríguez, Odalys; Cruz, Ramona; Hernández, Lizzie
Tuberculosis is currently a health problem in the municipality of Camagüey. To assess compliance of guidelines issued by the National Program for the Control of Tuberculosis for the follow-up of contacts of positive cases of pulmonary tuberculosis in the municipality of Camagüey, Cuba. Descriptive cross-sectional design. 1,242 contacts resulting from 39 reported cases of tuberculosis during the study period were included in the municipality of Camagüey between 2008 and 2011. Epidemiological surveys and records of reported cases were reviewed. The results were processed and analyzed in SPSS 17.0 statistical software and subsequently presented in tables and graphs. The results were summarized by percentages. The follow-up form for contacts of pulmonary tuberculosis was used as main guideline, which was created by experts of the Investigation and Monitoring of Tuberculosis, Acute Respiratory Infections, and Leprosy Workshop of Tropical Medicine Institute Pedro Kourí. Contacts that had an initial examination and four checkups had 96.2% of acceptability. Contacts that had fewer than four checkups showed less than 10% acceptability (3.3%). All contacts were assessed from the outset and were treated, in accordance with program guidelines. We found adequate compliance of National Program for the Control of the Tuberculosis guidelines for follow-up of contacts of positive cases of pulmonary tuberculosis. Compliance is greater in younger age groups and in the actively employed (25 to 54 years). This evaluation contributed to identify existing weaknesses in follow-up, such as low interest of this population to undergo appropriate testing in the National Program of Control of Tuberculosis.
Babalik, Aylin; Kilicaslan, Zeki; Caner, S Sevkan; Gungor, Gokay; Ortakoylu, M Gonenc; Gencer, Serap; McCurdy, Stephen A
The aim of this study is to evaluate the treatment outcomes and identify factors associated with adverse tuberculosis treatment outcomes for bacteriologically confirmed pulmonary tuberculosis. Treatment outcomes of pulmonary tuberculosis were evaluated retrospectively among 11,186 smear- and/or culture-positive patients treated between 2006 and 2009 in Istanbul, Turkey. Adverse treatment outcomes were identified in 1,010 (9.0%) patients including death (1.8%), treatment default (6.1%), and treatment failure (1.1%). Factors associated with adverse treatment outcomes included being born abroad (odds ratios [OR], 5.38; 95% confidence intervals [CI], 3.67-7.91), history of tuberculosis treatment (OR, 3.77; 95% CI, 3.26-4.36), age > 65 years (OR, 2.79; 95% CI, 2.21-3.53), and male gender (OR, 1.91; 95% CI, 1.59-2.27). Death was most strongly associated with age > 65 years (OR, 45.1; 95% CI, 27.0-75.6), followed by treatment default with history of interrupted treatment (OR, 11.6; 95% CI, 8.94-15.1), and treatment failure with prior history of treatment failure (OR, 17.1; 95% CI, 6.97-41.6). Multidrug resistance was strongly associated with adverse treatment outcomes (OR, 10.8; 95% CI, 8.02-14.6). Age > 65 years, male sex, being born abroad, and history of treatment failure were found to be risk factors for adverse treatment outcomes. Hence, patients with any of these characteristics should be carefully monitored and treated aggressively.
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)%.
Girard, D; Antoine, D; Che, D
In France, tuberculosis surveillance is based on mandatory notification (MN) of cases. However, the MN does not allow the full description of cases, and underreporting limits data interpretation. Aiming at better describing the cases of tuberculosis, the hospital record database (PMSI) was analyzed. Incident cases of active pulmonary tuberculosis identified in 2010 in France in the PMSI were included and their characteristics were compared with those of the cases identified through the MN. In 2010, 5158 incident cases of pulmonary tuberculosis were identified in the PMSI. The mean duration of hospitalization was higher for cases considered contagious — at least one positive test result on pulmonary sample — (22 vs 13 days, P < 0.001). Among all cases, 5% were infected by HIV. Death was reported for 4% of cases. The number of pulmonary TB cases reported in the MN was 3781 in 2010. PMSI data by sex, region of residence and month of diagnosis were similar with those of the MN but patients were older in the PMSI (52 vs 47 years, P < 0.001). Considering the PMSI as exhaustive, sensitivity of the MN was estimated at 73.3% in 2010. PMSI data were compatible with those of the MN and the estimation of the sensitivity was close to other French studies. PMSI can be considered as an interesting tool aiming at improving our knowledge about tuberculosis (TB) cases and strengthening awareness where the sensitivity of the MN is low.
Khalil, Kanwal Fatima; Ambreen, Asma; Butt, Tariq
To compare the sensitivity of tuberculin skin test (TST) and quantiFERON-TB gold test (QFT-G) in active pulmonary tuberculosis. Analytical study. Department of Pulmonology, Fauji Foundation Hospital, Rawalpindi, from July 2011 to January 2012. QuantiFERON-TB gold test (QFT-G) was evaluated and compared it with tuberculin skin test (TST) in 50 cases of active pulmonary tuberculosis, in whom tuberculous infection was suspected on clinical, radiological and microbiological grounds. Sensitivity was determined against postive growth for Mycobacterium tuberculosis. Out of 50 cases, 43 were females and 7 were males. The mean age was 41.84 ± 19.03 years. Sensitivity of QFT-G was 80% while that of TST was 28%. QFT-G has much higher sensitivity than TST for active pulmonary tuberculosis. It is unaffected by prior BCG administration and prior exposure to atypical mycobacteria. A positive QFT-G result can be an adjunct to diagnosis in patients having clinical and radiological data compatible with pulmonary tuberculosis.
Gopalan, Narendran; Chandrasekaran, Padmapriyadarsini; Swaminathan, Soumya; Tripathy, Srikanth
Human immunodeficiency virus (HIV) epidemic has undoubtedly increased the incidence of tuberculosis (TB) globally, posing a formidable global health challenge affecting 1.2 million cases. Pulmonary TB assumes utmost significance in the programmatic perspective as it is readily transmissible as well as easily diagnosable. HIV complicates every aspect of pulmonary tuberculosis from diagnosis to treatment, demanding a different approach to effectively tackle both the diseases. In order to control these converging epidemics, it is important to diagnose early, initiate appropriate therapy for both infections, prevent transmission and administer preventive therapy. Liquid culture methods and nucleic acid amplification tests for TB confirmation have replaced conventional solid media, enabling quicker and simultaneous detection of mycobacterium and its drug sensitivity profile Unique problems posed by the syndemic include Acquired rifampicin resistance, drug-drug interactions, malabsorption of drugs and immune reconstitution inflammatory syndrome or paradoxical reaction that complicate dual and concomitant therapy. While the antiretroviral therapy armamentarium is constantly reinforced by discovery of newer and safer drugs every year, only a few drugs for anti tuberculosis treatment have successfully emerged. These include bedaquiline, delamanid and pretomanid which have entered phase III B trials and are also available through conditional access national programmes. The current guidelines by WHO to start Antiretroviral therapy irrespective of CD4+ cell count based on benefits cited by recent trials could go a long way in preventing various complications caused by the deadly duo. This review provides a consolidated gist of the advancements, concepts and updates that have emerged in the management of HIV-associated pulmonary TB for maximizing efficacy, offering latest solutions for tackling drug-drug interactions and remedial measures for immune reconstitution inflammatory
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
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
Du Bois, Jeannine; van Brakel, Elana; Chheng, Phalkun; Venter, Amour; Peloquin, Charles A.; Alsultan, Abdullah; Thiel, Bonnie A.; Debanne, Sara M.; Boom, W. Henry; Diacon, Andreas H.; Johnson, John L.
AZD5847 is an oxazolidinone antibiotic with in vitro activity against Mycobacterium tuberculosis. The objective of this study was to evaluate the antimycobacterial activity, safety, and pharmacokinetics of AZD5847 in patients with pulmonary tuberculosis. Groups of 15 treatment-naive, sputum smear-positive adults with pulmonary tuberculosis were randomly assigned to receive AZD5847 at one of four doses (500 mg once daily, 500 mg twice daily, 1,200 mg once daily, and 800 mg twice daily) or daily standard chemotherapy. The primary efficacy endpoint was the mean daily rate of change in the log10 number of CFU of M. tuberculosis per milliliter of sputum, expressed as the change in log10 number of CFU per milliliter of sputum per day. The mean 14-day activity of the combination of isoniazid, rifampin, ethambutol, and pyrazinamide (−0.163 log10 CFU/ml sputum/day; 95% confidence interval [CI], −0.193, −0.133 log10 CFU/ml sputum/day) was consistent with that found in previous studies. AZD5847 at 500 mg twice daily significantly decreased the number of CFU on solid medium (−0.039; 95% CI, −0.069, −0.009; P = 0.0048). No bactericidal activity was detected at doses of AZD5847 of 500 mg once daily (mean early bactericidal activity [EBA], 0.02 [95% CI, −0.01, 0.05]), 1,200 mg once daily (mean EBA, 0.02 [95% CI, −0.01, 0.05]), and 800 mg twice daily (mean EBA, 0.02 [95% CI, −0.01, 0.05]). AZD5847 at doses of both 500 mg and 800 mg twice daily also showed an increase in the time to a positive culture in MGIT liquid culture medium. Two serious adverse events (grade 4 thrombocytopenia and grade 4 hyperbilirubinemia) occurred in patients receiving AZD5847 at higher doses. AZD5847 dosed twice daily kills tubercle bacilli in the sputum of patients with pulmonary tuberculosis and has modest early bactericidal activity. (This study has been registered at ClinicalTrials.gov under registration no. NCT01516203.) PMID:27550361
Balestrino, E A; Daniel, T M; de Latini, M D; 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.
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
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
Blount, Robert J; Tran, Minh-Chi; Everett, Charles K; Cattamanchi, Adithya; Metcalfe, John Z; Connor, Denise; Miller, Cecily R; Grinsdale, Jennifer; Higashi, Julie; Nahid, Payam
entry into the United States, risk of progression to active tuberculosis disease was higher in IGRA-positive participants compared with IGRA-negative participants. However, these findings did not reach statistical significance, and a positive IGRA at enrollment had a poor predictive value for progressing to active tuberculosis disease. Additional research is needed to identify biomarkers and develop clinical algorithms that can better predict progression to active tuberculosis disease among U.S. immigrants.
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.
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.
Yunda, Luisa Fernanda Imbachí; Sepúlveda, Eileen Viviana Fonseca; Herrera, Kelly Christina Márquez; Moreno, Germán Camacho
In Colombia, epidemiological and clinical information related to pediatric tuberculosis (TB) is scarce. Data are needed to define the impact of the disease and to strengthen measures for detection and treatment. It is proposed to analyze the pediatric population diagnosed with pulmonary TB in a national reference institution. Retrospective observational study including pediatric patients with pulmonary and miliary TB, and pulmonary and extrapulmonary involvement, treated between January 1, 2008 and December 31, 2016. A descriptive analysis of the selected variables was done. A total of 93 cases of diagnosed TB were identified, of which 61 cases were classified as pulmonary (65.6%). The location of TB occurred only in lungs in 51 patients (83.6%), was miliar in 3 (4.9%), pulmonary and extrapulmonary involvement in 7 patients (11.5%). The mean age was 7.5 years (0.5-18 years). Clinical criteria used for diagnosis was related to 98.3% of the cases, whereas radiological criteria in 90.2%. Bacteriological criterion was met in 42.6% of the cases. The most frequent symptoms were coughing (83.6%), fever (63.9%), and weight loss (26.2%); human immunodeficiency virus co-infection occurred in 3 cases (4.9%). During treatment, 5 mortality cases were recorded, although they were not attributable to TB. The epidemiological characterization of pediatric patients with pulmonary TB helps to achieve a better diagnostic approach in this population. Improving monitoring and follow-up activities in children with pulmonary TB, as well as promoting actions for adequate prevention and treatment is highly necessary.
Berhe, Gebretsadik; Enquselassie, Fikre; Aseffa, Abraham
Monitoring the outcome of tuberculosis treatment and understanding the specific reasons for unsuccessful treatment outcome are important in evaluating the effectiveness of tuberculosis control program. This study investigated tuberculosis treatment outcomes and predictors for unsuccessful treatment outcome in the Tigray region of Ethiopia. Medical records of smear-positive pulmonary tuberculosis (PTB) patients registered from September 2009 to June 2011 in 15 districts of Tigray region, Northern Ethiopia, were reviewed. Additional data were collected using a structured questionnaire administered through house-to-house visits by trained nurses. Tuberculosis treatment outcomes were assessed according to WHO guidelines. The association of unsuccessful treatment outcome with socio-demographic and clinical factors was analyzed using logistic regression model. Out of the 407 PTB patients (221 males and 186 females) aged 15 years and above, 89.2% had successful and 10.8% had unsuccessful treatment outcome. In the final multivariate logistic model, the odds of unsuccessful treatment outcome was higher among patients older than 40 years of age (adj. OR=2.50, 95% CI: 1.12-5.59), family size greater than 5 persons (adj. OR=3.26, 95% CI: 1.43-7.44), unemployed (adj. OR=3.10, 95% CI: 1.33-7.24) and among retreatment cases (adj. OR=2.00, 95% CI: 1.37-2.92) as compared to their respective comparison groups. Treatment outcome among smear-positive PTB patients was satisfactory in the Tigray region of Ethiopia. Nonetheless, those patients at high risk of an unfavorable treatment outcome should be identified early and given additional follow-up and social support.
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
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.
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. 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." 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. 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.
Mindolli, Preeti B; Salmani, Manjunath P; Parandekar, Prashant K
The bacteriological diagnosis of tuberculosis (TB) is largely dependent on the Ziehl-Neelsen (ZN) microscopy. This method has a low sensitivity, which can be improved by the concentration of the specimen with sodium hypochlorite (NaoCl), followed by centrifugation before doing acid fast staining (AFB). To study the improvement in the sensitivity of the sputum smear by the bleach method. Setting and Study Design: This study was conducted in BLDEU's Shri B.M. Patil Medical College, Hospital and Research Centre, Bijapur, Karnataka, India. Eighty five patients who visited Shri B.M. Patil Medical College, Hospital and Research Centre between January 2012 to December 2012 were investigated. On spot, morning and second on spot samples were collected from each patient. Direct smears were prepared and they were stained with the hot ZN technique and the remaining samples were concentrated by using 5% NaoCl, followed by centrifugation and staining with ZN stain. The improvement in the sensitivity following the bleach method was studied. The Fisher's exact test was used. A total of two hundred and fifty five specimens from eighty five patients were included in this study; each patient produced three specimens. AFB was detected in twenty five direct smears and in eighty four bleach smears. A statistically significant (p < 0.001) increase in the positivity with the use of the bleach method was detected as compared to that with the use of the direct method. The ZN sensitivity, specificity, positive predictive value (PPV), and the negative predictive value (NPV) were 29%, 99%, 96% and 74% respectively with a 95% confidence interval, with the use of the 5% NaoCl method. The bleach method has advantages over the direct ZN method, as it is simple and as it does not require any additional expertise beyond that which is required for the conventional direct smear microscopy. The materials and the reagents are also affordable and they are available locally.
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.
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
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
Nanoo, Ananta; Izu, Alane; Ismail, Nazir A; Ihekweazu, Chikwe; Abubakar, Ibrahim; Mametja, David; Madhi, Shabir A
South Africa has the highest incidence of tuberculosis in the world, largely resulting from a high population prevalence of HIV infection. We investigated the incidence of microbiologically confirmed pulmonary tuberculosis, and new cases of pulmonary tuberculosis registered for treatment, nationally and provincially in South Africa from 2004 to 2012, during which time there were changes in antiretroviral therapy (ART) coverage among individuals with HIV infection. We identified cases of microbiologically confirmed pulmonary tuberculosis from 2004 to 2012 from the National Health Laboratory Service Corporate Data Warehouse. New cases registered for treatment were identified from National Department of Health electronic registries. A time series analysis, using autoregressive models, was undertaken on incidence of microbiologically confirmed pulmonary disease nationally and provincially; this trend was also examined relative to ART coverage of adults with HIV infection. During the 9-year period, 3 523 371 cases of microbiologically confirmed pulmonary tuberculosis were recorded nationally. Annual incidence (per 100 000 population) increased from 650 (95% CI 648-652) in 2004 to 848 (845-850) in 2008, declining to 774 (771-776) by 2012 (9% decrease from 2008 to 2012). Incidence varied by age-group, sex, and province. There was an inverse association between incidence of microbiologically confirmed disease and ART coverage among HIV-infected individuals nationally and provincially. Trends in incidence of tuberculosis cases registered for treatment mirrored those of microbiologically confirmed cases nationally and provincially; however, incidence of microbiologically confirmed cases was consistently higher than cases registered for treatment nationally and in seven of nine provinces. Since its peak in 2008, the incidence of microbiologically confirmed pulmonary tuberculosis in South Africa had declined by 2012; this decline is associated with an increase in ART
Mindolli, Preeti B; Salmani, Manjunath P; Parandekar, Prashant K
Background: The bacteriological diagnosis of tuberculosis (TB) is largely dependent on the Ziehl-Neelsen (ZN) microscopy. This method has a low sensitivity, which can be improved by the concentration of the specimen with sodium hypochlorite (NaoCl), followed by centrifugation before doing acid fast staining (AFB). Aim: To study the improvement in the sensitivity of the sputum smear by the bleach method. Setting and Study Design: This study was conducted in BLDEU’s Shri B.M. Patil Medical College, Hospital and Research Centre, Bijapur, Karnataka, India. Eighty five patients who visited Shri B.M. Patil Medical College, Hospital and Research Centre between January 2012 to December 2012 were investigated. On spot, morning and second on spot samples were collected from each patient. Direct smears were prepared and they were stained with the hot ZN technique and the remaining samples were concentrated by using 5% NaoCl, followed by centrifugation and staining with ZN stain. The improvement in the sensitivity following the bleach method was studied. Statistical Analysis: The Fisher’s exact test was used. Results: A total of two hundred and fifty five specimens from eighty five patients were included in this study; each patient produced three specimens. AFB was detected in twenty five direct smears and in eighty four bleach smears. A statistically significant (p < 0.001) increase in the positivity with the use of the bleach method was detected as compared to that with the use of the direct method. The ZN sensitivity, specificity, positive predictive value (PPV), and the negative predictive value (NPV) were 29%, 99%, 96% and 74% respectively with a 95% confidence interval, with the use of the 5% NaoCl method. Conclusion: The bleach method has advantages over the direct ZN method, as it is simple and as it does not require any additional expertise beyond that which is required for the conventional direct smear microscopy. The materials and the reagents are also
Nsubuga, Peter; Johnson, John L; Okwera, Alphonse; Mugerwa, Roy D; Ellner, Jerrold J; Whalen, Christopher C
Tuberculosis is responsible for more female deaths around the earth than any other infectious disease. Reports have suggested that responses to tuberculosis may differ between men and women. We investigated gender related differences in the presentation and one year outcomes of HIV-infected adults with initial episodes of pulmonary tuberculosis in Uganda. We enrolled and followed up a cohort of 105 male and 109 female HIV-infected adults on treatment for initial episodes of culture-confirmed pulmonary tuberculosis between March 1993 and March 1995. A favorable outcome was defined as being cured and alive at one year while an unfavorable outcome was not being cured or dead. Subjects were followed-up by serial medical examinations, complete blood counts, serum beta2 microglobulin, CD4+ cell counts, sputum examinations, and chest x-rays. Male patients were older, had higher body mass indices, and lower serum beta2 microglobulin levels than female patients at presentation. At one year, there was no difference between male and female patients in the likelihood of experiencing a favorable outcome (RR 1.02, 95% CI 0.89-1.17). This effect persisted after controlling for symptoms, serum beta2 microglobulin, CD4+ cell count, and severity of disease on chest x-ray (OR 1.07, 95% CI 0.54-2.13) with a repeated measures model. While differences existed between males and females with HIV-associated pulmonary tuberculosis at presentation, the outcomes at one year after the initiation of tuberculosis treatment were similar in Uganda. Women in areas with a high HIV and tuberculosis prevalence should be encouraged to present for screening at the first sign of tuberculosis symptoms.
Tukvadze, Nestan; Sanikidze, Ekaterina; Kipiani, Maia; Hebbar, Gautam; Easley, Kirk A; Shenvi, Neeta; Kempker, Russell R; Frediani, Jennifer K; Mirtskhulava, Veriko; Alvarez, Jessica A; Lomtadze, Nino; Vashakidze, Lamara; Hao, Li; Del Rio, Carlos; Tangpricha, Vin; Blumberg, Henry M; Ziegler, Thomas R
Background: Tuberculosis, including multidrug-resistant tuberculosis (MDR-TB), is a major global health problem. Individuals with tuberculosis disease commonly exhibit vitamin D deficiency, which may adversely affect immunity and the response to therapy. Objective: We determined whether adjunctive high-dose vitamin D3 supplementation improves outcomes in individuals with pulmonary tuberculosis disease. Design: The study was a double-blind, randomized, placebo-controlled, intent-to-treat trial in 199 individuals with pulmonary tuberculosis disease in Tbilisi, Georgia. Subjects were randomly assigned to receive oral vitamin D3 [50,000 IUs (1.25 mg) thrice weekly for 8 wk and 50,000 IU every other week for 8 wk] or a placebo concomitant with standard first-line antituberculosis drugs. The primary outcome was the time for the conversion of a Mycobacterium tuberculosis (Mtb) sputum culture to negative. Results: Baseline characteristics between groups were similar. Most subjects (74%) were vitamin D deficient (plasma 25-hydroxyvitamin D [25(OH)D] concentration <50 nmol/L). With vitamin D3, plasma 25(OH)D concentrations peaked at ∼250 nmol/L by 8 wk and decreased to ∼125 nmol/L at week 16. Adverse events and plasma calcium concentrations were similar between groups. In 192 subjects with culture-confirmed tuberculosis, an adjusted efficacy analysis showed similar median culture-conversion times between vitamin D3 and placebo groups [29 and 27 d, respectively; HR: 0.86; 95% CI: 0.63, 1.18; P = 0.33). Eight-week culture-conversion rates were also similar (84.0% and 82.1% for vitamin D3 and placebo, respectively; P = 0.99). Conclusion: A high-dose vitamin D3 regimen safely corrected vitamin D deficiency but did not improve the rate of sputum Mtb clearance over 16 wk in this pulmonary tuberculosis cohort. This trial was registered at clinicaltrials.gov at NCT00918086. PMID:26399865
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. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail email@example.com.
... Can I Help Someone Who's Being Bullied? Volunteering 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 ...
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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
Yhi, J Y; Park, D W; Min, J-H; Park, Y K; Kim, S-H; Kim, T-H; Sohn, J W; Yoon, H J; Shin, D H; Moon, J-Y
The role of fractional exhaled nitric oxide (FeNO) in the diagnosis and treatment of pulmonary tuberculosis (PTB) is uncertain. To examine the value of FeNO as a biomarker for PTB. Baseline FeNO levels were compared in 69 PTB patients and 118 healthy controls. The correlation between baseline FeNO levels and clinical variables of tuberculosis were studied. FeNO levels were checked twice in the PTB group, at diagnosis and after 2 months of anti-tuberculosis medication, and factors affecting changes in FeNO levels after treatment were analysed. FeNO levels were not significantly different in the PTB group and controls (mean ± standard deviation 27.7 ± 17.6 parts per billion [ppb] vs. 27.0 ± 10.8 ppb, P = 0.531). In a multivariate regression analysis, no variable was shown to affect FeNO levels at diagnosis. FeNO levels did not significantly change after 2 months of treatment (26.8 ± 18.3 ppb vs. 24.0 ± 10.7 ppb, P = 0.257). Only PTB with a high FeNO level (>25 ppb) was related to a decline in FeNO levels after 2 months of treatment. FeNO levels do not appear to be affected in PTB patients.
Islam, Mohammad R; Khatun, Razia; Uddin, Mohammad Khaja Mafij; Khan, Md Siddiqur Rahman; Rahman, Md Toufiq; Ahmed, Tahmeed; Banu, Sayera
From long instances, it is debatable whether three sputum specimens are required for the diagnosis of pulmonary tuberculosis (TB) or TB can be diagnosed effectively using two consecutive sputum specimens. This study was set out to evaluate the significance of examining multiple sputum specimens in diagnosis of TB. We retrospectively reviewed the acid-fast bacillus (AFB) smear and culture results of three consecutive days' sputum specimens from 413 confirmed TB patients which were detected as part of a larger active case finding study in Dhaka Central Jail, the largest correctional facility in Bangladesh. AFB was detected from 81% (n = 334) patients, of which 89% (n = 297) were diagnosed from the first and additional 9% (n = 30) were from the second sputum specimen. M. tuberculosis growth was observed for 406 patients and 85% (n = 343) were obtained from the first sputum and additional 10% (n = 42) were from the second one. The third specimen didn't show significant additional diagnostic value for the detection of AFB by microscopy or growth of the M. tuberculosis. We concluded from our study results that examining two consecutive sputum specimens is sufficient enough for the effective diagnosis of TB. It can also decrease the laboratory workload and hence improve the quality of work in settings with high TB burden like Bangladesh.
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.
Belizario, Vicente; Totanes, Francis Isidore; Asuncion, Camille Ann; Leon, Winifreda De; Jorge, Manuel; Ang, Concepcion; Naig, June Rose
Background Pulmonary tuberculosis (PTB) and paragonimiasis remain as health problems in certain areas in the Philippines. Both share similar clinical manifestations, which include chronic productive cough, hemoptysis, dyspnea, fever, weight loss, and night sweats. This study aimed to determine the prevalence of PTB, paragonimiasis, and co-infections in Zamboanga del Norte, Philippines. Methods This study was conducted in selected villages in two municipalities in Zamboanga del Norte. Patients with chronic cough were interviewed, examined, and requested to submit two sputum samples which were processed using Ziehl–Neelsen method to detect acid-fast bacilli (AFB), and NaOH concentration technique for the detection of Paragonimus ova. Results A total of 836 patients submitted sputum samples for examination. Prevalence was 6.7% (2.5–12.7%) for paragonimiasis and 1.9% (0.9–6.3%) for PTB. Co-infection rate was 0.3%, with two identified cases. Positivity rates for males and females were 9.6 and 5.8% for paragonimiasis and 3.4 and 1.2% for PTB. Conclusion Pulmonary tuberculosis and paragonimiasis are co-endemic in Zamboanga del Norte, suggesting the need to integrate surveillance and control efforts. Strengthening local health systems through collaboration between different sectors is recommended for effective disease control. Development of more sensitive diagnostic tests is important for more accurate disease surveillance. PMID:24601907
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.
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. PMID:25996154
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.
O'Connor, D E; Frederix, K; Saito, S; Maama, L B; Hirsch-Moverman, Y; Pitt, B; Hayes-Larson, E; Lebelo, L; Shale, M; Howard, A A
Twelve health facilities in Berea District, Lesotho, that participated in the Start TB Patients on ART and Retain on Treatment (START) Study, a mixed-methods cluster-randomized trial evaluating a combination intervention package to improve early initiation of antiretroviral therapy (ART) and anti-tuberculosis treatment success among patients with tuberculosis (TB) and human immunodeficiency virus (HIV). To assess TB and HIV diagnostic practices among TB-HIV patients. A standardized survey assessed services at each facility at baseline. Routine clinical data were abstracted for all newly registered adult TB-HIV patients during the study period. Descriptive statistics were used to assess TB diagnostic practices, timing of the HIV diagnosis, and ART status at TB treatment initiation. Between April 2013 and March 2015, 1233 TB-HIV patients were enrolled. Among 1215 patients with available data, 87.2% had pulmonary TB, of which 34.8% were bacteriologically confirmed, 40.9% tested negative and 24.3% were not tested. Among 1138 patients with available data, 53.3% had an existing HIV diagnosis, of whom 39.3% were ART-naïve. The majority of pulmonary TB patients were clinically diagnosed, and many were unaware of their HIV status or were ART-naïve despite known status. The Test and Treat Strategy holds promise to prevent TB and reduce TB-related mortality among people living with HIV; however, enhanced TB diagnostic capacity and improved HIV case detection are urgently needed.
Dorman, Susan E; Savic, Radojka M; Goldberg, Stefan; Stout, Jason E; Schluger, Neil; Muzanyi, Grace; Johnson, John L; Nahid, Payam; Hecker, Emily J; Heilig, Charles M; Bozeman, Lorna; Feng, Pei-Jean I; Moro, Ruth N; MacKenzie, William; Dooley, Kelly E; Nuermberger, Eric L; Vernon, Andrew; Weiner, Marc
Rifapentine has potent activity in mouse models of tuberculosis chemotherapy but its optimal dose and exposure in humans are unknown. We conducted a randomized, partially blinded dose-ranging study to determine tolerability, safety, and antimicrobial activity of daily rifapentine for pulmonary tuberculosis treatment. Adults with sputum smear-positive pulmonary tuberculosis were assigned rifapentine 10, 15, or 20 mg/kg or rifampin 10 mg/kg daily for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. The primary tolerability end point was treatment discontinuation. The primary efficacy end point was negative sputum cultures at completion of intensive phase. A total of 334 participants were enrolled. At completion of intensive phase, cultures on solid media were negative in 81.3% of participants in the rifampin group versus 92.5% (P = 0.097), 89.4% (P = 0.29), and 94.7% (P = 0.049) in the rifapentine 10, 15, and 20 mg/kg groups. Liquid cultures were negative in 56.3% (rifampin group) versus 74.6% (P = 0.042), 69.7% (P = 0.16), and 82.5% (P = 0.004), respectively. Compared with the rifampin group, the proportion negative at the end of intensive phase was higher among rifapentine recipients who had high rifapentine areas under the concentration-time curve. Percentages of participants discontinuing assigned treatment for reasons other than microbiologic ineligibility were similar across groups (rifampin, 8.2%; rifapentine 10, 15, or 20 mg/kg, 3.4, 2.5, and 7.4%, respectively). Daily rifapentine was well-tolerated and safe. High rifapentine exposures were associated with high levels of sputum sterilization at completion of intensive phase. Further studies are warranted to determine if regimens that deliver high rifapentine exposures can shorten treatment duration to less than 6 months. Clinical trial registered with www.clinicaltrials.gov (NCT 00694629).
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.
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.
Proaño, Alvaro; Bravard, Marjory A; López, José W; Lee, Gwenyth O; Bui, David; Datta, Sumona; Comina, Germán; Zimic, Mirko; Coronel, Jorge; Caviedes, Luz; Cabrera, José L; Salas, Antonio; Ticona, Eduardo; Vu, Nancy M; Kirwan, Daniela E; Loader, Maria-Cristina I; Friedland, Jon S; Moore, David A J; Evans, Carlton A; Tracey, Brian H; Gilman, Robert H
Cough is the major determinant of tuberculosis transmission. Despite this, there is a paucity of information regarding characteristics of cough frequency throughout the day and in response to tuberculosis therapy. Here we evaluate the circadian cycle of cough, cough frequency risk factors, and the impact of appropriate treatment on cough and bacillary load. We prospectively evaluated human immunodeficiency virus-negative adults (n = 64) with a new diagnosis of culture-proven, drug-susceptible pulmonary tuberculosis immediately prior to treatment and repeatedly until treatment day 62. At each time point, participant cough was recorded (n = 670) and analyzed using the Cayetano Cough Monitor. Consecutive coughs at least 2 seconds apart were counted as separate cough episodes. Sputum samples (n = 426) were tested with microscopic-observation drug susceptibility broth culture, and in culture-positive samples (n = 252), the time to culture positivity was used to estimate bacillary load. The highest cough frequency occurred from 1 pm to 2 pm, and the lowest from 1 am to 2 am (2.4 vs 1.1 cough episodes/hour, respectively). Cough frequency was higher among participants who had higher sputum bacillary load (P < .01). Pretreatment median cough episodes/hour was 2.3 (interquartile range [IQR], 1.2-4.1), which at 14 treatment days decreased to 0.48 (IQR, 0.0-1.4) and at the end of the study decreased to 0.18 (IQR, 0.0-0.59) (both reductions P < .001). By 14 treatment days, the probability of culture conversion was 29% (95% confidence interval, 19%-41%). Coughs were most frequent during daytime. Two weeks of appropriate treatment significantly reduced cough frequency and resulted in one-third of participants achieving culture conversion. Thus, treatment by 2 weeks considerably diminishes, but does not eliminate, the potential for airborne tuberculosis transmission.
Tresoldi, Antonia T; Pereira, Ricardo M; Castro, Lelma C; Rigatto, Sumara Z P; Belangero, Vera M S
To describe the case of a child with paracoccidioidomycosis who presented hypercalcemia with multiple osteolytic lesions. A 6-year-old boy was admitted with a one-month history of fever and hepatosplenomegaly. On admission, he looked sick, pale, and had disseminated lymphadenopathy and hepatosplenomegaly. The laboratory findings included anemia (hemoglobin = 6.8 g/dl), eosinophilia (1,222/mm3), thrombocytopenia (102,000/mm3), and hypoalbuminemia (serum albumin = 2.2 g/dl). Paracoccidioides brasiliensis was identified in bone marrow examination. In the second week after admission, the patient presented joint pain, poor activity and difficulty in walking. He presented hypercalcemia (maximum value = 14.9 mg%) and reduction in renal function, which lasted for two weeks. On the 42nd day after admission, his chest X-ray showed lytic lesions in clavicle, scapula, ribs, and humerus, with bilateral slipped capital humeral epiphysis. The patient presented nephrocalcinosis and nephrolithiasis, reduction in creatinine clearance and evidence of tubular lesions. At the end of the second month after admission, Mycobacterium tuberculosis was isolated in gastric washing. The child received treatment for paracoccidioidomycosis and tuberculosis and has not had any sequelae for 3 years. The development of symptomatic hypercalcemia leading to renal lesion, associated with multiple osteolytic lesions, had never been described in paracoccidioidomycosis. Although pulmonary tuberculosis was diagnosed and could be related to hypercalcemia, the sudden onset of hypercalcemia and its normalization without specific treatment for tuberculosis suggests that bone lysis was the most important factor in the genesis of hypercalcemia.
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
Bravard, Marjory A.; López, José W.; Lee, Gwenyth O.; Bui, David; Datta, Sumona; Comina, Germán; Zimic, Mirko; Coronel, Jorge; Caviedes, Luz; Cabrera, José L.; Salas, Antonio; Ticona, Eduardo; Vu, Nancy M.; Kirwan, Daniela E.; Loader, Maria-Cristina I.; Friedland, Jon S.; Moore, David A. J.; Evans, Carlton A.; Tracey, Brian H.; Gilman, Robert H.
Abstract Background. Cough is the major determinant of tuberculosis transmission. Despite this, there is a paucity of information regarding characteristics of cough frequency throughout the day and in response to tuberculosis therapy. Here we evaluate the circadian cycle of cough, cough frequency risk factors, and the impact of appropriate treatment on cough and bacillary load. Methods. We prospectively evaluated human immunodeficiency virus–negative adults (n = 64) with a new diagnosis of culture-proven, drug-susceptible pulmonary tuberculosis immediately prior to treatment and repeatedly until treatment day 62. At each time point, participant cough was recorded (n = 670) and analyzed using the Cayetano Cough Monitor. Consecutive coughs at least 2 seconds apart were counted as separate cough episodes. Sputum samples (n = 426) were tested with microscopic-observation drug susceptibility broth culture, and in culture-positive samples (n = 252), the time to culture positivity was used to estimate bacillary load. Results. The highest cough frequency occurred from 1 pm to 2 pm, and the lowest from 1 am to 2 am (2.4 vs 1.1 cough episodes/hour, respectively). Cough frequency was higher among participants who had higher sputum bacillary load (P < .01). Pretreatment median cough episodes/hour was 2.3 (interquartile range [IQR], 1.2–4.1), which at 14 treatment days decreased to 0.48 (IQR, 0.0–1.4) and at the end of the study decreased to 0.18 (IQR, 0.0–0.59) (both reductions P < .001). By 14 treatment days, the probability of culture conversion was 29% (95% confidence interval, 19%–41%). Conclusions. Coughs were most frequent during daytime. Two weeks of appropriate treatment significantly reduced cough frequency and resulted in one-third of participants achieving culture conversion. Thus, treatment by 2 weeks considerably diminishes, but does not eliminate, the potential for airborne tuberculosis transmission. PMID:28329268
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
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. Copyright © 2016 Elsevier B.V. All rights reserved.
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
Gopi, P G; Subramani, R; Narayanan, P R
Prevalence of tuberculosis (TB) is an important epidemiological index to measure the load of the disease in a community. A series of disease surveys were undertaken in rural community in Tiruvallur district in Tamilnadu, south India To investigate the yield of pulmonary tuberculosis (TB) cases by different symptoms status and suggest predominant symptoms for detection of cases in the community based surveys. Three disease surveys were conducted during 1999-2006, in a random sample of 82,000 adults aged > or = 15 years to estimate the prevalence and incidence of pulmonary TB. All subjects were screened for chest symptoms and chest radiography. Sputum examination was done among those who were either symptomatic or abnormal on X-ray or both. Cases observed through symptom inquiry were included for analysis. In survey-I, 65.6% had cough of > or = 14 days and yielded 79.1% of the total cases. In surveys II and III, symptomatic subjects with cough contributed 69.5% and 69.2% of the cases respectively. In survey I, 26.8% had symptoms without cough but with at least chest pain > or = 1 month contributed 8.4% of total cases. The corresponding proportions in subsequent surveys were 29.3, 11.5%; and 23.4, 11.2% respectively. The number of symptomatics without cough and chest pain but with fever > or = 1 month was negligible. The relative importance of cough as a predominant symptom was reiterated. The yield of pulmonary TB cases from symptomatics having fever of > or = 1 month was negligible. Fever may be excluded from the definition of symptomatics for screening the population in community surveys.
Senkoro, Mbazi; Mfinanga, Sayoki G; Mørkve, Odd
Tanzania ranks 15th among the world's 22 countries with the largest tuberculosis burden and tuberculosis has continued to be among the major public health problems in the country. Limited data, especially in patients co infected with HIV, are available to predict the duration of time required for a smear positive pulmonary tuberculosis patient to achieve sputum conversion after starting effective treatment. In this study we assessed the sputum smear and culture conversion rates among HIV positive and HIV negative smear positive pulmonary tuberculosis patients in Dar es Salaam The study was a prospective cohort study which lasted for nine months, from April to December 2008 A total of 502 smear positive pulmonary tuberculosis patients were recruited. HIV test results were obtained for 498 patients, of which 33.7% were HIV positive. After two weeks of treatment the conversion rate by standard sputum microscopy was higher in HIV positive(72.8%) than HIV negative(63.3%) patients by univariate analysis(P = 0.046), but not in multivariate analysis. Also after two weeks of treatment the conversion rate by fluorescence microscopy was higher in HIV positive (72.8%) than in HIV negative(63.2%) patients by univariate analysis (P = 0.043) but not in the multivariate analysis. The conversion rates by both methods during the rest of the treatment period (8, 12, and 20 weeks) were not significantly different between HIV positive and HIV negative patients.With regards to culture, the conversion rate during the whole period of the treatment (2, 8, 12 and 20 weeks) were not significantly different between HIV positive and HIV negative patients. Conversion rates of standard smear microscopy, fluorescence microscopy and culture did not differ between HIV positive and HIV negative pulmonary tuberculosis patients.
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
Wu, Ming-Fang; Jian, Zhi-Hong; Huang, Jing-Yang; Jan, Cheng-Feng; Nfor, Oswald Ndi; Jhang, Kai-Ming; Ku, Wen-Yuan; Ho, Chien-Chang; Lung, Chia-Chi; Pan, Hui-Hsien; Wu, Min-Chen; Liaw, Yung-Po
Inhaled corticosteroids (ICS) have been associated with decreased lung cancer risk. However, they have been associated with pulmonary infections (tuberculosis [TB] and pneumonia) in patients with chronic obstructive pulmonary disease (COPD). TB and pneumonia have increased lung cancer risk. The association between post-ICS pulmonary infections and lung cancer remains unclear. We conducted a retrospective cohort study from 2003 to 2010 using the Taiwan National Health Insurance Research Database. Among the 1,089,955 patients with COPD, we identified 8813 new users of ICS prescribed for a period of 3 months or more and 35,252 non-ICS users who were randomly matched for sex, age and date of ICS use from 2003 to 2005. Cox proportional hazard regression was used to estimate the hazard ratio (HR) of pulmonary infections in patients with/without ICS use. The HRs for lung cancer in ICS users with sequential lung infections were as follows; 2.42 (95 % confidence interval [CI], 1.28-4.58) for individuals with TB, 2.37 (95 % CI, 1.01-5.54) for TB and pneumonia, and 1.17(95 % CI, 0.69-1.98) for those with pneumonia. For non-ICS users with pulmonary infections, the HRs were 1.68 (95 % CI, 0.78-3.65) for individual with TB and pneumonia, 1.42 (95 % CI, 0.89-2.26) for TB, and 0.95 (95 % CI, 0.62-1.46) for individuals with pneumonia. COPD patients with TB /or pneumonia who used ICS had increased risk of lung cancer. Because the overall prognosis of lung cancer remains poor, screening tests are recommended for patients with these conditions.
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
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
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
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
Al-Darraji, Haider Abdulrazzaq Abed; Altice, Frederick L; Kamarulzaman, Adeeba
To investigate the prevalence of previously undiagnosed active tuberculosis (TB) cases among prisoners in Malaysia's largest prison using an intensified TB case-finding strategy. From October 2012 to May 2013, prisoners housed in two distinct units (HIV-negative and HIV-positive) were approached to participate in the TB screening study. Consenting prisoners submitted two sputum samples that were examined using GeneXpert MTB/RIF, smear microscopy and liquid culture. Socio-demographic and clinical information was collected and correlates of active TB, defined as having either a positive GeneXpert MTB/RIF or culture results, were assessed using regression analyses. Among the total of 559 prisoners, 442 (79.1%) had complete data; 28.7% were HIV-infected, 80.8% were men and the average age was 36.4 (SD 9.8) years. Overall, 34 (7.7%) had previously undiagnosed active TB, of whom 64.7% were unable to complete their TB treatment in prison due to insufficient time (<6 months) remaining in prison. Previously undiagnosed active TB was independently associated with older age groups (AOR 11.44 and 6.06 for age ≥ 50 and age 40-49 years, respectively) and with higher levels of immunosuppression (CD4 < 200 cells/ml) in HIV-infected prisoners (AOR 3.07, 95% CI 1.03-9.17). The high prevalence of previously undiagnosed active TB in this prison highlights the inadequate performance of internationally recommended case-finding strategies and suggests that passive case-finding policies should be abandoned, especially in prison settings where HIV infection is prevalent. Moreover, partnerships between criminal justice and public health treatment systems are crucial to continue TB treatment after release. © 2016 John Wiley & Sons Ltd.
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. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.
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
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
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
Hanai, Shogo; Shinzato, Takashi; Inazu, Daiki; Tokuda, Yasuharu
Many diseases can cause hypercalcaemia, including primary hyperparathyroidism, cancer, drugs and granulomatous diseases. A nursing home resident aged 81 years was admitted because of altered mental status. The patient did not have fever, cough, sputum or night sweat. Hypercalcaemia was identified as a cause of the consciousness disturbance. Chest radiograph showed no acute process. Laboratory workups revealed elevated serum levels of 1,25-(OH)2 vitamin D3 and positive T-spot test. Microscopic examination of the suctioned sputum identified acid-fast bacilli, which was confirmed as Mycobactrium tuberculsosis Tuberculosis should be considered as the important cause of hypercalcaemia since early diagnosis and treatment is recommended for preventing its outbreak among people with close contacts with patients. 2017 BMJ Publishing Group Ltd.
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
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.
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
Tuberculosis (TB) is a disease caused by bacteria called Mycobacterium tuberculosis. The bacteria usually attack the lungs, but they can also damage other parts of the body. TB spreads through the air when a person with ...
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
Fujita, Kohei; Terashima, Tsuyoshi; Mio, Tadashi
Recently, cancer immunotherapy by immune checkpoint inhibitors has been considered one of the pillars for the treatment of cancer. Nivolumab is the first immune checkpoint inhibitor approved for lung cancer treatment in Japan. Although nivolumab has superior survival benefits and fewer adverse events than cytotoxic agents, it can generate dysimmune toxicities, known as immune-related adverse events. Although autoimmune manifestations are well-known immune-related adverse events, the development of infectious diseases is rare. Here, we report on a patient with advanced NSCLC in whom pulmonary tuberculosis developed rapidly during nivolumab treatment and discuss the potential mechanisms as well as what is known about infections during checkpoint inhibitor therapy. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
Kofman, J; Chevalier, J P; Baraton, G; Brun, J
A diagnosis of Niemann-Pick disease was made in a 26 years old man with chronic pulmonary miliary tuberculosis and splenomegaly. It was confirmed by the drop of sphingomyelinase level in leucocytes and fibroblasts of the skin. The authors showed the presence of foamy cells with sphingomyelin in the spleen and bone marrow. They underlined the value of dosing sphingomyelinase in leucocytes for diagnosis purposes. They also observed blue histocytes in the spleen and bone marrow, next to the foamy cells which are not specific of Niemann-Pick disease and can be found in numerous other affections. This pure visceral form with delayed development without neurological involvement, corresponds to the phenotype B of Crocker.
Lyrio Peres, Renata; do Prado, Thiago Nascimento; Macedo, Cristina Ribeiro; Palaci, Moisés; Alves Vinhas, Solange; Dietze, Reynaldo; Johnson, John L.; Struchiner, Claúdio Jose
The main objective is to assess whether nebulization before gastric lavage (GL) improves its sensitivity for the diagnosis of childhood tuberculosis (TB). Children and adolescents suspected of pulmonary TB were randomly assigned (1 : 2) to nebulization with hypertonic saline 30 min before GL (Neb group; n = 36) or GL without prior nebulization (controls; n = 68). The proportion of positive GL smears was greater in Neb group than in the control group; however, no statistical significance was observed (36.3% vs. 22.2%; p = 0.4). Inhalation of nebulized hypertonic saline before GL did not improve TB diagnosis in this study. Nevertheless, the validation of our data will require large longitudinal studies. PMID:20207695
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.
Luetkemeyer, Anne F; Firnhaber, Cynthia; Kendall, Michelle A; Wu, Xingye; Mazurek, Gerald H; Benator, Debra A; Arduino, Roberto; Fernandez, Michel; Guy, Elizabeth; Johnson, Pamela; Metchock, Beverly; Sattler, Fred; Telzak, Edward; Wang, Yun F; Weiner, Marc; Swindells, Susan; Sanne, Ian M; Havlir, Diane V; Grinsztejn, Beatriz; Alland, David
The Xpert MTB/RIF (Xpert) assay is a rapid nucleic acid amplification test widely used in settings of high tuberculosis prevalence to detect tuberculosis as well asrpoBmutations associated with rifampin resistance. Data are needed on the diagnostic performance of Xpert in lower-prevalence settings to inform appropriate use for both tuberculosis detection and the need for respiratory isolation. Xpert was compared to 2 sputum samples, each evaluated with acid-fast bacilli (AFB) smear and mycobacterial culture using liquid and solid culture media, from participants with suspected pulmonary tuberculosis from the United States, Brazil, and South Africa. Of 992 participants enrolled with evaluable results, 22% had culture-confirmed tuberculosis. In 638 (64%) US participants, 1 Xpert result demonstrated sensitivity of 85.2% (96.7% in participants with AFB smear-positive [AFB(+)] sputum, 59.3% with AFB smear-negative [AFB(-)] sputum), specificity of 99.2%, negative predictive value (NPV) of 97.6%, and positive predictive value of 94.9%. Results did not differ between higher- and low-prevalence settings. A second Xpert assay increased overall sensitivity to 91.1% (100% if AFB(+), 71.4% if AFB(-)), with specificity of 98.9%. In US participants, a single negative Xpert result predicted the absence of AFB(+)/culture-positive tuberculosis with an NPV of 99.7%; NPV of 2 Xpert assays was 100%, suggesting a role in removing patients from airborne infection isolation. Xpert detected tuberculosis DNA and mutations associated with rifampin resistance in 5 of 7 participants with rifampin-resistant, culture-positive tuberculosis. Specificity for rifampin resistance was 99.5% and NPV was 98.9%. In the United States, Xpert testing performed comparably to 2 higher-tuberculosis-prevalence settings. These data support the use of Xpert in the initial evaluation of tuberculosis suspects and in algorithms assessing need for respiratory isolation. © The Author 2016. Published by Oxford
Luetkemeyer, Anne F.; Firnhaber, Cynthia; Kendall, Michelle A.; Wu, Xingye; Mazurek, Gerald H.; Benator, Debra A.; Arduino, Roberto; Fernandez, Michel; Guy, Elizabeth; Johnson, Pamela; Metchock, Beverly; Sattler, Fred; Telzak, Edward; Wang, Yun F.; Weiner, Marc; Swindells, Susan; Sanne, Ian M.; Havlir, Diane V.; Grinsztejn, Beatriz; Alland, David
Background. The Xpert MTB/RIF (Xpert) assay is a rapid nucleic acid amplification test widely used in settings of high tuberculosis prevalence to detect tuberculosis as well as rpoB mutations associated with rifampin resistance. Data are needed on the diagnostic performance of Xpert in lower-prevalence settings to inform appropriate use for both tuberculosis detection and the need for respiratory isolation. Methods. Xpert was compared to 2 sputum samples, each evaluated with acid-fast bacilli (AFB) smear and mycobacterial culture using liquid and solid culture media, from participants with suspected pulmonary tuberculosis from the United States, Brazil, and South Africa. Results. Of 992 participants enrolled with evaluable results, 22% had culture-confirmed tuberculosis. In 638 (64%) US participants, 1 Xpert result demonstrated sensitivity of 85.2% (96.7% in participants with AFB smear-positive [AFB+] sputum, 59.3% with AFB smear-negative [AFB–] sputum), specificity of 99.2%, negative predictive value (NPV) of 97.6%, and positive predictive value of 94.9%. Results did not differ between higher- and low-prevalence settings. A second Xpert assay increased overall sensitivity to 91.1% (100% if AFB+, 71.4% if AFB–), with specificity of 98.9%. In US participants, a single negative Xpert result predicted the absence of AFB+/culture-positive tuberculosis with an NPV of 99.7%; NPV of 2 Xpert assays was 100%, suggesting a role in removing patients from airborne infection isolation. Xpert detected tuberculosis DNA and mutations associated with rifampin resistance in 5 of 7 participants with rifampin-resistant, culture-positive tuberculosis. Specificity for rifampin resistance was 99.5% and NPV was 98.9%. Conclusions. In the United States, Xpert testing performed comparably to 2 higher-tuberculosis-prevalence settings. These data support the use of Xpert in the initial evaluation of tuberculosis suspects and in algorithms assessing need for respiratory isolation
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.
Areias, C; Briz, T; Nunes, C
Portugal, a medium- to low-level endemic country (21·6 cases/100 000 population in 2012), has one of the highest European Union tuberculosis (TB) incidences. Although incidence is declining progressively, the country's heterogeneity in both regional endemics and their evolution suggests the importance of a better understanding of subnational epidemiology to customize TB control efforts. We aimed to update knowledge on municipality-years pulmonary TB incidence clustering, identify areas with different time trends, and show the potential of combining complementary clustering methods in control of infectious diseases. We used national surveillance municipality-level data (mainland Portugal, 2000-2010). Space-time clustering and spatial variation in temporal trends methods were applied. Space-time critical clusters identified (P < 0·001) were still the Lisbon and Oporto regions. The global incidence declined at a 5·81% mean annual percentage change, with high space-time heterogeneity and distinct time trend clusters (P < 0·001). Municipalities with incidences declining more rapidly belonged to critical areas. In particular, the Oporto trend cluster had a consistent -8·98% mean annual percentage change. Large space-time heterogeneities were identified, with critical incidences in the greater Lisbon and Oporto regions, but declining more rapidly in these regions. Oporto showed a consistent, steeper decrease and could represent a good example of local control strategy. Combining results from these approaches gives promise for prospects for infectious disease control and the design of more effective, focused interventions.
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
van't Hoog, Anna H; Laserson, Kayla F; Githui, Willie A; Meme, Helen K; Agaya, Janet A; Odeny, Lazarus O; Muchiri, Benson G; Marston, Barbara J; DeCock, Kevin M; Borgdorff, Martien W
Limited information exists on the prevalence of tuberculosis and adequacy of case finding in African populations with high rates of HIV. To estimate the prevalence of bacteriologically confirmed pulmonary tuberculosis (PTB) and the fraction attributable to HIV, and to evaluate case detection. Residents aged 15 years and older, from 40 randomly sampled clusters, provided two sputum samples for microscopy; those with chest radiograph abnormalities or symptoms suggestive of PTB provided one additional sputum sample for culture. PTB was defined by a culture positive for Mycobacterium tuberculosis or two positive smears. Persons with PTB were offered HIV testing and interviewed on care-seeking behavior. We estimated the population-attributable fraction of HIV on prevalent and notified PTB, the patient diagnostic rate, and case detection rate using provincial TB notification data. Among 20,566 participants, 123 had PTB. TB prevalence was 6.0/1,000 (95% confidence interval, 4.6-7.4) for all PTB and 2.5/1,000 (1.6-3.4) for smear-positive PTB. Of 101 prevalent TB cases tested, 52 (51%) were HIV infected, and 58 (64%) of 91 cases who were not on treatment and were interviewed had not sought care. Forty-eight percent of prevalent and 65% of notified PTB cases were attributable to HIV. For smear-positive and smear-negative PTB combined, the patient diagnostic rate was 1.4 cases detected per person-year among HIV-infected persons having PTB and 0.6 for those who were HIV uninfected, corresponding to case detection rates of 56 and 65%, respectively. Undiagnosed PTB is common in this community. TB case finding needs improvement, for instance through intensified case finding with mobile smear microscopy services, rigorous HIV testing, and improved diagnosis of smear-negative TB.
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
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.
Background The number of pulmonary tuberculosis (PTB) patients reported with resistance to first-line anti-tuberculosis drugs after a standardized retreatment regimen in Cameroon is increasing. Hence, the National Tuberculosis Control Program (NTP) implemented, in one of the ten Regions of the country, a pilot programme aimed at performing routine drug susceptibility testing (DST) for previously treated PTB cases. The objectives of the programme were to evaluate the feasibility of monitoring drug resistance among retreatment cases under programme conditions and to measure the presence and magnitude of anti-TB drug resistance in order to inform NTP policies. Findings This retrospective cohort study was conducted in the Littoral Region of Cameroon in 2009. It included all sputum smear positive (SM+) PTB cases registered for retreatment. TB cases were identified and classified according to World Health Organization (WHO) recommendations for national TB programs. Bacterial susceptibility testing to first-line anti-TB drugs was performed using standard culture methods. In 2009, 5,668 TB cases were reported in the Littoral Region, of which 438 (7.7%) were SM + PTB retreatment cases. DST results were available for 216 (49.4%) patients. Twenty six patients (12%) harbored multi-drug resistant (MDR) strains. Positive treatment outcome rates were particularly low in retreatment patients with MDR-TB (46.2%; 95% CI: 27.1-66.3). Thirteen MDR-TB patients were treated using a standardized MDR treatment regimen. Delivery of laboratory results took on average 17 (12-26) weeks. Conclusions WHO-recommended routine DST in retreatment patients seems feasible in Cameroon. However, coverage needs to be improved through better management. Moreover, diagnostic delay should be shortened by introducing more rapid diagnostic tools. The high risk of MDR in standard regimen failure cases virtually rules out the standard retreatment regimen for such patients without prior DST. PMID:22436423
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
Carroll, Matthew W.; Jeon, Doosoo; Mountz, James M.; Lee, Jong Doo; Jeong, Yeon Joo; Zia, Nadeem; Lee, Myungsun; Lee, Jongseok; Via, Laura E.; Lee, Soyoung; Eum, Seok-Yong; Lee, Sung-Joong; Goldfeder, Lisa C.; Cai, Ying; Jin, Boyoung; Kim, Youngran; Oh, Taegwon; Chen, Ray Y.; Dodd, Lori E.; Gu, Wenjuan; Dartois, Veronique; Park, Seung-Kyu; Kim, Cheon Tae
Pulmonary lesions from active tuberculosis patients are thought to contain persistent, nonreplicating bacilli that arise from hypoxic stress. Metronidazole, approved for anaerobic infections, has antituberculosis activity against anoxic bacilli in vitro and in some animal models and may target persistent, nonreplicating bacilli. In this double-blind, placebo-controlled trial, pulmonary multidrug-resistant tuberculosis subjects were randomly assigned to receive metronidazole (500 mg thrice daily) or placebo for 8 weeks in addition to an individualized background regimen. Outcomes were measured radiologically (change on high-resolution computed tomography [HRCT]), microbiologically (time to sputum smear and culture conversion), and clinically (status 6 months after stopping therapy). Enrollment was stopped early due to excessive peripheral neuropathies in the metronidazole arm. Among 35 randomized subjects, 31 (15 metronidazole, 16 placebo) were included in the modified intent-to-treat analysis. There were no significant differences by arm in improvement of HRCT lesions from baseline to 2 or 6 months. More subjects in the metronidazole arm converted their sputum smear (P = 0.04) and liquid culture (P = 0.04) to negative at 1 month, but these differences were lost by 2 months. Overall, 81% showed clinical success 6 months after stopping therapy, with no differences by arm. However, 8/16 (50%) of subjects in the metronidazole group and 2/17 (12%) of those in the placebo group developed peripheral neuropathy. Subjects who received metronidazole were 4.3-fold (95% confidence interval [CI], 1.1 to 17.1) more likely to develop peripheral neuropathies than subjects who received placebo. Metronidazole may have increased early sputum smear and culture conversion but was too neurotoxic to use over the longer term. Newer nitroimidazoles with both aerobic and anaerobic activity, now in clinical trials, may increase the sterilizing potency of future treatment regimens. PMID
Sakashita, Kentaro; Fujita, Akira; Takamori, Mikio; Nagai, Takayuki; Matsumoto, Tomoshige; Saito, Takefumi; Nakagawa, Taku; Ogawa, Kenji; Shigeto, Eriko; Nakatsumi, Yasuto; Goto, Hajime; Mitarai, Satoshi
High quality sputum helps increase the sensitivity of the diagnosis of pulmonary tuberculosis. To evaluate the efficiency of the acoustic device (Lung Flute; LF) in sputum induction compared with the conventional method, hypertonic saline inhalation (HSI). In this crossover study, patients with presumed pulmonary tuberculosis submitted three consecutive sputa: the first sputum without induction and the second and third ones using LF and HSI. We compared the efficiency of the two induction methods. Sixty-four participants were eligible. Thirty-five (54.6%) patients had negative smears on the first sputum without induction. Among those patients, 25.7% and 22.9% patients were smear-positive after using LF and HSI, respectively (p = 0.001). The positive conversion rate was not significantly different between the methods. The first samples without induction yielded 65.7% positive cultures, whereas 71.4% and 77.1% of the samples from LF and HSI were positive, respectively (p = 0.284). Similar results were observed in the nucleic acid amplification test [no induction (60.0%), LF (72.0%) and HSI (60.0%); p = 0.341]. In 29 smear-positive patients on the first sputum without induction, we observed no significant increase in smear grade, culture yield and nucleic acid amplification test positivity with either method. LF tended to induce fewer adverse events; desaturation (3.1% vs 11.1%; p = 0.082) and throat pain (1.5% vs 9.5%; p = 0.057). LF showed significantly fewer total adverse events (15.8% vs 34.9%; p = 0.023). Our study showed LF had similar sputum induction efficiency to HSI with relatively fewer complications. This article is protected by copyright. All rights reserved. © 2017 John Wiley & Sons Ltd.
Spinelli, Silvana V; Fernández, Rocío Del V; Zoff, Luciana; Bongiovanni, Bettina; Díaz, Ariana; D'Attilio, Luciano; Santucci, Natalia; Alvarez, Tomás; Marchesini, Marcela M; Bogue, Cristina; Bay, Maria L; Bottasso, Oscar A
Tuberculous pleurisy (PLTB) is a common form of extrapulmonary tuberculosis. It often resolves without chemotherapy being hence considered a rather benign manifestation of the disease. Patients with PLTB mount an effective anti-mycobacterial response, unlike those with active pulmonary TB (pTB) that were shown to present an imbalance in plasma immune and endocrine mediators. In this work, we explored whether expression of the active isoform of the glucocorticoid receptor (hGRα) in the context of the inflammatory-anti-inflammatory responses of TB patients may be associated to microRNA levels. As expected, the inflammatory response triggered in patients coexists with increased circulating cortisol and altered hGRα levels in the peripheral blood mononuclear cells. However, while hGRα expression is significantly downregulated in PLTB, its levels in pTB patients are higher within the control values. These results point out to the existence of an additional mechanism tending to preserve hGRα levels probably to deal with the chronic inflammation observed in pTB. In this regard, we found that miR-30c is strongly downregulated in mononuclear cells of pTB patients compared to PLTB cases, showing an expression profile opposite to that seen with hGRα. Interestingly, low levels of miR-30c are specific for this active form of TB, as its expression is not altered in mononuclear cells from either healthy controls or patients with tuberculous or non-tuberculous pleurisy. Moreover, miR-30c and hGRα also showed an inverse expression pattern in M. tuberculosis-stimulated THP-1 macrophage cultures. In sum, our studies identify miR-30c as a specific correlate of pulmonary manifestations of TB, potentially involved in the altered glucocorticoid sensitivity observed in these patients. Copyright © 2017 Elsevier Ltd. All rights reserved.
Carroll, Matthew W; Jeon, Doosoo; Mountz, James M; Lee, Jong Doo; Jeong, Yeon Joo; Zia, Nadeem; Lee, Myungsun; Lee, Jongseok; Via, Laura E; Lee, Soyoung; Eum, Seok-Yong; Lee, Sung-Joong; Goldfeder, Lisa C; Cai, Ying; Jin, Boyoung; Kim, Youngran; Oh, Taegwon; Chen, Ray Y; Dodd, Lori E; Gu, Wenjuan; Dartois, Veronique; Park, Seung-Kyu; Kim, Cheon Tae; Barry, Clifton E; Cho, Sang-Nae
Pulmonary lesions from active tuberculosis patients are thought to contain persistent, nonreplicating bacilli that arise from hypoxic stress. Metronidazole, approved for anaerobic infections, has antituberculosis activity against anoxic bacilli in vitro and in some animal models and may target persistent, nonreplicating bacilli. In this double-blind, placebo-controlled trial, pulmonary multidrug-resistant tuberculosis subjects were randomly assigned to receive metronidazole (500 mg thrice daily) or placebo for 8 weeks in addition to an individualized background regimen. Outcomes were measured radiologically (change on high-resolution computed tomography [HRCT]), microbiologically (time to sputum smear and culture conversion), and clinically (status 6 months after stopping therapy). Enrollment was stopped early due to excessive peripheral neuropathies in the metronidazole arm. Among 35 randomized subjects, 31 (15 metronidazole, 16 placebo) were included in the modified intent-to-treat analysis. There were no significant differences by arm in improvement of HRCT lesions from baseline to 2 or 6 months. More subjects in the metronidazole arm converted their sputum smear (P = 0.04) and liquid culture (P = 0.04) to negative at 1 month, but these differences were lost by 2 months. Overall, 81% showed clinical success 6 months after stopping therapy, with no differences by arm. However, 8/16 (50%) of subjects in the metronidazole group and 2/17 (12%) of those in the placebo group developed peripheral neuropathy. Subjects who received metronidazole were 4.3-fold (95% confidence interval [CI], 1.1 to 17.1) more likely to develop peripheral neuropathies than subjects who received placebo. Metronidazole may have increased early sputum smear and culture conversion but was too neurotoxic to use over the longer term. Newer nitroimidazoles with both aerobic and anaerobic activity, now in clinical trials, may increase the sterilizing potency of future treatment regimens.
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
Mendoza-Aguilar, Melby; García-Elorriaga, Guadalupe; Arce-Paredes, Patricia; González-Bonilla, César; Del Rey-Pineda, Guillermo; Rojas-Espinosa, Oscar
The phagocytic function in pulmonary tuberculosis (PTB) and Type 2 diabetes (T2D) has been explored mainly in macrophages but not in polymorphonuclears (PMN). The purpose of this study was to determine the functional status of PMN leukocytes in patients with pulmonary tuberculosis (PTB), Type 2 diabetes (T2D), and in patients with both diseases. An observational, prospective, and comparative study was carried out. 30 ambulatory patients with T2D, 10 with PTB undergoing treatment and 10 patients with PTB and T2D, and 44 healthy subjects were studied. PMN leukocytes were separated, the capacity of these cells to produce hydrogen peroxide and to reduce nitroblue tetrazolium (NBT) in response to stimulus with the phorbolic ester of myristic acid (PMA) was measured; and the capacity of PMN leukocytes to adhere to surfaces was determined. Concerning the test for adherence, on comparing healthy subjects with patients with T2D+PTB, we observed a clear decrease in cellular adherence in the group of patients with both diseases; it was statistically significant (p = 0.007).With regard to phagocytic function, we observed that in NBT reduction as well as in hydrogen peroxide production, statistically significant differences were not obtained on comparing healthy subjects with any of the three groups of patients. We observed a clear decrease in cellular adherence when both diseases co-exist. These results could indicate the need for the co-existence of T2D and TB to cause deterioration in the cells' adherence activity. The microtechniques employed permit the evaluation in a practical manner of certain phagocytic-activity expressions.
Okur, E; Yilmaz, A; Saygi, A; Selvi, A; Süngün, F; Oztürk, E; Dabak, G
In total, 151 newly diagnosed patients with smear-positive pulmonary tuberculosis were studied. The mean time from the onset of symptoms to the first visit to a physician was 46.4 days; the mean referral delay was 28.9 days; the mean delay in diagnosis was 2.4 days; and the mean delay in treatment initiation was 0.8 days. There was a delay in consulting a physician by 49% of patients. A low index of suspicion for tuberculosis on the part of the physician and healthcare system and laboratory delays were the most common reasons for delays in diagnosis.
Delarue, N C; Pearson, F G; Henderson, R D; Cooper, J D; Nelems, J M; Gale, G
The diminishing incidence of pulmonary tuberculosis and the increasing effectiveness of drug therapy have resulted in an almost complete disappearance of surgical problems in the management of patients with this disease. However, the lessons learned from the management of such problems should not be forgotten, for they are equally applicable to the management of disabling and life-endangering problems in general thoracic surgical practice. "Salvage" situations develop when therapeutic requirements for control of disease are combined with factors affecting a patient's health so as to increase the surgical risk beyond the range usually considered acceptable. Attempts to salvage patients are indicated when treatment has failed to arrest disease, when life expectancy is threatened, or when return to normal activity is imperiled. Risk may be increased because of age, inadequate cardiopulmonary reserve, or chronic toxemia; in tuberculosis, risk may be increased because of positive sputum culture or resistance of organisms. Experience with 146 tuberculous patients has provided a basis for evaluation of the indications for resection, prophylactic and therapeutic thoracoplasty, and closure of bronchopleural fistulas in general thoracic surgical salvage. Both infection in residual spaces and bronchopleural fistulas are serious complications that can be controlled by thoracoplasty and pedicled muscle grafts. Prophylactic use of osteoplastic thoracoplasty and intercostal muscle grafts warrant more serious consideration. In established complications a "tailored" thoracoplasty can also be combined with an intercostal muscle graft.
Grant, A. V.; Sabri, A.; Abid, A.; Rhorfi, I. Abderrahmani; Benkirane, M.; Souhi, H.; Amrani, H. Naji; Alaoui-Tahiri, K.; Gharbaoui, Y.; Lazrak, F.; Sentissi, I.; Manessouri, M.; Belkheiri, S.; Zaid, S.; Bouraqadi, A.; El Amraoui, N.; Hakam, M.; Belkadi, A.; Orlova, M.; Boland, A.; Deswarte, C.; Amar, L.; Bustamante, J.; Boisson-Dupuis, S.; Casanova, J. L.; Schurr, E.
Although epidemiological evidence suggests a human genetic basis of pulmonary tuberculosis (PTB) susceptibility, the identification of specific genes and alleles influencing PTB risk has proven to be difficult. Previous genome-wide association (GWA) studies have identified only three novel loci with modest effect sizes in sub-Saharan African and Russian populations. We performed a GWA study of 550,352 autosomal SNPs in a family-based discovery Moroccan sample (on the full population and on the subset with PTB diagnosis at <25 years), which identified 143 SNPs with p < 1 × 10−4. The replication study in an independent case/control sample identified four SNPs displaying a p < 0.01 implicating the same risk allele. In the combined sample including 556 PTB subjects and 650 controls these four SNPs showed suggestive association (2 × 10−6 < p < 4 × 10−5): rs358793 and rs17590261 were intergenic, while rs6786408 and rs916943 were located in introns of FOXP1 and AGMO, respectively. Both genes are involved in the function of macrophages, which are the site of latency and reactivation of Mycobacterium tuberculosis. The most significant finding (p = 2 × 10−6) was obtained for the AGMO SNP in an early (<25 years) age-at-onset subset, confirming the importance of considering age-at-onset to decipher the genetic basis of PTB. Although only suggestive, these findings highlight several avenues for future research in the human genetics of PTB. PMID:26767831
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
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
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
Ongkhammy, S; Amstutz, V; Barennes, H; Buisson, Y
Laos has a high prevalence of tuberculosis (TB) and a low prevalence of human immunodeficiency virus/acquired immune-deficiency syndrome (HIV/AIDS). Mycobacterium tuberculosis culture is not yet available. Case finding is based on the microscopic detection of acid-fast bacilli (AFB) in sputum. Liquefaction and concentration using sodium hypochlorite (bleach) could improve its yield. To assess the gain due to the bleach method and its feasibility in Laos, and to compare the classical method sputum processing (direct microscopy) and the bleach method for AFB detection over 3 consecutive months at a central site (Vientiane) and for 1 month at a peripheral site (Attapeu). Of 1675 sputum samples collected from 612 patients, respectively 206 (12.3%) and 275 (16.4%) were AFB-positive by the direct and bleach methods (P = 0.0007), i.e., an increase in smear positivity rate of 33.5% (95%CI 31.2-35.8). The superiority of the bleach method was confirmed, regardless of the site, the aspect of the sputum and delay before analysis. This method yielded 24 more TB patients. The bleach method, which is very easy to use, could significantly increase the yield of sputum smear microscopy for the detection of pulmonary TB in Laos.
Sánchez-Pérez, H; Flores-Hernández, J; Jansá, J; Caylá, J; Martín-Mateo, M
To estimate the prevalence of pulmonary tuberculosis (PTB) and factors associated with PTB in areas of high levels of poverty in Chiapas, Mexico. In 1998 active case-finding was carried out among those aged over 14 years who had a cough of > or =15 days duration, in a convenience sample of 1894 households in 32 communities selected at random based on the level of poverty and on the level of access to health services, measured by travelling time (<1 hour, > or =1 hour) from the community to the nearest health care unit. Of the 277 identified with a productive cough, we obtained sputum samples from 228 for the purposes of detecting PTB through acid-fast smears and cultures. Mycobacteria characterization was carried out using the BACTEC method. The identification of factors associated with PTB was performed using bivariate analysis and via logistic regression models. A PTB rate of 276.9 per 100 000 persons aged > or =15 years was found (95% CI : 161-443). Blood in sputum was the only factor associated with PTB (none of the demographic or socioeconomic characteristics were). Of 16 positive cultures, 14 became contaminated. The two cultures characterized were Mycobacterium tuberculosis (one being multiresistant). The high prevalence of PTB detected indicates the need, both in the area studied and in others with similar conditions, to develop PTB control programmes which give priority to early diagnosis and to the provision of adequate treatment.
Bell, David J; Dacombe, Russell; Graham, Stephen M; Hicks, Alexander; Cohen, Danielle; Chikaonda, Tarsizio; French, Neil; Molyneux, Malcolm E; Zijlstra, Ed E; Squire, S Bertel; Gordon, Stephen B
Setting Detection of smear-positive pulmonary tuberculosis (PTB) cases is vital for tuberculosis control. Methods to augment sputum collection are available but their additional benefit is uncertain in resource-limited settings. Objective To compare the diagnostic yields using five methods to obtain sputum from adults diagnosed with smear-negative PTB in Malawi. Design Self-expectorated sputum was collected under supervision for microscopy and mycobacterial culture in the study laboratory. Confirmed smear-negative patients, provided physiotherapy-assisted sputum and induced sputum followed, the next morning, by gastric washing and bronchoalveolar-lavage samples. Results 150 patients, diagnosed with smear-negative PTB by the hospital service, were screened. 39 (26%) were smear-positive from sup