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Sample records for active tuberculosis diagnosis

  1. 38 CFR 3.374 - Effect of diagnosis of active tuberculosis.

    2010-07-01

    ... diagnosis. Service department diagnosis of active pulmonary tuberculosis will be accepted unless a board of... Affairs diagnosis. Diagnosis of active pulmonary tuberculosis by the medical authorities of the Department... diagnosis. Diagnosis of active pulmonary tuberculosis by private physicians on the basis of...

  2. Rapid Diagnosis of Active Tuberculosis by Lipoarabinomanna test

    Urmila A.Sharma

    2000-04-01

    Full Text Available Presence of antimicrobial antibodies were repidly detected in 47 out of 50 cases of active pulmonaryand extra-pulmonary tuberculosis. The lipoarabinomanan (LAM antigen binds with the opllmumconcentration of anti LAM antibodies from the serum. Our findll1gs showed that the LAM test ISsimple, low cost, rapi~ and reliable test for detecting active tuberculosis.

  3. Mycobacterium tuberculosis lipolytic enzymes as potential biomarkers for the diagnosis of active tuberculosis.

    Belinda Brust

    Full Text Available BACKGROUND: New diagnosis tests are urgently needed to address the global tuberculosis (TB burden and to improve control programs especially in resource-limited settings. An effective in vitro diagnostic of TB based on serological methods would be regarded as an attractive progress because immunoassays are simple, rapid, inexpensive, and may offer the possibility to detect cases missed by standard sputum smear microscopy. However, currently available serology tests for TB are highly variable in sensitivity and specificity. Lipolytic enzymes have recently emerged as key factors in lipid metabolization during dormancy and/or exit of the non-replicating growth phase, a prerequisite step of TB reactivation. The focus of this study was to analyze and compare the potential of four Mycobacterium tuberculosis lipolytic enzymes (LipY, Rv0183, Rv1984c and Rv3452 as new markers in the serodiagnosis of active TB. METHODS: Recombinant proteins were produced and used in optimized ELISA aimed to detect IgG and IgM serum antibodies against the four lipolytic enzymes. The capacity of the assays to identify infection was evaluated in patients with either active TB or latent TB and compared with two distinct control groups consisting of BCG-vaccinated blood donors and hospitalized non-TB individuals. RESULTS: A robust humoral response was detected in patients with active TB whereas antibodies against lipolytic enzymes were infrequently detected in either uninfected groups or in subjects with latent infection. High specifity levels, ranging from 93.9% to 97.5%, were obtained for all four antigens with sensitivity values ranging from 73.4% to 90.5%, with Rv3452 displaying the highest performances. Patients with active TB usually exhibited strong IgG responses but poor IgM responses. CONCLUSION: These results clearly indicate that the lipolytic enzymes tested are strongly immunogenic allowing to distinguish active from latent TB infections. They appear as potent

  4. Prospective evaluation of a whole-blood test using Mycobacterium tuberculosis-specific antigens ESAT-6 and CFP-10 for diagnosis of active tuberculosis

    Ravn, Pernille; Munk, Martin E; Andersen, Ase B; Lundgren, Bettina; Lundgren, Jens Dilling; Nielsen, Lars Nørregaard; Kok-Jensen, Axel; Andersen, Peter; Weldingh, Karin

    2005-01-01

    A new immunodiagnostic test based on the Mycobacterium tuberculosis-specific antigens CFP-10/ESAT-6(QFT-RD1) has been launched as an aid in the diagnosis of latent tuberculosis (TB) infection (LTBI). The aim of this study was to evaluate this test for the diagnosis of active TB. Eighty-two patients...

  5. Peritoneal tuberculosis: radiographic diagnosis

    Carolina Ospina-Moreno

    2014-12-01

    Full Text Available Peritoneal tuberculosis (TB is an extrapulmonary form of presentation of tuberculosis. HIV infection is a primary risk factor for this condition. Diagnosis requires microbiological or histopathological confirmation in addition to supporting radiological imaging studies. Abdominal ultrasonography and CT are useful to obtain a radiographic diagnosis, with typical findings including diffuse peritoneal thickening, presence of ascites in varying volumes, adenopathies, and caseating nodes. We report 2 cases of patients with ascites and nodular peritoneal thickening on diagnostic images, as well as high CA-125 levels in laboratory tests. In both patients, a diagnosis of peritoneal tuberculosis was reached following a US-guided peritoneal biopsy.

  6. Pathogen-derived biomarkers for active tuberculosis diagnosis

    Tucci, Paula; González-Sapienza, Gualberto; Monica MARIN

    2014-01-01

    Tuberculosis (TB) is an infectious disease caused by members of Mycobacterium tuberculosis complex. Despite the availability of effective treatments, TB remains a major public health concern in most low and middle-income countries, representing worldwide the second leading cause of death from an infectious disease. Inadequate case detection and failures to classify the disease status hamper proper TB control. The limitations of the conventional diagnostic methods have encouraged much research...

  7. Interferon-¿ release assays for the diagnosis of active tuberculosis: a systematic review and meta-analysis

    Sester, M; Sotgiu, G; Lange, C; Giehl, C; Girardi, E; Migliori, G B; Bossink, A; Dheda, K; Diel, R; Dominguez, J; Lipman, M; Nemeth, J; Ravn, P; Winkler, S; Huitric, E; Sandgren, A; Manissero, D

    2011-01-01

    Interferon-¿ release assays (IGRAs) are now established for the immunodiagnosis of latent infection with Mycobacterium tuberculosis in many countries. However, the role of IGRAs for the diagnosis of active tuberculosis (TB) remains unclear. Following preferred reporting items for systematic reviews......-SPOT.TB® directly on blood or extrasanguinous specimens for the diagnosis of active TB. The literature search yielded 844 studies and 27 met the inclusion criteria. In blood and extrasanguinous fluids, the pooled sensitivity for the diagnosis of active TB was 80% (95% CI 75-84%) and 48% (95% CI 39-58%) for QFT...

  8. Evaluation of adenosine deaminase seric activity in the diagnosis of bovine tuberculosis

    Márcio Roberto Silva

    2006-06-01

    Full Text Available Determination of seric levels of adenosine deaminase (ADA, an enzyme produced by monocytes/macrophages and lymphocytes, has been used in the diagnosis of human tuberculosis (TB. In the present study, ADA seric activity was evaluated comparatively to the comparative tuberculin test in the diagnosis of bovine tuberculosis. Two hundred fifty-six cattle were classified by origin and by the comparative tuberculin test as TB-positive animals (n = 52, from herds where the Mycobacterium bovis had previously been isolated, and TB-negative animals (n = 204, TB-free herds. The mean ADA seric value from the TB-positive group (4.45 ± 2.33 U/L was significantly lower (p = 0.008 than that observed in sera from the TB-negative group (6.12 ± 4.47 U/L. When animals from a herd with clinical cases of enzootic bovine leukosis of TB-negative group were withdrawn from analysis, the mean ADA seric values of TB-negative group (5.12 ± 3.75 U/L was not significantly different anymore from that of the TB-positive group (p = 0.28. There was no agreement in the diagnosis of bovine TB between comparative tuberculin test and determination of ADA seric values, using two different cutoff points, being 6.12 U/L and 15.0 U/L, (kappa = -0.086 and kappa = -0.082, respectively. In conclusion, the determination of ADA seric activity was not a good auxiliary test for bovine TB, because it was not able to distinguish between TB-positive and TB-negative animals.

  9. Comparison of Tuberculin Activity in the Interferon-gamma Assay for the Diagnosis of Bovine Tuberculosis

    Cattle infected with bovine tuberculosis still represent a serious regulatory and health concern in a variety of countries. Early diagnosis using the in vitro interferon gamma (IFN-gamma) assay has been applied for more than a decade. Briefly, IFN-gamma responses in whole blood cultures stimulated w...

  10. Cost-Effectiveness of Automated Digital Microscopy for Diagnosis of Active Tuberculosis

    Jha, Swati; Ismail, Nazir; Clark, David; Lewis, James J.; Omar, Shaheed; Dreyer, Andries; Chihota, Violet; Churchyard, Gavin; David W Dowdy

    2016-01-01

    Background Automated digital microscopy has the potential to improve the diagnosis of tuberculosis (TB), particularly in settings where molecular testing is too expensive to perform routinely. The cost-effectiveness of TB diagnostic algorithms using automated digital microscopy remains uncertain. Methods Using data from a demonstration study of an automated digital microscopy system (TBDx, Applied Visual Systems, Inc.), we performed an economic evaluation of TB diagnosis in South Africa from ...

  11. Cost-Effectiveness of Automated Digital Microscopy for Diagnosis of Active Tuberculosis.

    Jha, S. (Stefania); Ismail, N; Clark, D. (David); Lewis, JJ; Omar, S; A. Dreyer; Chihota, V.; Churchyard, G.; Dowdy, DW

    2016-01-01

    Automated digital microscopy has the potential to improve the diagnosis of tuberculosis (TB), particularly in settings where molecular testing is too expensive to perform routinely. The cost-effectiveness of TB diagnostic algorithms using automated digital microscopy remains uncertain. Using data from a demonstration study of an automated digital microscopy system (TBDx, Applied Visual Systems, Inc.), we performed an economic evaluation of TB diagnosis in South Africa from the health sy...

  12. Cost-Effectiveness of Automated Digital Microscopy for Diagnosis of Active Tuberculosis.

    Swati Jha

    Full Text Available Automated digital microscopy has the potential to improve the diagnosis of tuberculosis (TB, particularly in settings where molecular testing is too expensive to perform routinely. The cost-effectiveness of TB diagnostic algorithms using automated digital microscopy remains uncertain.Using data from a demonstration study of an automated digital microscopy system (TBDx, Applied Visual Systems, Inc., we performed an economic evaluation of TB diagnosis in South Africa from the health system perspective. The primary outcome was the incremental cost per new TB diagnosis made. We considered costs and effectiveness of different algorithms for automated digital microscopy, including as a stand-alone test and with confirmation of positive results with Xpert MTB/RIF ('Xpert', Cepheid, Inc.. Results were compared against both manual microscopy and universal Xpert testing.In settings willing to pay $2000 per incremental TB diagnosis, universal Xpert was the preferred strategy. However, where resources were not sufficient to support universal Xpert, and a testing volume of at least 30 specimens per day could be ensured, automated digital microscopy with Xpert confirmation of low-positive results could facilitate the diagnosis of 79-84% of all Xpert-positive TB cases, at 50-60% of the total cost. The cost-effectiveness of this strategy was $1280 per incremental TB diagnosis (95% uncertainty range, UR: $340-$3440 in the base case, but improved under conditions likely reflective of many settings in sub-Saharan Africa: $677 per diagnosis (95% UR: $450-$935 when sensitivity of manual smear microscopy was lowered to 0.5, and $956 per diagnosis (95% UR: $40-$2910 when the prevalence of multidrug-resistant TB was lowered to 1%.Although universal Xpert testing is the preferred algorithm for TB diagnosis when resources are sufficient, automated digital microscopy can identify the majority of cases and halve the cost of diagnosis and treatment when resources are more

  13. Prospective evaluation of a whole-blood test using Mycobacterium tuberculosis-specific antigens ESAT-6 and CFP-10 for diagnosis of active tuberculosis

    Ravn, Pernille; Munk, Martin E; Andersen, Ase B;

    2005-01-01

    A new immunodiagnostic test based on the Mycobacterium tuberculosis-specific antigens CFP-10/ESAT-6(QFT-RD1) has been launched as an aid in the diagnosis of latent tuberculosis (TB) infection (LTBI). The aim of this study was to evaluate this test for the diagnosis of active TB. Eighty-two patients...... with suspicion of TB and 39 healthy BCG-vaccinated persons were enrolled. Forty-eight had active TB, 25 did not, and 9 were excluded. Sensitivity and specificity of the test for active TB were evaluated in a prospective blinded manner in patients suspected of TB. The sensitivity of the QFT-RD1 was 85......% (40/48; confidence interval [CI], 75 to 96), and it was higher than the sensitivity of microscopy, 42% (20/48; CI, 27 to 56; P = 0.001), and culture, 59% (27/46; CI, 44 to 73; P = 0.009). Of patients with extrapulmonary TB, 92% (12/13) were QFT-RD1 positive, whereas only 31% (4/13) were positive by...

  14. Diagnostic value of the commercial MycoDotTM test in the diagnosis of active pulmonary tuberculosis in Nepalese population

    Anil Chander

    2012-10-01

    Full Text Available Background: A rapid, technically non-demanding and inexpensive diagnostic test is needed to improve the early detection and better management of active pulmonary tuberculosis especially in resource limited areas. Objective: To assess the diagnostic value and usefulness of the commercially available MycoDotTM (DynaGen Inc., Cambridge, MA, USA in the diagnosis of active pulmonary tuberculosis in Nepalese population. Materials and Methods: A prospective study was done from January 2008 to August 2008 on a group of 120 sputum smear positive adult patient group aged 17 to 78 years, confirmed cases of active pulmonary tuberculosis (with TB were enrolled and sera samples collected from them. The second group comprised of 105 healthy controls with no history of pulmonary tuberculosis (without TB and sera samples collected from them. The MycoDotTM serologic test was done on the sera samples collected from both the study groups according to the manufacturer’s instructions. Results: Of the sera collected from 120 sputum smear positive cases (with TB group, 48 sera specimens were MycoDotTM test positive (sensitivity = 40%; 95% CI 31.68–48.94. Healthy controls (without-TB group – 8 sera samples were found to be positive by the MycoDotTM test and the remaining 97 sera samples tested negative by this serologic test (specificity = 92.38%; 95% CI 85.68–96.09. The value for % false positive was 7.61% and for % false negative was 60%. The positive predictive value and the negative predictive value was 85.71% (95% CI 73.22–93.20 and 57.4% (95% CI 49.56–64.88, respectively. Conclusion: The MycoDotTM test with its rapidity (completed within 20 min, easy – to – perform format and no expensive instrumentation required – had high specificity but a relatively low sensitivity in the study group subjects and thus could be used only as an additional test in the diagnosis of active pulmonary tuberculosis and to be interpreted judiciously alongwith clinical

  15. Evaluation of the ICT Tuberculosis test for the routine diagnosis of tuberculosis

    Donmez Levent

    2006-02-01

    Full Text Available Abstract Background Rapid and accurate diagnosis of tuberculosis (TB is crucial to facilitate early treatment of infectious cases and thus to reduce its spread. To improve the diagnosis of TB, more rapid diagnostic techniques such as antibody detection methods including enzyme-linked immunosorbent assay (ELISA-based serological tests and immunochromatographic methods were developed. This study was designed to evaluate the validity of an immunochromatographic assay, ICT Tuberculosis test for the serologic diagnosis of TB in Antalya, Turkey. Methods Sera from 72 patients with active pulmonary (53 smear-positive and 19 smear-negative cases and eight extrapulmonary (6 smear-positive and 2 smear-negative cases TB, and 54 controls from different outpatient clinics with similar demographic characteristics as patients were tested by ICT Tuberculosis test. Results The sensitivity, specificity, and negative predictive value of the ICT Tuberculosis test for pulmonary TB were 33.3%, 100%, and 52.9%, respectively. Smear-positive pulmonary TB patients showed a higher positivity rate for antibodies than smear-negative patients, but the difference was not statistically significant. Of the eight patients with extrapulmonary TB, antibody was detected in four patients. Conclusion Our results suggest that ICT Tuberculosis test can be used to aid TB diagnosis in smear-positive patients until the culture results are available.

  16. Synthesis of new radiotracers for tuberculosis diagnosis

    Tuberculosis remains a worldwide health problem and its diagnosis presents a major challenge. The examinations currently employed are little appreciable and so far there is no reliable diagnosis test. These last years, the development of the new radiopharmaceuticals, referred to diagnosis, has revived interest in the search for new molecules with a tropism to a particular disease. Thanks to this field, which lies at the interface of organic and organometallic chemistry, nuclear medicine and biology, we have been led to synthesize a technetium radiotracer linked to isoniazid. For the identification of this radiotracer, we used its similar rhenium model. (Author)

  17. Polymerase chain reaction in the diagnosis of tuberculosis

    Sritharan, Manjula; Sritharan, Venkataraman

    2000-01-01

    A rapid, sensitive, specific and yet economical method for the diagnosis ofM. tuberculosis and other mycobacteria in clinical specimen is a desperate and urgent requirement of the day in the laboratory diagnosis and hence management of tuberculosis. This need is further accentuated by emerging diseases like multi drug resistant tuberculosis, tuberculosis in AIDS patients and opportunistic mycobacterial infections, which do not respond to conventional anti TB therapy. Molecular methods, partic...

  18. Interferon-gamma release assays for the diagnosis of active tuberculosis in HIV-infected patients: a systematic review and meta-analysis.

    Jun Chen

    Full Text Available BACKGROUND: Interferon-gamma release assays (IGRAs have provided a new method for the diagnosis of Mycobacterium tuberculosis infection. However, the role of IGRAs for the diagnosis of active tuberculosis (TB, especially in HIV-infected patients remains unclear. METHODS: We searched PubMed, EMBASE and Cochrane databases to identify studies published in January 2001-July 2011 that evaluated the evidence of using QuantiFERON-TB Gold in-tube (QFT-GIT and T-SPOT.TB (T-SPOT on blood for the diagnosis of active TB in HIV-infected patients. RESULTS: The search identified 16 eligible studies that included 2801 HIV-infected individuals (637 culture confirmed TB cases. The pooled sensitivity for the diagnosis of active TB was 76.7% (95%CI, 71.6-80.5% and 77.4% (95%CI, 71.4-82.6% for QFT-GIT and T-SPOT, respectively, while the specificity was 76.1% (95%CI, 74.0-78.0% and 63.1% (95%CI, 57.6-68.3% after excluding the indeterminate results. Studies conducted in low/middle income countries showed slightly lower sensitivity and specificity when compared to that in high-income countries. The proportion of indeterminate results was as high as 10% (95%CI, 8.8-11.3% and 13.2% (95%CI, 10.6-16.0% for QFT-GIT and T-SPOT, respectively. CONCLUSION: IGRAs in their current formulations have limited accuracy in diagnosing active TB in HIV-infected patients, and should not be used alone to rule out or rule in active TB cases in HIV-infected patients. Further modification is needed to improve their accuracy.

  19. Clinical and Laboratory Diagnosis of Intestinal Tuberculosis

    Shi, Xiao-Chun; Zhang, Li-Fan; Zhang, Yue-Qiu; Liu, Xiao-Qing; Fei, Gui-Jun

    2016-01-01

    Background: Tuberculosis (TB) remains a worldwide problem. Intestinal TB (ITB) constitutes a major public health problem in developing countries and has been associated with significant morbidity and mortality. The aim of this study was to characterize the clinical, radiological, endoscopic, and pathological features of ITB and to define the strategy for establishing the diagnosis. Methods: A retrospective study (from January 2000 to June 2015) was carried out in Peking Union Medical College Hospital and all hospitalized cases were diagnosed as ITB during the study period were included. The relevant clinical information, laboratory results, microbiological, and radiological investigations were recorded. Results: Of the 85 cases, 61 cases (71.8%) were ranged from 20 to 50 years. The ileocecal region was involved in about 83.5% (71/85) of patients. About 41.2% (35/85) of patients had co-existing extra ITB, especially active pulmonary TB. Abdominal pain (82.4%) was the most common presenting symptom followed by weight loss (72.9%) and fever (64.7%). Both T-cell spot of TB test (T-SPOT.TB) and purified protein derivatives (PPD) tests were performed in 26 patients: 20 (76.9%) positive T-SPOT.TB and 13 (50.0%) positive PPD were detected, with a statistical significant difference (P = 0.046). Twenty cases (23.5%) were histopathology and/or pathogen confirmed TB; 27 cases (31.8%) were diagnosed by clinical manifestation consistent with ITB and evidence of active extra ITB; 38 cases (44.7%) were diagnosed by good response to diagnostic anti-TB therapy. Conclusions: ITB is difficult to diagnose even with modern medical techniques due to its nonspecific clinical and laboratory features. At present, combination of clinical, endoscopic, radiological, and pathological features continues to be the key to the diagnosis of ITB. PMID:27231171

  20. Commercial Serological Tests for the Diagnosis of Active Pulmonary and Extrapulmonary Tuberculosis: An Updated Systematic Review and Meta-Analysis

    Dowdy, David W; Steingart, Karen R; Pai, Madhukar

    2011-01-01

    Editors' Summary Background Every year, about 2 million people develop tuberculosis in India—a fifth of the global incidence of this highly contagious bacterial infection. Mycobacterium tuberculosis, the bacterium that causes tuberculosis, is spread in airborne droplets when people with the disease cough or sneeze and usually infects the lungs although it can also infect other organs. The characteristic symptoms of tuberculosis are a persistent cough, weight loss, and night sweats. Diagnostic...

  1. Serological Testing Versus Other Strategies for Diagnosis of Active Tuberculosis in India: A Cost-Effectiveness Analysis

    Steingart, Karen R; Flores, Laura L.; Dendukuri, Nandini; Schiller, Ian; Laal, Suman; Ramsay, Andrew,; Hopewell, Philip C.; Pai, Madhukar

    2011-01-01

    Editors' Summary Background Every year nearly 10 million people develop tuberculosis—a contagious bacterial infection—and about two million people die from the disease. Mycobacterium tuberculosis, the bacterium that causes tuberculosis, is spread in airborne droplets when people with the disease cough or sneeze. It usually infects the lungs (pulmonary tuberculosis) but can also infect the lymph nodes, bones, and other tissues (extrapulmonary tuberculosis). The characteristic symptoms of tuber...

  2. Pulmonary tuberculosis - current radiological diagnosis of the ancient disease

    Incidence. Decreasing numbers of tuberculosis cases in the western countries have led to diminished attention towards this disease. But worldwide, tuberculosis still is the leading cause of mortality due to any one single infectious agent. In the industrialized countries, immigration, growth of low-income groups and increasing numbers of immunocompromised patients, mainly due to the HIV epidemic, supply a reservoir for tuberculosis. Diagnosis. Because of the option of a specific therapy, early diagnosis of tuberculosis is crucial for the course of the disease. In cases of multidrug resistant strains, further spread has to be prevented. Radiology with chest films and computed tomography has a central role in diagnosing tuberculosis. Findings. However, as the disease produces a broad spectrum of radiographic findings, there are often difficulties in determining the underlying diagnosis. Additionally, there have been reports of a typical presentations of tuberculosis in immunocompromised as well as immunocompetent patients. This article reviews the current state of radiological diagnosis of pulmonary tuberculosis. (orig.)

  3. Rapid Diagnosis of Extrapulmonary Tuberculosis by Ligase Chain Reaction Amplification

    Gamboa, Fredy; Dominguez, José; Padilla, Eduardo; Manterola, José M.; Gazapo, Elena; Lonca, Joan; Matas, Lurdes; Hernandez, Agueda; Cardona, Pere Joan; Ausina, Vicente

    1998-01-01

    A rapid amplification-based test for the diagnosis of extrapulmonary tuberculosis, the LCx Mycobacterium tuberculosis Assay from Abbott Laboratories, was evaluated. Results from the LCx M. tuberculosis Assay were compared with those from culture and the final clinical diagnosis for each patient. A total of 526 nonrespiratory specimens from 492 patients were tested. The specimens included urine; feces; lymph node exudates; pleural, cerebrospinal, articular, and ascitic fluids; tissue biopsies;...

  4. Peritoneal tuberculosis: how to obtain a confident diagnosis?

    The peritoneum is a frequent site of involvement by peritoneal tuberculosis. Generally, computed tomography appears to be the imaging modality of choice in the detection and assessment of abdominal tuberculosis. The computed tomography findings can help in the diagnosis of peritoneal tuberculosis, that is confirmed by a positive culture or hystologic analysis of biopsy obtained through laparoscopic examination. Peritoneal carcinomatosis is the main differential diagnosis. In this article we present the spectrum of tomographic manifestation of peritoneal tuberculosis and how we can differentiate it from peritoneal carcinomatosis. (author)

  5. Challenges from Tuberculosis Diagnosis to Care in Community-Based Active Case Finding among the Urban Poor in Cambodia: A Mixed-Methods Study.

    Natalie Lorent

    Full Text Available While community-based active case finding (ACF for tuberculosis (TB holds promise for increasing early case detection among hard-to-reach populations, limited data exist on the acceptability of active screening. We aimed to identify barriers and explore facilitators on the pathway from diagnosis to care among TB patients and health providers.Mixed-methods study. We administered a survey questionnaire to, and performed in-depth interviews with, TB patients identified through ACF from poor urban settlements in Phnom Penh, Cambodia. Additionally, we conducted focus group discussions and in-depth interviews with community and public health providers involved in ACF, respectively.Acceptance of home TB screening was strong among key stakeholders due to perceived reductions in access barriers and in direct and indirect patient costs. Privacy and stigma were not an issue. To build trust and facilitate communication, the participation of community representatives alongside health workers was preferred. Most health providers saw ACF as complementary to existing TB services; however, additional workload as a result of ACF was perceived as straining operating capacity at public sector sites. Proximity to a health facility and disease severity were the strongest determinants of prompt care-seeking. The main reasons reported for delays in treatment-seeking were non-acceptance of diagnosis, high indirect costs related to lost income/productivity and transportation expenses, and anticipated side-effects from TB drugs.TB patients and health providers considered home-based ACF complementary to facility-based TB screening. Strong engagement with community representatives was believed critical in gaining access to high risk communities. The main barriers to prompt treatment uptake in ACF were refusal of diagnosis, high indirect costs, and anticipated treatment side-effects. A patient-centred approach and community involvement were essential in mitigating barriers

  6. Caecal pole tuberculosis - an often neglected differential diagnosis

    If the barium enema reveals stenosing changes of the terminal ileum and caecum, tuberculosis must be considered in differential diagnosis, even if pulmonary evidence of the illness is lacking. Since, however, radiographically no exclusive typical changes for the tuberculosis of the terminal ileum and caecum can be seen, the diagnosis must be checked histologically and bacteriologically. Under drug therapy an obvious decrease of the inflammation of the mucosa of the colon could be seen. (orig.)

  7. Controlling the seedbeds of tuberculosis: diagnosis and treatment of tuberculosis infection.

    Rangaka, Molebogeng X; Cavalcante, Solange C; Marais, Ben J; Thim, Sok; Martinson, Neil A; Swaminathan, Soumya; Chaisson, Richard E

    2015-12-01

    The billions of people with latent tuberculosis infection serve as the seedbeds for future cases of active tuberculosis. Virtually all episodes of tuberculosis disease are preceded by a period of asymptomatic Mycobacterium tuberculosis infection; therefore, identifying infected individuals most likely to progress to disease and treating such subclinical infections to prevent future disease provides a crucial opportunity to interrupt tuberculosis transmission and reduce the global burden of tuberculosis disease. Programmes focusing on single strategies rather than comprehensive programmes that deliver an integrated arsenal for tuberculosis control might continue to struggle. Tuberculosis preventive therapy is a poorly used method that is essential for controlling the reservoirs of disease that drive the epidemic. Comprehensive control strategies that combine preventive therapy for the most high-risk populations and communities with improved case-finding and treatment, control of transmission, and health systems strengthening could ultimately lead to worldwide tuberculosis elimination. In this Series paper we outline challenges to implementation of preventive therapy and provide pragmatic suggestions for overcoming them. We further advocate for tuberculosis preventive therapy as the core of a renewed worldwide focus to implement a comprehensive epidemic control strategy that would reduce new tuberculosis cases to elimination targets. This strategy would be underpinned by accelerated research to further understand the biology of subclinical tuberculosis infections, develop novel diagnostics and drug regimens specifically for subclinical tuberculosis infection, strengthen health systems and community engagement, and enhance sustainable large scale implementation of preventive therapy programmes. PMID:26515679

  8. Diagnosis of intestinal tuberculosis using a monoclonal antibody to Mycobacterium tuberculosis

    Yasushi Ihama; Akira Hokama; Kenji Hibiya; Kazuto Kishimoto; Manabu Nakamoto; Tetsuo Hirata; Nagisa Kinjo

    2012-01-01

    AIM:To investigate the utility of immunohistochemical (IHC) staining with an antibody to Mycobacterium tuberculosis (M.tuberculosis) for the diagnosis of intestinal tuberculosis (TB).METHODS:We retrospectively identified 10 patients (4 males and 6 females; mean age =65.1 ± 13.6 years)with intestinal TB.Clinical characteristics,including age,gender,underlying disease,and symptoms were obtained.Chest radiograph and laboratory tests,including sputum Ziehl-Neelsen (ZN) staining,M.tuberculosis culture,and sputum polymerase chain reaction (PCR)for tubercle bacilli DNA,as well as Tuberculin skin test (TST) and QuantiFERON-TB gold test (QFT),were examined.Colonoscopic records recorded on the basis of Sato's classification were also reviewed,in addition to data from intestinal biopsies examined for histopathological findings,including hematoxylin and eosin staining,and ZN staining,as well as M.tuberculosis culture,and PCR for tubercle bacilli DNA.For the present study,archived formalin-fixed paraffin-embedded (FFPE) intestinal tissue samples were immunohistochemically stained using a commercially available species-specific monoclonal antibody to the 38-kDa antigen of the M.tuberculosis complex.These sections were also stained with the pan-macrophage marker CD68 antibody.RESULTS:From the clinical data,we found that no patients were immunocompromised,and that the main symptoms were diarrhea and weight loss.Three patients displayed active pulmonary TB,six patients (60%) had a positive TST,and 4 patients (40%) had a positive QFT.Colonoscopic findings revealed that all patients had type 1 findings (linear ulcers in a circumferential arrangement or linear ulcers arranged circumferentially with mucosa showing multiple nodules),all of which were located in the right hemicolon and/or terminal ileum.Seven patients (70%) had concomitant healed lesions in the ileocecal area.No acid-fast bacilli were detected with ZN staining of the intestinal tissue samples,and both M.tuberculosis

  9. A novel whole-blood miRNA signature for a rapid diagnosis of pulmonary tuberculosis.

    Latorre, Irene; Leidinger, Petra; Backes, Christina; Dom??nguez, Jose; de Souza-Galvao, Mal??; Maldonado, Jose; Prat, Cristina; Ruiz, Juan Jes??s; S??nchez Mart??nez, Francisca; Casas, Irma; Keller, Andreas; Briesen, Hagen von; Knobel Freud, Hernando; Meese, Eckart; Meyerhans, Andreas

    2015-01-01

    Background: Deregulation of microRNAs (miRNAs)has been associated with various human pathologies including bacterial infections.Aim: To investigate the role of miRNAs as blood biomarkers for the diagnosis of active pulmonary tuberculosis (TB).Materials and methods: We studied 50 patients, classified into 3 groups:(i) 17individuals with latent tuberculosis infection (LTBI) (ii) 17 active pulmonary TB patients (iii) 16 healthy individuals. Blood was collected in a PAXgene Blood RNA tubefor thel...

  10. Evaluation of the ICT Tuberculosis test for the routine diagnosis of tuberculosis

    Donmez Levent; Ogus Candan; Gunseren Filiz; Ogunc Dilara; Ongut Gozde; Colak Dilek; Gultekin Meral

    2006-01-01

    Abstract Background Rapid and accurate diagnosis of tuberculosis (TB) is crucial to facilitate early treatment of infectious cases and thus to reduce its spread. To improve the diagnosis of TB, more rapid diagnostic techniques such as antibody detection methods including enzyme-linked immunosorbent assay (ELISA)-based serological tests and immunochromatographic methods were developed. This study was designed to evaluate the validity of an immunochromatographic assay, ICT Tuberculosis test for...

  11. Infection Control for Drug-Resistant Tuberculosis: Early Diagnosis and Treatment Is the Key.

    van Cutsem, Gilles; Isaakidis, Petros; Farley, Jason; Nardell, Ed; Volchenkov, Grigory; Cox, Helen

    2016-05-15

    Multidrug-resistant (MDR) tuberculosis, "Ebola with wings," is a significant threat to tuberculosis control efforts. Previous prevailing views that resistance was mainly acquired through poor treatment led to decades of focus on drug-sensitive rather than drug-resistant (DR) tuberculosis, driven by the World Health Organization's directly observed therapy, short course strategy. The paradigm has shifted toward recognition that most DR tuberculosis is transmitted and that there is a need for increased efforts to control DR tuberculosis. Yet most people with DR tuberculosis are untested and untreated, driving transmission in the community and in health systems in high-burden settings. The risk of nosocomial transmission is high for patients and staff alike. Lowering transmission risk for MDR tuberculosis requires a combination approach centered on rapid identification of active tuberculosis disease and tuberculosis drug resistance, followed by rapid initiation of appropriate treatment and adherence support, complemented by universal tuberculosis infection control measures in healthcare facilities. It also requires a second paradigm shift, from the classic infection control hierarchy to a novel, decentralized approach across the continuum from early diagnosis and treatment to community awareness and support. A massive scale-up of rapid diagnosis and treatment is necessary to control the MDR tuberculosis epidemic. This will not be possible without intense efforts toward the implementation of decentralized, ambulatory models of care. Increasing political will and resources need to be accompanied by a paradigm shift. Instead of focusing on diagnosed cases, recognition that transmission is driven largely by undiagnosed, untreated cases, both in the community and in healthcare settings, is necessary. This article discusses this comprehensive approach, strategies available, and associated challenges. PMID:27118853

  12. Tuberculosis in the head and neck - a forgotten differential diagnosis

    The aim of the present review is to illustrate the pathogenesis and imaging findings of tuberculosis in specific head and neck regions to avoid pitfalls in diagnosis. It is imperative to be aware of, and provide an early diagnosis for, extra-pulmonary tubercular lesions in the head and neck. A high index of suspicion combined with an appropriate clinical setting serves as an important background to diagnose tubercular lesions in the head and neck region and differentiate them from malignancy and other disease entities. Early diagnosis and treatment can prevent irreversible and debilitating complications and mortality from disseminated tuberculosis.

  13. Tuberculosis in the head and neck - a forgotten differential diagnosis

    Vaid, S., E-mail: vaids@vsnl.co [Department of Radiology and Imaging, Grant Medical Foundation, Pune (India); Lee, Y.Y.P. [Department of Diagnostic Radiology and Organ Imaging, Chinese University of Hong Kong, Hong Kong (China); Rawat, S.; Luthra, A.; Shah, D. [Department of Radiology and Imaging, Grant Medical Foundation, Pune (India); Ahuja, A.T. [Department of Diagnostic Radiology and Organ Imaging, Chinese University of Hongkong, Hong Kong (China)

    2010-01-15

    The aim of the present review is to illustrate the pathogenesis and imaging findings of tuberculosis in specific head and neck regions to avoid pitfalls in diagnosis. It is imperative to be aware of, and provide an early diagnosis for, extra-pulmonary tubercular lesions in the head and neck. A high index of suspicion combined with an appropriate clinical setting serves as an important background to diagnose tubercular lesions in the head and neck region and differentiate them from malignancy and other disease entities. Early diagnosis and treatment can prevent irreversible and debilitating complications and mortality from disseminated tuberculosis.

  14. The clinical utility of tuberculin skin test and interferon-γ release assay in the diagnosis of active tuberculosis among young adults: a prospective observational study

    Lee Sei Won

    2011-04-01

    Full Text Available Abstract Background The roles of the tuberculin skin test (TST and QuantiFERON®-TB Gold In-Tube assay (QFT-IT in the diagnosis of active tuberculosis (TB are not clear in young adults. We evaluated the diagnostic accuracy of the TST and QFT-IT in smear-negative TB among young adults with no underlying disease. Methods We prospectively enrolled 166 young participants 20-29 years of age with suspected active TB in a military hospital of South Korea. The TST and QFT-IT were performed for all participants. Results Of the 143 patients included in the analysis, active TB was diagnosed in 100 (69.9%. There were 141 male patients, none of whom had immunosuppressive disease. The sensitivity, specificity, positive predictive value (PPV, and negative predictive value (NPV of TST were 94% (95% CI, 87-98%, 88% (95% CI, 74-96%, 95% (95% CI, 88-98%, and 86% (95% CI, 72-94%, respectively. The sensitivity, specificity, PPV, and NPV of the QFT-IT were 93% (95% CI, 86-97%, 95% (95% CI, 81-99%, 98% (95% CI, 92-99%, and 84% (95% CI, 69-93%, respectively. No significant differences were found between the TST and QFT-IT in any statistic. Conclusions Both the TST and QFT-IT showed high sensitivity and specificity in differentiating active TB from other diseases. The diagnostic accuracy of these two tests did not differ significantly when applied to this clinical population of young, immunocompetent adults in whom neonatal BCG vaccination was common, there was no history of previous TB and in whom suspicion of TB was high. Trial registration ClinicalTrials.gov: NCT00982969

  15. Access to health care and diagnosis of tuberculosis

    Dândara Nayara Azevêdo Dantas; Bertha Cruz Enders; Rosemary Álvares Medeiros; Rudhere Judson Fernandes Santos; Caroline Evelin Nascimento Kluczynik Vieira; Ana Angélica Rêgo Queiroz

    2014-01-01

    The objective was to know the evaluation of patients with tuberculosis regarding the access to health care and the diagnosis of the disease. It is a cross-sectional quantitative study made in Natal, RN, Brazil, from February to September 2012, with 60 patients diagnosed with tuberculosis. Data were collected using a questionnaire and analyzed using descriptive statistics. Access to health care was considered easy by 80% of patients. Of those, 35% considered it easy because of the short time t...

  16. Laboratory Diagnosis of Mycobacterium tuberculosis Infection and Disease in Children.

    Dunn, James J; Starke, Jeffrey R; Revell, Paula A

    2016-06-01

    Diagnosis of tuberculosis in children is challenging; even with advanced technologies, the diagnosis is often difficult to confirm microbiologically in part due to the paucibacillary nature of the disease. Clinical diagnosis lacks standardization, and traditional and molecular microbiologic methods lack sensitivity, particularly in children. Immunodiagnostic tests may improve sensitivity, but these tests cannot distinguish tuberculosis disease from latent infection and some lack specificity. While molecular tools like Xpert MTB/RIF have advanced our ability to detect Mycobacterium tuberculosis and to determine antimicrobial resistance, decades old technologies remain the standard in most locales. Today, the battle against this ancient disease still poses one of the primary diagnostic challenges in pediatric laboratory medicine. PMID:26984977

  17. Diagnosis of latent tuberculosis: Can we do better?

    Al-Orainey Ibrahim

    2009-01-01

    Full Text Available Latent tuberculosis infection (LTBI is often diagnosed by the tuberculin skin test (TST. The latter has several limitations with regard to its sensitivity and specificity. It may be positive in people with prior bacille Calmette-Guιrin (BCG vaccination or exposure to nontuberculous mycobacteria. False negative TST results frequently occur in patients with impaired T-cell function. Therefore TST results have to be interpreted taking into consideration the pretest risk of TB infection or reactivation. Recently, interferon gamma release assays (IGRA were introduced for the diagnosis of LTBI. These include the T-SPOT-TB and the QuantiFERON ® -TB Gold tests .These tests measure interferon gamma released in response to T-cell stimulation by specific Mycobacterium tuberculosis antigens. These tests have been shown to be more specific than the TST as they are not affected by BCG vaccination. Their sensitivity was similar to that of the TST and in some studies they correlated better with the degree of exposure. In immune-compromised patients their sensitivity was better than that of the TST. IGRA tests were shown to have better predictive value for the development of active disease among individuals with LTBI. These tests are expensive. Their most cost-effective utilization is as confirmatory tests in patients with positive TST results, particularly in areas with high rates of BCG vaccination.

  18. Cost implications of delays to tuberculosis diagnosis among pulmonary tuberculosis patients in Ethiopia

    Kifle Yohannes T

    2010-03-01

    Full Text Available Abstract 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

  19. Molecular biology in medicine: laboratory diagnosis of tuberculosis.

    Ling, M L

    1996-01-01

    Clinical mycobacteriology has benefited much from the application of molecular biology techniques. Early detection and identification of Mycobacterium tuberculosis are achieved by the combined use of the BACTEC system and deoxyribonucleic acid (DNA) probes. High-performance liquid chromatography is the other alternative used in some laboratories. Polymerase chain reaction is still a research tool because of its many problems and limitations. Other promising techniques for rapid diagnosis of Mycobacterium tuberculosis, for example, the serological diagnosis by enzyme-linked immunosorbent assay (ELISA), the Gen-Probe Amplified Mycobacterium tuberculosis Direct Test, DNA hybridization, the Mycobacteria Growth Indicator Tubes System and the strand displacement amplification system are currently under evaluation. The discovery of drug resistant genes such as katG and apoB has important implications for the development of new tests for the rapid detection of resistance to anti-tuberculous drugs. PMID:8779555

  20. Advances in the Diagnosis and Treatment of Tuberculosis

    Nahid, Payam; Pai, Madhukar; Hopewell, Philip C.

    2006-01-01

    Although truly major advances that would revolutionize tuberculosis (TB) diagnosis and treatment have not been realized, we are beginning to see the innovations that have been prompted by the recognition of the economic potential of the market for new diagnostic tests and treatments for TB and considerably increased public and private funding. Despite the enormous global burden of TB and the overall low rates of case detection worldwide, conventional approaches to diagnosis have, until recent...

  1. Gallbladder tuberculosis: False-positive PET diagnosis of gallbladder cancer

    JM Ramia; K Muffak; A Fernández; J Villar; D Garrote; JA Ferron

    2006-01-01

    Gallbladder tuberculosis (GT) is an extremely rare disease, and very few cases have been reported in the literature. The first case of GT was described in 1870 by Gaucher. A correct preoperative diagnosis of GT is unusual, and it is frequently confused with various gallbladder diseases. We present a new case of a patient who underwent surgery with the preoperative diagnosis of gallbladder cancer after a false positive positron emission tomography scan in the diagnostic work-up.

  2. Pulmonary tuberculosis as differential diagnosis of lung cancer

    MLB Bhatt; Surya Kant; Ravi Bhaskar

    2012-01-01

    Patients with lung cancer are often misdiagnosed as pulmonary tuberculosis leading to delay in the correct diagnosis as well as exposure to inappropriate medication. Several factors are responsible for this situation in developing countries, including lack of awareness, inadequate infrastructure and socio-economic factors. This article outlines the differences between the two diseases as well as features that would make a clinician suspect the right diagnosis early.

  3. Clinical application of whole blood interferon-γ release assay on diagnosis of active pulmonary tuberculosis%全血γ干扰素释放试验在活动性肺结核诊断中的应用

    周祖模; 金嘉琳; 王森; 黄河清; 石勇明; 陈林; 张文宏; 翁心华

    2012-01-01

    Objective To evaluate the application of whole blood interferon-γ release assay QuantiFERON-TB gold in tube (QFT-GIT) on the diagnosis of active pulmonary tuberculosis in China. Methods With the commercial whole blood interferon-γ QFT-GIT kit, interferon-γ released by specific T cells stimulated under early secreted antigenic target 6 kD protein ( ESAT-6) , culture filtrate protein 10 (CFP-10) and TB7. 7 were measured among 48 cases with active pulmonary tuberculosis and 55 BCG (bacillus calmette-guerin ) -vaccinated healthy controls, who had no tuberculosis contact history by questionnaire. Results The QFT-GIT was positive in 93. 8% patients with active pulmonary tuberculosis and 11.1% healthy controls, respectively. The sensitivity, specificity, positive predictive value and negative predictive value of QFT-GIT were 93. 8% , 88. 9% , 88. 2% and 94. 1% , respectively. The antigen-specific IFN-γ release was significantly higher in patients with active pulmonary tuberculosis in comparison with that in the controls (P < 0.0001). Furthermore, after anti-tuberculosis treatment, the antigen-specific IFN-γ decreased significantly (P < 0.05). Conclusions QFT-GIT is a sensitive and specific assay for detecting tuberculosis, which could discriminate the active tuberculosis patients from BCG vaccinated healthy controls and could be a convenient and useful diagnostic tool for the diagnosis of tuberculosis.%目的 评价全血γ干扰素释放试验在活动性肺结核诊断中的应用价值.方法 应用一种全血γ干扰素释放检测试剂盒QuantiFERON-TB gold in tube(QFT-GIT)对48例活动性肺结核患者(活动性结核组)进行检测,同时选取55例健康者作为对照(对照组),均通过调查问卷排除结核病接触史.结果 本研究活动性结核组患者和对照组QFT-GIT阳性率分别为93.8%和11.1%,QFT-GIT诊断活动性肺结核的总体敏感性和特异性分别为93.8%和88.9%,阳性和阴性预测值分别为88.2%和94.1%.活动性

  4. Multidrug-resistant tuberculosis that required 2 years for diagnosis.

    Yano, Shuichi; Kobayashi, Kanako; Ikeda, Toshikazu

    2012-01-01

    Isoniazid (H) or rifampicin (R) mono-resistant disease can be treated easily and effectively with first-line drugs, while combined H and R resistance (ie, multidrug-resistant tuberculosis (MDRTB)) requires treatment with at least four agents, including a quinolone and an injectable agent. Drug-resistant Mycobacterium tuberculosis strains are reported to be extremely difficult to cultivate invitro. The authors report a case of MDRTB that required 2 years for diagnosis, and was detected only in sputum culture on solid medium. Physicians should consider MDRTB if TB is suspected but pathogens are not detected. PMID:22605803

  5. Bronchoscopic lung biopsy for diagnosis of miliary tuberculosis

    Aggarwal A

    2005-01-01

    Full Text Available Background: Miliary tuberculosis is often treated empirically in India in the absence of a positive diagnosis based on sputum examination. We investigated the role of fiberoptic bronchoscopy for diagnosis of this disease. Methods : Records of patients undergoing fiberoptic bronchoscopy and bronchoscopic lung biopsy, and diagnosed to have miliary tuberculosis, over a four year period were evaluated. Two to four lung biopsy specimens were obtained from each patient and examined microscopically after Hematoxylin-eosin and Zeihl-Neelson staining. Results : Thirty one patients of miliary tuberculosis (19 men and 12 women underwent fiberoptic bronchoscopy during the study period. No endobronchial abnormality was noted in any patient. Bronchoscopic lung biopsy yielded adeqaute specimen in all but one patient. Granulomatous inflammation was noted in 21 (67.7% patients on histopathological evaluation of biopsy specimens; of them, acid-fast bacilli were demonstrated in one patient. One patient (3.2% had normal alveolar architecture. In the other 8 patients (25.8%, nonspecific pulmonary interstitial inflammation and/or mild fibrosis were seen. Bronchial wash specimens showed acid-fast bacilli in only one patient; this patient also had granulomatous inflammation on lung biopsy. All patients tolerated bronchoscopy well and there were no procedure-related complications. Conclusion: Bronchoscopic lung biopsy is a safe procedure and an effective method of establishing diagnosis of miliary tuberculosis in a majority of patients with this disease. Bronchial washings do not provide significant additional information in this regard.

  6. [Bacteriological diagnosis of tuberculosis: current hieratic classification of methods].

    Carbonnelle, B; Carpentier, E

    1995-01-01

    To assure the diagnosis of tuberculosis, one needs the observation, the isolation and the identification of the causative agent Mycobacterium tuberculosis. In this approach, the microscopic exam occurs as a fast but neither sensitive or specific test. The isolation on solid media is slow and needs more than three weeks before becoming positive. Nevertheless, it is a sensitive and specific one. The identification of the isolated strain and the study of sensitivity to antibiotic agents require an equal delay. Then, 2 months are necessary to achieve the analysis. The AIDS epidemic with the increase of opportunistic mycobacterial diseases, and the unexpected arrival of resistant Mycobacteria is creating as a difficult therapeutic problem. The cultivation in liquid media with the radiometric method (Bactec) shortens the time of culture by half. The genomic amplification assay has been hopeful because it allowed results in 2 days. However, some technical difficulties happen when the test is conducted and it is less sensitive than the isolation process. The hierarchical classification of the laboratory useful process to establish the diagnosis of tuberculosis disease remains the microscopic observation of the bacilli and their isolation. Today, the use of PCR alone does not assure the diagnosis of tuberculosis, however it may be used as a additional diagnostic test. PMID:7569420

  7. Commercial serological antibody detection tests for the diagnosis of pulmonary tuberculosis: a systematic review.

    Karen R Steingart

    2007-06-01

    commercial tests in smear microscopy-negative patients, as well as their performance in children or persons with HIV infection. CONCLUSIONS: None of the commercial tests evaluated perform well enough to replace sputum smear microscopy. Thus, these tests have little or no role in the diagnosis of pulmonary tuberculosis. Lack of methodological rigor in these studies was identified as a concern. It will be important to review the basic science literature evaluating serological tests for the diagnosis of pulmonary tuberculosis to determine whether useful antigens have been described but their potential has not been fully exploited. Activities leading to the discovery of new antigens with immunodiagnostic potential need to be intensified.

  8. Tuberculosis Diagnosis: Assay Optimization, Validation, and Antigens for Specific Diagnosis

    Interferon (IFN)-gamma release assays (i.e. Bovigam®, Prionics AG) are components of tuberculosis (TB) eradication programs in many countries. Because this test relies on functional leukocytes, environmental conditions before and during the in vitro culture period have the potential to influence the...

  9. [Tuberculosis in 2015: From diagnosis to the detection of multiresistant cases].

    Hervé, C; Bergot, E; Veziris, N; Blanc, F-X

    2015-10-01

    Incidence of pulmonary tuberculosis, a contagious infectious disease, decreases in France with 4934 reported cases in 2013. Tuberculosis remains a global health problem as smear is positive in only 50% cases and culture methods require time. In such a context, genotypic diagnostic tools such as Xpert® MTB/RIF gained interest. This rapid and simple-to-use nucleic acid amplification test allows a diagnosis in two hours and prevents further invasive investigations in pulmonary and mediastinal tuberculosis. Because of its low sensitivity, it cannot be used in pleural fluid. Indirect immunologic tests are of no use to diagnose active tuberculosis disease. Another current area of interest is the emergence of resistant tuberculosis. In France, approximately 100 cases of multidrug resistant tuberculosis and a few extensively drug resistant tuberculosis have been reported in 2014. Even though these forms of tuberculosis are imported, it is crucial to identify hazardous situations and to optimize care of these patients. Xpert® MTB/RIF is again of marked interest here as it detects rifampin resistance with a 95% sensitivity and a 98% specificity. Interpretation of genotypic tests such as Genotype® MTBDR or Xpert® MTB/RIF depends on known detected mutations, although they do not always have a clinical or phenotypic expression. In multidrug resistant tuberculosis, the new drug bedaquiline obtained approval for temporarily use in combination with other molecules when there is no other treatment option. Results of bedaquiline are encouraging but adverse events like QT prolongation or the development of new specific drug resistance should convince clinicians to use it with caution. PMID:26169235

  10. Rapid Diagnosis of Tuberculosis by Real-Time High-Resolution Imaging of Mycobacterium tuberculosis Colonies.

    Ghodbane, Ramzi; Asmar, Shady; Betzner, Marlena; Linet, Marie; Pierquin, Joseph; Raoult, Didier; Drancourt, Michel

    2015-08-01

    Culture remains the cornerstone of diagnosis for pulmonary tuberculosis, but the fastidiousness of Mycobacterium tuberculosis may delay culture-based diagnosis for weeks. We evaluated the performance of real-time high-resolution imaging for the rapid detection of M. tuberculosis colonies growing on a solid medium. A total of 50 clinical specimens, including 42 sputum specimens, 4 stool specimens, 2 bronchoalveolar lavage fluid specimens, and 2 bronchial aspirate fluid specimens were prospectively inoculated into (i) a commercially available Middlebrook broth and evaluated for mycobacterial growth indirectly detected by measuring oxygen consumption (standard protocol) and (ii) a home-made solid medium incubated in an incubator featuring real-time high-resolution imaging of colonies (real-time protocol). Isolates were identified by Ziehl-Neelsen staining and matrix-assisted laser desorption ionization-time of flight mass spectrometry. Use of the standard protocol yielded 14/50 (28%) M. tuberculosis isolates, which is not significantly different from the 13/50 (26%) M. tuberculosis isolates found using the real-time protocol (P = 1.00 by Fisher's exact test), and the contamination rate of 1/50 (2%) was not significantly different from the contamination rate of 2/50 (4%) using the real-time protocol (P = 1.00). The real-time imaging protocol showed a 4.4-fold reduction in time to detection, 82 ± 54 h versus 360 ± 142 h (P technology that shortens the time to growth detection and the laboratory diagnosis of pulmonary tuberculosis. PMID:26085608

  11. The use of polymerase chain reaction for early diagnosis of tuberculosis in Mycobacterium tuberculosis culture

    M. Chagas

    2010-06-01

    Full Text Available Early diagnosis plays a vital role in controlling tuberculosis. The conventional methodology is slow, with results taking several weeks, in addition to having low sensitivity, especially in clinical paucibacillary samples. The objective of this study was to evaluate the use of polymerase chain reaction (PCR on solid medium culture for a rapid diagnosis of tuberculosis, mainly in cases of negative sputum smears. Forty sputum samples were collected from inpatients with tuberculosis treated for less than 2 days. Bacilloscopy, PCR for sputum, culture on Löwestein-Jensen (LJ solid medium, and daily PCR from culture were performed on each sample. DNA extracted from the BCG vaccine, which contains attenuated bacillus Calmette-Guérin, was used as the positive control. Smear microscopy showed 68.6% sensitivity, 80% specificity, 96% positive predictive value, and 26.7% negative predictive value, with culture on LJ medium as the gold standard. Culture at day 28 showed 74.3% sensitivity and 100% specificity. PCR of DNA extracted from sputum amplified a 1027-bp fragment of the 16s RNA gene, showing 22.9% sensitivity and 60% specificity. PCR performed with DNA extracted from daily culture showed that, from the 17th to the 40th day, the sensitivity (85.7% and specificity (60% were constant. We conclude that a 17-day culture is a good choice for rapid diagnosis and to interfere with the transmission chain of tuberculosis.

  12. DIFFERENTIAL DIAGNOSIS OF ROSACEA AND SKIN TUBERCULOSIS AS AN EXAMPLE OF A CLINICAL CASE

    M. L. Aripova

    2014-01-01

    Full Text Available In this paper for a clinical observation of a patient with rosacea, and patients with a flat form of lupus tuberculosis presented a differential clinical diagnosis of tuberculosis of the skin.

  13. Evaluation of laboratory diagnosis for cutaneous tuberculosis

    Ilhan Afsar

    2016-01-01

    Full Text Available Background and Aim: Cutaneous tuberculosis (CTB is still difficult to diagnose due to its varied clinical presentation and limitations of diagnostic methods. The aim of this study was to evaluate the results of diagnostic laboratory tests available for CTB. Materials and Methods: Twenty-six skin biopsy specimens belonging to clinically suspected cases of CTB were studied retrospectively. The specimens were divided into two portions, one part processed for histopathological evaluation and the other was used for microscopy and inoculation for the isolation of mycobacteria. Polymerase chain reaction (PCR technique was applied to 14 of 26 specimens to detect Mycobacterium tuberculosis complex (MTBC DNA. Results: Of the 26 biopsy specimens, 11 were confirmed as CTB by identification of MTBC in culture and/or histopathologic affirmation. Of these, four were lupus vulgaris, four were TB verrucosa cutis, one was scrofuloderma, one was primary inoculation TB, and one was periorifical CTB. Culture for mycobacteria was positive for five (45.45% specimens, while histopathologic affirmation was obtained in ten (90.90% specimens. Acid-fast Bacilli were not demonstrated in any of the specimens on microscopic examination. The PCR was found to be applied to six of the 11 specimens diagnosed as CTB and was positive in two specimens (33.3%, which were positive for growth in culture and histopathological correlation. Conclusion: The recovery rate of MTBC from biopsy specimens was found to be satisfactory for CTB with histopathological correlation, but the combination of culture with a rapid method, PCR, may improve the diagnostic rate.

  14. Tuberculosis of the calcaneus. Treatment and differential diagnosis

    Richter, R.; Koehler, G.; Michels, P.

    1981-11-01

    Eight lesions in the calcaneus have been treated surgically between 1955 and 1979; of these, six were due to tuberculosis, one to chronic osteomyelitis and the other was a cyst. The diagnosis was confirmed bacteriologically and histologically. In all cases (average age 49.1 years) the human bacillus was proved to be the cause of an haematogenous infection. The lesion was confined to the posterior part of the bone and there was no extension into the calcaneo-navicular joint. One focus extended into the ankle joint. Two patients presented with fistulae. The interval from the onset of symptoms to confirmation of the diagnosis averaged 9.1 months. Three patients had previously been treated for tuberculosis (lung, pleura, kidney) and another patient, who had a simultaneous tuberculous infection of a sternoclavicular joint had suffered from tuberculous cervical lymphadenitis at the age of nine years.

  15. Diagnosis of endometrial tuberculosis: culture versus histopathological examination

    Objective: To compare the relative efficacy of histopathological examination and culture method in the diagnosis of endometrial tuberculosis. Design: It was a prospective, comparative in-vitro study. Place and Duration of Study: The study was conducted at the Armed Forces Institute of Pathology, Rawalpindi and Department of Obstetrics and Gynecology, Military Hospital, Rawalpindi from August 1998 to April 1999. Materiel and Methods: A total number of 50 cases of primary and secondary infertility were selected. Endometrial biopsies of all patients were subjected to histopathological as well as culture examination on BACTEC. Results: Culture method yielded 10% (n=5) positive results compared with 6% (n=3) positive results obtained by histopathological examination. P value was 0.096 by chi-square test. Conclusion: Culture is a more effective method compared with histopathological examination in the diagnosis of endometrial tuberculosis. (author)

  16. Recent advances in the molecular diagnosis of tuberculosis.

    Su, Wei-Juin

    2002-12-01

    To date, the diagnosis of tuberculosis has not improved significantly and still relies heavily on staining and culture of sputum or other clinical specimens which were developed more than 100 years ago. Staining does not differentiate tuberculosis from other mycobacterial infections, and culture requires at least 4 to 8 weeks. These are the major problems faced by tuberculosis control programs. In response to this demand, new rapid diagnostic methods are urgently sought. In recent years, much hope has been laid on the development of molecular techniques in the routine tuberculosis laboratory. This review concentrates on 4 techniques that are increasingly used in clinical laboratories: polymerase chain reaction to detect mycobacterial DNA in clinical specimens, nucleic acid probes to identify culture, restriction fragment length polymorphism analysis to compare strains for epidemiologic purposes, and genetic-base susceptibility testing methods for rapid detection of drug resistance. Finally, the increase in the use of clinically-useful molecular biological techniques that affect turnaround time, length of stay, and patient outcome, and reduce overall hospitalization costs will continue until universal standardization for molecular diagnostic procedures are provided. At present, conventional methods should not be replaced by novel methods until the latter are shown to be of equal or greater sensitivity, specificity, reliability, and user-friendliness. However, it is expected that the newly developed molecular techniques will complement our armamentarium of diagnostic tools in the detection of tuberculosis. It is also expected that clinical protocols based on molecular methods will increase the chances for cure by selecting the most appropriate treatment and improving the quality of life of tuberculosis patients. PMID:12542245

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

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

    2007-01-01

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

  18. Current Diagnosis and Management of Female Genital Tuberculosis.

    Sharma, Jai B

    2015-12-01

    Female genital tuberculosis (FGTB) is an important cause of significant morbidity, short- and long-term sequelae especially infertility whose incidence varies from 3 to 16 % cases in India. Mycobacterium tuberculosis is the etiological agent for tuberculosis. The fallopian tubes are involved in 90-100 % cases, endometrium is involved in 50-80 % cases, ovaries are involved in 20-30 % cases, and cervix is involved in 5-15 % cases of genital TB. Tuberculosis of vagina and vulva is rare (1-2 %). The diagnosis is made by detection of acid-fast bacilli on microscopy or culture on endometrial biopsy or on histopathological detection of epithelioid granuloma on biopsy. Polymerase chain reaction may be false positive and alone is not sufficient to make the diagnosis. Laparoscopy and hysteroscopy can diagnose genital tuberculosis by various findings. Treatment is by giving daily therapy of rifampicin (R), isoniazid (H), pyrazinamide (Z) and ethambutol (E) for 2 months followed by daily 4 month therapy of rifampicin (R) and isoniazid (H). Alternatively 2 months intensive phase of RHZE can be daily followed by alternate day combination phase (RH) of 4 months. Three weekly dosing throughout therapy (RHZE thrice weekly for 2 months followed by RH thrice weekly for 4 months) can be given as directly observed treatment short-course. Surgery is rarely required only as drainage of abscesses. There is a role of in vitro fertilization and embryo transfer in women whose fallopian tubes are damaged but endometrium is healthy. Surrogacy or adoption is needed for women whose endometrium is also damaged. PMID:26663993

  19. Diagnosis of intracranial tuberculosis by computed tomography

    25 cases of clinically proved intracranial tuberculosis were studied by CT in the Hanyang Hospital from Feb. 1979 to July 1981. The medical records and CT films were reviewed. The results were as follows; 1. The age distribution was broad from 8 months to 43 years old. The incidence was higher in the age group from 0 to 5 years old. The male to female ratio was 1.8 : 1. 2. Clinical symptoms and signs revealed headache, nausea and vomiting, neck stiffness, positive Kernig's sign, and paralysis of the extremities. 3. At the time of CT examination 8 out of 25 cases were conscious, stuporous in 14 and unconscious in 3. 4. In CT, total or partial obliterations of the basal cisterns were observed in 21 out of 25 cases. 5. Intense abnormal contrast enhancement of the basal cistern were observed in 9 out of 25 cases. 6. Tuberculoma was found in 3 cases. Among these 3 cases had multiple tuberculomas and 1 case had single tuberculoma. 7. Moderate to marked dilatation of both lateral ventricles were observed in 21 cases. The 3rd and 4th ventricles were also dilated in 19 and 12 cases respectively. 8. 2 cases of cerebral infarction were observed, all in the bilateral basal gangilas. 9. Intracranial calcifications were observed in 2 cases who had histories of tuberculous meningitis, 4 to 9 years prior to CT examinations. The calcifications were multiple and located in the suprasellar areas

  20. Diagnosis of Mycobacterium tuberculosis using molecular biology technology

    Juan Garberi; Jorge Labrador; Federico Garberi; Juan Ezequiel Garberi; Julian Peneipil; Miguel Garberi; Luis Scigliano; Alcides Troncoso

    2011-01-01

    Objective:To present an integrated molecular biology dedicated system for tuberculosis diagnosis.Methods:One hundred and five sputum specimens from patients strongly suspected by clinical parameters of tuberculosis were studied by Ziehl-Neelsen staining, by cultivation on solid medium and by a balanced heminested fluorometricPCR system (OrangeG3TB) that could preserve worker safety and produce a rather pure material free of potential inhibitors. DNA amplification was performed in a low cost tuberculosis termocycler-fluorometer. Produced double stranded DNA was flurometrically detected. The whole reaction was conducted in one single tube which would not be opened after adding the processed sample in order to minimize the risk of cross contamination with amplicons.Results: The assay was able to detect30 bacillus per sample mL with99.8% interassay variation coefficient.PCR was positive in23 (21.9%) tested samples (21 of them were smear negative). In our study it showed a preliminary sensitivity of 94.5% for sputum and an overall specificity of98.7%.Conclusions:Total run time of the test is4 h with2.5 real working time. AllPCR positive samples are also positive by microbiological culture and clinical criteria. Results show that it could be a very useful tool to increase detection efficiency of tuberculosis disease in low bacilus load samples. Furthermore, its low cost and friendly using make it feasible to run in poor regions.

  1. Current issues on molecular and immunological diagnosis of tuberculosis.

    Cho, Sang-Nae

    2007-06-30

    Laboratory diagnosis of tuberculosis (TB) traditionally relies on smear microscopy and culture of Mycobacterium tuberculosis from clinical samples. With recent advances in technology, there have been numerous efforts to develop new diagnostic tests for TB that overcome the low sensitivity and specificity and long turnover time associated with current diagnostic tests. Molecular biological tests based on nucleic acid amplification have brought an unprecedented opportunity for the rapid and specific detection of M. tuberculosis from clinical specimens. With automated sequencing analysis, species identification of mycobacteria is now easier and more accurate than with conventional methods, and rapid detection of mutations in the genes associated with resistance to TB drugs provides early information on the potential drug resistance for each clinical isolate or for clinical samples. In addition, immunological tests for the detection of M. tuberculosis antigens and antibodies to the antigens have been explored to identify individuals at risk of developing TB or with latent TB infection (LTBI). The recent introduction of commercial IFN-gamma assay kits for the detection of LTBI provides a new approach for TB control even in areas with a high incidence of TB. However, these molecular and immunological tools still require further evaluation using large scale cohort studies before implementation in TB control programs. PMID:17594141

  2. Clinical Evaluation of the Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test for Rapid Diagnosis of Tuberculosis Lymphadenitis

    Kerleguer, A.; Fabre, M.; Bernatas, J. J.; Gerome, P.; E. Nicand; Herve, V; Koeck, J.L.

    2004-01-01

    This prospective study evaluated the performance of the Amplified Mycobacterium Tuberculosis Direct Test (MTD) for the diagnosis of lymph node tuberculosis in Djibouti, Republic of Djibouti. Of 197 specimens sampled from 153 patients, 123 were from 95 tuberculous patients. The sensitivity and specificity of MTD were 93 and 100%, respectively. The sensitivity of culture was 89%.

  3. Reminder systems to improve patient adherence to tuberculosis clinic appointments for diagnosis and treatment

    Liu, Qin; Abba, Katharine; Alejandria, Marissa M; Sinclair, David; Balanag, Vincent M; Lansang, Mary Ann D

    2014-01-01

    Background People with active tuberculosis (TB) require six months of treatment. Some people find it difficult to complete treatment, and there are several approaches to help ensure completion. One such system relies on reminders, where the health system prompts patients to attend for appointments on time, or re-engages people who have missed or defaulted on a scheduled appointment. Objectives To assess the effects of reminder systems on improving attendance at TB diagnosis, prophylaxis, and ...

  4. Detection of Antibodies Secreted from Circulating Mycobacterium tuberculosis-Specific Plasma Cells in the Diagnosis of Pediatric Tuberculosis▿

    Raqib, Rubhana; Mondal, Dinesh; Karim, M. Anwarul; Chowdhury, Fahima; Ahmed, Sultan; Luby, Stephen; Cravioto, Alejandro; Andersson, Jan; Sack, David

    2009-01-01

    Diagnosis of tuberculosis (TB) in children is difficult because symptoms are often nonspecific or absent in infected children, diagnostic specimens are difficult to obtain from younger children, and >50% have negative TB cultures. Thus, there is an urgent need for improved diagnosis of pediatric TB. This study aimed to evaluate the diagnostic value of a new serological method, the ALS (antibodies in lymphocyte supernatant) assay, for the diagnosis of active TB in children with clinically iden...

  5. s-Findings of active pulmonary tuberculosis in computed tomography

    Purpose: Tuberculosis remains the most important infectious disease all over the world. We report on the CT findings of lung tuberculosis. Material and methods: Standardised retrospective analysis of the computed tomographic examinations in a total of 100 patients suffering from cultural or histological proven pulmonary tuberculosis. Results: The most common finding in our study group were micronodules and lobular opacities accompanied by enlarged lymph nodes. Cavitation and alteration of the bronchial system (esp. bronchial wall thickening) were found less common. The so-called tree- in bud-appearance which had been estimated by other authors to be rather characteristic for active pulmonary tuberculosis was seen in only 12/100 examinations. It is often found in cases showing severe bronchogenic spreading of the disease. Conclusion: The active pulmonary tuberculosis does not show any pathognomonic sign but the combination of findings as opacities and cavitation and segmental spreaded micronodules make the diagnosis probable. This holds also for the so-called tree- in-bud appearances which may be rather suggestive but is seen only in cases suffering from severe bronchiogenic propagation. (orig.)

  6. Access to health care and diagnosis of tuberculosis

    Dândara Nayara Azevêdo Dantas

    2014-12-01

    Full Text Available The objective was to know the evaluation of patients with tuberculosis regarding the access to health care and the diagnosis of the disease. It is a cross-sectional quantitative study made in Natal, RN, Brazil, from February to September 2012, with 60 patients diagnosed with tuberculosis. Data were collected using a questionnaire and analyzed using descriptive statistics. Access to health care was considered easy by 80% of patients. Of those, 35% considered it easy because of the short time to get a doctor’s appointment and 21.7% because of their relationship with the health professionals. The access to the diagnosis of the disease was also evaluated as easy (85%. Of this total, 33.3% rated it as easy, once the exams were made in the health service and 13.3% due to the short time to get immediate doctor’s appointment. It is concluded that the organization of the services was crucial for the good or bad evaluation of the access to the assistance to health and diagnosis of the disease.

  7. Automatic sputum color image segmentation for tuberculosis diagnosis

    Forero-Vargas, Manuel G.; Sierra-Ballen, Eduard L.; Alvarez-Borrego, Josue; Pech-Pacheco, Jose L.; Cristobal-Perez, Gabriel; Alcala, Luis; Desco, Manuel

    2001-11-01

    Tuberculosis (TB) and other mycobacteriosis are serious illnesses which control is mainly based on presumptive diagnosis. Besides of clinical suspicion, the diagnosis of mycobacteriosis must be done through genus specific smears of clinical specimens. However, these techniques lack of sensitivity and consequently clinicians must wait culture results as much as two months. Computer analysis of digital images from these smears could improve sensitivity of the test and, moreover, decrease workload of the micobacteriologist. Bacteria segmentation of particular species entails a complex process. Bacteria shape is not enough as a discriminant feature, because there are many species that share the same shape. Therefore the segmentation procedure requires to be improved using the color image information. In this paper we present two segmentation procedures based on fuzzy rules and phase-only correlation techniques respectively that will provide the basis of a future automatic particle' screening.

  8. Determination of the activity of pulmonary tuberculosis : the utility of high-resolution computed tomography

    Chung, Myung Hee; Lee, Hae Giu; Yu, Won Jong; Chung, Hong Jun; Yang, Bo Sung; Kwon, Soon Suck; Park, Seog Hee [The Catholic University of Korea, Seoul (Korea, Republic of)

    2000-05-01

    To evaluate the utility of high-resolution computed tomography (HRCT), as used to determine the activity of tuberculosis, and to analyze the HRCT findings in active and in inactive tuberculosis. We analyzed the HRCT findings of 100 patients (54 men, 46 women; average age, 54 years) who according to the results of chest radiography had pulmonary tuberculosis of undetermined activity. We assessed HRCT findings such as the presence of a centrilobular, macro-, or micronodule; consolidation, ground-glass opacity, cavity, interlobular septal thickening, irregular linear opacities, bronchial wall thickening, bronchovascular bundle distortion, bronchiectasis, atelectasis, and pericicatrical emphysema. We compared the ratio of the area of nodule and consolidation to that of whole lung, and compared the findings between active and inactive tuberculosis. Eleven of 100 patients were excluded because the final diagnosis was other than tuberculosis. In 59 patients, the presence of active pulmonary tuberculosis was proven by positive sputum smear and/or culture for mycobacterium tuberculosis. On the basis of the negative results of these tests, pulmonary tuberculosis was found to be inactive in 30 patients; serial chest radiographs indicated that their condition remained stable over a 6-month period. For HRCT, sensitivity was 96.6%, specificity 56.7%, positive predictive value 81.4%, negative predictive value 89.5%, and accuracy 83.1%. For active tuberculosis, the presence of centrilobular nodules, tree-in-bud, macronodules, cavity within the nodule, and consolidations was statistically significant, while for inactive tuberculosis, that of irregular linear opacities, micronodules, bronchiectasis, and cicatrization atectasis was similarly significant. The CT score for the area of nodules and consolidations was higher in active than in inactive tuberculosis, but only the nodule score showed statistical significance. HRCT can be a useful diagnostic tool for evaluating the activity

  9. Determination of the activity of pulmonary tuberculosis : the utility of high-resolution computed tomography

    To evaluate the utility of high-resolution computed tomography (HRCT), as used to determine the activity of tuberculosis, and to analyze the HRCT findings in active and in inactive tuberculosis. We analyzed the HRCT findings of 100 patients (54 men, 46 women; average age, 54 years) who according to the results of chest radiography had pulmonary tuberculosis of undetermined activity. We assessed HRCT findings such as the presence of a centrilobular, macro-, or micronodule; consolidation, ground-glass opacity, cavity, interlobular septal thickening, irregular linear opacities, bronchial wall thickening, bronchovascular bundle distortion, bronchiectasis, atelectasis, and pericicatrical emphysema. We compared the ratio of the area of nodule and consolidation to that of whole lung, and compared the findings between active and inactive tuberculosis. Eleven of 100 patients were excluded because the final diagnosis was other than tuberculosis. In 59 patients, the presence of active pulmonary tuberculosis was proven by positive sputum smear and/or culture for mycobacterium tuberculosis. On the basis of the negative results of these tests, pulmonary tuberculosis was found to be inactive in 30 patients; serial chest radiographs indicated that their condition remained stable over a 6-month period. For HRCT, sensitivity was 96.6%, specificity 56.7%, positive predictive value 81.4%, negative predictive value 89.5%, and accuracy 83.1%. For active tuberculosis, the presence of centrilobular nodules, tree-in-bud, macronodules, cavity within the nodule, and consolidations was statistically significant, while for inactive tuberculosis, that of irregular linear opacities, micronodules, bronchiectasis, and cicatrization atectasis was similarly significant. The CT score for the area of nodules and consolidations was higher in active than in inactive tuberculosis, but only the nodule score showed statistical significance. HRCT can be a useful diagnostic tool for evaluating the activity

  10. Determination of Urinary Neopterin/Creatinine Ratio to Distinguish Active Tuberculosis from Latent Mycobacterium tuberculosis Infection

    Michael Eisenhut

    2016-01-01

    Full Text Available Background. Biomarkers to distinguish latent from active Mycobacterium (M. tuberculosis infection in clinical practice are lacking. The urinary neopterin/creatinine ratio can quantify the systemic interferon-gamma effect in patients with M. tuberculosis infection. Methods. In a prospective observational study, urinary neopterin levels were measured by enzyme linked immunosorbent assay in patients with active tuberculosis, in people with latent M. tuberculosis infection, and in healthy controls and the urinary neopterin/creatinine ratio was calculated. Results. We included a total of 44 patients with M. tuberculosis infection and nine controls. 12 patients had active tuberculosis (8 of them culture-confirmed. The median age was 15 years (range 4.5 to 49. Median urinary neopterin/creatinine ratio in patients with active tuberculosis was 374.1 micromol/mol (129.0 to 1072.3, in patients with latent M. tuberculosis infection it was 142.1 (28.0 to 384.1, and in controls it was 146.0 (40.3 to 200.0, with significantly higher levels in patients with active tuberculosis (p<0.01. The receiver operating characteristics curve had an area under the curve of 0.84 (95% CI 0.70 to 0.97 (p<0.01. Conclusions. Urinary neopterin/creatinine ratios are significantly higher in patients with active tuberculosis compared to patients with latent infection and may be a significant predictor of active tuberculosis in patients with M. tuberculosis infection.

  11. Peritoneal tuberculosis: how to obtain a confident diagnosis?; Tuberculose peritoneal: como diagnosticar?

    Peixoto Filho, Anibal Araujo Alves; Peixoto, Mila Correia Gois [Hospital Sao Luiz, Sao Paulo, SP (Brazil). Setor de US/TC/RM; D' Ippolito, Giuseppe [Universidade Federal de Sao Paulo (UNIFESP-EPM), Sao Paulo, SP (Brazil). Dept. de Diagnostico por Imagem]. E-mail: giuseppe_dr@uol.com.br

    2007-07-01

    The peritoneum is a frequent site of involvement by peritoneal tuberculosis. Generally, computed tomography appears to be the imaging modality of choice in the detection and assessment of abdominal tuberculosis. The computed tomography findings can help in the diagnosis of peritoneal tuberculosis, that is confirmed by a positive culture or hystologic analysis of biopsy obtained through laparoscopic examination. Peritoneal carcinomatosis is the main differential diagnosis. In this article we present the spectrum of tomographic manifestation of peritoneal tuberculosis and how we can differentiate it from peritoneal carcinomatosis. (author)

  12. Delay in diagnosis of tuberculosis in Rawalpindi, Pakistan

    Tahseen Sabira

    2011-05-01

    Full Text Available Abstract Background Delay in diagnosis and treatment of tuberculosis (TB may enhance the chances of morbidity and mortality and play a key role in continuous transmission of the bacilli. The objective of this study was to describe health care seeking behavior of suspected TB patients and initial diagnostic work up prior to consultation and diagnosis at National TB Center (NTC. Findings Interviews of 252 sputum smear positive patients were taken from NTC, Rawalpindi. The duration between on-set of symptoms and start of treatment was considered as the total delay and correlated with general characteristics of TB patients. The proportion of males and females were 49.6% and 50.4% with median age of 25 and 24 years respectively. A median delay of 56 days (8 weeks was observed which was significantly associated with age, cough and fever. More than 50% of the current patients had a history of contact with previously diagnosed TB patients. The majority of patients (63% visited health care providers within three weeks of appearance of symptoms but only thirty five percent were investigated for TB diagnosis. Conclusion Cough and fever are being ignored as likely symptoms of TB by patients as well as health care providers resulting in delay. Engaging private practitioners through public private mix (PPM approach for expansion of TB diagnosis and increasing public awareness could be more beneficial to reduce delay.

  13. Falso diagnóstico de tuberculosis por cultivo False diagnosis of tuberculosis by culture

    Valeria Alonso

    2007-06-01

    result in a wrong diagnosis of tuberculosis and the initiation of a long-lasting treatment with potentially toxic drugs. This series of errors implies the mismanagement of patients, the distraction of public health system resources, and the distortion of epidemiological data. M. tuberculosis laboratory cross-contamination was detected wherever investigated systematically, with a median rate of 3% of all positive cultures. The confirmation of this error requires a critical appraisal of bacteriological, clinical, epidemiological and genotyping results. We present here a review of national and international information on laboratory cross-contamination and describe measures recommended for minimizing the risk, surveying the occurrence, and avoiding clinical consequences of this laboratory error that raises a question on the reliability of a positive culture.

  14. Isolated Pancreatic/Periampullary Tuberculosis Remains a Diagnosis of Exclusion

    Mallika Tewari

    2009-05-01

    Full Text Available Dear Sir, Although tuberculosis is endemic in this part of the world, isolated pancreatic tuberculosis is extremely rare. Thus, all lesions are first suspected as carcinoma and not tuberculosis unless the clinical features are suggestive of tuberculosis, for example, a history of miliary tuberculosis with enlarged peripancreatic nodes especially in an immunocompromised host. As our patient had none of these findings, we investigated her as one with possible periampullary carcinoma.

  15. Bronchoalveolar Lavage Enzyme-Linked Immunospot for Diagnosis of Smear-Negative Tuberculosis in HIV-Infected Patients

    Cattamanchi, Adithya; Ssewenyana, Isaac; Nabatanzi, Rose; Cecily R Miller; den Boon, Saskia; Davis, J. Lucian; Andama, Alfred; Worodria, William; Samuel D Yoo; Cao, Huyen; Huang, Laurence

    2012-01-01

    Background Peripheral blood interferon-gamma release assays (IGRAs) have sub-optimal sensitivity and specificity for diagnosis of active pulmonary tuberculosis (TB). However, assessment of local immune responses has been reported to improve the accuracy of TB diagnosis. Methods We enrolled HIV-infected adults with cough ≥2 weeks’ duration admitted to Mulago Hospital in Kampala, Uganda and referred for bronchoscopy following two negative sputum acid-fast bacillus smears. We performed an ELISPO...

  16. Spontaneous and induced sputum values in the diagnosis of pulmonary tuberculosis among patients with suspected pulmonary tuberculosis

    Katayoun Haji Bagheri; Shahla Afrasiabian; Behzad Mohsenpour; Naser Reshadmanesh

    2015-01-01

    Objectives: The quality of sputum samples is important for the diagnosis of pulmonary tuberculosis (TB). Unfortunately, it is not always possible to get a proper sputum sample. Now, sputum induction (SI) has been found to be useful for the diagnosis of many lung diseases. Therefore, this study compares the role of spontaneous sputum and induced sputum in the diagnosis of pulmonary TB among suspected pulmonary TB patients. Materials and Methods: A total of 27 patients admitted with suspected p...

  17. Host Protein Biomarkers Identify Active Tuberculosis in HIV Uninfected and Co-infected Individuals

    Achkar, Jacqueline M.; Laetitia Cortes; Pascal Croteau; Corey Yanofsky; Marija Mentinova; Isabelle Rajotte; Michael Schirm; Yiyong Zhou; Ana Paula Junqueira-Kipnis; Kasprowicz, Victoria O.; Michelle Larsen; René Allard; Joanna Hunter; Eustache Paramithiotis

    2015-01-01

    Biomarkers for active tuberculosis (TB) are urgently needed to improve rapid TB diagnosis. The objective of this study was to identify serum protein expression changes associated with TB but not latent Mycobacterium tuberculosis infection (LTBI), uninfected states, or respiratory diseases other than TB (ORD). Serum samples from 209 HIV uninfected (HIV−) and co-infected (HIV+) individuals were studied. In the discovery phase samples were analyzed via liquid chromatography and mass spectrometry...

  18. Bone scintigraphy, radiography and MRI in the diagnosis and evaluation of treatment response of calcaneal tuberculosis

    Aim: We describe the role of various imaging modalities in the diagnosis and follow up of calcaneal tuberculosis. Materials and methods: Six patients (5 males, 1 female; age range 16-49 years) presented with heel pain. All patients underwent routine laboratory and radiological investigations e.g. radiographs, MRI and skeletal scintigraphy as part of initial diagnostic work-up. In all patients the diagnosis of tuberculosis was confirmed based on histopathology or culture. Standard multi-drug anti-tubercular therapy (ATT) was administered for 15 months. All patients were subsequently followed up with clinical evaluation, laboratory investigations and imaging. Skeletal scintigraphy, MRI and radiographs were repeated at 12 to 15 months from the initiation of anti-tubercular treatment in all patients. Results: Five out of six patients had lytic lesions at presentation on radiographs. Four of these 5 patients also had surrounding sclerosis. Follow-up radiographs obtained 12-15 months after starting ATT, showed an increase in surrounding sclerosis with progressive reduction in area of osteopenia in four and mild sclerotic changes in one. In the remaining one patient radiograph were normal both at presentation and follow up. Three phase bone scintigraphy revealed increased blood flow and blood pool activity and 'hot spots' in 5 and a central photopenic area in the calcaneum in one patient at the time of diagnosis. After starting ATT, significant reduction in vascularity and reactive bone changes in 5 patients and mild improvement in one patient. MRI was done in three patients, which revealed hyperintense lesion with erosion of the superior articular surface in 2 and 'Bull's eye' lesion with a hypointense centre and a surrounding hyperintense rim on post contrast T1W images in one patient. Follow-up MRI showed intermediate signal intensity on T2 weighted images that corresponded to caseous necrosis and high signal intensity related to granulomas or effusion. Conclusion

  19. The PCR-Based Diagnosis of Central Nervous System Tuberculosis: Up to Date

    Teruyuki Takahashi

    2012-01-01

    Full Text Available Central nervous system (CNS tuberculosis, particularly tuberculous meningitis (TBM, is the severest form of Mycobacterium tuberculosis (M.Tb infection, causing death or severe neurological defects in more than half of those affected, in spite of recent advancements in available anti-tuberculosis treatment. The definitive diagnosis of CNS tuberculosis depends upon the detection of M.Tb bacilli in the cerebrospinal fluid (CSF. At present, the diagnosis of CNS tuberculosis remains a complex issue because the most widely used conventional “gold standard” based on bacteriological detection methods, such as direct smear and culture identification, cannot rapidly detect M.Tb in CSF specimens with sufficient sensitivity in the acute phase of TBM. Recently, instead of the conventional “gold standard”, the various molecular-based methods including nucleic acid amplification (NAA assay technique, particularly polymerase chain reaction (PCR assay, has emerged as a promising new method for the diagnosis of CNS tuberculosis because of its rapidity, sensitivity and specificity. In addition, the innovation of nested PCR assay technique is worthy of note given its contribution to improve the diagnosis of CNS tuberculosis. In this review, an overview of recent progress of the NAA methods, mainly highlighting the PCR assay technique, was presented.

  20. Whole Blood Interferon-γ Release Assay Is Insufficient for the Diagnosis of Sputum Smear Negative Pulmonary Tuberculosis

    Park, Heejin; Shin, Jung Ar; Kim, Hyung Jung; Ahn, Chul Min; CHANG, YOON SOO

    2014-01-01

    Purpose We investigated the value of an interferon-γ release assay (IGRA) for the diagnosis of active pulmonary tuberculosis (PTB) among sputum smear negative PTB suspects in an environment with intermediate burden of PTB and high Bacillus Calmette-Guérin (BCG) vaccination rate. Materials and Methods We retrospectively reviewed IGRA, medical records, chest PA and CT scan of PTB suspects seen at Gangnam Severance Hospital, Seoul, Korea from Oct. 2007 to Apr. 2013. "Active PTB" was diagnosed wh...

  1. Pathogenesis, Immunology, and Diagnosis of Latent Mycobacterium tuberculosis Infection

    Suhail Ahmad

    2011-01-01

    Full Text Available Phagocytosis of tubercle bacilli by antigen-presenting cells in human lung alveoli initiates a complex infection process by Mycobacterium tuberculosis and a potentially protective immune response by the host. M. tuberculosis has devoted a large part of its genome towards functions that allow it to successfully establish latent or progressive infection in the majority of infected individuals. The failure of immune-mediated clearance is due to multiple strategies adopted by M. tuberculosis that blunt the microbicidal mechanisms of infected immune cells and formation of distinct granulomatous lesions that differ in their ability to support or suppress the persistence of viable M. tuberculosis. In this paper, current understanding of various immune processes that lead to the establishment of latent M. tuberculosis infection, bacterial spreading, persistence, reactivation, and waning or elimination of latent infection as well as new diagnostic approaches being used for identification of latently infected individuals for possible control of tuberculosis epidemic are described.

  2. Immune responses to the Mycobacterium tuberculosis-specific antigen ESAT-6 signal subclinical infection among contacts of tuberculosis patients

    Doherty, T Mark; Demissie, Abebech; Olobo, Joseph; Wolday, Dawit; Britton, Sven; Eguale, Tewodros; Ravn, Pernille; Andersen, Peter

    2002-01-01

    Diagnosis of latent Mycobacterium tuberculosis infection is considered essential for tuberculosis control but is hampered by the lack of specific reagents. We report that strong recognition of tuberculosis complex-specific antigen ESAT-6 by healthy household contacts of tuberculosis patients...... correlates with the subsequent development of active tuberculosis during a 2-year follow-up period....

  3. Arginine Adjunctive Therapy in Active Tuberculosis

    Aliasghar Farazi

    2015-01-01

    Full Text Available Background. Dietary supplementation has been used as a mechanism to augment the immune system. Adjunctive therapy with L-arginine has the potential to improve outcomes in active tuberculosis. Methods. In a randomized clinical trial 63 participants with smear-positive pulmonary tuberculosis in Markazi Province of Iran were given arginine or placebo for 4 weeks in addition to conventional chemotherapy. The final treatment success, sputum conversion, weight gain, and clinical symptoms after one and two months were considered as primary outcomes and secondary outcomes were ESR, CRP, and Hg. Data were collected and analyzed with SPSS software (ver. 18. Results. Arginine supplementation reduced constitutional symptoms (P=0.032 in patients with smear-positive TB at the end of the first month of treatment. Arginine treated patients had significantly increased BMI at the end of the first and second months of treatment (P=0.032 and P=0.04 and a reduced CRP at the end of the first month of treatment (P=0.03 versus placebo group. Conclusion. Arginine is useful as an adjunctive therapy in patients with active tuberculosis, in which the effects are more likely mediated by the increased production of nitric oxide and improved constitutional symptoms and weight gain. This trial is registered with Clinical Trials Registry of Iran: IRCT201211179855N2.

  4. Comparison of Sputum Smear Microscopy and Rapid Tuberculosisantibody Detection Test Kits for Diagnosis of Pulmonary Tuberculosis in Abia State, Nigeria

    Emmanuel Olufemi Ekundayo[1; Sam D. Abbey[2; Onuka Okorie[3

    2014-01-01

    The SSM (sputum smear microscopy) and five immunochromatographic tuberculosis antibody detection tests (DiaSpot TB, Spodex TB, SD Rapid TB, Clinotech TB Screen and Precious One-step TB) were compared for diagnosis of active TB at the Leprosy and Tuberculosis Referral Hospital, Uzuakoli, Abia State, Nigeria. Sputum specimens from 150 study participants (male/female ratio, 0.81) were cultured on Lowenstein-Jensen slopes and direct smears were stained by Ziehl-Neelsen technique and examined by light microscopy. Sera were tested for anti-TB antibodies using the rapid TB tests. A total of 91 participants were culture positive, 79 (86.8%) for M. tuberculosis and 12 (13.2%) for nontuberculous mycobacteria. The sensitivity of SSM was 50% (95% CI: 39.0-61.0) and specificity was 92.3% (95% CI: 86.4-98.2) in those culture positive for M. tuberculosis. The sensitivity and specificity of the Rapid TB tests ranged from 24.1-39.2% and 78.4-87.8%, respectively. None of the five rapid TB tests had acceptable level of accuracy for diagnosis of active TB. The sensitivity of SSM though moderate is inadequate for long term TB control in this setting.

  5. The discourse of health managers on aspects related to the delay in tuberculosis diagnosis

    Lenilde Duarte de Sa

    2013-10-01

    Full Text Available The aim of this study was to analyze the discourse of health managers on aspects related to delay in tuberculosis diagnosis. This was a qualitative research study, conducted with 16 Family Health Unit managers. The empirical data were obtained through semi-structured interviews. The analysis was based on the theoretical framework of the French school of discourse analysis. According to the managers’ statements, the delay in tuberculosis diagnosis is related to patient and health service aspects. As for patient aspects, managers report fear, prejudice and lack of information as factors that may promote a delayed diagnosis. Regarding health service aspects, structural problems and lack of professional skills were reported. The discourse of managers should be considered to qualify tuberculosis control actions and to prevent delays in diagnosis.

  6. Active Tuberculosis among Homeless Persons, Toronto, Ontario, Canada, 1998–2007

    Khan, Kamran; Rea, Elizabeth; McDermaid, Cameron; Stuart, Rebecca; Chambers, Catharine; Wang, Jun; Chan, Angie; Gardam, Michael; Jamieson, Frances; Yang, Jae; Hwang, Stephen W.

    2011-01-01

    While tuberculosis (TB) in Canadian cities is increasingly affecting foreign-born persons, homeless persons remain at high risk. To assess trends in TB, we studied all homeless persons in Toronto who had a diagnosis of active TB during 1998–2007. We compared Canada-born and foreign-born homeless persons and assessed changes over time. We identified 91 homeless persons with active TB; they typically had highly contagious, advanced disease, and 19% died within 12 months of diagnosis. The propor...

  7. Imaging diagnosis of pulmonary tuberculosis in immunocompromised patients

    Objective: To evaluate CT and X-ray features of pulmonary tuberculosis in diabetic patients, patients post kidney transplantation, and patients with acquired immunodeficiency syndrome (AIDS). Methods: The authors reviewed CT scans in 20 patients with diabetic patients, X-ray films in 10 cases after kidney transplantation, and CT scans in 2 patients with AIDS. Results: CT features of pulmonary tuberculosis in diabetic diseases included larger confluent consolidation (10 cases ), multiple small cavities within any given lesion (9 cases ) and non-segmental distribution (2 cases). Satellite lesions were found in most films. The X-ray appearances of pulmonary tuberculosis post kidney transplantation included patch and larger confluent consolidation (6 cases), and miliary tuberculosis(4 cases). The CT findings of pulmonary tuberculosis with AIDS were enlarged mediastinal lymph nodes (1 case), pulmonary infiltration (1 case), and extra chest lesions(2 cases) such as enlarged neck lymph nodes and post-peritoneal lymph nodes. Conclusion: The Main radiological findings of pulmonary tuberculosis in immunocompromised patients appear larger confluent consolidation, multiple small cavities within a given lesion, miliary tuberculosis, enlarged mediastinal lymph nodes, and extra chest enlarged lymph nodes

  8. Pleural tuberculosis in the state of Roraima, Brazil, between 2005 and 2013: quality of diagnosis

    Tao Machado

    2016-04-01

    Full Text Available Objective: To evaluate the quality of diagnosis and the epidemiological profile of patients with pleural tuberculosis in the state of Roraima, Brazil, in order to provide technical support for the development and implementation of public policies to combat the disease. Methods: This was a cross-sectional study designed to determine the prevalence of pleural forms of tuberculosis in Roraima between 2005 and 2013 and to evaluate the diagnostic criteria used, as well as their determinants. This study was based on secondary data from the Brazilian Case Registry Database, including all reported cases of pleural tuberculosis in the state during the study period. Diagnoses based on bacteriological or histopathological confirmation were defined as high-quality diagnoses. Results: Among the 1,395 cases of tuberculosis reported during the study period, 116 (8.3% were cases of pleural tuberculosis, accounting for 38.9% of all cases of extrapulmonary tuberculosis in the sample. The incidence rate of pleural tuberculosis did not follow the downward trend observed for the pulmonary form of the disease during the same period. The prevalence of cases with a high-quality diagnosis was 28.5% (95% CI: 20.4-37.6%. In a univariate analysis, none of the demographic or clinical characteristics collected from the database were found to have a significant impact on the outcome (as explanatory variables. Conclusions: The quality of the diagnoses in our study sample was considered unsatisfactory. Limited access to specific diagnostic methods might have contributed to these results.

  9. Advances in ante-mortem diagnosis of tuberculosis in cattle.

    Buddle, B M; Livingstone, P G; de Lisle, G W

    2009-08-01

    The tuberculin skin test is effective in the early detection of pre-clinical cases of Mycobacterium bovis infection in cattle. This allows the rapid removal of infected animals, thus limiting transmission of the disease, and has resulted in the eradication of bovine tuberculosis (Tb) from many countries. This test is very likely to remain the primary screening test for M. bovis infection in cattle as it is a simple, robust and inexpensive test. However, a number of ancillary tests are being used, or are currently being validated. These ancillary tests are likely to provide a more accurate diagnosis following skin-testing. The blood-based BOVIGAM interferon-gamma (IFN-gamma) test is a cellular immune assay which can detect early infection, and has become the main ancillary test in New Zealand. It can be used for re-testing skin test-positive animals, to improve specificity and minimise wastage from slaughtering animals with false-positive tests. Alternatively, it can be used in locations of increased risk of infection in parallel with skin-testing, for examining skin test-negative animals for pre-movement testing or in problem herds to identify M. bovis-infected animals that do not respond to the skin test. Several modifications of the test are now being used to improve specificity by altering the cut-off or using specific antigens present in virulent mycobacteria such as the 6 kDa early secreted antigenic target (ESAT-6) and 10 kDa culture filtrate protein (CFP-10). While antibody based tests generally lack sensitivity, as high levels of antibodies tend to occur late in the disease process, they may have unique desirable properties such as the ability to be used as a cow-side test. The use of these new ancillary tests in association with skin-testing will improve the detection of M. bovis-infected cattle and reduce the unnecessary slaughter of false-positive reactors. PMID:19649010

  10. Patho-TB test for the rapid diagnosis of pulmonary tuberculosis

    Roya Alavi-Naini

    2009-09-01

    Full Text Available

    • BACKGROUND: Despite recent technologic improvements in identifying mycobacterium tuberculosis, we are still facing problems in rapid diagnosis of tuberculosis. The objective of this study is to determine the diagnostic value of a new rapid screening test (Patho-TB™ for diagnosis of pulmonary tuberculosis.
    • METHODS: Between September 2006 to August 2007, 178 patients were enrolled in the study who were finally classified into two groups; a group of documented pulmonary tuberculosis (n = 67 and a group of non-tuberculous pulmonary infection (n = 111. Patho-TB™ test, Ziehl-Neelsen staining and culture were done on all specimens.
    • RESULTS: Of all, 43 patients with pulmonary tuberculosis were sputum smear positive for acid fast bacilli and the rest were smear negative. Mean age of the patients was 59.8 ± 16.1 years and 44% of them were men. The results of Patho- TB™ test were positive in 40 of smear positive and 20 of smear negative tuberculous patients and 33 cases of nontuberculous control group. The sensitivity, specificity, positive and negative predictive values and accuracy of Patho- TB™ test were estimated 89.5%, 70.2%, 64.5%, 91.7% and 77.5%, respectively.
    • CONCLUSIONS: According to the present study it would be suggested that Patho-TB™ test could be a rapid and inexpensive method for diagnosis of pulmonary tuberculosis, given by its high sensitivity and negative predictive value. Concerning the high number of false positive results, using a confirmatory diagnostic procedure is mandatory.
    • KEYWORDS: Pulmonary Tuberculosis, Rapid Diagnosis, Mycobacterium Tuberculosis Antigens, Iran

  11. Pleural tuberculosis in the state of Roraima, Brazil, between 2005 and 2013: quality of diagnosis

    Machado, Tao; da Fonseca, Allex Jardim; Buenafuente, Sandra Maria Franco

    2016-01-01

    Objective: To evaluate the quality of diagnosis and the epidemiological profile of patients with pleural tuberculosis in the state of Roraima, Brazil, in order to provide technical support for the development and implementation of public policies to combat the disease. Methods: This was a cross-sectional study designed to determine the prevalence of pleural forms of tuberculosis in Roraima between 2005 and 2013 and to evaluate the diagnostic criteria used, as well as their determinants. This ...

  12. Pleural tuberculosis in the state of Roraima, Brazil, between 2005 and 2013: quality of diagnosis

    Tao Machado; Allex Jardim da Fonseca; Sandra Maria Franco Buenafuente

    2016-01-01

    Objective: To evaluate the quality of diagnosis and the epidemiological profile of patients with pleural tuberculosis in the state of Roraima, Brazil, in order to provide technical support for the development and implementation of public policies to combat the disease. Methods: This was a cross-sectional study designed to determine the prevalence of pleural forms of tuberculosis in Roraima between 2005 and 2013 and to evaluate the diagnostic criteria used, as well as their determinants. Th...

  13. Primary pancreatic tuberculosis: a rare and elusive diagnosis

    Primary pancreatic tuberculosis is an extremely rare entity, even in tuberculosis endemic areas. A 22-year-old male presented with features of obstructive jaundice. Ultrasonography and computed tomography scan showed mass in the pancreatic head for which he underwent a pancreatoduodenectomy. Histological examination of the specimen showed caseating granulomas. Antituberculous medicines were started and he remained well 18 months after surgery. Pancreatic tuberculosis is rare and is frequently confused with pancreatic cancer on clinical presentation as well as on imaging studies. A high index of suspicion is vital to avoid surgeries in this medically treatable, often misdiagnosed condition. (author)

  14. Active case finding of tuberculosis in Europe: a Tuberculosis Network European Trials Group (TBNET) survey

    Bothamley, G.H.; Ditiu, L.; Migliori, G.B.;

    2008-01-01

    Tuberculosis control depends on successful case finding and treatment of individuals infected with Mycobacterium tuberculosis. Passive case finding is widely practised: the present study aims to ascertain the consensus and possible improvements in active case finding across Europe. Recommendations...... from national guidelines were collected from 50 countries of the World Health Organization European region using a standard questionnaire. Contacts are universally screened for active tuberculosis and latent tuberculosis infection (LTBI). Most countries (>70%) screen those with HIV infection, prisoners...... and in-patient contacts. Screening of immigrants is related to their contribution to national rates of tuberculosis. Only 25 (50%) out of 50 advise a request for symptoms in their guidelines. A total of 36 (72%) out of 50 countries recommend sputum examination for those with a persistent cough; 13...

  15. Imaging and differential diagnosis of pediatric spinal tuberculosis

    Xiao-ying Xing

    2015-03-01

    Conclusion: Pediatric spinal tuberculosis often occurs in the cervical and thoracic vertebrae with typical imaging findings. The cases with atypical manifestations should be differentiated from other diseases such as Langerhans cell histiocytosis and metastatic neoplasm.

  16. Differential diagnosis between pulmonary tuberculosis and lung abscess by contrast enhanced CT

    The contrast enhanced CT findings in 14 patients with active tuberculosis and 26 patients with lung abscess were retrospectively analyzed. Reflecting the difference of pathogenesis between tuberculosis and abscess, the findings are widely different. The findings suggesting pulmonary tuberculosis rather than lung abscess were as follows; multiple and irregular necrotic areas, positive CT angiogram sign, no marginal enhancement surrounding necrosis. Contrast enhanced CT may help to distinguish pulmonary tuberculosis from lung abscess, especially in cases of caseous pneumonia showing broad consolidations or mass-like shadows. (author)

  17. Pulmonary Tuberculosis in a Young Pregnant Female: Challenges in Diagnosis and Management

    Manogna Maddineni

    2008-01-01

    Full Text Available Background. With the world becoming a global village, tuberculosis is no longer limited to endemic areas. Our case emphasizes the impact of immigration on infectious disease epidemiology and challenges associated with diagnosis and treatment in pregnancy. Case. A 21-year-old Hispanic female presented in preterm labor and was found to be hypoxic. Chest X-ray revealed a paratracheal mass which a CT scan confirmed. PPD test was positive. Bronchoalveolar lavage did not reveal acid-fast bacilli and biopsy revealed caseating granulomas. Diagnosis and treatment were challenging due to constraints in radiological investigations, lack of initial evidence of acid-fast bacilli, and toxic profile of medications. Due to her high risk, she was started on antituberculosis regimen. The diagnosis was confirmed on Day 26 when Mycobacterium tuberculosis was isolated by DNA probe. Conclusion. A high index of suspicion is required to recognize the changing face and disease spectrum of tuberculosis and initiate treatment for better outcomes.

  18. Falso diagnóstico de tuberculosis por cultivo False diagnosis of tuberculosis by culture

    Valeria Alonso; Roxana Paul; Lucía Barrera; Viviana Ritacco

    2007-01-01

    Las herramientas de genotipificación intra-especie de Mycobacterium tuberculosis desarrolladas durante los años 90 no sólo dieron un impulso notable a la epidemiología de la tuberculosis, también pusieron de manifiesto un fenómeno hasta entonces soslayado en los laboratorios de tuberculosis: la contaminación cruzada de muestras. Este error consiste en la transferencia accidental de bacilos de una muestra con alta carga bacilar a la o las procesadas subsecuentemente. La consiguiente aparición ...

  19. Delay in diagnosis of generalized miliary tuberculosis with osseo-articular involvement: a case report

    Atukorala Inoshi

    2011-10-01

    Full Text Available Abstract Introduction Diagnosis of atypical tuberculosis is difficult. Therefore, it is important that physicians are aware of rare presentations of tuberculosis to avoid diagnostic delays. Case presentation We present the case of a 17-year-old Sri Lankan man who presented to our facility with an ill-defined large induration over the skin of his left buttock and thigh. A cause could not be found despite extensive investigations. He also complained of chronic knee pain, but this was not investigated further at the time due to spontaneous resolution. Three years later his knee disease flared up again, with pain, swelling and restriction of movement. A synovial biopsy was suggestive of tuberculosis. He was started on antituberculosis therapy, to which he responded well. Our patient was asymptomatic two months after completion of therapy without any subsequent flare-ups. A chest roentgenogram taken on his second presentation showed evidence of tuberculosis sequelae in his lungs. The most likely diagnosis for the buttock and thigh swelling, when considering the entire clinical picture, is a tuberculous abscess. The constellation of skin and skeletal symptoms and pulmonary tuberculosis is a rare occurrence in an immunocompetent individual, but cases have been reported. Conclusions This case demonstrates the different presentations and the diagnostic difficulties posed by atypical manifestations of tuberculosis. It also demonstrates the value of maintaining a high degree of suspicion in endemic areas, even in the absence of microbiological evidence.

  20. Diffuse calcification of the urinary system and miliary tuberculosis due to delayed diagnosis of genitourinary tuberculosis: a case report.

    Hairong Chen

    2015-02-01

    Full Text Available Genitourinary tuberculosis (GUTB is difficult to diagnose in the earlier stage owing to the non-specific symptoms. Usually, renal tuberculous involvement is unilateral and the imaging finding is renal calcification, but associated calcifications of bilateral ureter and bladder are rare. We report a 66-year-old man who presented with diffuse calcification of the urinary system (including bilateral pelvicalyceal system, both ureters and bladder and disseminated miliary tuberculosis due to GUTB. He had been misdiagnosed with urinary tract infection and urinary lithiasis for two years before the diagnosis of GUTB was confirmed by microbiological examination of the urine. This case highlights the importance of maintaining a high index of clinical suspicion for GUTB.

  1. IP-10 release assays in the diagnosis of tuberculosis infection

    Ruhwald, Morten; Aabye, Martine G; Ravn, Pernille

    2012-01-01

    The current state-of-the-art tests for infection with Mycobacterium tuberculosis - the IFN-γ release assays - rely on accurate measurement of the cytokine IFN-γ. Many other potential biomarkers are expressed in concert with IFN-γ, and IP-10 in particular has shown promising results. IP-10 is...

  2. Interferon Gamma Assay for the Diagnosis of Bovine Tuberculosis

    Contact Irene Schiller Prionics AG Wagistrasse 27A CH-8952 Schlieren Switzerland irene.schiller@prionics.com Introduction Bovine tuberculosis (bTB), a zoonotic disease with a major economic impact, continues to be a significant problem with a global perspective and increasing prevalence in vario...

  3. Tuberculosis Diagnosis: Relevancy of Veterinary Applications to Human Disease

    Veterinary applications of tuberculosis (TB) tests may provide insight into the diagnostic potential and technical development of emerging tests for human TB. Interferon (IFN)-gamma release assays (IGRA) were developed initially for bovine TB eradication programs. As the test relies on functional le...

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

    Qi Yuhua

    2012-12-01

    Full Text Available Abstract Background Pulmonary tuberculosis (TB is a highly lethal infectious disease and early diagnosis of TB is critical for the control of disease progression. The objective of this study was to profile a panel of serum microRNAs (miRNAs as potential biomarkers for the early diagnosis of pulmonary TB infection. Methods Using TaqMan Low-Density Array (TLDA analysis followed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR validation, expression levels of miRNAs in serum samples from 30 patients with active tuberculosis and 60 patients with Bordetella pertussis (BP, varicella-zoster virus (VZV and enterovirus (EV were analyzed. Results The Low-Density Array data showed that 97 miRNAs were differentially expressed in pulmonary TB patient sera compared with healthy controls (90 up-regulated and 7 down-regulated. Following qRT-PCR confirmation and receiver operational curve (ROC analysis, three miRNAs (miR-361-5p, miR-889 and miR-576-3p were shown to distinguish TB infected patients from healthy controls and other microbial infections with moderate sensitivity and specificity (area under curve (AUC value range, 0.711-0.848. Multiple logistic regression analysis of a combination of these three miRNAs showed an enhanced ability to discriminate between these two groups with an AUC value of 0.863. Conclusions Our study suggests that altered levels of serum miRNAs have great potential to serve as non-invasive biomarkers for early detection of pulmonary TB infection.

  5. Improved Diagnosis of Pleural Tuberculosis Using the Microscopic-Observation Drug-Susceptibility Technique

    TOVAR, MARCO; Mark J Siedner; Robert H Gilman; Santillan, Carlos; Caviedes, Luz; Valencia, Teresa; Jave, Oswaldo; Rod Escombe, A.; Moore, David A. J.; Evans, Carlton A.

    2008-01-01

    Tests for pleural tuberculosis are insensitive and expensive. We compared nonproprietary microscopic-observation drug-susceptibility (MODS) culture with Löwenstein-Jensen culture for evaluation of pleural specimens. MODS culture was associated with greatly increased diagnostic sensitivity and shorter time to diagnosis, compared with Löwenstein-Jensen culture (sensitivity of culture of biopsy specimens, 81% vs. 51%; time to diagnosis, 11 days vs. 24 days; P < .001). The MODS technique is inexp...

  6. Socio-cultural and knowledge-based barriers to tuberculosis diagnosis for women in Bhopal, India

    Evonne McArthur; Surya Bali; Azim A Khan

    2016-01-01

    Background: In India, only one woman is diagnosed with tuberculosis (TB) for every 2.4 men. Previous studies have indicated gender disparities in care-seeking behavior and TB diagnosis; however, little is known about the specific barriers women face. Objectives: This study aimed to characterize socio-cultural and knowledge-based barriers that affected TB diagnosis for women in Bhopal, India. Materials and Methods: In-depth interviews were conducted with 13 affected women and 6 health-care wor...

  7. Socio-cultural and Knowledge-Based Barriers to Tuberculosis Diagnosis for Women in Bhopal, India

    McArthur, Evonne; Bali, Surya; Azim A Khan

    2016-01-01

    Background: In India, only one woman is diagnosed with tuberculosis (TB) for every 2.4 men. Previous studies have indicated gender disparities in care-seeking behavior and TB diagnosis; however, little is known about the specific barriers women face. Objectives: This study aimed to characterize socio-cultural and knowledge-based barriers that affected TB diagnosis for women in Bhopal, India. Materials and Methods: In-depth interviews were conducted with 13 affected women and 6 health-care wor...

  8. Importance of polymerase chain reaction in diagnosis of pulmonary and extra-pulmonary tuberculosis

    Pakistan ranks eighth on the list of 22 high-burden tuberculosis (TB) countries in the world according to the World Health Organisation's (WHO) Global Tuberculosis Control 2009. Including other reasons the main cause is improper and late diagnosis of the disease. PCR may play an important role to control the disease with its rapid, sensitive and specific diagnosis. But in Pakistan due to lake of knowledge about this latest technique we are not using this technique appropriately. Clinicians still trust on conventional methods of TB diagnosis, which are time consuming or insensitive. The present study was arranged to highlight the importance of PCR in TB diagnosis in pulmonary and extra-pulmonary cases and its comparison with conventional methods. Methods: Samples obtained from 290 patients of suspected TB (pulmonary or extra-pulmonary) were subjected to ZN smear examination, LJ medium culture and PCR test by amplifying 541 bp fragment of Mycobacterium tuberculosis complex genome. The present prospective study is performed at Shalamar Hospital Lahore from November 2008 to November 2010. Results: A distinctly difference was observed in the test results done by PCR and other conventional techniques in pulmonary or extra-pulmonary tuberculosis samples (p<0.001). The sensitivity of different tests was 68.62% for PCR, 26.90% for LJ medium culture, and 14.14% for ZN smear examination (p<0.05). However, there was no significant difference between different tests as for as specificity was concerned. PCR test sensitivity in pulmonary and extra-pulmonary clinical samples was 78.34 and 61.76% respectively, being significantly higher (p<0.05) when compared with sensitivity of other tests. The mean detection time for M. tuberculosis was 25 days by LJ medium culture and less than 1 day by smear examination and PCR test. Conclusion: PCR test is more sensitive than ZN smear examination and LJ medium culture for the diagnosis of TB in pulmonary and extra-pulmonary clinical samples

  9. Tuberculosis

    C. Robert Horsburgh, Jr

    2014-03-01

    Full Text Available This article reviews the published literature on tuberculosis from September 2012 to August 2013 and describes important advances in tuberculosis epidemiology, microbiology, pathology, clinical pharmacology, genetics, treatment and prevention.

  10. QTF-Gold assay for monitoring of anti-tuberculosis therapy in subjects with active TB

    Ilaria Sauzullo

    2008-09-01

    Full Text Available Introduction: The identification and characterization of two M. tuberculosis-specific antigens (ESAT-6 and CFP- 10 has led to the development of a whole blood new generation of M. tuberculosis specific diagnostic tests, that have several advantages over tuberculin skin test (TST, in terms of higher specificity, better correlation with surrogate measures of exposure to M. tuberculosis in low-incidence setting, and less cross-reactivity with M. bovis (BCG vaccine and environmental mycobacteria.The role of these new tests in evaluating post-therapy tuberculosis eradication has not been investigated yet. Aim of this longitudinal study was to determinate changes of response to M. tuberculosis-specific antigens in patients during the standard tuberculosis treatment and to investigate the in vitro effects of tuberculosis drugs on the IFN-γ release. Methods: 23 individuals with active tuberculosis were enrolled and followed over time.They were tested with QuantiFERON TB-Gold (QFT-Gold at four time points: at diagnosis (t0, after 3 and 6 months of treatment (t1- t2 and at the end of the specific treatment (t3. Results: At baseline all patients were positive by QFT-Gold.At second time-point 17 out of 23 (74% were positive, at third time-point 11 of 23 (47% were positive, at treatment completion 3/23 (13% were positive.The conversion to negative response to M. tuberculosis-specific antigens was found in 87% patients analyzed after successful therapy. Longitudinal QFT-Gold testing shown a significant decrease (p<0.001 of IFN-γ response during the therapy. No inhibitory effect on IFN-γ release was noted in vitro for chemotherapy using at concentrations compatible with those achieved in serum of treated patients.We have revealed an inhibitory effect only at concentrations 2-3 times greater than those previously tested. Conclusion: A successful therapy for tuberculosis causes a significant decrease of the ESAT-6 and CFP-10 response and this data suggest

  11. Polymerase chain reaction targeting insertion sequence for the diagnosis of extrapulmonary tuberculosis

    V Makeshkumar

    2014-01-01

    Full Text Available Background & objectives: Diagnosis of extrapulmonary tuberculosis (EPTB is difficult using conventional diagnostic methods. This study was conducted to evaluate the use of polymerase chain reaction (PCR in diagnosis of definitive and probable extrapulmonary tuberculosis patients, and to assess the performance of insertion sequence (IS 6110 based PCR assay as compared to conventional culture by Lowenstein-Jensen (LJ method for the diagnosis of EPTB. Methods: A total of 178 non repeated clinical specimens were collected from clinically suspected extrapulmonary tuberculosis patients. The specimens included 59 ascitic fluid, 54 pleural fluid, 25 cerebrospinal fluid (CSF, 12 fine needle aspiration (FNA, 8 urine, 7 pus, 6 synovial fluid, 2 skin tissue, one pericardial fluid, one liver abscess, one pancreatic cyst fluid, one omental biopsy and one semen sample. All these clinical samples were subjected to Ziehl-Neelsen staining (ZN for acid fast bacilli (AFB and culture on LJ medium. PCR was performed by targeting 123bp fragment of insertion sequence IS6110 of Mycobacterium tuberculosis (MTB. Results: Of the 178 specimens, 10 (5.61% were ZN smear positive for AFB, six (3.37% were L-J culture positive from 10 AFB smear positive cases and 48 (26.96% were PCR IS 6110 positive for M. tuberculosis. Interpretation & conclusions: PCR using IS6110 primer was able to pick up more EPTB patients compared to conventional L-J culture method for detection of M. tuberculosis. False positive PCR IS6110 in three CSF samples may be due to latent TB infection which was limitation in this study.

  12. Direct diagnosis ofMycobacterium tuberculosis in blood samples of HIV infected patients by polymerase chain reaction

    Kamatchiammal, Senthilkumar; Saravanakumar, Dhashinamoorthy; Kumarasamy, Nagalingeswaran; Solomon, Sunithi; Sritharan, Manjula; Sritharan, Venkataraman

    2000-01-01

    We have developed a simple, economical and reproducible method for processing blood samples from HIV infected patients for diagnosis of tuberculosis. The procedure was validated on 55 samples selected for tuberculosis based on clinical criteria. 52 patients had radiological changes indicative of pulmonary tuberculosis of which only 28 were positive for AFB in sputum (sensitivity 54%) and 27 for tuberculin (sensitivity 52%). 26 HIV positive patients who showed positive X-ray did not react to t...

  13. Antibacterial Activity of Medicinal Aqueous Plant Extracts against Mycobacterium tuberculosis

    Muna Mohammed Buzayan

    2012-09-01

    Full Text Available Tuberculosis (TB remains a serious health problem in many regions of the world, and the development of resistance to antibiotics by this microbe created the need for new drugs to replace those which have lost effectiveness. This study assesses the medicinal anti-Mycobacterium tuberculosis properties of natural products obtained from plants collected from Eastern Libya. In this study aqueous extracts of nine different plants were assayed for their Mycobacterium tuberculosis inhibitory activity using the BACTEC MGIT960 susceptibility test method. The aqueous extracts of Ceratonia siliqua L, Helichrysum stoechas (L. Moench and Thymus algeriensis did not show any activity against M. tuberculosis in different concentrations. The aqueous extract of Marrubium vulgare L. from Syria showed high activity against M. tuberculosis. Marrubium alysson L., Marrubium vulgare L., Pistacia lentiscus L, Quercus coccifera L, Thymus capitatus (L. Hoffm. & Link, showed varying degrees of activity against M. tuberculosis. The results of this study show that aqueous extracts from six different medicinal plants have different effects against M. tuberculosis in vitro.

  14. Dried plasma spots in the diagnosis of tuberculosis

    Aabye, Martine G; Latorre, Irene; Diaz, Jessica;

    2013-01-01

    have comparable performance to IGRA. The aim of this study was to explore the diagnostic potential of a novel IP-10 release assay based on dried plasma spots (DPS).IP-10 and IFN-γ was determined in plasma and in DPS by ELISA. Diagnostic algorithms for IP-10 plasma and DPS tests were developed on a......Interferon-γ release assays (IGRA) are probably the most accurate tests for detection of latent M.tuberculosis infection, but IGRAs are labour intensive and transport of samples over longer distances is difficult. IP-10 is expressed at 100-fold higher levels than IFN-γ, and IP-10 release assays...

  15. A Data Mining Approach to the Diagnosis of Tuberculosis by Cascading Clustering and Classification

    T, Asha; Murthy, K N B

    2011-01-01

    In this paper, a methodology for the automated detection and classification of Tuberculosis(TB) is presented. Tuberculosis is a disease caused by mycobacterium which spreads through the air and attacks low immune bodies easily. Our methodology is based on clustering and classification that classifies TB into two categories, Pulmonary Tuberculosis(PTB) and retroviral PTB(RPTB) that is those with Human Immunodeficiency Virus (HIV) infection. Initially K-means clustering is used to group the TB data into two clusters and assigns classes to clusters. Subsequently multiple different classification algorithms are trained on the result set to build the final classifier model based on K-fold cross validation method. This methodology is evaluated using 700 raw TB data obtained from a city hospital. The best obtained accuracy was 98.7% from support vector machine (SVM) compared to other classifiers. The proposed approach helps doctors in their diagnosis decisions and also in their treatment planning procedures for diff...

  16. Specific T-cell epitopes for immunoassay-based diagnosis of Mycobacterium tuberculosis infection

    Brock, I; Weldingh, K; Leyten, EM; Arend, SM; Ravn, Pernille; Andersen, P

    2004-01-01

    Specific T-cell epitopes for immunoassay-based diagnosis of Mycobacterium tuberculosis infection.Brock I, Weldingh K, Leyten EM, Arend SM, Ravn P, Andersen P. Department of Infectious Disease Immunology, Statens Serum Institute, Artillerivej 5, DK-2300 Copenhagen S, Denmark. The currently used...... method for immunological detection of tuberculosis infection, the tuberculin skin test, has low specificity. Antigens specific for Mycobacterium tuberculosis to replace purified protein derivative are therefore urgently needed. We have performed a rigorous assessment of the diagnostic potential of four...... recently identified antigens (Rv2653, Rv2654, Rv3873, and Rv3878) from genomic regions that are lacking from the Mycobacterium bovis bacillus Calmette-Guerin (BCG) vaccine strains as well as from the most common nontuberculous mycobacteria. The fine specificity of potential epitopes in these molecules was...

  17. Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis

    DeBarber, Andrea E.; Mdluli, Khisimuzi; Bosman, Marlein; Bekker, Linda-Gail; Barry, Clifton E.

    2000-01-01

    Ethionamide (ETA) is an important component of second-line therapy for the treatment of multidrug-resistant tuberculosis. Synthesis of radiolabeled ETA and an examination of drug metabolites formed by whole cells of Mycobacterium tuberculosis (MTb) have allowed us to demonstrate that ETA is activated by S-oxidation before interacting with its cellular target. ETA is metabolized by MTb to a 4-pyridylmethanol product remarkably similar in structure to that formed by the activation of isoniazid ...

  18. Diagnosis of pulmonary tuberculosis among asymptomatic HIV+ patients in Guangxi, China

    ZHANG Yao; ZHANG Fu-jie; YU Lan; TANG Zhi-rong; HUANG Shao-biao; ZHENG Yuan-jia; MENG Zhi-hao; SUN Kai; WANG Li-ming; Ray Y.CHEN

    2010-01-01

    Background Pulmonary tuberculosis (PTB) among asymptomatic Chinese patients with HIV infection has not been investigated despite high tuberculosis burden in China. This study was aimed to evaluate the prevalence, risk factors and clinical outcomes of PTB among asymptomatic patients with HIV/AIDS in Guangxi to facilitate the development of diagnostic and treatment strategies.Methods All asymptomatic adult HIV-infected patients with CD4 <350 cells/μl who attended four HIV clinics in Guangxi between August 2006 and March 2008 were evaluated for active PTB with physical examination, chest X-ray (CXR),sputum smear and/or sputum liquid culture. Data were described using median (interquartile range, IQR) and frequencies.Univariate and multivariate Logistic regression analyses were performed to identify risk factors associated with PTB.Results Among 340 asymptomatic subjects, 15 (4%) were diagnosed with PTB, with 4 (27%) sputum smear positive and 8 (53%) sputum culture positive. CXR has higher diagnostic sensitivity (87%) than sputum smear (25%) and sputum culture (67%), but lower specificity (56%) compared with sputum smear (99%) and culture (100%). In univariate analysis,injection drug user, body mass index (BMI) <18 kg/m2, CD4 <50 cells/μl and presence of peripheral lymphadenopathy were associated with an increased risk of asymptomatic PTB, while in multivariate analysis only peripheral lymphadenopathy maintained statistical significance (OR=7.6, 95% CI 1.4-40). Patients with negative smear and minor or no abnormalities on CXR had longer interval between screening and TB treatment.Conclusions PTB was relatively common in this group of HIV+ asymptomatic Chinese patients. Diagnosis is challenging especially where sputum culture is unavailable. These findings suggest that an enhanced evaluation for PTB needs to be integrated with HIV care in China and transmission prevention in China to control at both households and health care facilities, especially for patients

  19. An experience with a rare diagnosis of isolated tuberculosis of sternum at JNMC Hospital, Aligarh, India

    Objective was to diagnose isolated tuberculosis of sternum in patients presenting with signs and symptoms suggestive of tuberculosis. A prospective study conducted at Jawaharlal Nehru Medical College, Aligrah Muslim University, Aligarh, India from July 2000 to July 2006 of 2512 patients presenting with a suspected case of tuberculosis. Cases were confirmed using different investigations along with treatment of the patients with antitubercular treatment (ATT) with further follow up for next 2 years. Nineteen patients were suffering from isolated tuberculosis of sternum. The main presenting feature was retrosternal discomfort (100%) while 14 (73.6%) patients presented with a cold abscess of sternum. All the patients were treated successfully with 12 months of ATT and followed up for 2 years for any relapse. Although tuberculosis of sternum is rare, it should be considered as an important differential diagnosis in patients presenting with chronic lesions of the sternum, particularly in endemic/developing countries. Twelve months of treatment with ATT is optimal for achieving cure without any risk of relapse. (author)

  20. Interference of paratuberculosis with the diagnosis of tuberculosis in a goat flock with a natural mixed infection

    Álvarez, Julio; De Juan, Lucía; Bezos, Javier; Romero, Beatriz; Sáez, Jose Luis; Gordejo, F.J. Reviriego; Briones, Víctor; Moreno, Miguel Ángel; Mateos, Ana; Domínguez, Lucas; Aranaz, Alicia

    2008-01-01

    Interference of paratuberculosis with the diagnosis of tuberculosis in a goat flock with a natural mixed infection SPAIN (Alvarez, Julio) SPAIN Received: 2007-07-06 Revised: 2007-08-14 Accepted: 2007-08-17

  1. Potential of Rapid Diagnosis for Controlling Drug-Susceptible and Drug-Resistant Tuberculosis in Communities Where Mycobacterium tuberculosis Infections Are Highly Prevalent ▿

    Uys, Pieter W.; Warren, Robin; van Helden, Paul D.; Murray, Megan; Victor, Thomas C.

    2009-01-01

    The long-term persistence of Mycobacterium tuberculosis in communities with high tuberculosis prevalence is a serious problem aggravated by the presence of drug-resistant tuberculosis strains. Drug resistance in an individual patient is often discovered only after a long delay, particularly if the diagnosis is based on current culture-based drug sensitivity testing methods. During such delays, the patient may transmit tuberculosis to his or her contacts. Rapid diagnosis of drug resistance would be expected to reduce this transmission and hence to decrease the prevalence of drug-resistant strains. To investigate this quantitatively, a mathematical model was constructed, assuming a homogeneous population structure typical of communities in South Africa where tuberculosis incidence is high. Computer simulations performed with this model showed that current control strategies will not halt the spread of multidrug-resistant tuberculosis in such communities. The simulations showed that the rapid diagnosis of drug resistance can be expected to reduce the incidence of drug-resistant cases provided the additional measure of screening within the community is implemented. PMID:19297604

  2. Potential of rapid diagnosis for controlling drug-susceptible and drug-resistant tuberculosis in communities where Mycobacterium tuberculosis infections are highly prevalent.

    Uys, Pieter W; Warren, Robin; van Helden, Paul D; Murray, Megan; Victor, Thomas C

    2009-05-01

    The long-term persistence of Mycobacterium tuberculosis in communities with high tuberculosis prevalence is a serious problem aggravated by the presence of drug-resistant tuberculosis strains. Drug resistance in an individual patient is often discovered only after a long delay, particularly if the diagnosis is based on current culture-based drug sensitivity testing methods. During such delays, the patient may transmit tuberculosis to his or her contacts. Rapid diagnosis of drug resistance would be expected to reduce this transmission and hence to decrease the prevalence of drug-resistant strains. To investigate this quantitatively, a mathematical model was constructed, assuming a homogeneous population structure typical of communities in South Africa where tuberculosis incidence is high. Computer simulations performed with this model showed that current control strategies will not halt the spread of multidrug-resistant tuberculosis in such communities. The simulations showed that the rapid diagnosis of drug resistance can be expected to reduce the incidence of drug-resistant cases provided the additional measure of screening within the community is implemented. PMID:19297604

  3. Elementwise Business Diagnosis of Enterprise Activity

    Skrynkovskyy Ruslan M.

    2016-02-01

    Full Text Available The article presents methodological and indicator apparatus for elementwise business diagnosis of enterprise activity directed at achieving such elementwise diagnostic objectives: diagnosis of return on assets; diagnosis of return on equity capital; diagnosis of production profitability; diagnosis of gross profit margin of product sales; diagnosis of operating margin of product sales; diagnosis of net margin of product sales; diagnosis of absolute liquidity; diagnosis of instant liquidity; diagnosis of overall liquidity; diagnosis of coverage; diagnosis of financial independence; diagnosis of equity capital maneuverability; diagnosis of financial leverage; diagnosis of the long-term investment structure; diagnosis of accounts payable turnover; diagnosis of the accounts payable repayment period, diagnosis of receivables turnover; diagnosis of receivables repayment period; diagnosis of assets turnover; diagnosis of inventories turnover; diagnosis of the inventories turnover period; diagnosis of equity capital turnover; diagnosis of fixed assets turnover (return on assets; diagnosis of capital coefficient; diagnosis of the ratio of output value to the materials cost; diagnosis of material consumption; diagnosis of the total production cost; diagnosis of enterprise market share; diagnosis of fixed assets wear; diagnosis of fixed assets renewal; diagnosis of fixed assets retirement; performance diagnosis; diagnosis of labor intensity, diagnosis of the capital-labour ratio; diagnosis of efficiency; diagnosis of conducting the business; diagnosis of business relations; diagnosis of administrative-legal relations; diagnosis of knowledge management. The elementwise diagnostic objectives of the enterprise system of diagnostic objectives are aimed at a narrow highly detailed diagnostics of individual indicators of the enterprise activity, i.e. the evaluation of specific analytical indicators,monitoring (research of their dynamics, comparison of the planned

  4. Clinical diagnosis of tuberculosis by specialists and non-specialists.

    Lam, P K; Lobue, P A; Catanzaro, A

    2009-05-01

    In resource-limited settings, tuberculosis (TB) is often diagnosed by non-physicians using the acid-fast bacilli (AFB) smear only. This study examines the diagnostic accuracy of various clinicians using patient-risk history, radiography and AFB smear. A total of 321 physicians, nurses and medical students evaluated 22 profiles of TB suspects and quantified their clinical suspicion (1-99%). Culture results determined diagnostic accuracy. Overall, high-level physician training may not be required; nurses working on TB, given radiograph readings, were as accurate as TB physicians and more accurate than other physicians and clinicians. By considering clinical findings with smear results, TB specialists were significantly more accurate than smear results alone. PMID:19383202

  5. Smears and cultures for diagnosis of pulmonary tuberculosis in an asymptomatic immigrant population

    Assael, Roberto; Cervantes, Joaquin; Barrera, Gerardo

    2013-01-01

    Background The World Health Organization estimated in 2010 that 8.8 million new tuberculosis (TB) cases. About one-third of the world’s population is infected and 10% will develop active TB disease. While cultures remain the international gold standard for diagnosing TB disease, in many other low-income countries, sputum smears remain the only and most accessible tool with which to diagnose active TB disease. As a consequence, in patients with TB who have negative smears, their TB remains undetected. Aim The objective of the study reported here was to demonstrate the proportion of smear-positive/culture-positive cases compared with smear-negative/culture-positive TB cases in Mexican immigrants bound for the USA. Methods A retrospective study was undertaken of the medical records of 122 active TB cases diagnosed at a clinic in Ciudad Juarez, Mexico, from 2009 to 2012. All cases were confirmed by culture, regardless of the sputum smear results. Results Of the cases, 80% (97 active TB cases) had negative sputum smears, while only 25 cases (20%) had at least one positive smear. All of the cultures were confirmed as positive for Mycobacterium tuberculosis complex. Conclusion The fact that 80% of the TB cases were smear negative and 20% smear positive shows that there is a clear gap between the actual state of active TB disease within patients under screening conditions, meaning that eight out of ten actual cases are being missed when sputum smear is the only diagnostic tool in asymptomatic patients with abnormal chest X-rays. Based on these results, it is highly recommended that countries that have not standardized culturing as the gold standard for the diagnosis of active TB do so, so that TB cases – which may endanger global public health – are not missed. It is also recommended that further studies be undertaken to determine the clinical background of the patients diagnosed by smear and culture to identify a direct relationship between clinical signs and

  6. Smears and cultures for diagnosis of pulmonary tuberculosis in an asymptomatic immigrant population

    Assael R

    2013-09-01

    Full Text Available Roberto Assael, Joaquin Cervantes, Gerardo Barrera Clinica Medica Internacional, Ciudad Juarez, Mexico Background: The World Health Organization estimated in 2010 that 8.8 million new tuberculosis (TB cases. About one-third of the world's population is infected and 10% will develop active TB disease. While cultures remain the international gold standard for diagnosing TB disease, in many other low-income countries, sputum smears remain the only and most accessible tool with which to diagnose active TB disease. As a consequence, in patients with TB who have negative smears, their TB remains undetected. Aim: The objective of the study reported here was to demonstrate the proportion of smear-positive/culture-positive cases compared with smear-negative/culture-positive TB cases in Mexican immigrants bound for the USA. Methods: A retrospective study was undertaken of the medical records of 122 active TB cases diagnosed at a clinic in Ciudad Juarez, Mexico, from 2009 to 2012. All cases were confirmed by culture, regardless of the sputum smear results. Results: Of the cases, 80% (97 active TB cases had negative sputum smears, while only 25 cases (20% had at least one positive smear. All of the cultures were confirmed as positive for Mycobacterium tuberculosis complex. Conclusion: The fact that 80% of the TB cases were smear negative and 20% smear positive shows that there is a clear gap between the actual state of active TB disease within patients under screening conditions, meaning that eight out of ten actual cases are being missed when sputum smear is the only diagnostic tool in asymptomatic patients with abnormal chest X-rays. Based on these results, it is highly recommended that countries that have not standardized culturing as the gold standard for the diagnosis of active TB do so, so that TB cases – which may endanger global public health – are not missed. It is also recommended that further studies be undertaken to determine the clinical

  7. The impact of helminth infection in patients with active tuberculosis

    Abate, Ebba

    2013-01-01

    The geographic distribution of helminth infection and tuberculosis (TB) overlap substantially. Experimental animal models and limited data from humans have shown that intestinal helminths could subvert the host immune response towards a T-helper 2 (Th2)-type immune response and an increased regulatory T-cell activity (Tregs). This in turn affects the host's ability to mount an effective Th1 immune-mediated protection against Mycobacterium tuberculosis. However, evidence for this hypothesis in...

  8. INFLUENCE OF HOSPITALIZATION UPON DIAGNOSIS ON THE RISK OF TUBERCULOSIS CLUSTERING

    Giuseppe Lapadula; Fabio Zanini; Luigi Codecasa

    2013-01-01

    Setting: Culture-positive tuberculosis (TB) diagnosed in the metropolitan area of Milan (Italy) over a 5-year period (1995-1999). Objective: To assess the impact of short-course hospitalization upon diagnosis on the overall risk of TB clusterization. Design: Restriction fragment length polymorphism profiles with a similarity of 100% defined a cluster. Uni- and multivariable logistic regression models were performed to assess factors associated with clusterization. Results: Among 1139 patie...

  9. SIGNIFICANCE OF ADENOSINE DEAMINASE SERUM CONCENTRATIONS IN THE DIAGNOSIS OF EXTRA-PULMONARY TUBERCULOSIS

    Stevanovic G.; Pelemis M.; Pavlovic M.; Lavadinovic L,; Dakic Z,; Milosevic I,; Milosevic B.

    2011-01-01

    Extra pulmonary tuberculosis (EPTB) is a growing problem worldwide. Due to the nature of the disease, the diversity of clinical pictures as well as its minor epidemiological importance, the diagnosis is difficult and often late.In addition to standard TB diagnostic techniques use of new biochemical (surrogate markers) are increased. With this work we wanted to examine the usefulness of serum adenosine deaminase levels as a diagnostic parameter for EPTB.The work included 116 patients with feve...

  10. SIGNIFICANCE OF ADENOSINE DEAMINASE SERUM CONCENTRATIONS IN THE DIAGNOSIS OF EXTRA-PULMONARY TUBERCULOSIS

    Stevanovic G,

    2011-06-01

    Full Text Available Extra pulmonary tuberculosis (EPTB is a growing problem worldwide. Due to the nature of the disease, the diversity of clinical pictures as well as its minor epidemiological importance, the diagnosis is difficult and often late.In addition to standard TB diagnostic techniques use of new biochemical (surrogate markers are increased. With this work we wanted to examine the usefulness of serum adenosine deaminase levels as a diagnostic parameter for EPTB.The work included 116 patients with fever of unknown origin in which tuberculosis or infectious mononucleosis was not proven and 51 person who had proven EPTB. Correlated adenosine deaminase levels between these two groups we obtained significantly higher values ​​in patients with EPTB. The calculated sensitivity was 0.56, specificity 0.89, positive predictive value 0.80 and negative predictive value 0.72. Certain reducing of the values observed during anti TB therapy. In previous studies the diagnostic importance of adenosine deaminase in the diagnosis of tuberculosis serosityes was demonstrated. The significance of serum levels in diagnosis is rarely evaluated during EPTB. Our findings are similar to the results of authors who have conducted such testing in the pediatric population.Increased concentrations of serum adenosine deaminase have shown the potential of usable screening test and can be used as an indicative EPTB parameter. To fully assess its diagnostic significance require future clinical research.

  11. Use of anabolic-androgenic steroids masking the diagnosis of pleural tuberculosis: a case report

    de Larrea Carlos

    2009-01-01

    Full Text Available Abstract Introduction Tuberculous pleural effusions are not always easy to diagnose but the presence of a lymphocyte-rich exudate associated with an increased adenosine deaminase level and a positive skin test result are highly sensitive diagnostic signs. Case presentation We report a case of pleural tuberculosis in a 31-year-old white male patient from Caracas, Venezuela who was negative for human immunodeficiency virus and presented 2 weeks after injecting the anabolic-androgenic steroid nandrolone decanoate, in whom all the tests for tuberculosis were initially negative; an eosinophilic pleural effusion with a low adenosine deaminase level, a negative tuberculin skin test and negative for acid-fast bacilli staining and culture of the pleural fluid. After excluding other causes of eosinophilic pleural effusion malignant pleural effusion was suspected. The patient did not return until 4 months later. The second thoracentesis obtained a pleural fluid suggestive for tuberculosis, with a predominance of lymphocytes, an elevated adenosine deaminase level (51 U/l and a positive tuberculin skin test. Culture of pleural fragments confirmed pleural tuberculosis. Conclusion This case suggests that the use of an anabolic-androgenic steroid masks the definitive diagnosis of pleural tuberculosis by changing the key diagnostic parameters of the pleural fluid, a finding not previously reported. Available evidence of the effects of anabolic steroids on the immune system also suggests that patients using anabolic-androgenic steroids might be susceptible to developing tuberculosis in either reactivating a latent infection or facilitating development of the disease after a recent infection.

  12. La Tuberculosis infantil y su diagnóstico en la Argentina Childhood tuberculosis and its diagnosis in Argentina

    I.N.P. Miceli

    2002-12-01

    Full Text Available La incidencia de tuberculosis (TBC en menores de 5 años en Argentina fue 24.3/ 100.000 habitantes en el año 2000, y la tasa global 31.8/ 100.000. Un 17% de los casos fueron menores de 15 años, lo que indica una activa transmisión de la infección, que se diagnostica generalmente ya con enfermedad avanzada, por la historia de foco, la reacción tuberculínica positiva, y los signos y síntomas clínico- radiológicos. El aporte de la bacteriología al diagnóstico es escaso, empleándose en 0-4 años el aspirado o lavado gástrico. Para el cultivo se usan los medios sólidos a base de huevo o, en laboratorios de referencia, los de detección temprana. Las pruebas de amplificación de ácidos nucleicos están disponibles en algunos laboratorios, pero sin un sistema de garantía de calidad; sus resultados deben considerarse sólo dentro del contexto clínico. El fortalecimiento de la red de laboratorios de cultivo facilitará el diagnóstico de certeza de la TBC infantil, la confiabilidad de la notificación, y el conocimiento de la resistencia bacteriana. Para revertir la actual situación epidemiológica es necesario incrementar la investigación de los niños contactos de casos bacilíferos, seguida de quimioprofilaxis o tratamiento según corresponda. La meningitis TBC en menores de 5 años tuvo una disminución significativamente mayor que la de la TBC en adultos, en los últimos 20 años en Argentina. En 2000 se notificaron sólo 10 casos de meningitis en esas edades (0.29/ 100.000. Esto confirma la protección conferida por la vacunación BCG al nacimiento, con alta y continuada cobertura.TB notification rate in infants and children 0-4 years was 24.3/ 100.000 in Argentina, in 2000, for a global incidence of 31.8/ 100.000. A 17% of all TB cases occurred in children (0-14 years, indicating a very active TB transmission. Usually TB is diagnosed when the disease is already advanced. Main criteria for the diagnosis are: a previous contact

  13. Evaluation of interferon-γ release assay in the diagnosis of osteoarticular tuberculosis.

    Jia, Hongyan; Pan, Liping; Qin, Shibing; Liu, Fei; Du, Fengjiao; Lan, Tinglong; Zhang, Xia; Wei, Rongrong; Du, Boping; Liu, Zhongquan; Huang, Hairong; Zhang, Zongde

    2013-07-01

    The aim of this study was to assess the value of interferon-γ (IFN-γ) release assay (IGRA) (T-SPOT.TB) for patients with suspected osteoarticular tuberculosis (TB) in comparison with conventional and molecular methods. Of 145 patients with suspected osteoarticular TB, recruited from Beijing Chest Hospital between July 2011 and June 2012, 86 (59.3%)had osteoarticular TB (26 with culture-confirmed TB, 60 with probable TB), 24 (16.6%) were not having active TB. The remaining 17 (11.7%) inconclusive TB and 18 (12.4%) possible TB were excluded from final analysis. In addition to conventional tests and molecular method, T-SPOT.TB assay using peripheral blood mononuclear cells to examine IFN-γ response to early secretory antigenic target 6 and culture filtrate protein 10 was also performed. The sensitivity and specificity for T-SPOT.TB assay were 94.2% and 70.8%, respectively. A statistically significant difference in sensitivity was found between T-SPOT.TB assay (94.2%) and other tests (acid-fast bacilli smear (19.7%), culture (34.2%), real-time PCR (36.8%); P < 0.01, respectively). These results suggested that the IGRA assay could provide useful aids in the diagnosis of osteoarticular TB. PMID:23647965

  14. The evaluation of CT and MRI in the diagnosis of pancreatic tuberculosis and peripancreatic tuberculous lymphadenopathy

    Objective: To study the manifestations and its pathologic basis of pancreatic tubeiculosis and peripancreatic tuberculous lymphadenopathy. And evaluate the diagnostic values of CT and MRI. Methods: Two cases of pancreatic tuberculosis and eleven cases of peripancreatic tuberculous lymphadenopathy were collected. All cases were conformed by pathology or clinic. Plain scan and enhanced scan with spiral CT were performed in all cases. Plain scan and enhanced scan with MRI were performed in two cases. The CT and MRI features of 13 cases were analyzed retrospectively. Results: Pancreatic tuberculosis showed that the lesion was located mainly at the head of the pancreas and displayed on CT as a low-density mass with marginal or honeycomb enhancement. Peripancreatic tuberculous lymphadenopathy was seen in 11 cases, of which ring-like enhancement was seen in seven cases, calcifications in two cases and mixed in two cases. Splenic involvement was found in five cases. Conclusion: Pancreatic tuberculosis and peripancreatic tuberculous lymphadenopathy have the main features of low-density mass With marginal or honeycomb enhancement and ting-like enhancement in petipancreatic lymphadenopathy. CT and MRI are feasible methods in diagnosis of pancreatic tuberculosis and peripancreatic tuberculous lymphadenopathy. (authors)

  15. Analysis of immune responses against a wide range of Mycobacterium tuberculosis antigens in patients with active pulmonary tuberculosis

    Kassa, D.; Ran, L.; Geberemeskel, W.; Tebeje, M; Alemu, A.; Selase, A.; Tegbaru, B.; Franken, K. L. M. C.; Friggen, A. H.; van Meijgaarden, K. E.; Ottenhoff, T. H. M.; Wolday, D.; Messele, T.; van Baarle, D.

    2012-01-01

    Characterizing host immune responses to molecular targets of Mycobacterium tuberculosis is essential to develop effective immunodiagnostics and better vaccines. We investigated the immune response against a large series of M. tuberculosis antigens, including 5 classical and 64 nonclassical (39 DosR regulon-encoded, 4 resuscitation-promoting factor [RPF], and 21 reactivation-associated) antigens in active-pulmonary-tuberculosis (TB) patients. Whole blood from TB patients (n = 34) was stimulate...

  16. Mobile digital fluorescence microscopy for diagnosis of tuberculosis.

    Tapley, Asa; Switz, Neil; Reber, Clay; Davis, J Lucian; Miller, Cecily; Matovu, John Baptist; Worodria, William; Huang, Laurence; Fletcher, Daniel A; Cattamanchi, Adithya

    2013-06-01

    Access to sputum smear microscopy in high-tuberculosis (TB)-burden regions is limited by a scarcity of microscopes and experienced technicians. We evaluated the accuracy of CellScope, a novel digital fluorescence microscope that may expand access to microscopy. The study utilized smear microscopy slides prepared from sputum specimens submitted by consecutive adults with ≥ 2 weeks of cough who were admitted to Mulago Hospital (Kampala, Uganda). Conventional light-emitting diode (LED) fluorescence microscopy (FM) and mycobacterial culture were performed by experienced technicians. Two U.S.-based postgraduate researchers without prior microscopy experience restained, imaged, and interpreted the slides using CellScope. We assessed whether sensitivity and specificity of CellScope-based LED FM was noninferior to conventional LED FM by using a preselected margin of inferiority of 15%. Of 525 patients included, 72% were HIV seropositive and 39% had culture-confirmed TB. The proportions of positive results were similar with CellScope and conventional LED FM (34% versus 32%, respectively; P = 0.32), and agreement was substantial. CellScope accuracy was within the noninferiority margin for both sensitivity (63% versus 70%; difference, -7%; 95% confidence interval [CI], -13% to -1%) and specificity (85% versus 92%; difference, -7%; 95% CI, -12% to -3%). A subanalysis of 43 slides evaluated by each CellScope reader found substantial interreader reliability (custom-weighted kappa, 0.65) and variable intrareader reliability (custom-weighted kappa, 0.11 versus 0.48). CellScope offers promise for expanding microscopy services. Future studies should evaluate the device when operated by health workers in low-resource settings, the feasibility of image transmission and analysis by experienced microscopists, and the accuracy of automated image analysis algorithms. PMID:23554191

  17. Tuberculosis.

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

    2016-03-19

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

  18. Determining the Diagnostic Value of Mycobacterium Tuberculosis DNA in the Differentiation of Blood Samples of Patients with Active Pulmonary Tuberculosis and Healthy Controls Using Polymerase Chain Reaction

    Abasali Niazi; Nezarali Muolai; Mosayeb Shahriar; Reza Karimian; Farzaneh Peykfalak

    2013-01-01

    Background: Tuberculosis (TB) is now a major cause of mortality and morbidity in the world. Nowadays, different methods are used to diagnose tuberculosis. Although classical microbiological methods (such as sputum smear) are specific, they have little sensitivity and the culture is also time-consuming. Using Polymerase Chain Reaction (PCR) in blood samples in terms of Mycobacterium tuberculosis DNA, this study examines diagnostic power of this test in the diagnosis of pulmonary tuberculosis c...

  19. Pseudotumoral form of primary progressive tuberculosis: a diagnosis to be considered

    Franco Rosana

    2003-01-01

    Full Text Available The diversity of clinical presentations of primary progressive tuberculosis (TB and the difficulty in establishing the diagnosis of paucibacillary forms is the subject of painstaking research, as well as a cause of delay in therapy. We report the case of a 10-year-old black child who presented with chest pain and progressive widening of the upper mediastinum. Computerized tomography of the chest revealed multiple calcifications that were not identified with X-rays. Biopsy through mediastinoscopy was compatible with a diagnosis of tuberculosis. Despite exhaustive investigation that included direct examination, culture for mycobacteria and PCR (Polymerase Chain Reaction of tissue samples, the etiologic agent was not revealed. Tuberculin conversion was observed during the follow-up and resolution period of the lesion, after administration of isoniazid, rifampicin and pyrazinamide. The nodal pseudotumoral form of tuberculosis is rare in immunocompetent children and it may simulate neoplastic disease; therefore, it should be included in the list of differential diagnoses of masses located in the anterosuperior mediastinum.

  20. Tc-99m Isoniazid: A specific agent for diagnosis of tuberculosis

    Currently there is not a single radionuclide method to detect and locate tubercular lesions with high sensitivity and specificity. Conventional modalities (Microbiological, Radiological, Immunological and Molecular Biological) have their proven utility but they suffer from one or other drawbacks. The present work is based on radionuclide imaging technique using Tc-99m INH (Isoniazid) complex to detect and locate tuberculosis (TB) at an early stage at any anatomical site. Isoniazid (INH) was chosen as ligand because it is a specific anti-tubercular drug and has shown selective uptake in live Mycobacteria sensitive to INH. After complexation of INH with Tc-99m using an indirect labeling approach (Patent pending), labeling efficiency, in-vitro and in-vivo stability, blood kinetics and organ distribution studies were carried out in balb/c mice and New Zealand White rabbits at different time intervals up to 24 hrs. Biological activity of INH was studied after labeling by Colony Forming Unit (CFU) assay of Mycobacterium tuberculosis, on solid media (Middlebrook 7H10 Agar, DIFCO). Thigh model of localized tubercular lesion was prepared in four rabbits by injecting 500μl of 3 x 108 cells/ml of Mycobacterium tuberculosis (Clinical Human Isolate) live bacteria in growing phase. The localization kinetics of the radiolabeled complex wa studied in the developed animal model by injecting 70-75MBq of Tc-99m INH intravenously in the ear of rabbit and the images were taken with a Gamma-camera (ECIL) at different time intervals after injection. Labeling efficiency of Tc-99m INH was found to be >95%. Only 2-3.5% of the tracer leached out from the complex at 24 hrs when incubated in serum at 37 deg. C, confirming its high stability. Blood kinetic studies exhibited biphasic pattern and 50% of Tc-99m INH cleared from the blood within 5 minutes of intravenous administration Tc-99m INH. The radiolabeled complex was found to be 90% bound to blood protein resulting in long duration imaging

  1. A Controlled Study of Tuberculosis Diagnosis in HIV-Infected and Uninfected Children in Peru.

    Richard A Oberhelman

    Full Text Available Diagnosing tuberculosis in children is challenging because specimens are difficult to obtain and contain low tuberculosis concentrations, especially with HIV-coinfection. Few studies included well-controls so test specificities are poorly defined. We studied tuberculosis diagnosis in 525 children with and without HIV-infection.'Cases' were children with suspected pulmonary tuberculosis (n = 209 HIV-negative; n = 81 HIV-positive and asymptomatic 'well-control' children (n = 200 HIV-negative; n = 35 HIV-positive. Specimens (n = 2422 were gastric aspirates, nasopharyngeal aspirates and stools analyzed by a total of 9688 tests. All specimens were tested with an in-house hemi-nested IS6110 PCR that took 0.2 for HIV-positive versus HIV-negative cases. All specimens were also tested with auramine acid-fast microscopy, microscopic-observation drug-susceptibility (MODS liquid culture, and Lowenstein-Jensen solid culture that took ≤6 weeks and had 100% specificity (all 2112 tests on 704 specimens from 235 well-controls were negative. Microscopy-positivity was rare (0.21%, 5/2422 specimens and all microscopy-positive specimens were culture-positive. Culture-positivity was less frequent (P≤0.01 in HIV-infection: 1.2% (1/81 HIV-positive cases versus 11% (22/209 HIV-negative cases; caused by 0.42% (2/481 versus 4.7% (58/1235 of their specimens, respectively.In HIV-positive children with suspected tuberculosis, diagnostic yield was so low that 1458 microscopy and culture tests were done per case confirmed and even in children with culture-proven tuberculosis most tests and specimens were false-negative; whereas PCR was so prone to false-positives that PCR-positivity was as likely in specimens from well-controls as suspected-tuberculosis cases. This demonstrates the importance of control participants in diagnostic test evaluation and that even extensive laboratory testing only rarely contributed to the care of children with suspected TB.This study did not

  2. Fluoroquinolone susceptibility in Mycobacterium tuberculosis after pre-diagnosis exposure to older- versus newer-generation fluoroquinolones☆

    van der Heijden, Yuri F.; Maruri, Fernanda; Blackman, Amondrea; Mitchel, Ed; Bian, Aihua; Shintani, Ayumi K; Eden, Svetlana; Warkentin, Jon V.; Sterling, Timothy R.

    2013-01-01

    Fluoroquinolone exposure before tuberculosis (TB) diagnosis is common. We anticipated that exposure to older-generation fluoroquinolones is associated with greater fluoroquinolone MICs in Mycobacterium tuberculosis than exposure to newer agents. A nested case–control study was performed among newly diagnosed TB patients reported to the Tennessee Department of Health (January 2002–December 2009). Each fluoroquinolone-resistant case (n = 25) was matched to two fluoroquinolone-susceptible contro...

  3. Generation and application of ssDNA aptamers against glycolipid antigen ManLAM of Mycobacterium tuberculosis for TB diagnosis.

    Tang, Xiao-Lei; Wu, Shi-Min; Xie, Yan; Song, Neng; Guan, Qing; Yuan, Chunhui; Zhou, Xiang; Zhang, Xiao-Lian

    2016-05-01

    The development of effective Mycobacterial antigen diagnostic reagents remains a high priority. Mannose-capped lipoarabinomannan (ManLAM) is a lipoglycan serving as a major cell wall component. ManLAM is also an early released antigen in the blood circulation system during Mycobacteria tuberculosis (M.tb) infection and is a perfect target antigen for TB diagnosis. In this study, ssDNA aptamers "antibodies" against ManLAM of the predominant clinical epidemic M.tb Beijing genotype strains were generated by the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) technique. The selected single aptamer T9 demonstrated the highest specificity and binding affinity, with an equilibrium dissociation constant (Kd) of 668 ± 159 nmol/L. We further detected ManLAM antigens in serum and sputum samples from active pulmonary tuberculosis (aPTB) patients, extrapulmonary TB (EPTB) patients and healthy donors by using a T9 based enzyme-linked oligonucleotide assay (ELONA). The results showed that the specificity and sensitivity were 95.31% and 83.00% (for 100 aPTB serum samples), 98.70% and 92.71% (for 96 aPTB sputum samples), and 94.44% and 88.71% (for 62 EPTB serum samples), respectively. A good correlation was observed between the T9 aptamer-based ELONA and the clinical T-SPOT.TB. Thus, T9 based ELONA has potentials for diagnosis of TB, including inactive TB, smear-negative TB, EPTB, and TB with immunodeficiency, and assist the diagnosis of LTBI albeit it could not distinguish LTBI and active TB. PMID:26850356

  4. Diagnóstico molecular da tuberculose pulmonar Molecular diagnosis of pulmonary tuberculosis

    Nelma Cristina Sousa de Assis

    2007-02-01

    Full Text Available A reação em cadeia da polimerase (PCR e suas variações, como a nested-PCR, têm sido destacadas como técnicas moleculares promissoras para o diagnóstico rápido da tuberculose (TB. No presente estudo avaliou-se a nested-PCR utilizando-se como marcadores moleculares a seqüência IS6110 e o antígeno b aplicados ao diagnóstico da TB. Foram submetidas a baciloscopia, cultura e nested-PCR 136 amostras clínicas de pacientes com suspeita de TB. O diagnóstico de tuberculose pulmonar foi atribuído a 116 pacientes e, desses, 97 foram multibacilares e 111 apresentaram cultura positiva para M. tuberculosis. As reações de nested-PCR identificaram 70% (antígeno b e 94% (IS6110 dos casos paucibacilares. Os valores de sensibilidade determinados para cultura, nested-PCR do IS6110 e antígeno b foram 95%, 98% e 86%, respectivamente. A especificidade foi de 100%, 15% e 45% para cultura, nested-PCR do IS6110 e antígeno b, respectivamente. O diagnóstico molecular da tuberculose deve estar fundamentado na análise conjunta de vários parâmetros, como baciloscopia, cultura, manifestações clínicas, prova terapêutica e história prévia de tuberculose.Chain reaction of polimerase (PCR and its variations such as the nested-PCR have been outstanding as promising molecular techniques for the fast diagnosis of the tuberculosis (TB. In the present study the nested-PCR was evaluated using as molecular markers the sequence IS6110 and the antigen b applied to the diagnosis of TB. One hundred and thirty six clinical samples of patients with suspicion of TB were submitted to the baciloscopia, culture and nested-PCR. The diagnosis of pulmonary tuberculosis was attributed to 116 patients, of these, 97 were multi-bacilli and 111 presented positive culture for M. tuberculosis. The nested-PCR reactions identified 70% (antigen b and 94% (IS6110 of the acid-fast smear negative cases of tuberculosis. The sensibility values determined for culture, and nested-PCR of

  5. Microscopic observation drug susceptibility assay (MODS for early diagnosis of tuberculosis in children.

    Dang Thi Minh Ha

    Full Text Available MODS is a novel liquid culture based technique that has been shown to be effective and rapid for early diagnosis of tuberculosis (TB. We evaluated the MODS assay for diagnosis of TB in children in Viet Nam. 217 consecutive samples including sputum (n = 132, gastric fluid (n = 50, CSF (n = 32 and pleural fluid (n = 3 collected from 96 children with suspected TB, were tested by smear, MODS and MGIT. When test results were aggregated by patient, the sensitivity and specificity of smear, MGIT and MODS against "clinical diagnosis" (confirmed and probable groups as the gold standard were 28.2% and 100%, 42.3% and 100%, 39.7% and 94.4%, respectively. The sensitivity of MGIT and MODS was not significantly different in this analysis (P = 0.5, but MGIT was more sensitive than MODS when analysed on the sample level using a marginal model (P = 0.03. The median time to detection of MODS and MGIT were 8 days and 13 days, respectively, and the time to detection was significantly shorter for MODS in samples where both tests were positive (P<0.001. An analysis of time-dependent sensitivity showed that the detection rates were significantly higher for MODS than for MGIT by day 7 or day 14 (P<0.001 and P = 0.04, respectively. MODS is a rapid and sensitive alternative method for the isolation of M.tuberculosis from children.

  6. Nutritional supplements for people being treated for active tuberculosis

    Grobler, Liesl; Nagpal, Sukrti; Sudarsanam, Thambu D; Sinclair, David

    2016-01-01

    Background Tuberculosis and malnutrition are linked in a complex relationship. Tuberculosis may cause undernutrition through increased metabolic demands and decreased intake, and nutritional deficiencies may worsen the disease, or delay recovery by depressing important immune functions. At present, there is no evidence-based nutritional guidance for adults and children being treated for tuberculosis. Objectives To assess the effects of oral nutritional supplements in people being treated with antituberculous drug therapy for active tuberculosis. Search methods We searched the Cochrane Infectious Disease Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL; Issue 1, 2016), MEDLINE (from 1946 to 4 February 2016), EMBASE (from 1980 to 4 February 2016), LILACS (from 1982 to 4 February 2016), the metaRegister of Controlled Trials (mRCT), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and the Indian Journal of Tuberculosis up to 4 February 2016, and checked the reference lists of all included studies. Selection criteria Randomized controlled trials that compared any oral nutritional supplement given for at least four weeks with no nutritional intervention, placebo, or dietary advice only for people being treated for active tuberculosis. The primary outcomes of interest were all-cause death, and cure at six and 12 months. Data collection and analysis Two review authors independently selected trials for inclusion, and extracted data and assessed the risk of bias in the included trials. We presented the results as risk ratios (RR) for dichotomous variables, and mean differences (MD) for continuous variables, with 95% confidence intervals (CIs). Where appropriate, we pooled data from trials with similar interventions and outcomes. We assessed the quality of the evidence using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Main results Thirty-five trials

  7. An acidic sphingomyelinase Type C activity from Mycobacterium tuberculosis.

    Castro-Garza, Jorge; González-Salazar, Francisco; Quinn, Frederick D; Karls, Russell K; De La Garza-Salinas, Laura Hermila; Guzmán-de la Garza, Francisco J; Vargas-Villarreal, Javier

    2016-01-01

    Sphingomyelinases (SMases) catalyze the hydrolysis of sphingomyelin to ceramide and phosphorylcholine. Sphingolipids are recognized as diverse and dynamic regulators of a multitude of cellular processes mediating cell cycle control, differentiation, stress response, cell migration, adhesion, and apoptosis. Bacterial SMases are virulence factors for several species of pathogens. Whole cell extracts of Mycobacterium tuberculosis strains H37Rv and CDC1551 were assayed using [N-methyl-(14)C]-sphingomyelin as substrate. Acidic Zn(2+)-dependent SMase activity was identified in both strains. Peak SMase activity was observed at pH 5.5. Interestingly, overall SMase activity levels from CDC1551 extracts are approximately 1/3 of those of H37Rv. The presence of exogenous SMase produced by M. tuberculosis during infection may interfere with the normal host inflammatory response thus allowing the establishment of infection and disease development. This Type C activity is different from previously identified M. tuberculosis SMases. Defining the biochemical characteristics of M. tuberculosis SMases helps to elucidate the roles that these enzymes play during infection and disease. PMID:26948102

  8. Diabetes Mellitus Increases the Risk of Active Tuberculosis: A Systematic Review of 13 Observational Studies

    Jeon, Christie Y.; Murray, Megan B.

    2008-01-01

    Editors' Summary Background. Every year, 8.8 million people develop active tuberculosis and 1.6 million people die from this highly contagious infection that usually affects the lungs. Tuberculosis is caused by Mycobacterium tuberculosis, bacteria that are spread through the air when people with active tuberculosis cough or sneeze. Most infected people never become ill—a third of the world's population is actually infected with M. tuberculosis—because the human immune system usually contains ...

  9. 脊柱结核诊疗进展%Advances in Diagnosis and Treatment of Spinal Tuberculosis

    肖伟

    2012-01-01

    With the improvement of diagnostic techniques and surgical technology, the diagnosis and treatment of the spinal tuberculosism which is regarded as an ancient and greater dangerous disease, have improved significantly. For example MR1 diagnosis of spinal tuberculosis has high sensitivity and specificity, while PCR is a fast and effective method. However in the course of treatment there are still problems including, the therapy of neurological deficit, correction of kyphosis in active disease, and instrumented stabilization in surgical therapy. Here is to make a review on the research progress of spinal tuberculosis diagnosis and treatment.%脊柱结核是一种古老而危害性较大的疾病,随着诊断技术的提高及外科技术的应用,其诊疗水平显著提高,如磁共振成像对脊柱结核病变诊断的灵敏性及特异性较高,聚合酶链反应能快速有效地诊断脊柱结核.但在治疗过程中存在很多问题,如对有神经功能缺陷的脊柱结核的治疗,有活动性病变的后凸畸形的矫正及内固定技术在手术治疗过程中的应用.现就脊柱结核诊疗的研究进展予以综述.

  10. Macrophage activation and resistance to pulmonary tuberculosis.

    Lefford, M J

    1980-01-01

    Mice were vaccinated with 300 micrograms of BCG cell walls (BCG-CW) in oil-in-water emulsion intravenously or with a high or low dose of living BCG by inhalation (BCG-HD or BCG-LD, respectively). The consequences of vaccination were evaluated in terms of the growth of BCG in the lungs and spleen, lung and spleen weight, resistance to intravenous and airborne challenge with Listeria monocytogenes, airborne challenge with virulent Mycobacterium tuberculosis H37Rv, and transfer of adoptive immun...

  11. Epidemiology of tuberculosis in a high HIV prevalence population provided with enhanced diagnosis of symptomatic disease.

    Elizabeth L Corbett

    2007-01-01

    Full Text Available BACKGROUND: Directly observed treatment short course (DOTS, the global control strategy aimed at controlling tuberculosis (TB transmission through prompt diagnosis of symptomatic smear-positive disease, has failed to prevent rising tuberculosis incidence rates in Africa brought about by the HIV epidemic. However, rising incidence does not necessarily imply failure to control tuberculosis transmission, which is primarily driven by prevalent infectious disease. We investigated the epidemiology of prevalent and incident TB in a high HIV prevalence population provided with enhanced primary health care. METHODS AND FINDINGS: Twenty-two businesses in Harare, Zimbabwe, were provided with free smear- and culture-based investigation of TB symptoms through occupational clinics. Anonymised HIV tests were requested from all employees. After 2 y of follow-up for incident TB, a culture-based survey for undiagnosed prevalent TB was conducted. A total of 6,440 of 7,478 eligible employees participated. HIV prevalence was 19%. For HIV-positive and -negative participants, the incidence of culture-positive tuberculosis was 25.3 and 1.3 per 1,000 person-years, respectively (adjusted incidence rate ratio = 18.8; 95% confidence interval [CI] = 10.3 to 34.5: population attributable fraction = 78%, and point prevalence after 2 y was 5.7 and 2.6 per 1,000 population (adjusted odds ratio = 1.7; 95% CI = 0.5 to 6.8: population attributable fraction = 14%. Most patients with prevalent culture-positive TB had subclinical disease when first detected. CONCLUSIONS: Strategies based on prompt investigation of TB symptoms, such as DOTS, may be an effective way of controlling prevalent TB in high HIV prevalence populations. This may translate into effective control of TB transmission despite high TB incidence rates and a period of subclinical infectiousness in some patients.

  12. Synthesis and biological evaluation of 99mTc-ECF. A new ethionamide derivative for tuberculosis diagnosis

    In this work we propose a technetium-99m-labeled derivative from Ethionamide (ETH), further referred to as 99mTc-ECF for tuberculosis diagnosis. The biological features of this radioactive agent have been studied. The 2-ethylpyridine-4-carbothioamide-ferrocene (ECF) was chemically synthesized and then labeled with technetium-99m. It has been confirmed through this work that 99mTc-ECF is obtained with high radiolabelling yield (>90 %). Radiochemical analysis of 99mTc-ECF revealed that the molecule was efficiently labeled with a little free remaining pertechnetate. Only 1-2 % of the tracer was leached out from the complex at 24 h when incubated in serum at 37 deg C which confirmed its high stability. The sensitivity test of ECF showed that the group of grafted ferrocenyl does not seem to have largely altered the active site of the molecule. In-vitro investigations were conducted using BCG (Bacille Calmette-Guerin) as analogue of Mycobacterium Tuberculosis and Listeria Monocytogenes as negative control. It was proved that for BCG, ECF has kept the bacteriostatic properties of the parent compound (ETH). In physiological conditions, the measured up-take of the tracer with live bacteria was about 24.1 and 7.1 % for BCG and Listeria Monocytogenese, respectively. The comparison of the 99mTc-ECF accumulation at sites of BCG infected animals, which is expressed as target-to-non-target ratio (found to be equal to 2.15) with other radiotracers was discussed. This allowed us to consider that 99mTc-ECF could be a reasonable radiotracer for mycobacterial infections. Obtained results were good and encourage to undergo a similar labeling for the Mycobacterium tuberculosis as perspective of this work. (author)

  13. FINE NEEDLE ASPIRATION CYTOLOGY IN DIAGNOSIS OF LYMPHADENOPATHY ASSOCIATED WITH TUBERCULOSIS

    Sunil Vitthalrao

    2015-11-01

    Full Text Available BACKGROUND: Tuberculosis remains most common infectious disease in the developing world. Cytomorphological studies with detection of acid fast bacilli prove to be valuable diagnostic method in case of tuberculosis lymphadenopathy. AIMS: To study the various cytomorp hological patterns of tuberculous lymphadenopathy and role of Ziehl - Neelsen stain (ZN to detect acid fast bacilli (AFB. MATERIAL AND METHOD: This study was descriptive, cross - sectional and analytical, conducted at Krishna hospital and medical research c entre, tertiary care and rural hospital from a period of January 2014 to December 2014. Patients with lymphadenopathy having clinical suspicion of tuberculosis were referred to Pathology department for cytopathological evaluation. Clinical presentation, ro utine investigations and fine needle aspiration cytology (FNAC smear study with Hematoxylin and eosin, Giemsa and Ziehl - Neelsen stain was done. RESULT: In this study total 135 patients of lymphadenopathy were studied for aspiration cytology. Incidence of tuberculous lymphadenitis was noted in 52 cases (38.51 %. The cervical group of lymph node enlargement was most common site. Most patients presented in 21 to 30 years of age group with M:F ratio 1.2:1. The most common cytological feature was epithelioid granuloma without necrosis was in 25 cases (48.07%. Others were epithelioid granuloma with caseous necrosis in 16 cases (30.76%, necrosis without granuloma in 6 cases (11.52% and polymorphs with necrosis with/ without epithelioid granuloma seen in 5 cas es (9.61%.AFB positivity was noted in 17 cases ( 32.69 %. CONCLUSION: FNAC is a very important investigation in diagnosis of tuberculous lymphadenitis, if it is supported with ZN stain for AFB will help to confirmatory diagnosis of the disease and for bet ter management of the patients.

  14. Delays in the diagnosis and treatment of tuberculosis patients in Vietnam: a cross-sectional study

    Khanh Vu T

    2007-06-01

    Full Text Available Abstract Background Treatment delay is an important indicator of access to tuberculosis diagnosis and treatment. Analyses of patient delay (i.e. time interval between onset of symptoms and first consultation of a health care provider and health care delay (i.e. time interval between first consultation and start of treatment can inform policies to improve access. This study assesses the patient, health care provider and total delay in diagnosis and treatment of new smear-positive pulmonary tuberculosis patients, and the risk factors for long delay, in Vietnam. Methods A cross-sectional survey of new patients treated by the National Tuberculosis Control Programme was conducted in 70 randomly selected districts in Vietnam. All consecutively registered patients in one quarter of 2002 were interviewed using a pre-coded structured questionnaire. Results Median (range delay was 4 weeks (1–48 for total, 3 (1–48 weeks for patient and 1 (0–25 week for health care delay. Patients with long total delay (≥ 12 weeks, 15% accounted for 49% of the cumulative number of delay-weeks. Independent risk factors (p 5 km distance from a health facility or in the northern area. For long health care delay (≥ 6 weeks this was urban setting, residence in the central area and initial visit to a communal health post, TB hospital or the private sector. Conclusion Analyses of patient and treatment delays can indicate target groups and areas for health education and strengthening of the referral system, in particular between the private sector and the NTP.

  15. Improved sensitivity, safety and laboratory turnaround time in the diagnosis of pulmonary tuberculosis by use of bleach sedimentation

    Ameh James

    2015-05-01

    Full Text Available Background: Inadequate diagnostic processes and human resources in laboratories contribute to a high burden of tuberculosis (TB in low- and middle-income countries. Direct smear microscopy is relied on for TB diagnosis; however, sensitivity rates vary. To improve sensitivity of direct microscopy, the researchers employed several approaches, including sputum digestion and concentration of acid-fast bacilli (AFB, a technique which uses commercial bleach.Objectives: This study compared methods used to diagnose active Mycobacterium tuberculosis infections.Methods: Three sputum specimens were collected from each of 340 participants in Abuja, Nigeria, over two consecutive days. Direct microscopy was performed on all specimens; following microscopy, one specimen from each patient was selected randomly for bleach sedimentation and one for Lowenstein-Jensen culture.Results: Direct microscopy produced 28.8% AFB-positive results, whilst bleach sedimentation resulted in 30.3%. When compared with the cultures, 26.5% were AFB true positive using direct microscopy and 27.1% using bleach sedimentation. Whilst the specificity rate between these two methods was not statistically significant (P = 0.548, the sensitivity rate was significant (P = 0.004.Conclusion: Based on these results, bleach increases the sensitivity of microscopy compared with direct smear and has similar specificity. When diagnosing new cases of pulmonary TB, one bleach-digested smear is as sensitive as three direct smears, reducing waiting times for patients and ensuring the safety of laboratory technicians.

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

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

    2016-01-01

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

  17. Identifying an active case of tuberculosis.

    Williams, G; Alarcon, E; Jittimanee, S; Walusimbi, M; Sebek, M; Berga, E; Villa, T S

    2008-04-01

    The best practice standards set out in chapter 2 of the Best Practice guide focus on the various aspects of identifying an active case of TB and aim to address some of the challenges associated with case detection. The importance of developing a good relationship with the patient from the start, when he or she is often most vulnerable, is emphasised. The first standard focuses on the assessment of someone who might have TB and the second gives detailed guidance about the collection of sputum for diagnosis. The standards are aimed at the health care worker, who assesses the patient when he or she presents at a health care facility and therefore needs to be familiar with the signs, symptoms and risk factors associated with TB. Having suspected TB, the health care worker then needs to ensure that the correct tests are ordered and procedures are followed so that the best quality samples possible are sent to the laboratory and all documentation is filled out clearly and correctly. The successful implementation of these standards can be measured by the accurate and prompt reporting of results, the registration of every case detected and the continued attendance of every patient who needs treatment. PMID:18371262

  18. A comparison of interview methods to ascertain fluoroquinolone exposure before tuberculosis diagnosis.

    Van Der Heijden, Y F; Maruri, F; Holt, E; Mitchel, E; Warkentin, J; Sterling, T R

    2015-04-01

    SUMMARY Fluoroquinolone use before tuberculosis (TB) diagnosis delays the time to diagnosis and treatment, and increases the risk of fluoroquinolone-resistant TB and death. Ascertainment of fluoroquinolone exposure could identify such high-risk patients. We compared four methods of ascertaining fluoroquinolone exposure in the 6 months prior to TB diagnosis in culture-confirmed TB patients in Tennessee from January 2007 to December 2009. The four methods included a simple questionnaire administered to all TB suspects by health department personnel (FQ-Form), an in-home interview conducted by research staff, outpatient and inpatient medical record review, and TennCare pharmacy database review. Of 177 TB patients included, 72 (41%) received fluoroquinolones during the 6 months before TB diagnosis. Fluoroquinolone exposure determined by review of inpatient and outpatient medical records was considered the gold standard for comparison. The FQ-Form had 61% [95% confidence interval (CI) 48-73] sensitivity and 93% (95% CI 85-98) specificity (agreement 79%, kappa = 0.56) while the in-home interview had 28% (95% CI 18-40) sensitivity and 99% (94-100%) specificity (agreement 68%, kappa = 0.29). A simple questionnaire administered by health department personnel identified fluoroquinolone exposure before TB diagnosis with moderate reliability. PMID:25420688

  19. Application of the polymerase chain reaction and molecular probe technology for the diagnosis of tuberculosis

    Conventional methods for the diagnosis of tubercolosis based on microscopic examination and in vitro culture is both time consuming and tedious. Molecular methods of diagnosis have been suggested as an alternative which may provide the clinical laboratory with a means for rapid diagnosis. The present study was carried out to determined the feasibility of this approach for the detection of mycobacteria. Clinical specimens received from patients with suspected diagnosis of tuberculous infection were used. All specimens were examined microscopically and those that were smear positive were cultured. An aliquot of each specimen were kept for analysis by in vitro amplification using the polymerase chain reaction (PCR). The primers used for PCR were 20-mers specific for the insertion element IS986, which is restricted to the M. tuberculosis complex group. All specimens were analysed in quintriplicate, with 2 samples unspiked and 3 sampled spiked with M. tuberculosis. Appropriate positive and negative controls were included in all essays. Following amplification, the specimens were analysed by agarose gel electrophoresis (AGE). All specimens were further subject to hybridization studies using a specific radiolabelled probe. The sensitivity of the amplification assay coupled with visualization of the amplified targets using eithidium bromide staining was found to be about 1 fg of DNA. A total of 40 smear positive specimens were analyzed, 29 of which were culture positive. Twenty-eight of the 29 culture positive specimens tested positive by PCR/hybridization analysis. Of the 11 culture negative specimens, 9 were positive by PCR. Overall 37/40 (92.5%) specimens were positive by PCR/hybridization analysis. (author). 13 refs, 1 tab

  20. Time-kill kinetics of anti-tuberculosis drugs, and emergence of resistance, in relation to metabolic activity of Mycobacterium tuberculosis.

    Steenwinkel, J.E. de; Knegt, G.J. de; Kate, M.T. Ten; Belkum, A. van; Verbrugh, H.A.; Kremer, K.; Soolingen, D. van; Bakker-Woudenberg, I.A.

    2010-01-01

    OBJECTIVES: The pharmacodynamics of tuberculosis (TB) treatment should be further explored, to prevent emergence of resistance, treatment failure and relapse of infection. The diagnostic drug susceptibility tests guiding TB therapy investigate metabolically active Mycobacterium tuberculosis (Mtb) is

  1. Using IGRA in the diagnosis of tuberculosis or latent tuberculosis infection in HIV-positive persons

    Ravn, P.

    2010-01-01

    a positive IGRA response. There are, however, important unresolved issues that require further studies. What is the added value of using IGRAs in a clinical setting to correctly diagnose patients and prevent new cases? Are the differences between QFT-GIT and T-SPOT clinically relevant? Will we ever have......Persons with HIV and LTBI are at very high risk of developing active TB. The CD4 count drops in persons during the natural course of HIV/AIDS and at the same time the risk of TB increases. It is clear that there is a TB protective effect when HIV patients are placed on highly active antiretroviral......-positive individuals, and our learning curve is going up with new knowledge and circumstantial evidence. There is clearly an effect on the performance of the IGRA test when persons with active TB are co-infected with HIV. Studies looking at the performance of QFT-GIT in HIV-positive/negative TB patients show...

  2. Using IGRA in the diagnosis of tuberculosis or latent tuberculosis infection in HIV-positive persons

    Ravn, P.

    2010-01-01

    Persons with HIV and LTBI are at very high risk of developing active TB. The CD4 count drops in persons during the natural course of HIV/AIDS and at the same time the risk of TB increases. It is clear that there is a TB protective effect when HIV patients are placed on highly active antiretroviral......-positive individuals, and our learning curve is going up with new knowledge and circumstantial evidence. There is clearly an effect on the performance of the IGRA test when persons with active TB are co-infected with HIV. Studies looking at the performance of QFT-GIT in HIV-positive/negative TB patients show...... a positive IGRA response. There are, however, important unresolved issues that require further studies. What is the added value of using IGRAs in a clinical setting to correctly diagnose patients and prevent new cases? Are the differences between QFT-GIT and T-SPOT clinically relevant? Will we ever have...

  3. AN ANALYSIS OF THE CLINICAL PRESENTATION , DIAGNOSIS , MANAGEMENT OPTIONS AND OUTCOME OF THE PATIENTS WITH GENITO - URINARY TUBERCULOSIS

    Bhagavan

    2015-06-01

    Full Text Available AIMS AND OBJECTIVES: To analyze various clinical presentations and the treatment options in the management of the patients with genitourinary tuberculosis and to evaluate the role of urinary PCR in the detection of mycobacterium tuberculosis in patients with a clinical suspici on of genito urinary tuberculosis and to compare its sensitivity with urine for AFB smear, urine for myc. tuberculosis culture and bladder biopsy. MATERIALS AND METHODS: This is a retrospective and prospective study of patients with a diagnosis of genitour inary tuberculosis who underwent treatment in Gandhi General Hospital between January 2009 to December 2014. 62 patients with a diagnosis of genitourinary tuberculosis who underwent treatment were taken initially into the study. Five patients lost follow u p after initial visits. These patients were excluded from the study. The remaining 57 patients were managed. RESULTS: Irritative voiding symptoms (Frequency / Urgency / Dysuria were the most common symptoms. Gross hematuria seen in 22(38.5% patients and microscopic hematuria seen in 53% of patients. Urine for AFB attaining was positive in 16(31.3% patients, urine for MTb culture was positive in 21(41.1% patients and pus for MTb culture was positive in 4 of 7 cases. Urinary PCR to identify the mycobacter ial DNA was performed in 37 patients and was positive in 25(67.5% of 37 clinically suspected cases. The urinary PCR was falsely positive in 1(2.7% and falsely negative in 12(32.5% patients. Kidney was involved in 26(45.6% cases and ureter in 24(42.1%, and bladder in 28(49.1% cases. Overall surgical intervention was done in 36 patients. All patients received 4 to 8 weeks ATT before they were taken up for surgical intervention. In 24 patients who presented with ureteric strictures, 7 patients had nonfun ctioning kidneys and subsequently underwent nephroureterectomy, 8 patients had subnormal renal function in whom DJ stenting was done in 6 patients and PCN was done in 2

  4. The elephant interferon gamma assay: a contribution to diagnosis of tuberculosis in elephants.

    Angkawanish, T; Morar, D; van Kooten, P; Bontekoning, I; Schreuder, J; Maas, M; Wajjwalku, W; Sirimalaisuwan, A; Michel, A; Tijhaar, E; Rutten, V

    2013-11-01

    Mycobacterium tuberculosis (M. tb) has been shown to be the main causative agent of tuberculosis in elephants worldwide. M. tb may be transmitted from infected humans to other species including elephants and vice versa, in case of prolonged intensive contact. An accurate diagnostic approach covering all phases of the infection in elephants is required. As M. tb is an intracellular pathogen and cell-mediated immune (CMI) responses are elicited early after infection, the skin test is the CMI assay of choice in humans and cattle. However, this test is not applicable in elephants. The interferon gamma (IFN-γ) assay is considered a good alternative for the skin test in general, validated for use in cattle and humans. This study was aimed at development of an IFN-γ assay applicable for diagnosis of tuberculosis in elephants. Recombinant elephant IFN-γ (rEpIFN-γ) produced in eukaryotic cells was used to immunize mice and generate the monoclonal antibodies. Hybridomas were screened for IFN-γ-specific monoclonal antibody production and subcloned, and antibodies were isotyped and affinity purified. Western blot confirmed recognition of the rEpIFN-γ. The optimal combination of capture and detection antibodies selected was able to detect rEpIFN-γ in concentrations as low as 1 pg/ml. The assay was shown to be able to detect the native elephant IFN-γ, elicited in positive-control cultures (pokeweed mitogen (PWM), phorbol myristate acetate plus ionomycin (PMA/I)) of both Asian and African elephant whole-blood cultures (WBC). Preliminary data were generated using WBC from non-infected elephants, a M. tb infection-suspected elephant and a culture-confirmed M. tb-infected elephant. The latter showed measurable production of IFN-γ after stimulation with ESAT6/CFP10 PPDB and PPDA in concentration ranges as elicited in WBC by Mycobacterium tuberculosis complex (MTBC)-specific antigens in other species. Hence, the IFN-γ assay presented potential as a diagnostic tool for the

  5. Diagnosis of abdominal tuberculosis:Experience from 11 cases and review of the literature

    Ali Uzunkoy; Muge Harma; Mehmet Harma

    2004-01-01

    AIM: To analyze the experience within our hospital and to review the literature so as to establish the best means of diagnosis of abdominal tuberculosis.METHODS: The records of 11 patients (4 males, 7 females,mean age 39 years, range 18-65 years) diagnosed with abdominal tuberculosis in Harran University Hospital between January 1996 and October 2003 were analyzed retrospectively and the literature was reviewed.RESULTS: Ascites was present in all cases. Other common findings were weight loss (81%), weakness (81%), abdominal mass (72%), abdominal pain (72%), abdominal distension (63%), anorexia (45%) and night sweat (36%). The average hemoglobin was 8.2 g/dL and the average ESR was 50 mm/h (range 30-125). Elevated levels of cancer antigen CA-125were determined in four patients. Abdominal ultrasound showed abnormalities in all cases: ascites in all, tuboovarian mass in five, omental thickening in 3, and enlarged lymph nodes (mesenteric, para-aortic) in 2. CT scans showed ascites in all, pelvic mass in 5, retroperitoneal lymphadenopathy in 4, mesenteric stranding in 4, omental stranding in 3,bowel wall thickening in 2 and mesenteric lymphadenopathy in 2. Only one patient had a chest radiograph suggestive of a new TB lesion. Two had a positive family history of pulmonary TB. None had acid-fast bacilli (AFB) in the sputum and the tuberculin test was positive in only two. Laparotomy was performed in 6 cases, laparoscopy in 4 and ultrasoundguided fine needle aspiration in 2. In those patients subjected to operation, the findings were multiple diffuse involvement of the visceral and parietal peritoneum, white 'miliary nodules' or plaques, enlarged lymph nodes, ascites,'violin string' fibrinous strands, and omental thickening.Biopsy specimens showed granulomas, while ascitic fluid showed numerous lymphocytes. Both were negative for acid-fast bacilli by staining. PCR of ascitic fluid was positive for Mycobacterium tuberculosis ( M. tuberculosis) in all cases

  6. Comparison of sensitivity of quantiferon-tb gold test and tuberculin skin test in active pulmonary tuberculosis

    Objective: To compare the sensitivity of tuberculin skin test (TST) and quantiFERON-TB gold test (QFT-G) in active pulmonary tuberculosis. Study Design: Analytical study. Place and Duration of Study: Department of Pulmonology, Fauji Foundation Hospital, Rawalpindi, from July 2011 to January 2012. Methodology: 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 positive growth for Mycobacterium tuberculosis. Results: Out of 50 cases, 43 were females and 7 were males. The mean age was 41.84 A+- 19.03 years. Sensitivity of QFT-G was 80% while that of TST was 28%. Conclusion: 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. (author)

  7. Tuberculosis of the Gallbladder

    2000-01-01

    Analysis of 5 patients with gallbladder tuberculosis who had open cholecystectomy and review of literature have shown that, although still rare it presents as a part of systemic miliary tuberculosis, abdominal tuberculosis, isolated gallbladder tuberculosis and as acalculus cholecystitis in anergic patients. There are no pathognomonic signs, the diagnosis depends on suspicion of tuberculosis, peroperative findings and histological examination.

  8. End-stage renal disease due to delayed diagnosis of renal tuberculosis: a fatal case report

    Elizabeth De Francesco Daher

    2007-02-01

    Full Text Available Renal TB is difficult to diagnose, because many patients present themselves with lower urinary symptoms which are typical of bacterial cystitis. We report a case of a young woman with renal TB and ESRD. She was admitted with complaints of adynamia, anorexia, fever, weight loss, dysuria and generalized edema for 10 months. At physical examination she was febrile (39ºC, and her abdomen had increased volume and was painful at palpation. Laboratorial tests showed serum urea=220mg/dL, creatinine=6.6mg/dL, hemoglobin=7.9g/dL, hematocrit=24.3%, leukocytes=33,600/mm³ and platelets=664,000/mm³. Urinalysis showed an acid urine (pH=5.0, leukocyturia (2+/4+ and mild proteinuria (1+/4+. She was also oliguric (urinary volume <400mL/day. Abdominal echography showed thick and contracted bladder walls and heterogeneous liquid collection in the left pelvic region. Two laparotomies were performed, in which abscess in pelvic region was found. Anti-peritoneal tuberculosis treatment with rifampin, isoniazid and pyrazinamide was started. During the follow-up, the urine culture was found to be positive for M. tuberculosis. Six months later the patient had complaints of abdominal pain and dysuria. New laboratorial tests showed serum urea=187mg/dL, creatinine=8.0mg/dL, potassium=6.5mEq/L. Hemodialysis was then started. The CT scan showed signs of chronic nephropathy, dilated calyces and thinning of renal cortex in both kidneys and severe dilation of ureter. The patient developed neurologic symptoms, suggesting tuberculous meningoencephalitis, and died despite of support measures adopted. The patient had ESRD due to secondary uropathy to prolonged tuberculosis of urinary tract that was caused by delayed clinical and laboratorial diagnosis, and probably also due to inadequate antituberculous drugs administration.

  9. Bronchoalveolar lavage enzyme-linked immunospot for diagnosis of smear-negative tuberculosis in HIV-infected patients.

    Adithya Cattamanchi

    Full Text Available Peripheral blood interferon-gamma release assays (IGRAs have sub-optimal sensitivity and specificity for diagnosis of active pulmonary tuberculosis (TB. However, assessment of local immune responses has been reported to improve the accuracy of TB diagnosis.We enrolled HIV-infected adults with cough ≥2 weeks' duration admitted to Mulago Hospital in Kampala, Uganda and referred for bronchoscopy following two negative sputum acid-fast bacillus smears. We performed an ELISPOT-based IGRA (T-SPOT.TB®, Oxford Immunotec, Oxford, UK using peripheral blood and bronchoalveolar lavage (BAL fluid mononuclear cells, and determined the accuracy of IGRAs using mycobacterial culture results as a reference standard.94 HIV-infected patients with paired peripheral blood and BAL IGRA results were included. The study population was young (median age 34 years [IQR 28-40 years] and had advanced HIV/AIDS (median CD4+ T-lymphocyte count 60 cells/µl [IQR 22-200 cells/µl]. The proportion of indeterminate IGRA results was higher in BAL fluid than in peripheral blood specimens (34% vs. 14%, difference 20%, 95% CI 7-33%, p = 0.002. BAL IGRA had moderate sensitivity (73%, 95% CI 50-89% but poor specificity (48%, 95% CI 32-64% for TB diagnosis. Sensitivity was similar (75%, 95% CI 57-89% and specificity was higher (78%, 95% CI 63-88% when IGRA was performed on peripheral blood.BAL IGRA performed poorly for the diagnosis of smear-negative TB in a high HIV/TB burden setting. Further studies are needed to examine reasons for the large proportion of indeterminate results and low specificity of BAL IGRA for active TB in high HIV/TB burden settings.

  10. DIAGNOSIS OF TUBERCULOSIS BY PHAGE AMPLIFICATION TECHNIQUE: A SIMPLE B UT RAPID & RELIABLE ALTERNATIVE

    Bhattacharya

    2015-09-01

    Full Text Available In view of the grim scenario that exists in India as far as tuberculosis is concerned, despite various plans and programmes like RNTCP, ‘E arly diagnosis’ of the disease particularly of sputum - positive cases and their treatments are of paramount importance to contain the disease. Sputum microscopy – the mainstay of diagnosis proves inadequate because of its wide variation in sensitivity. There has been more concern in this era of MDR - TB and HIV co - infection. To address these problems the present study has been taken to detect the tubercle bacilli by phage amplification technique (FAST plaque TB TM with comparison to BACTEC 460 TB culture system in 12B vial. 42 smear - positive and 62 smear - negative samples were selected. In 42 smear - positive cases, radiometric culture positivity was seen in 40(95% and plaque positivity in 35(83%. In 62 smear - negative cases, culture positive cases were 30(48%, but plaque positivity was seen in only 10(16%. Overall culture positivity was 67% (total no. 70 and plaque positivity being 43% (T otal no. 46; whereas smear microscopy showed only 24.1% positivity. So phage amplification showed greater sensitivity than smear microscopy; higher specificity ( D etects only live bacilli of M. tuberculosis. This is rapid, simple, and no need for specialized technical skill and no expensive equipment is required.

  11. Microscopic Observation Drug Susceptibility Assay (MODS) for Early Diagnosis of Tuberculosis in Children

    Ha, Dang Thi Minh; Lan, Nguyen Thi Ngoc; Wolbers, Marcel; Duong, Tran Ngoc; Quang, Nguyen Dang; Thi Van Thinh, Tran; Thi Hong Ngoc, Le; Thi Ngoc Anh, Nguyen; Van Quyet, Tran; Thi Bich Tuyen, Nguyen; Thi Ha, Vo; Day, Jeremy; Thi Thanh Hang, Hoang; Kiet, Vo Sy; Thi Nho, Nguyen; Hoa, Dai Viet; Dung, Nguyen Huy; Huu Lan, Nguyen; Farrar, Jeremy; Caws, Maxine

    2009-01-01

    MODS is a novel liquid culture based technique that has been shown to be effective and rapid for early diagnosis of tuberculosis (TB). We evaluated the MODS assay for diagnosis of TB in children in Viet Nam. 217 consecutive samples including sputum (n = 132), gastric fluid (n = 50), CSF (n = 32) and pleural fluid (n = 3) collected from 96 children with suspected TB, were tested by smear, MODS and MGIT. When test results were aggregated by patient, the sensitivity and specificity of smear, MGIT and MODS against “clinical diagnosis” (confirmed and probable groups) as the gold standard were 28.2% and 100%, 42.3% and 100%, 39.7% and 94.4%, respectively. The sensitivity of MGIT and MODS was not significantly different in this analysis (P = 0.5), but MGIT was more sensitive than MODS when analysed on the sample level using a marginal model (P = 0.03). The median time to detection of MODS and MGIT were 8 days and 13 days, respectively, and the time to detection was significantly shorter for MODS in samples where both tests were positive (P<0.001). An analysis of time-dependent sensitivity showed that the detection rates were significantly higher for MODS than for MGIT by day 7 or day 14 (P<0.001 and P = 0.04), respectively. MODS is a rapid and sensitive alternative method for the isolation of M.tuberculosis from children. PMID:20020056

  12. Factors associated with delays in treatment initiation after tuberculosis diagnosis in two districts of India.

    Durba Paul

    Full Text Available BACKGROUND: Excessive time between diagnosis and initiation of tuberculosis (TB treatment contributes to ongoing TB transmission and should be minimized. In India, Revised National TB Control Programme (RNTCP focuses on indicator start of treatment within 7 days of diagnosis for patients with sputum smear-positive PTB for monitoring DOTS implementation. OBJECTIVES: To determine length of time between diagnosis and initiation of treatment and factors associated with delays of more than 7 days in smear-positive pulmonary TB. METHODS: Using existing programme records such as the TB Register, treatment cards, and the laboratory register, we conducted a retrospective cohort study of all patients with smear-positive pulmonary TB registered from July-September 2010 in two districts in India. A random sample of patients with pulmonary TB who experienced treatment delay of more than 7 days was interviewed using structured questionnaire. RESULTS: 2027 of 3411 patients registered with pulmonary TB were smear-positive. 711(35% patients had >7 days between diagnosis and treatment and 262(13% had delays >15 days. Mean duration between TB diagnosis and treatment initiation was 8 days (range = 0-128 days. Odds of treatment delay >7 days was 1.8 times more likely among those who had been previously treated (95% confidence interval [CI] 1.5-2.3 and 1.6 (95% CI 1.3-1.8 times more likely among those diagnosed in health facilities without microscopy centers. The main factors associated with a delay >7 days were: patient reluctance to start a re-treatment regimen, patients seeking second opinions, delay in transportation of drugs to the DOT centers and delay in initial home visits. To conclude, treatment delay >7 days was associated with a number of factors that included history of previous treatment and absence of TB diagnostic services in the local health facility. Decentralized diagnostic facilities and improved referral procedures may reduce such treatment

  13. Anti-Mycobacterium tuberculosis activity of fungus Phomopsis stipata

    Karina Andrade de Prince

    2012-03-01

    Full Text Available Our purpose was to determine the anti-Mycobacterium tuberculosis activity of the metabolites produced by the endophitic fungus Phomopsis stipata (Lib. B. Sutton, (Diaporthaceae, cultivated in different media. The antimycobacterial activity was assessed through the Resazurin Microtiter Assay (REMA and the cytotoxicity test performed on macrophage cell line. The extracts derived from fungi grown on Corn Medium and Potato Dextrose Broth presented the smallest values of Minimum Inhibitory Concentration (MIC and low cytotoxicity, which implies a high selectivity index. This is the first report on the chemical composition and antitubercular activity of metabolites of P. stipata, as well as the influence of culture medium on these properties.

  14. QuantiFERON® TB Gold IT in the diagnosis of active pulmonary TB

    Clara Fabris; Adriana Abrami; Daiana Bevilacqua; Tiziana Bordon; Franca Cian; Bruno Biasioli

    2010-01-01

    The IGRAs (Interferon-γ Release Assays) are commercial assays which measure T-cell-mediated response in vitro after specific stimulation, and represent the alternative to TST (Tuberculin Skin Test) in the diagnosis of latent tuberculosis infection (ILTB) and of active tuberculosis (TB). Among these we choose the assay QuantiFERON ®-TB Gold IT (Cellestis Ltd, Carnegie,Victoria, Australia) (QFT) in which interferon-γ (IFN-γ) was measured after lymphocyte stimulation with 3 antigens of the RD1 r...

  15. Diagnosis of Tuberculosis in Three Zoo Elephants and a Human Contact - Oregon, 2013.

    Zlot, Amy; Vines, Jennifer; Nystrom, Laura; Lane, Lindsey; Behm, Heidi; Denny, Justin; Finnegan, Mitch; Hostetler, Trevor; Matthews, Gloria; Storms, Tim; DeBess, Emilio

    2016-01-01

    In 2013, public health officials in Multnomah County, Oregon, started an investigation of a tuberculosis (TB) outbreak among elephants and humans at a local zoo. The investigation ultimately identified three bull elephants with active TB and 118 human contacts of the elephants. Ninety-six (81%) contacts were evaluated, and seven close contacts were found to have latent TB infection. The three bulls were isolated and treated (elephants with TB typically are not euthanized) to prevent infection of other animals and humans, and persons with latent infection were offered treatment. Improved TB screening methods for elephants are needed to prevent exposure of human contacts. PMID:26741355

  16. Diagnosis of tuberculosis based on the two specific antigens ESAT-6 and CFP10

    van Pinxteren, L A; Ravn, P; Agger, E M; Pollock, J; Andersen, P

    2000-01-01

    Tests based on tuberculin purified protein derivative (PPD) cannot distinguish between tuberculosis infection, Mycobacterium bovis BCG vaccination, or exposure to environmental mycobacteria. The present study investigated the diagnostic potential of two Mycobacterium tuberculosis-specific antigens...

  17. Interferon-γ release assays for the diagnosis of latent Mycobacterium tuberculosis infection: a systematic review and meta-analysis

    Diel, R; Goletti, D; Ferrara, G; Bothamley, G; Cirillo, D; Kampmann, B; Lange, C; Losi, M; Markova, R; Migliori, G B; Nienhaus, A; Ruhwald, M; Wagner, D; Zellweger, J P; Huitric, E; Sandgren, A; Manissero, D

    2011-01-01

    We conducted a systematic review and meta-analysis to compare the accuracy of the QuantiFERON-TB® Gold In-Tube (QFT-G-IT) and the T-SPOT®.TB assays with the tuberculin skin test (TST) for the diagnosis of latent Mycobacterium tuberculosis infection (LTBI). The Medline, Embase and Cochrane databases...... were explored for relevant articles in November 2009. Specificities, and negative (NPV) and positive (PPV) predictive values of interferon-γ release assays (IGRAs) and the TST, and the exposure gradient influences on test results among bacille Calmette-Guérin (BCG) vaccinees were evaluated. Specificity...... of IGRAs varied 98-100%. In immunocompetent adults, NPV for progression to tuberculosis within 2 yrs were 97.8% for T-SPOT®.TB and 99.8% for QFT-G-IT. When test performance of an immunodiagnostic test was not restricted to prior positivity of another test, progression rates to tuberculosis among IGRA...

  18. Seasonality of tuberculosis

    Auda Fares

    2011-01-01

    Full Text Available Objectives: This study was designed to review previous studies and analyse the current knowledge and controversies related to seasonal variability of tuberculosis (TB to examine whether TB has an annual seasonal pattern. Study Design and Methods: Systematic review of peer reviewed studies identified through literature searches using online databases belonging to PubMed and the Cochrane library with key words "Tuberculosis, Seasonal influence" and " Tuberculosis, Seasonal variation". The search was restricted to articles published in English. The references of the identified papers for further relevant publications were also reviewed. Results: Twelve studies conducted between the period 1971 and 2006 from 11 countries/regions around the world (South Western Cameroon, South Africa, India, Hong Kong, Japan, Kuwait, Spain, UK, Ireland, Russia, and Mongolia were reviewed. A seasonal pattern of tuberculosis with a mostly predominant peak is seen during the spring and summer seasons in all of the countries (except South Western Cameroon and Russia. Conclusions: The observation of seasonality leads to assume that the risk of transmission of M. tuberculosis does appear to be the greatest during winter months. Vitamin D level variability, indoor activities, seasonal change in immune function, and delays in the diagnosis and treatment of tuberculosis are potential stimuli of seasonal tuberculosis disease. Additionally, seasonal variation in food availability and food intake, age, and sex are important factors which can play a role in the tuberculosis notification variability. Prospective studies regarding this topic and other related subjects are highly recommended.

  19. INFLUENCE OF HOSPITALIZATION UPON DIAGNOSIS ON THE RISK OF TUBERCULOSIS CLUSTERING

    Giuseppe Lapadula

    2013-11-01

    Full Text Available 800x600 Setting: Culture-positive tuberculosis (TB diagnosed in the metropolitan area of Milan (Italy over a 5-year period (1995-1999. Objective: To assess the impact of short-course hospitalization upon diagnosis on the overall risk of TB clusterization. Design: Restriction fragment length polymorphism profiles with a similarity of 100% defined a cluster. Uni- and multivariable logistic regression models were performed to assess factors associated with clusterization. Results: Among 1139 patients, 392 (34.4% were hospitalized before or soon after diagnosis, 405 (35.6% received domiciliary treatment since the diagnosis and 392 (30% had no information about initial clinical management. One hundred fifteen molecular clusters involving 363 patients were identified. Using multivariable analysis, hospitalization was not significantly associated with clusterization (OR 1.06, 95%CI 0.75-1.50, p=0.575. Subjects aged >65 years old (OR 0.60; 95CI%:0.37-0.95; p=0.016 and non-Italian born patients (OR 0.56; 95%CI:0.41-0.76; p<0.001 were running a lower risk of clusterization. Conversely, HIV co-infected patients (OR 1.88, 95%CI:1.20-2.95, p=0.006 and those with MDR TB (OR 2.50, 95%CI:1.46-4.25, p=0.001 were significantly more likely to be involved in clusters. Conclusion: In our cohort, domiciliary treatment was not associated with TB clusterization. Expanding domiciliary treatment upon diagnosis appears as an advisable measure to reduce unnecessary costs for the health care system. Normal 0 14 false false false IT X-NONE X-NONE MicrosoftInternetExplorer4

  20. Role of Gist and PHOG features in computer-aided diagnosis of tuberculosis without segmentation.

    Arun Chauhan

    Full Text Available Effective diagnosis of tuberculosis (TB relies on accurate interpretation of radiological patterns found in a chest radiograph (CXR. Lack of skilled radiologists and other resources, especially in developing countries, hinders its efficient diagnosis. Computer-aided diagnosis (CAD methods provide second opinion to the radiologists for their findings and thereby assist in better diagnosis of cancer and other diseases including TB. However, existing CAD methods for TB are based on the extraction of textural features from manually or semi-automatically segmented CXRs. These methods are prone to errors and cannot be implemented in X-ray machines for automated classification.Gabor, Gist, histogram of oriented gradients (HOG, and pyramid histogram of oriented gradients (PHOG features extracted from the whole image can be implemented into existing X-ray machines to discriminate between TB and non-TB CXRs in an automated manner. Localized features were extracted for the above methods using various parameters, such as frequency range, blocks and region of interest. The performance of these features was evaluated against textural features. Two digital CXR image datasets (8-bit DA and 14-bit DB were used for evaluating the performance of these features.Gist (accuracy 94.2% for DA, 86.0% for DB and PHOG (accuracy 92.3% for DA, 92.0% for DB features provided better results for both the datasets. These features were implemented to develop a MATLAB toolbox, TB-Xpredict, which is freely available for academic use at http://sourceforge.net/projects/tbxpredict/. This toolbox provides both automated training and prediction modules and does not require expertise in image processing for operation.Since the features used in TB-Xpredict do not require segmentation, the toolbox can easily be implemented in X-ray machines. This toolbox can effectively be used for the mass screening of TB in high-burden areas with improved efficiency.

  1. Serum adenosine deaminase activity and its isoenzyme in patients treated for tuberculosis

    Objective: Increased serum adenosine deaminase (ADA) activity, mainly associated with tuberculosis can also occur in a number of other diseases thus negatively affecting the diagnostic utility of ADA measurements in tuberculosis. The aim of the study was to determine whether or not the combined use of the activity of ADA, its isoenzymes and differential cell counts would provide a more efficient means of diagnosing tuberculosis than the use of ADA levels alone. Results: Data suggested significant (p0.75) of ADA/sub 2/ADA was found to be better indicator of tuberculosis. Lymphocyte neutrophil ratio (L/N)> 0.69 gave additional benefit to increase the sensitivity and specificity for the use of ADA as marker in diagnosing tuberculosis. Conclusion: The combined use of activity of ADA, its isoenzymes and total and differential cell counts is a better indicator and gives better understanding to diagnose and evaluate tuberculosis and response to therapy. (author)

  2. Clinical,radiological and molecular diagnosis correlation in serum samples from patients with osteoarticular tuberculosis

    Guadalupe; Garcia-Elorriaga; Olga; Martinez-Elizondo; Guillermo; del; Rey-Pineda; Cesar; Gonzalez-Bonilla

    2014-01-01

    Objective:To assess the role of polymerase chain reaction(PCR)in serum sauples,in the diagnosis of osteoarticular tuberculosis(OTB)in a setting where only clinical and imaging diagnoses determine the treatment.Methods:A total of 44 consecutive serum specimens were collected from clinically suspected OTB patients,based on clinical and radiological[X-ray or magnetic resonance imagng/computecl tomography]features.They were scrcened by in-house nested PCR.In addition,a few specimens were examined by Gram stain,acid-fast bacilli stain,histand routine bacterial culture.A total of 39 specimens were collected from patients suffering from other bone diseases of nontuberculous origin and included as negative controls.Results:of the 44 clinically suspected OTB patients,in-house nested PCR was positive in 40(91%)cases;PCR was negative in 38(97%)negative controls.Sensitivity and specificity of our in—house nested PCR was 90.3%and 97.4%,respectively.The PCR report was available within 48 h.It was possible to standardize serum PCR technique and in positive cases,a good n was observed in terms of an adequate treatment response.Conclusions:Nested PCR in serum samples is a rapid,highly sensitive and specific modality for OTB detection,PCR should be performed in addition to clinical evaluation,imaging studies,acidfast bacilli staining,culture and histopathology diagnosis,if possible.

  3. The Impact of Ventilation and Early Diagnosis on Tuberculosis Transmission in Brazilian Prisons.

    Urrego, Juliana; Ko, Albert I; da Silva Santos Carbone, Andrea; Paião, Dayse Sanchez Guimarães; Sgarbi, Renata Viebrantz Enne; Yeckel, Catherine W; Andrews, Jason R; Croda, Julio

    2015-10-01

    Prisoners have among the highest incidence of tuberculosis (TB) globally. However, the contribution of the prison environment on transmission is not well understood and structural characteristics have received little attention as effective epidemiological interventions in TB control. We evaluated architectural characteristics and estimated ventilation rates in 141 cells in three prisons in central west Brazil using steady-state exhaled carbon dioxide (CO2) levels. We used a modified Wells-Riley equation to estimate the probability of infection for inmates sharing a cell with an infectious case and projected the impact of interventions, including early diagnosis and improved ventilation. Overall, prison cells were densely populated (mean 2.1 m(2) per occupant) and poorly ventilated, with only three cells meeting World Health Organization (WHO) standards for per-person ventilation (60 L/s) applied in infection control settings. In the absence of interventions, projected mean risk of infection was 78.0% during a 6-month period. Decreasing time-to-diagnosis by 25% reduced transmission risk by 8.3%. Improving ventilation to WHO standards decreased transmission by 38.2%, whereas optimizing cross-ventilation reduced transmission by 64.4%. Prison environments promote high infection risk over short-time intervals. In this context, enhanced diagnostics have a limited impact on reducing transmission. Improving natural ventilation may be required to effectively control TB in prisons. PMID:26195459

  4. Clinical, radiological and molecular diagnosis correlation in serum samples from patients with osteoarticular tuberculosis

    Guadalupe Garca-Elorriaga; Olga Martnez-Elizondo; Guillermo del Rey-Pineda; Csar Gonzlez-Bonilla

    2014-01-01

    Objective: To assess the role of polymerase chain reaction (PCR) in serum samples, in the diagnosis of osteoarticular tuberculosis (OTB) in a setting where only clinical and imaging diagnoses determine the treatment.Methods:A total of 44 consecutive serum specimens were collected from clinically suspected OTB patients, based on clinical and radiological [X-ray or magnetic resonance imaging/computed tomography] features. They were screened by in-house nested PCR. In addition, a few specimens were examined by Gram stain, acid-fast bacilli stain, histopathology and routine bacterial culture. A total of 39 specimens were collected from patients suffering from other bone diseases of nontuberculous origin and included as negative controls.Results:Of the 44 clinically suspected OTB patients, in-house nested PCR was positive in 40 (91%) cases; PCR was negative in 38 (97%) negative controls. Sensitivity and specificity of our in-house nested PCR was 90.9% and 97.4%, respectively. The PCR report was available within 48 h. It was possible to standardize serum PCR technique and in positive cases, a good correlation was observed in terms of an adequate treatment response.Conclusions:Nested PCR in serum samples is a rapid, highly sensitive and specific modality for OTB detection. PCR should be performed in addition to clinical evaluation, imaging studies, acid-fast bacilli staining, culture and histopathology diagnosis, if possible.

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

    Yan, Liping; Xiao, Heping; Zhang, Qing

    2016-01-01

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

  6. Impact and cost-effectiveness of culture for diagnosis of tuberculosis in HIV-infected Brazilian adults.

    David W Dowdy

    Full Text Available BACKGROUND: Culture of Mycobacterium tuberculosis currently represents the closest "gold standard" for diagnosis of tuberculosis (TB, but operational data are scant on the impact and cost-effectiveness of TB culture for human immunodeficiency (HIV- infected individuals in resource-limited settings. METHODOLOGY/PRINCIPAL FINDINGS: We recorded costs, laboratory results, and dates of initiating TB therapy in a centralized TB culture program for HIV-infected patients in Rio de Janeiro, Brazil, constructing a decision-analysis model to estimate the incremental cost-effectiveness of TB culture from the perspective of a public-sector TB control program. Of 217 TB suspects presenting between January 2006 and March 2008, 33 (15% had culture-confirmed active tuberculosis; 23 (70% were smear-negative. Among smear-negative, culture-positive patients, 6 (26% began TB therapy before culture results were available, 11 (48% began TB therapy after culture result availability, and 6 (26% did not begin TB therapy within 180 days of presentation. The cost per negative culture was US$17.52 (solid media-$23.50 (liquid media. Per 1,000 TB suspects and compared with smear alone, TB culture with solid media would avert an estimated eight TB deaths (95% simulation interval [SI]: 4, 15 and 37 disability-adjusted life years (DALYs (95% SI: 13, 76, at a cost of $36 (95% SI: $25, $50 per TB suspect or $962 (95% SI: $469, $2642 per DALY averted. Replacing solid media with automated liquid culture would avert one further death (95% SI: -1, 4 and eight DALYs (95% SI: -4, 23 at $2751 per DALY (95% SI: $680, dominated. The cost-effectiveness of TB culture was more sensitive to characteristics of the existing TB diagnostic system than to the accuracy or cost of TB culture. CONCLUSIONS/SIGNIFICANCE: TB culture is potentially effective and cost-effective for HIV-positive patients in resource-constrained settings. Reliable transmission of culture results to patients and integration

  7. Interferon-gamma assay in combination with tuberculin skin test are insufficient for the diagnosis of culture-negative pulmonary tuberculosis.

    Marcin Wlodarczyk

    Full Text Available OBJECTIVE: Early diagnosis of infectious cases and treatment of tuberculosis (TB are important strategies for reducing the incidence of this disease. Unfortunately, traditional TB diagnostic methods are time-consuming and often unreliable. This study compared the accuracy and reliability of the tuberculin skin test (TST and interferon (IFN-γ-based assay (IGRA for the diagnosis of active pulmonary TB Polish cases that could or could not be confirmed by M. tuberculosis (M.tb culture. METHODS: In total, 126 adult patients with clinically active TB or non-mycobacterial, community-acquired lung diseases (NMLD hospitalised at the Regional Specialised Hospital of Tuberculosis, Lung Diseases and Rehabilitation in Tuszyn, Poland were enrolled in the present study. Sensitivity, specificity, positive predicted value (PPV, negative predicted value (NPV, and analytic accuracy (Acc of TST and IGRA testing for the diagnosis of culture-positive and culture-negative TB patients were calculated. The quantities of IFN-γ produced in the response to M.tb specific antigens (TB Ag - Nil in the cultures of blood from patients with active TB and NMLD patients were also analysed. RESULTS: The IGRA sensitivity in culture-positive and culture-negative TB patients was similar, measuring 65.1% and 55.6%, respectively. The sensitivity of TST did not differ from the parameters designated for IGRA, measuring 55.8% in culture-positive and 64.9% in culture-negative TB. The sensitivity of TST and IGRA was age-dependent and decreased significantly with the age of the patients. No differences in the frequency or intensity of M.tb-stimulated IFN-γ production, as assessed by IGRA testing between culture-positive and culture-negative TB were noticed. Significantly lower concentrations of IFN-γ were observed in patients with advanced TB forms compared with those with mild or moderate TB pathologies. CONCLUSIONS: Our results do not show that a combination of IGRA and TST might be a

  8. QuantiFERON®-TB gold in-tube performance for diagnosing active tuberculosis in children and adults in a high burden setting

    Rose, Michala Vaaben; Kimaro, Godfather; Nissen, Thomas N;

    2012-01-01

    To determine whether QuantiFERON®-TB Gold In-Tube (QFT) can contribute to the diagnosis of active tuberculosis (TB) in children in a high-burden setting and to assess the performance of QFT and tuberculin skin test (TST) in a prospective cohort of TB suspect children compared to adults with...... confirmed TB in Tanzania....

  9. Meta-analysis to compare the accuracy of GeneXpert, MODS and the WHO 2007 algorithm for diagnosis of smear-negative pulmonary tuberculosis

    Walusimbi, Simon; Bwanga, Freddie; Costa, Ayesha; Haile, Melles; Joloba, Moses; Hoffner, Sven

    2013-01-01

    Background Smear-negative pulmonary tuberculosis (SN-PTB), which is common in HIV-infected patients, is difficult to diagnose using smear microscopy alone. In 2007, the WHO developed an algorithm to improve the diagnosis and management of smear-negative tuberculosis in HIV prevalent and resource constrained settings. Implementation of the algorithm required individuals with presumptive TB to be initially evaluated using two sputum microscopy examinations followed by clinical diagnosis that ma...

  10. Higher blood volumes improve the sensitivity of direct PCR diagnosis of blood stream tuberculosis among HIV-positive patients: an observation study

    Bwanga, Freddie; Disqué, Claudia; Lorenz, Michael G.; Allerheiligen, Vera; Worodria, William; Luyombya, Allan; Najjingo, Irene; Weizenegger, Michael

    2015-01-01

    Background Blood stream tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB) is common among HIV-positive patients, turning rapidly fatal unless detected and treated promptly. Blood culture is currently the standard test for the detection of MTB in whole blood but results take weeks; patients deteriorate markedly and often die before a diagnosis of blood stream TB is made. Rapid molecular tests on whole blood, with potential for same day diagnosis of blood stream TB usually show low ...

  11. Chest radiography and thoracic computed tomography findings in children who have family members with active pulmonary tuberculosis

    Objective: The chest radiography and TCT findings in children who had contacted with adult family members with active pulmonary tuberculosis were compared. The contributions of thoracic computed tomography to the diagnosis of tuberculosis were investigated. Methods and material: The children who were 0-16 years old (n=173) and children of families with an adult member which was diagnosed as pulmonary tuberculosis were evaluated. The children were considered in two groups based on the absence (n=125) or presence (n=48) of complaints and/or ambiguous symptoms such as lack of appetite, mild cough, sweating, history of lung infection, low body weight and those with suspicious chest radiography findings (12 cases) were included in this study. Asymptomatic patients (n=125) did not undergo TCT. Patients who had positive PPD skin tests only received isoniazid. If the TCT demonstrated enlarged lymph nodes or parenchymal lesions, minimally active pulmonary tuberculosis was diagnosed and antituberculous treatment was given. Results and discussions: TCT revealed lymph node enlargement or parenchymal lesions in 39 children (81.2%). Of the 12 children whose CXRs revealed suspicious lymph node enlargement and/or infiltration, five had normal findings in TCT whereas the initial findings were confirmed in the remaining seven. These data suggest that there is a correlation between the presence of ambiguous symptoms in exposed children and TCT findings; chest radiography and TCT findings do not yield parallel findings. All the patients who received anti-TB treatment were resolved in the control examinations. Conclusion: In this study there is a correlation between presence of ambiguous symptoms and TCT findings, but the chest radiography and TCT findings do not yield harmony in exposed children with ambiguous symptoms (suspicious tuberculosis cases). These observations should be considered in children with symptoms similar to those of exposed children, but with no definite history of

  12. A comparison of interferon-γ and IP-10 for the diagnosis of tuberculosis

    Holm, Line Lindebo; Rose, Michala Vaaben; Kimaro, Godfather;

    2014-01-01

    symptoms of TB were tested with the QFT-IT and IP-10 tests and retrospectively classified into diagnostic groups. Adults with confirmed TB were assessed in parallel. RESULTS: A total of 203 children were included. The median age was 3.0 years (interquartile range: 1.2-7.0), 38% were HIV infected, 36% were......OBJECTIVE: Interferon-γ and IP-10 release assays are diagnostic tests for tuberculosis infection. We have compared the accuracy of IP-10 and QuantiFERON-TB Gold In-tube [QFT-IT] in Tanzanian children suspected of having active tuberculosis (TB). METHODS: Hospitalized Tanzanian children with...... aged <2 years, and 58% had a low weight-for-age. IP-10 and QFT-IT test performance was comparable but sensitivity was low: 33% (1 of 3) in children with confirmed TB and 29% (8 of 28) in children with probable TB. Rates of indeterminate responders were high: 29% (59 of 203) for IP-10 and 26% (53 of 203...

  13. Radioiodinated DPA-713 Imaging Correlates with Bactericidal Activity of Tuberculosis Treatments in Mice

    Ordonez, Alvaro A.; Pokkali, Supriya; DeMarco, Vincent P.; Klunk, Mariah; Mease, Ronnie C.; Foss, Catherine A.; Pomper, Martin G.; Jain, Sanjay K.

    2014-01-01

    Current tools for monitoring response to tuberculosis treatments have several limitations. Noninvasive biomarkers could accelerate tuberculosis drug development and clinical studies, but to date little progress has been made in developing new imaging technologies for this application. In this study, we developed pulmonary single-photon emission computed tomography (SPECT) using radioiodinated DPA-713 to serially monitor the activity of tuberculosis treatments in live mice, which develop necro...

  14. Rapid, Semiquantitative Assay To Discriminate among Compounds with Activity against Replicating or Nonreplicating Mycobacterium tuberculosis

    Gold, Ben; Roberts, Julia; Ling, Yan; Quezada, Landys Lopez; Glasheen, Jou; Ballinger, Elaine; Somersan-Karakaya, Selin; Warrier, Thulasi; Warren, J. David; Nathan, Carl

    2015-01-01

    The search for drugs that can kill replicating and nonreplicating Mycobacterium tuberculosis faces practical bottlenecks. Measurement of CFU and discrimination of bacteriostatic from bactericidal activity are costly in compounds, supplies, labor, and time. Testing compounds against M. tuberculosis under conditions that prevent the replication of M. tuberculosis often involves a second phase of the test in which conditions are altered to permit the replication of bacteria that survived the fir...

  15. MICROSCOPIC-OBSERVATION DRUG-SUSCEPTIBILITY (MODS) FOR RAPID DIAGNOSIS OF LYMPH NODE TUBERCULOSIS AND DETECTION OF DRUG RESISTANCE.

    Kirwan, DE; Ugarte-Gil, C.; GILMAN, RH; Caviedes, L.; Rizvi, SM; Ticona, E; G. Chavez; Cabrera, JL; Matos, ED; Evans, CA; Moore, DA; Friedland, JS; Lymph Node TB Working Group Peru.

    2015-01-01

    In this study, 132 patients with lymphadenopathy were investigated. Fifty-two (39.4%) were diagnosed with tuberculosis (TB). The microscopic observation drug susceptibility (MODS) assay provided rapid (13 days), accurate diagnosis (sensitivity, 65.4%) and reliable drug susceptibility testing (DST). Despite its lower sensitivity than that of other methods, its faster results and simultaneous DST are advantageous in resource-poor settings, supporting the incorporation of MODS into diagnostic al...

  16. Place of digital X-ray tomography in improving the diagnosis of pulmonary tuberculosis, lung cancer and mediastinal abnormality

    To assess the role of current digital X-ray fluorography in the diagnosis of various diseases of the lung (primarily its tuberculosis and cancer, and abnormalities of the mediastinum). 2500 cases from different patient groups (those registered at dispensary or identified at screening, those with a previously verified pathology). In addition to a particularly diagnostic section organizational and methodological problems in the introduction of digital X-ray fluorography into practical public health of Russia are discussed

  17. Improved rapid molecular diagnosis of multidrug-resistant tuberculosis using a new reverse hybridization assay, REBA MTB-MDR

    Bang, Hyeeun; Park, Sangjung; Hwang, Joohwan; Jin, Hyunwoo; Cho, Eunjin; Kim, Dae Yoon; Song, Taeksun; Shamputa, Isdore Chola; Via, Laura E.; Barry, Clifton E.; Cho, Sang-Nae; Lee, Hyeyoung

    2011-01-01

    Rapid diagnosis of multidrug-resistant tuberculosis (MDR-TB) is essential for the prompt initiation of effective second-line therapy to improve treatment outcome and limit transmission of this obstinate disease. A variety of molecular methods that enable the rapid detection of mutations implicated in MDR-TB have been developed. The sensitivity of the methods is dependent, in principle, on the repertoire of mutations being detected, which is typically limited to mutations in the genes rpoB, ka...

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

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Pulmonary tuberculosis... Rating Considerations Relative to Specific Diseases § 3.370 Pulmonary tuberculosis shown by X-ray in active service. (a) Active disease. X-ray evidence alone may be adequate for grant of direct...

  19. The usefulness of 99mTc-MIBI in the detection of active pulmonary tuberculosis

    The use of radiopharmaceuticals in evaluation of pulmonary tuberculosis may help to resolve difficult diagnostic problems such as discordance between sputum examinations and chest roentgenographic findings. We investigated the usefulness of 99mTc-methoxyisobutylisonitrile (MIBI) scintigraphy in the detection of active pulmonary tuberculosis. Forty-six patients with suspected active pulmonary tuberculosis were studied with sputum smear of AFB, sputum AFB culture, chest X-ray and MIBI scan. MIBI image was obtained 15 and 60 min after intravenous injection of 370MBq(10mCi) 99mTc-MIBI. In 16 patients of them Ga scans were performed in addition to MIBI scan. Repeated MIBI scans were done in 7 patients with active pulmonary tuberculosis after 4∼6 months of antituberculous chemotherapy. Thirty-two patients were confirmed as active tuberculosis by sputum culture. Sensitivity of MIBI scan to active tuberculosis was 87.5%(28/32) and MIBI findings were negative in all of 14 patients with inactive disease. Focal uptake of MIBI was dense in the area that was strongly suggested active tuberculous lesions by chest roentgenogram. There was no discordance between MIBI and Ga image in 16 patients. But the uptake areas of Ga images were broader than that of MIBI images. After 4∼6 months of antituberculous treatment all repeated MIBI scans revealed negative findings except 1 patient with persistent active pulmonary tuberculosis due to drug resistance. MIBI scan could be used in the detection of active pulmonary tuberculosis as a useful noninvasive diagnostic tool

  20. Latent and Active Tuberculosis Infection Increase Immune Activation in Individuals Co-Infected with HIV

    Zuri A. Sullivan

    2015-04-01

    Significance: Latent tuberculosis, which affects an estimated 1/3 of the world's population, has long been thought to be a relatively benign, quiescent state of M. tuberculosis infection. While HIV co-infection is known to exacerbate M. tuberculosis infection and increase the risk of developing active TB, little is known about the potential effect of latent TB infection on HIV disease. This study shows that HIV-infected individuals with both active and latent TB have elevated levels of inflammation and immune activation, biomarkers of HIV disease progression and elevated risk of mortality. These results suggest that, in the context of HIV, latent TB infection may be associated with increased risk of progression to AIDS and mortality.

  1. Mycobacterium tuberculosis exposure of livestock in a German dairy farm: implications for intra vitam diagnosis of bovine tuberculosis in an officially tuberculosis-free country.

    Eisenberg, T; Nesseler, A; Sauerwald, C; Kling, U; Riße, K; Kaim, U; Althoff, G; Fiege, N; Schlez, K; Hamann, H-P; Fawzy, A; Moser, I; Riße, R; Kraft, G; Zschöck, M; Menge, C

    2016-03-01

    Germany has been an officially bovine tuberculosis (bTB)-free (OTF) country since 1996. Gradually rising numbers of bTB herd incidents due to Mycobacterium bovis and M. caprae in North-Western and Southern Germany during the last few years prompted the competent authorities to conduct a nationwide bTB survey in 2013/2014. This led to the detection of a dairy herd in which as many as 55 cattle reacted positively to consecutive intra vitam testing. Test-positive animals lacked visible lesions indicative of bTB at necropsy. Extensive mycobacterial culturing as well as molecular testing of samples from 11 tissues for members of the M. tuberculosis complex (MTC) yielded negative results throughout. However, caseous lymphadenitis of Ln. mandibularis accessorius was observed during meat inspection of a fattening pig from the same farm at regular slaughter at that time. Respective tissue samples tested MTC positive by polymerase chain reaction, and M. tuberculosis T1 family were identified by spoligotyping. Four human reactors within the farmer's family were also found to be immunoreactive. As exposure of livestock to M. tuberculosis is not generally considered, its impact may result in regulatory and practical difficulties when using protocols designed to detect classical bTB, particularly in OTF countries. PMID:26344380

  2. Diagnosis of latent tuberculosis infection among HIV discordant partners using interferon gamma release assays

    Mwananyanda Lawrence

    2011-09-01

    Full Text Available Abstract Background There is limited data on the effect of HIV status and CD4 counts on performance of Interferon-g Release assays (IGRAs for diagnosis of latent tuberculosis infection (LTBI. Methods A cross sectional study was conducted to assess the prevalence of and risk factors for a positive diagnostic test for LTBI, using tuberculin skin test (TST and IGRAs among HIV-discordant couples in Zambia. Results A total of 596 subjects (298 couples were enrolled. Median CD4 count among HIV positive persons was 388 cells/μl, (range 51-1330. HIV negative persons were more likely than their HIV positive partner, to have a positive diagnostic test for LTBI with TST (203 vs 128, QFT (171 vs 109 and TSPOT (156 vs. 109. On multivariate analysis, HIV negative status was an independent predictor for a positive QFT (OR = 2.22, 95% CI 1.42- 3.46 and TSPOT (OR = 1.79, 95% CI 1.16-2.77. Among HIV positive subjects a CD4 count ≥ 388 cells/μl was associated with a positive TST (OR = 1.76 95% CI 1.10-2.82 and QFT (OR = 1.71 95% CI 1.06-2.77 but not TSPOT (OR = 1.20 95% CI 0.74-1.94. Conclusions Persons with HIV had significantly fewer positive diagnostic tests for LTBI with TST, QFT and TSPOT. Persons with a CD4 count

  3. Diagnosis and management of miliary tuberculosis: current state and future perspectives [Retraction

    Ray S

    2015-09-01

    Full Text Available Ray S, Talukdar A, Kundu S, Khanra D, Sonthalia N. Ther Clin Risk Mngmt. 2013;9:9–26.The editor of the Indian Journal of Medical Research has brought to our attention the unacknowledged re-use of significant portions of text in the above article. The source of much of the text appears to be from:Sharma SK, Mohan A, Sharma A. Challenges in the diagnosis and treatment of miliary tuberculosis. Indian J Med Res. 135, May 2012, pp 703–730.Dr Ray comments thus: “Regarding the similarities found we want to clarify that this apparent plagiarism is not an intentional act and likely to be factual error. In any way, we do not want to undermine scientific pursuit or vitiate the investigational spirit of hard work and creativity. Please be informed that the different portions of the review were written by different co-authors and most of them were postgraduate students at that time. It seems that they have taken materials/ideas from previously published source unaware of the issues of plagiarism.” This retraction relates to this paper

  4. Predictive Role of Serum Tumor Markers in Diagnosis of Pulmonary Tuberculosis

    MA, Jingjing; XIA, Dan; HU, Jing; FU, Rui; XU, Lijun; ZHANG, Ying; ZHANG, Mengying; LI, Benhe; YANG, Jianghua; WEN, Yufeng

    2016-01-01

    Background: The diagnosis of pulmonary tuberculosis (PTB) is complicated and time-consuming currently. There was association of PTB with serum tumor markers. In this study we aimed to evaluate the predictive role of serum CA125, CA199 and CEA as diagnostic tools for PTB. Methods: This study was designed as a case-control study with 565 subjects who visited the Yijishan Hospital from Jun to Dec in 2014.This case-control study matched as for age and sex with 113 cases and 452 controls. Serum CA125, CA199 and CEA levels were detected by electrochemiluminescence instrument. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic value on PTB. Results: Serum levels of CA125, CA199 and CEA in PTB patients were significantly higher than those in control group (P<0.001). There was no significantly different of three tumor markers between initial treatment group and retreatment group. The logistic regression analysis showed that CA125 was an impact factor to PTB. The ROC analysis revealed that AUC of CA125 was 0.966 (95%CI: 0.951–0.981), the sensitivity, specificity in serum and cut-off were 95.6%, 85.0% and 10.30 U/ml, respectively. Conclusion: The serum CA125 has potential good diagnostic performance for PTB. PMID:27252912

  5. Comparative performance of Thin Layer Agar and Löwenstein-Jensen culture for diagnosis of tuberculosis.

    Battaglioli, T; Rintiswati, N; Martin, A; Palupi, K R; Bernaerts, G; Dwihardiani, B; Ahmad, R A; Matthys, F; Mahendradhata, Y; Van der Stuyft, P

    2013-11-01

    Sputum smear microscopy for the diagnosis of tuberculosis (TB) is cheap and simple but its sensitivity is low. Culture on Löwenstein-Jensen (LJ) is more sensitive but it takes a long time to yield results. Thin-Layer Agar (TLA) culture was suggested as an equally sensitive and faster alternative. We evaluated the performance of TLA for diagnosing TB in Jogjakarta, Indonesia. People with suspected TB presenting from July 2010 to July 2011 to two chest clinics of the National TB Control Programme network of Jogjakarta were eligible for inclusion. A sputum sample was sent to the Gadjah Mada University microbiology laboratory for concentration, smearing, Ziehl-Neelsen staining and culture on LJ and TLA. Sensitivity of cultures was evaluated against a composite reference standard (any positive culture). Time to detection of Mycobacteria was recorded. Out of 1414 samples, 164 (12%) were smear positive, 99 (7%) were scanty and 1151 (81%) were negative. On TLA and LJ respectively, 168 (12%) and 149 (11%) samples were positive, 72 (5%) and 32 (2%) were contaminated (κ = 0.64; 95% CI 0.59-0.69, p evaluate the cost-effectiveness and impact of its introduction into programmatic settings are urgently needed. PMID:23738759

  6. Gallbladder tuberculosis: case report

    余日胜; 刘奕青

    2002-01-01

    @@ Abdominal tuberculosis is common in developing countries, but gallbladder involvement is extremely rare. The diagnosis of gallbladder tuberculosis is often not suspected prior to surgery or biopsy.This paper describes the CT and ultrasonographic features of gallbladder tuberculosis in a 35-year-old patient and reviews the literature of gallbladder tuberculosis.

  7. Comparison of the conventional diagnostic modalities, bactec culture and polymerase chain reaction test for diagnosis of tuberculosis

    Negi S

    2005-01-01

    Full Text Available PURPOSE: To evaluate the performance of 65 kDa antigen based PCR assay in clinical samples obtained from pulmonary and extrapulmonary cases of tuberculosis. METHODS: One hundred and fifty six samples were processed for detection of Mycobacterium tuberculosis by ZN smear examination, LJ medium culture, BACTEC radiometric culture and PCR tests. RESULTS: A significant difference was seen in the sensitivities of different tests, the figures being 74.4% for PCR test, 33.79% for ZN smear examination, 48.9% for LJ culture and 55.8% for BACTEC culture (P0.05 as far as specificity of different tests was concerned. PCR test sensitivity in pulmonary and extrapulmonary clinical samples were 72.7% and 75.9% respectively and found to be significantly higher (PM.tuberculosis was 24.03 days by LJ medium culture, 12.89 days by BACTEC culture and less than one day by PCR test. CONCLUSIONS: PCR is a rapid and sensitive method for the early diagnosis of pulmonary and extrapulmonary tuberculosis.

  8. The elephant interferon gamma assay: a contribution to diagnosis of tuberculosis in elephants

    Angkawanish, T.; Morar, D.; Kooten, P.J.; Bontekoning, I.; Schreuder, J.; Maas, M.; Wajjwalku, W.; Sirimalaisuwan, A.; Michel, A.L.; Tijhaar, E.; Rutten, V.P.M.G.

    2013-01-01

    Mycobacterium tuberculosis (M. tb) has been shown to be the main causative agent of tuberculosis in elephants worldwide. M. tb may be transmitted from infected humans to other species including elephants and vice versa, in case of prolonged intensive contact. An accurate diagnostic approach covering

  9. Why do tuberculosis patients look for urgency and emergency unities for diagnosis: a study on social representation

    Regiane de Paula

    2014-09-01

    Full Text Available Objective: To understand the social representations of patients and professionals working in the field of tuberculosis, on the reasons for seeking diagnosis and treatment in the emergency room and not in the primary health care units called Unidades Básicas de Saúde (UBS or in the health program Programa de Saúde da Família near their residence. Methods: The survey was conducted in the health services in the municipalities of São Paulo and Guarulhos, Brazil, in hospitals and UBS. We interviewed 20 patients and 20 employees of these units, using the Collective Subject Discourse methodology to analyze their statements. The question presented to the users was: "Why did you seek the urgent emergency hospital and not the UBS to see if you had tuberculosis?" For professionals it was asked: "Why do you think the patient seeks diagnosis in the hospital and not in the UBS?" Results: As a result, two categories were found: (A the cultural patterns; and (B faults of the basic network. Conclusion: Analysis of the two explanatory dimensions show that the actions triggered by the health services should take into account the cultural patterns present in the social imaginary of the population; the health staff should receive training on specific knowledge of tuberculosis; there is a necessity of hiring human resources for the UBS and more inputs for programming.

  10. Tuberculosis treatment outcome in a tertiary care setting

    The outcome of the chemotherapy for pulmonary, extraplumonary and disseminated tuberculosis is not well documented, especially in developing countries. This study assessed tuberculosis treatment outcome, cure-to-treatment ratio and mortality among all types of tuberculosis patients in a tertiary care setting in Saudi Arabia. All cases diagnosed and treated for active Mycobacterium tuberculosis infection between 1991 and 2000 were included retrospectively. Data collected included type of tuberculosis involvement, treatment outcome, relapse and co-morbidities. Over a ten-year period, 535 case of tuberculosis were diagnosed and treated. Isolated pulmonary tuberculosis was identified in 141 cases (26.4%), extrapulmonary tuberculosis in 339 cases (63.3%). Co-morbidities were noted in 277 (52%) patients. Immunosuppression was found in 181 (34%) cases. The cure rate was 82%. The cure-to-treatment ratio was 86% in extrapulmonary tuberculosis and 65% in disseminated tuberculosis. Overall mortality was 18%. Disseminated tuberculosis had the highest mortality (34.9%), followed by pulmonary (21.8%), the extrapulmonary tuberculosis (13.6%). Forty-seven percent of all mortalities were directly related to tuberculosis. Relapse was documented in 14 out of 349 patients (4%) who had 24 months of follow-up. Despite tertiary care support, complicated tuberculosis carries a high mortality. Earlier diagnosis and complete appropriate chemotherapy are essential for improved outcome. (author)

  11. Comparison between 18F-FDG PET and CT in evaluating the activity of pulmonary tuberculosis

    Objective: To compare the difference between 18F-FDG PET and CT for evaluating the activity of pulmonary tuberculosis. Methods: 18F-FDG PET-CT was performed in 31 pulmonary tuberculosis patients,the activity of the tuberculosis lesions was evaluated by PET and CT images, the results of the two imaging methods were compared separately. Results: The results obtained with the two imaging methods were consistent in 26 cases and inconsistent in 5 cases.6 eases which CT diagnosed as inactive tuberculosis (healed lesions) were also judged as inactive lesions by PET imaging. In 16 cases, CT displayed that most of the lesions were calcified and associated with little streaks and diagnosed as inactive tuberculosis (obsolete lesions), among them PET judged 5 cases as active lesions, of which 3 cases with partly calcified lesion associated with mild radioactive uptake, 2 eases with streaks associated with mild radioactive uptake. 9 cases which CT diagnosed as active pulmonary tuberculosis, PET judged as active lesions too. Conclusions: 18FFDG PET and CT have the same judgment in diagnosing healed and active tuberculosis lesions, while 18FFDG PET is superior to CT in evaluating the active lesions residue in obsolete lesions. (authors)

  12. Immunologic evaluation and validation of methods using synthetic peptides derived from Mycobacterium tuberculosis for the diagnosis of tuberculosis infection

    Zaida Araujo

    2013-04-01

    Full Text Available The goal of this study was to demonstrate the usefulness of an enzyme-linked immunosorbent assay (ELISA for the serodiagnosis of pulmonary tuberculosis (PTB and extrapulmonary TB (EPTB. This assay used 20 amino acid-long, non-overlapped synthetic peptides that spanned the complete Mycobacterium tuberculosis ESAT-6 and Ag85A sequences. The validation cohort consisted of 1,102 individuals who were grouped into the following five diagnostic groups: 455 patients with PTB, 60 patients with EPTB, 40 individuals with non-EPTB, 33 individuals with leprosy and 514 healthy controls. For the PTB group, two ESAT-6 peptides (12033 and 12034 had the highest sensitivity levels of 96.9% and 96.2%, respectively, and an Ag85A-peptide (29878 was the most specific (97.4% in the PTB groups. For the EPTB group, two Ag85A peptides (11005 and 11006 were observed to have a sensitivity of 98.3% and an Ag85A-peptide (29878 was also the most specific (96.4%. When combinations of peptides were used, such as 12033 and 12034 or 11005 and 11006, 99.5% and 100% sensitivities in the PTB and EPTB groups were observed, respectively. In conclusion, for a cohort that consists entirely of individuals from Venezuela, a multi-antigen immunoassay using highly sensitive ESAT-6 and Ag85A peptides alone and in combination could be used to more rapidly diagnose PTB and EPTB infection.

  13. We nuclear physicians might have used the term 'activity' of pulmonary tuberculosis differently from clinicians who treat patients with tuberculosis

    It is difficult to determine the activity of tuberculosis radiologically. Therefore there have been efforts to assess the activity using radiopharmaceuticals such as 67Ga, 99mTc-tetrofosmin, and 99mTc-MIBI. But there may be some discrepancy in difining the term 'activity' between clinicians and nuclear physicians. While negative conversion of sputum acid fast bacilli (AFB) is defined as 'disappearance of activity' by clinicians, a loss of uptake in previously positive lesion is accepted as 'disappearance of activity' by nuclear physicians. We designed a prospective study to see if the negative conversion of sputum AFB could directly match the disappearance of radioactivity of the lesion. Fifteen patients with bacteriologically confirmed active localized pulmonary tuberculosis were scanned 10 and 60 min after intravenous injection of 550 MBq 99mTc-MIBI. In 6 patients, who showed negative conversion of sputum AFB after 3-7 months of chemotherapy, 99mTc-MIBI scan was repeated. For the purpose of comparison, target/nontarget raitos of the lesions were determined. 12/15 (80%) patients with active pulmonary tuberculosis showed increased uptake of 99mTc-MIBI in tuberculous lesion. After negative conversion of sputum AFB, 5/6 (83%) patients still showed increased uptake, although the intensity of uptake decreased. Uptake of radioactivity decreased but did not disappear after negative conversion of sputum AFB. 99mTc-MIBI scan may be useful to address the degree of inflammation of pulmonary tuberculous lesion, but the uptake did not directly match the activity defined by positivity of sputum AFB. We nuclear physicians might have used the term 'activity' somewhat differently from clinicians who treat patients with tuberculosis

  14. Antibacterial Activity of Medicinal Aqueous Plant Extracts against Mycobacterium tuberculosis

    Muna Mohammed Buzayan; Fauzia Rajab El-Garbulli

    2012-01-01

    Tuberculosis (TB) remains a serious health problem in many regions of the world, and the development of resistance to antibiotics by this microbe created the need for new drugs to replace those which have lost effectiveness. This study assesses the medicinal anti-Mycobacterium tuberculosis properties of natural products obtained from plants collected from Eastern Libya. In this study aqueous extracts of nine different plants were assayed for their Mycobacterium tuberculosis inhibitory activit...

  15. An evaluation of Universal Sample Processing method under Revised National Tuberculosis Control Programme set up for the diagnosis of pulmonary tuberculosis

    Savitha Parashuram

    2013-10-01

    Full Text Available Context: The main stay in the management of tuberculosis is its early diagnosis and treatment. Aim: To evaluate the utility of Universal Sample Processing (USP method, claimed to be more sensitive than direct smear microscopy. Materials and Methods: Sputum samples from 1000 patients with history of cough for more than two weeks, visiting the two RNTCP centers between November 2011 and November 2012, were subjected to direct Ziehl-Neelsen staining and staining after USP method. To find out if there was any difference in the time taken to detect Acid Fast Bacilli (AFB between the methods, the smears were screened by two trained RNTCP technicians. Sputum samples positive for AFB in the USP method were put up for culture on Lowenstein-Jensen medium to evaluate the suitability of USP method as a pre-treatment procedure before culture. The growth was identified as Mycobacterium tuberculosis (MTB by the Niacin test. Results: Ninety four samples were positive for AFB by both methods. The USP method did not detect more positives among those which were found negative by direct microscopy. There was no significant difference in the time taken to detect AFB between the methods. Among the 94 smear positive samples subjected to USP method as a pre-treatment procedure, only 40 (42.5% samples yielded growth of MTB. Conclusions: USP technique did not offer additional advantage over direct microscopy for detection of AFB to diagnose pulmonary tuberculosis. As a pre-treatment procedure, USP method yielded low mycobacterial growth even from those samples positive for AFB by microscopy, making it unsuitable for culture of MTB.

  16. Diagnosis and management of tuberculosis (Mycobacterium tuberculosis) in an Asian elephant (Elephas maximus) with a newborn calf.

    Vogelnest, Larry; Hulst, Frances; Thompson, Paul; Lyashchenko, Konstantin P; Herrin, Kimberly A Vinette

    2015-03-01

    In 2006, five Asian elephants (Elephas maximus) were imported to Taronga Zoo, Australia, from Thailand. Pre-import and initial postarrival tuberculosis screening was performed by trunk wash (TW) culture and was negative for Mycobacterium tuberculosis. In April 2009, the ElephantTB STAT-PAK (SP) assay was used to test the elephants. A 15.5-yr-old pregnant cow was reactive. TW frequency for this cow was increased from annually to quarterly. TW cultures remained negative on all other elephants. In February 2010, the Dual Path Platform (DPP) VetTB assay was used for the first time, and the SP-reactive cow also reacted on the DPP. A SP was run concurrently and was reactive. All other elephants were nonreactive on both assays. Treatment was not initiated due to concern about the effect of antituberculous drugs on the fetus. Quarterly TW cultures continued. The cow gave birth on 2 November 2010. A routine TW on 24 November 2010 was culture positive for M. tuberculosis. Although previous shedding could not be ruled out, reactivation of latent infection or exacerbation of subclinical disease due to parturition was suspected. Treatment with isoniazid, pyrazinamide, rifampicin, and ethambutol commenced. A 12-mo treatment course was completed within a 15-mo period. The isolate was susceptible to these drugs and genotyped as a Beijing strain. Stored serum samples from 2004 and 2006 were tested retrospectively and were reactive on SP and DPP. TW, SP, and DPP screening frequency increased to monthly for the positive cow on commencement of treatment in January 2011. Monthly serum biochemistry indicated drug-induced hepatitis. Therapeutic drug monitoring was conducted to ensure therapeutic levels were achieved. The infant calf was reactive on DPP, but TW culture negative, and was not treated. Serial DPP results for the cow and calf during and after treatment indicated that the antibody levels were declining, suggesting a favorable response to therapy in the dam, and that the origin

  17. Determining the Diagnostic Value of Mycobacterium Tuberculosis DNA in the Differentiation of Blood Samples of Patients with Active Pulmonary Tuberculosis and Healthy Controls Using Polymerase Chain Reaction

    Abasali Niazi

    2013-10-01

    Full Text Available Background: Tuberculosis (TB is now a major cause of mortality and morbidity in the world. Nowadays, different methods are used to diagnose tuberculosis. Although classical microbiological methods (such as sputum smear are specific, they have little sensitivity and the culture is also time-consuming. Using Polymerase Chain Reaction (PCR in blood samples in terms of Mycobacterium tuberculosis DNA, this study examines diagnostic power of this test in the diagnosis of pulmonary tuberculosis compared with other standard methods. Materials and Methods: In a cross-sectional descriptive-analytic study, blood samples were taken from 40 TB patients and 40 non-TB cases. Following DNA extraction by the commercial kit QIAGEN, the PCR assay was performed using IS6110 primer.Results: In this study, there were 80 people in two groups of TB and non-TB cases. Each group composed of 14 men (35% and 26 women (65%. Sensitivity, specificity as well as positive and negative predictive values obtained 37.5, 100, 100 and 61.5%, respectively.Conclusion: Despite high costs of using PCR for TB diagnosis, sensitivity of this method is low due to various factors and cannot replace current standard methods for TB diagnosis such as smear and culture. It can only be used as a complementary method to confirm diagnosis in strongly suspected cases of tuberculosis.

  18. Implementation of Xpert MTB/RIF in Uganda: Missed Opportunities to Improve Diagnosis of Tuberculosis

    Hanrahan, Colleen F.; Haguma, Priscilla; Ochom, Emmanuel; Kinera, Irene; Cobelens, Frank; Cattamanchi, Adithya; Davis, Luke; Katamba, Achilles; Dowdy, David

    2016-01-01

    Background. The effect of Xpert MTB/RIF (Xpert) scale-up on patient outcomes in low-income settings with a high tuberculosis (TB) burden has not been established. We sought to characterize the effectiveness of Xpert as implemented across different levels of the healthcare system in Uganda. Methods. We reviewed laboratory records from 2012 to 2014 at 18 health facilities throughout Uganda. In 8 facilities, Xpert had been implemented onsite since 2012, and in 10 sites Xpert was available as an offsite referral test from another facility. We describe Xpert testing volumes by facility, Xpert and smear microscopy results, and downtime due to malfunction and cartridge stockouts. We compare TB treatment initiation as well as time to treatment between facilities implementing Xpert and those that did not. Results. The median number of Xpert assays run at implementing facilities was 25/month (interquartile range [IQR], 10–63), amounting to 8% of total capacity. Among 1251 assays run for a new TB diagnosis, 19% were positive. Among 1899 patients with smear-negative presumptive TB, the proportion starting TB treatment was similar between Xpert facilities (11%; 95% confidence interval [CI], 9%–13%) and non-Xpert facilities (9%; 95% CI, 8%–11%; P = .325). In Xpert facilities, a positive Xpert preceded TB treatment initiation in only 12 of 70 (17%) smear-negative patients initiated on treatment. Conclusions. Xpert was underutilized in Uganda and did not significantly increase the number of patients starting treatment for TB. Greater attention must be paid to appropriate implementation of novel diagnostic tests for TB if these new tools are to impact patient important outcomes. PMID:27186589

  19. Diagnostic Accuracy of the GenoType MTBDRsl Assay for Rapid Diagnosis of Extensively Drug-Resistant Tuberculosis in HIV-Coinfected Patients

    Kontsevaya, Irina; Ignatyeva, Olga; Nikolayevskyy, Vladyslav; Balabanova, Yanina; Kovalyov, Alexander; Kritsky, Andrey; Matskevich, Olesya; Drobniewski, Francis

    2013-01-01

    The Russian Federation is a high-tuberculosis (TB)-burden country with high rates of Mycobacterium tuberculosis multidrug resistance (MDR) and extensive drug resistance (XDR), especially in HIV-coinfected patients. Rapid and reliable diagnosis for detection of resistance to second-line drugs is vital for adequate patient management. We evaluated the performance of the GenoType MTBDRsl (Hain Lifescience GmbH, Nehren, Germany) assay on smear-positive sputum specimens obtained from 90 HIV-infect...

  20. Tuberculosis (TB): Treatment

    ... 2/13 By Dr. Iseman Michael Iseman, MD Tuberculosis (TB): Treatment Given the many effective medications available ... is treated longer. NEXT: Preventive Treatment More Treating Tuberculosis Information Active TB Disease Drug-Resistant Tuberculosis Latent ...

  1. Imaging in Tuberculosis abdominal

    In this article we illustrate and discuss imaging features resulting from Tuberculosis abdominal affectation. We present patients evaluated with several imaging modalities who had abdominal symptoms and findings suggestive of granulomatous disease. Diagnosis was confirm including hystopatology and clinical outgoing. Cases involved presented many affected organs such as lymphatic system, peritoneum, liver, spleen, pancreas, kidneys, ureters, adrenal glands and pelvic organs Tuberculosis, Tuberculosis renal, Tuberculosis hepatic, Tuberculosis splenic Tomography, x-ray, computed

  2. The patellar tuberculosis

    Taser, Omer; Cakmak, Mehmet; Karamehmetoglu, Mahmut; Durmaz, Hayati; Cubuk, Mustafa Kemal

    2004-01-01

    A case has been reported herein with isolated patellar tuberculosis, which is very rarely enconsitered. Attempts have been made to review under the light of literature the significance of early diagnosis and treatment of choice in patellar tuberculosis.

  3. Ratio of monocytes to lymphocytes in peripheral blood in patients diagnosed with active tuberculosis

    Jun Wang

    2015-04-01

    Full Text Available Objective:The ratio of monocytes to lymphocytes in peripheral blood could reflect an indi- vidual's immunity to Mycobacterium tuberculosis. The objective of this study was to evaluate the relationship between ratio of monocytes to lymphocytes and clinical status of patients with active tuberculosis.Methods:This was a retrospective review of data collected from the clinical database of The Fifth People's Hospital of Wuxi, Medical College of Jiangnan University. A total of 419 patients who had newly diagnosed active tuberculosis and 108 cases from 419 patients with tuberculosis therapy either near completion or completed were selected. Controls were 327 healthy donors.Results:Median ratio of monocytes to lymphocytes was 0.36 (IQR, 0.22-0.54 in patients before treatment, and 0.16 (IQR, 0.12-0.20 in controls (p25% was significant predictors for active tuberculosis (OR = 114.73, 95% CI, 39.80-330.71; OR = 89.81, 95% CI, 53.18-151.68, respectively. After treatment, the median ratio of monocytes to lymphocytes recovered to be nearly normal. Compared to other patients, patients with extrapulmonary tuberculosis and of age >60 years were more likely to have extreme ratio of monocytes to lymphocytes (AOR = 2.57, 95% CI, 1.08-6.09; AOR = 4.36, 95% CI, 1.43-13.29, respectively.Conclusions:Ratio of monocytes to lymphocytes 25% is predictive of active tuberculosis.

  4. Rapid Diagnosis of Childhood Pulmonary Tuberculosis by Xpert MTB/RIF Assay Using Bronchoalveolar Lavage Fluid

    Qing-Qin Yin; Wei-Wei Jiao; Rui Han; An-Xia Jiao; Lin Sun; Jian-Ling Tian; Yu-Yan Ma; Xiao-Chun Rao; Chen Shen; Qin-Jing Li; A-Dong Shen

    2014-01-01

    In order to evaluate the diagnostic accuracy of the Xpert MTB/RIF assay on childhood pulmonary tuberculosis (PTB) using bronchoalveolar lavage fluid (BALF), we evaluated the sensitivity, specificity, positive predictive value, and negative predictive value of Xpert MTB/RIF assay using BALF in comparison with acid-fast bacilli (AFB) microscopy and Mycobacterium tuberculosis (MTB) culture for diagnosing childhood PTB using Chinese “composite clinical reference standard” (CCRS) as reference stan...

  5. Tuberculosis latente Latent tuberculosis

    Juan C Rodríguez D

    2012-03-01

    los portadores de tuberculosis latente es una acción crucial en los esfuerzos para disminuir la incidencia de tuberculosis en países en desarrollo con tasas de incidencia de tuberculosis intermedias o bajas.Tuberculosis continues being a huge public health problem. It has been estimated that worldwide every year about 9 million people adquire the disease and 2 million of deaths are because of tuberculosis. Exposure to Mycobacterium tuberculosis causes active disease in nearly 10% of the people. In the remaining 90% of the exposed population the immune response inhibits M. tuberculosis multiplication. In part of the exposed people (~40% some bacilli are not killed remaining in a non-replicating condition, generating the so called latent tuberculosis infection. The inactive bacilli can regain their vitality (replication capacity and cause active tuberculosis if the immune response is disrupted. Targeted screening and treatment for latent tuberculosis infection has been recognized as an effective strategy for tuberculosis control. Until recently, the only test available for the detection of latent tuberculosis infection was the tuberculin (PPD skin test. Recently it has been developed an in vitro T-cell-based interferon-gamma release assay (IGRA. This assay use antigens specific to M. tuberculosis and is not affected by previous BCG vaccination, making it a useful screening test for latent tuberculosis in BCG-vaccinated populations. FDA has approved two commercial IGRAs: a QuantiFERON-TB Gold (QFT, Cellestis which simplified variation is called Quantiferon T in Tube (QFT-G-IT and b T-SPOT TB test (Oxford, Immunotec. According to the Chilean National Program of Tuberculosis Control, therapy for latent tuberculosis infection is daily administration of isoniazid for 9 months; administered regularly this therapy gives over 90% of protection. Another option used in USA and Europe is to prescribe rifampicin for 4 months. Identification of latent tuberculosis carriers and

  6. Chemical constituents and anti-tuberculosis activity of ink extracts of cuttlefish, Sepiella inermis

    Muthusamy Ravichandiran

    2013-11-01

    Full Text Available Objective: To study the chemical constituents and the anti-tuberculosis activity of methanol and chloroform ink extracts of Sepiella inermis. Methods: Pulverized ink powder was extracted separately with chloroform and methanol. Chemical analysis was carried out by UV-VIS spectrophotometer, FT-IR and GC-MS. Crude extracts were tested in vitro for their activity against Mycobacterium tuberculosis using Lowenstein Jensen (L-J medium. Activity in L-J medium was assessed by mean reduction in number of colonies on extract containing bottles as compared to extract free controls. Results: GC-MS of methanol extract revealed four compounds viz. hexadecanoic acid, 9, 12- octadecadienoic acid, 9-octadecenoic acid and octadecanoic acid. The chloroform extract containing fourteen compounds. The methanol extract exhibited anti-tuberculosis activity in L-J medium at 64 µg/mL with the observed inhibition of 14 CFU. Chloroform extract displayed a weak activity against Mycobacterium tuberculosis. Conclusions: This investigation showed the methanol extract exhibited significant activity against Mycobacterium tuberculosis than chloroform extract. Since ink of sepia is available abundantly as a waste material, further studies aimed at isolation and efficacy of active substances pave the way for new anti-tuberculosis drugs.

  7. Early Bactericidal Activity of Moxifloxacin in Treatment of Pulmonary Tuberculosis: a Prospective, Randomized Study

    Pletz, Mathias W. R.; De Roux, Andres; Roth, Andreas; NEUMANN, Karl-Heinz; Mauch, Harald; Lode, Hartmut

    2004-01-01

    Moxifloxacin is the most active fluoroquinolone against Mycobacterium tuberculosis in vitro. However, data about the efficacy in patients are not available. We enrolled 17 patients with tuberculosis in a prospective, randomized study. After 5 days of monotherapy with either moxifloxacin or isoniazid, we detected significant decreases in mean CFU per milliliter in sputum in both groups. The calculated early bactericidal activities for isoniazid and moxifloxacin were 0.209 and 0.273 log10 CFU p...

  8. Plasma Drug Activity in Patients on Treatment for Multidrug-Resistant Tuberculosis

    Mpagama, Stellah G.; Ndusilo, Norah; Stroup, Suzanne; Kumburu, Happiness; Peloquin, Charles A; Gratz, Jean; Houpt, Eric R.; Kibiki, Gibson S; Scott K. Heysell

    2014-01-01

    Little is known about plasma drug concentrations relative to quantitative susceptibility in patients with multidrug-resistant tuberculosis (MDR-TB). We previously described a TB drug activity (TDA) assay that determines the ratio of the time to detection of plasma-cocultured Mycobacterium tuberculosis versus control growth in a Bactec MGIT system. Here, we assess the activity of individual drugs in a typical MDR-TB regimen using the TDA assay. We also examined the relationship of the TDA to t...

  9. Active case finding of tuberculosis in Europe: a Tuberculosis Network European Trials Group (TBNET) survey

    Bothamley, G H; Ditiu, L; Migliori, G B;

    2008-01-01

    and in-patient contacts. Screening of immigrants is related to their contribution to national rates of tuberculosis. Only 25 (50%) out of 50 advise a request for symptoms in their guidelines. A total of 36 (72%) out of 50 countries recommend sputum examination for those with a persistent cough; 13...

  10. Prevalence of patients with respiratory symptoms through active case finding and diagnosis of pulmonary tuberculosis among prisoners and related predictors in a jail in the city of Carapicuíba, Brazil Prevalência de sintomáticos respiratórios através da busca ativa, diagnóstico de tuberculose pulmonar entre pessoas privadas de liberdade e fatores associados em uma cadeia pública no município de Carapicuíba, Brasil

    Vieira, Amadeu A.; Sandra A. Ribeiro; Ana M. de Siqueira; Galesi, Vera M. N.; Laedi A. R. dos Santos; Jonathan E. Golub

    2010-01-01

    BACKGROUND: Prisons offer a fertile setting for the transmission of tuberculosis due to the presence of many classic risk factors for both infection and disease: overcrowding, poor ventilation, and little sunlight. Prisoners are often malnourished and have poor hygiene and are more likely to have a background of alcohol and drug abuse. OBJECTIVES: To determine the prevalence of prisoners with respiratory symptoms and pulmonary tuberculosis (PTB) through active case finding in a prisoner popul...

  11. Concomitant active tuberculosis prolongs survival in non-small cell lung cancer: a study in a tuberculosis-endemic country.

    Chih-Hsi Kuo

    Full Text Available BACKGROUND: Adjuvant tumor cell vaccine with chemotherapy against non-small cell lung cancer (NSCLC shows limited clinical response. Whether it provokes effective cellular immunity in tumor microenvironment is questionable. Concomitant active tuberculosis in NSCLC (TBLC resembles locoregional immunotherapy of tumor cell vaccine; thus, maximally enriches effective anti-tumor immunity. This study compares the survival and immunological cell profile in TBLC over NSCLC alone. METHODS: Retrospective review of NSCLC patients within 1-year-period of 2007 and follow-up till 2010. RESULTS: A total 276 NSCLC patients were included. The median survival of TBLC is longer than those of NSCLC alone (11.6 vs. 8.8 month, p<0.01. Active tuberculosis is an independent predictor of better survival with HR of 0.68 (95% CI, 0.48 ~ 0.97. Squamous cell carcinoma (SCC (55.8 vs. 31.7%, p<0.01 is a significant risk factor for NSCLC with active TB. The median survival of SCC with active tuberculosis is significantly longer than adenocarcinoma or undetermined NSCLC with TB (14.2 vs. 6.6 and 2.8 months, p<0.05. Active tuberculosis in SCC increases the expression of CD3 (46.4 ± 24.8 vs. 24.0 ± 16.0, p<0.05, CXCR3 (35.1 ± 16.4 vs. 19.2 ± 13.3, p<0.01 and IP-10 (63.5 ± 21.9 vs. 35.5 ± 21.0, p<0.01, while expression of FOXP3 is decreased (3.5 ± 0.5 vs. 13.3 ± 3.7 p<0.05, p<0.05. Survival of SCC with high expression of CD3 (12.1 vs. 3.6 month, p<0.05 and CXCR3 (12.1 vs. 4.4 month, p<0.05 is longer than that with low expression. CONCLUSIONS: Active tuberculosis in NSCLC shows better survival outcome. The effective T lymphocyte infiltration in tumor possibly underlies the mechanism. Locoregional immunotherapy of tumor cell vaccine may deserve further researches.

  12. Immune responses to ESAT-6 and CFP-10 by FASCIA and multiplex technology for diagnosis of M. tuberculosis infection; IP-10 is a promising marker.

    Emilie Borgström

    Full Text Available BACKGROUND: There is a need for reliable markers to diagnose active and latent tuberculosis (TB. The interferon gamma release assays (IGRAs are compared to the tuberculin skin test (TST more specific, but cannot discriminate between recent or remote TB infection. Here the Flow-cytometric Assay for Specific Cell-mediated Immune-response in Activated whole blood (FASCIA, which quantifies expanded T-lymphoblasts by flow-cytometric analysis after long-term antigen stimulation of whole blood, is combined with cytokine/chemokine analysis in the supernatant by multiplex technology for diagnosis of Mycobacterium tuberculosis (Mtb infection. METHODS AND FINDINGS: Consecutive patients with suspected TB (n = 85, with microbiologically verified active pulmonary TB (n = 33, extra pulmonary TB (n = 21, clinical TB (n = 11, presumed latent TB infection (LTBI (n = 23, patients negative for TB (n = 8 and 21 healthy controls were studied. Blood samples were analyzed with FASCIA and multiplex technology to determine and correlate proliferative responses and the value of 14 cytokines for diagnosis of Mtb infection: IFN- γ, IL-2, TNF-α, IP-10, IL-12, IL-6, IL-4, IL-5, IL-13, IL-17, MIP-1β, GM-CSF, IFN-α2 and IL-10. Cytokine levels for IFN-γ, IP-10, MIP-1β, IL-2, TNF-α, IL-6, IL-10, IL-13 and GM-CSF were significantly higher after stimulation with the Mtb specific antigens ESAT-6 and CFP-10 in patients with active TB compared to healthy controls (p<0.05 and correlated with proliferative responses. IP-10 was positive in all patients with verified TB, if using a combination of ESAT-6 and CFP-10 and was the only marker significantly more sensitive in detecting active TB then IFN-γ (p = 0.012. Cytokine responses in patients with active TB were more frequent and detected at higher levels than in patients with LTBI. CONCLUSIONS: IP-10 seems to be an important marker for diagnosis of active and latent TB. Patients with active TB and LTBI

  13. The Mycobacterium tuberculosis PPE protein Rv1168c induces stronger B cell response than Rv0256c in active TB patients.

    Abraham, Philip Raj; Udgata, Atul; Latha, Gaddam Suman; Mukhopadhyay, Sangita

    2016-06-01

    Tuberculosis (TB) caused by Mycobacterium tuberculosis is a serious global health problem and is responsible for millions of deaths every year. For effective control of this dreadful disease, it is necessary to diagnose TB cases at the initial stages of infection. The serodiagnosis of disease represents simple, rapid and inexpensive method that can be used at the primary health care levels. In this study we have compared sensitivity of two PPE proteins of M. tuberculosis, i.e., Rv0256c and Rv1168c for their use as serodiagnostic markers in active tuberculosis patients. Employing a standardized enzyme immunoassay with these PPE proteins as candidate antigens we were able to successfully discriminate the TB patients' sera from the BCG-vaccinated healthy controls. Further, we observed that Rv1168c displayed higher sensitivity in detecting extrapulmonary and smear negative pulmonary TB cases which are difficult to diagnose by available diagnostic methods. Overall the study highlights that Rv1168c can be used as a potential serodiagnostic marker for the diagnosis of active tuberculosis disease. PMID:26364913

  14. Exogenous Re-infection by Multiple Exposures to Mycobacterium tuberculosis Contributes to Subsequent Development of Active Tuberculosis

    Diane J. Ordway

    2005-01-01

    Full Text Available The majority of tuberculosis (TB exists in the world’s poorest countries, where costly biosafety level three facilities for containment of infectious TB patients and diagnostic facilities are not affordable. Health care workers (HCWs, in countries with high burdens of tuberculosis (TB are at risk of nosocomially acquired TB, as there are increased numbers of cases of TB on open hospital wards and minimal or absent TB infection control. This setting provides a means to study development of immune profiles associated with human exposure to Mycobacterium tuberculosis (Mtb. Individuals with multiple exposures to Mtb develop a Th1 response, involving IFN-γ. However early expression of a Th2 response, consisting of IL-4, was found to be associated with development of active TB disease. A Th2 response was confined to T cells of the CD8 and γδ T cell phenotype which can result in reduced bactericidal function of mycobacterial infected cells. The facets of the immune response which are responsible for failure of elimination of intracellular Mtb leading to active disease are poorly understood.

  15. Point-of-Care Diagnosis of Tuberculosis - Past, Present and Future

    Dheda, Keertan; Ruhwald, Morten; Theron, Grant;

    2013-01-01

    -day results at point-of-care (POC). When a return visit is required to access test results, time to treatment is prolonged and default rates are significant. However, a good diagnostic tool is also critically dependent on obtaining an adequate biological sample. Here we review the accuracy and potential...... impact of established and newer potential POC diagnostic tests for TB including smear microscopy, the Xpert MTB/RIF assay (Cepheid) and the Determine TB LAM antigen test (Alere). Novel experimental approaches and detection technologies for POC diagnosis of active TB, including nucleic acid amplification...... tests, detection of volatile organic compounds or metabolites, mass spectroscopy, microfluidics, SERS, electrochemical approaches, and aptamers amongst others, are discussed. We also discuss future applications, including the potential POC diagnosis of drug-resistant TB and presumed latent TB infection...

  16. Leveraging Advances in Tuberculosis Diagnosis and Treatment to Address Nontuberculous Mycobacterial Disease.

    Raju, Ravikiran M; Raju, Sagar M; Zhao, Yanlin; Rubin, Eric J

    2016-03-01

    The nontuberculous mycobacteria (NTM), defined as any mycobacterial pathogen other than Mycobacterium tuberculosis or Mycobacterium leprae, are a diverse group of pathogens that collectively cause a substantive but often unappreciated worldwide burden of illness. Although NTMs may cause illness similar to M. tuberculosis, these pathogens generally do not respond to classic tuberculosis (TB) drug regimens, resulting in misdiagnosis and poor treatment, particularly in resource-poor settings. Although a few high-quality epidemiologic surveys have been made on the topic, existing evidence suggests that NTM-associated disease is much more common than previously thought: more common than TB in the industrialized world and likely increasing in prevalence globally. Despite this evidence, these organisms remain markedly understudied, and few international grants support basic science and clinical research. Here we suggest that the considerable efforts in developing new treatments and diagnostics for TB can be harnessed in the fight against NTM-associated illnesses. PMID:26886068

  17. Sodium Hypochlorite Sedimentation Technique: A Simple Way to Enhance Sensitivity of Ziehl-Neelsen Stain in Diagnosis of Smear Negative Pulmonary Tuberculosis

    B. V. Peerapur

    2014-07-01

    Full Text Available Background: With the looming global HIV pandemic, the problem of tuberculosis tiptoes as a perpetual companion. Smear negative pulmonary tuberculosis which pose substantially a challenge for diagnosis, hoots this combination into noxious health problem. There is, therefore, an urgent need to establish more sensitive, safe and fairly rapid methodologies that could confirm diagnosis particularly in smear negative pulmonary tuberculosis patients. Aim: This study was carried out to establish whether, 3.5% sodium hypochlorite overnight sedimentation method improves the sensitivity of Ziehl-Neelsen (ZN stain in samples declared as smear negative. Material and Methods: A total of 605 direct ZN smear negative sputum specimens were examined after concentration with 3.5% sodium hypochlorite overnight sedimentation method. Results: Forty one (6.77% samples were found to be positive when smears were repeated after performing sodium hypochlorite sedimentation technique. Sensitivity and specificity of this method was found to be 76.31% and 97.88% respectively. Conclusion: 3.5% Sodium hypochlorite sedimentation technique has the potential to improve the diagnosis in tuberculosis in smear negative pulmonary tuberculosis cases especially in resource poor countries.

  18. Immunochromatographic IgG/IgM Test for Rapid Diagnosis of Active Tuberculosis▿

    Ben-Selma, Walid; Harizi, Hedi; Boukadida, Jalel

    2011-01-01

    For rapid diagnosis and discrimination between active tuberculosis (TB) and other pulmonary diseases, we evaluated the clinical usefulness of detection of serum immunoglobulin IgG and IgM antibodies raised against mycobacterial 38-kDa, 16-kDa, and 6-kDa antigens by a commercial rapid immunochromatographic IgG/IgM test (Standard Diagnostics, South Korea) in 246 serum samples from three groups of patients: (i) 171 patients with active TB (128 with pulmonary TB [pTB] and 43 with extrapulmonary T...

  19. Perinatal tuberculosis: Diagnostic and therapeutic approach

    Čegar Svetlana

    2012-01-01

    Full Text Available Introduction. The number of people suffering from tuberculosis has increased rapidly in the whole world over the past three decades. The classical age distribution of disease has also changed. According to the epidemiological data the number of pregnant women having tuberculosis has also risen with the resulting increase in the incidence of perinatal tuberculosis. Pregnancy and Tuberculosis. The presentation of tuberculosis in pregnancy varies. The effects of tuberculosis on pregnancy depend upon various factors: site and extent of the disease, nutritional status and immune status of mother, concomitant diseases, stage of pregnancy when the treatment started and others. A delay between the onset and diagnosis occurs regularly. Treatment response, time to clearance of bacilli from sputum, and prognosis are similar to non pregnant women. Prinatal tuberculosis. Perinatal tuberculosis is extremely rare if the mother is effectively treated in pregnancy, but disease is usually fatal if untreated. Diagnosis of perinatal tuberculosis is very often problematic and difficult. The reason of this is the fact that the initial manifestations of disease are nonspecific and may be delayed. In practice, congenital and early neonatal infections have almost the same mode of presentations, treatment and prognosis. Epidemiological data on the active tuberculosis in mother or some other family member are of the utmost importance in diagnoing tuberculosis. Differences in immune responses in the fetus and neonate add to the diagnostic difficulties already recognised in young children. Tuberculin tests are negative in at least 75% of cases. Conclusion. If the condition is recognized and treated according to existing tuberculosis protocols, the outcome is favourable.

  20. Screening strategies for active tuberculosis: focus on cost-effectiveness

    Dobler, Claudia Caroline

    2016-01-01

    In recent years, there has been renewed interest in screening for active tuberculosis (TB), also called active case-finding (ACF), as a possible means to achieve control of the global TB epidemic. ACF aims to increase the detection of TB, in order to diagnose and treat patients with TB earlier than if they had been diagnosed and treated only at the time when they sought health care because of symptoms. This will reduce or avoid secondary transmission of TB to other people, with the long-term goal of reducing the incidence of TB. Here, the history of screening for active TB, current screening practices, and the role of TB-diagnostic tools are summarized and the literature on cost-effectiveness of screening for active TB reviewed. Cost-effectiveness analyses indicate that community-wide ACF can be cost-effective in settings with a high incidence of TB. ACF among close TB contacts is cost-effective in settings with a low as well as a high incidence of TB. The evidence for cost-effectiveness of screening among HIV-infected persons is not as strong as for TB contacts, but the reviewed studies suggest that the intervention can be cost-effective depending on the background prevalence of TB and test volume. None of the cost-effectiveness analyses were informed by data from randomized controlled trials. As the results of randomized controlled trials evaluating different ACF strategies will become available in future, we will hopefully gain a better understanding of the role that ACF can play in achieving global TB control. PMID:27418848

  1. Rare congenital hearth disease as a cause of tuberculosis activation

    Radović Milan

    2010-01-01

    Full Text Available Introduction. Patients with congenital cyanotic heart defects and the left-to-right shunt are at a three times higher risk of getting tuberculosis than acyanotic ones. No TB cases have been recorded in adult patients with the right-to-left shunt having cyanosis since their birth. Case report. A 34-year-old man was referred to our Clinic with the discomforts such as chronic cough, hemoptysis and insomnia. At the admission he was pale, cyanotic, with a partial manifest respiratory insufficiency and characteristic TB pulmonary lesions detected by x-rays and tomography. After the sputum positive TB recidivism had been diagnosed, the antituberculotics treatment was introduced resulting in the successful smear and culture conversion and radiological regression of pulmonary lesions, but associated with non-explicable deterioration of cyanosis and chronic respiratory insufficiency until Doppler-echocardiographic examination verified the presence of tetralogy of Fallot. Conclusion. Congenital cyanotic heart defects are extremely rare in adults. Nevertheless, it is necessary to maintain a very high level of clinical suspicion regarding TB activation even in the cases of defects with the right-to-left shunt.

  2. The pattern of active pulmonary tuberculosis in adults at King Hussein Medical Center, Jordan

    To identify the pattern of the clinical, radiological, and diagnostic procedures of the diagnosed cases of active pulmonary tuberculosis (TB) patients presented to the Respiratory Medicine Division at King Hussein Medical Center over the last 10 years. This is a retrospective analysis of the medical records and chest radiographs of 137 active pulmonary TB patients who were diagnosed between March 1995 and October 2005. Patient's symptoms were recorded and analyzed. Radiological findings were assessed. Procedures used to identify Mycobacterium TB were identified. One hundred and thirty-seven patients medical records were retrieved and analyzed (84 males and 53 females). The mean age (range) was 48.43 +/- 14.65 (14-83) years. The most common presenting symptoms were cough (79%), weight loss (74%), and fatigue (69%). Other presenting complaints were fever (69%), excessive night sweating (55%), chest pain (41%) and dyspnea (39%). Thirty-one percent of the cohort presented with hemoptysis. Seventy-one patients had different types of opacities and infiltrates in their chest x-ray. Micro- or macro- nodular lung changes were reported in 22 (16%) patients. Lung cavitations and pleural effusions were present in 13% of the studied patients. In 7% of cases, bronchiectasis was noted as a sequelae of long-standing lung disease. The right lung was involved in 51% of cases; the left lung in 27% and bilateral lung involvement was noted in 22% of patients. The upper lobes were involved in 63%. Sputum for acid-fast bacilli (AFB) Z-Nielson stain and culture was positive in 51%, bronchial wash was positive in 27% of cases. The diagnosis was made by histopathological examination in 15% of cases. This study showed that active pulmonary TB patients vary in clinical presentation. The radiological manifestations of pulmonary TB are heterogeneous. Sputum for AFB remains an important, easy and inexpensive measure for TB diagnosis, but may not be always helpful in early diagnosis. Bronchoscopy

  3. Delay in the Diagnosis and Treatment of Pulmonary Tuberculosis in Uzbekistan: A Cross-Sectional Study

    Belkina, T.V.; Khojiev, D.S.; Tillyashaykhov, M.N.; Tigay, Z.N.; Kudenov, M.U.; Duintjer Tebbens, Jurjen; Vlček, J.

    2014-01-01

    Roč. 14, November (2014), article 624. ISSN 1471-2334 Grant ostatní: SVV UK(CZ) 260 066 Institutional support: RVO:67985807 Keywords : cross-sectional study * pulmonary tuberculosis * self-medication * Uzbekistan Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 2.613, year: 2014

  4. Angiotensin-Converting Enzyme Inhibitors and Active Tuberculosis

    Wu, Jiunn-Yih; Lee, Meng-Tse Gabriel; Lee, Si-Huei; Lee, Shih-Hao; Tsai, Yi-Wen; Hsu, Shou-Chien; Chang, Shy-Shin; Lee, Chien-Chang

    2016-01-01

    Abstract Numerous epidemiological data suggest that the use of angiotensin-converting enzyme inhibitors (ACEis) can improve the clinical outcomes of pneumonia. Tuberculosis (TB) is an airborne bacteria like pneumonia, and we aimed to find out whether the use of ACEis can decrease the risk of active TB. We conducted a nested case–control analysis by using a 1 million longitudinally followed cohort, from Taiwan national health insurance research database. The rate ratios (RRs) for TB were estimated by conditional logistic regression, and adjusted using a TB-specific disease risk score (DRS) with 71 TB-related covariates. From January, 1997 to December, 2011, a total of 75,536 users of ACEis, and 7720 cases of new active TB were identified. Current use (DRS adjusted RR, 0.87 [95% CI, 0.78–0.97]), but not recent and past use of ACEis, was associated with a decrease in risk of active TB. Interestingly, it was found that chronic use (>90 days) of ACEis was associated with a further decrease in the risk of TB (aRR, 0.74, [95% CI, 0.66–0.83]). There was also a duration response effect, correlating decrease in TB risk with longer duration of ACEis use. The decrease in TB risk was also consistent across all patient subgroups (age, sex, heart failure, cerebrovascular diseases, myocardial infraction, renal diseases, and diabetes) and patients receiving other cardiovascular medicine. In this large population-based study, we found that subjects with recent and chronic use of ACEis were associated with decrease in TB risk. PMID:27175655

  5. Role of digital tomosynthesis and dual energy subtraction digital radiography in detection of parenchymal lesions in active pulmonary tuberculosis

    Sharma, Madhurima, E-mail: madhurimashrm88@gmail.com [Department of Radiodiagnosis and Imaging, PGIMER, Chandigarh 160012 (India); Sandhu, Manavjit Singh, E-mail: manavjitsandhu@yahoo.com [Department of Radiodiagnosis and Imaging, PGIMER, Chandigarh 160012 (India); Gorsi, Ujjwal, E-mail: ujjwalgorsi@gmail.com [Department of Radiodiagnosis and Imaging, PGIMER, Chandigarh 160012 (India); Gupta, Dheeraj, E-mail: dheeraj1910@gmail.com [Department of Pulmonary Medicine, PGIMER, Chandigarh 160012 (India); Khandelwal, Niranjan, E-mail: khandelwaln@hotmail.com [Department of Radiodiagnosis and Imaging, PGIMER, Chandigarh 160012 (India)

    2015-09-15

    Highlights: • Digital tomosynthesis and dual energy subtraction digital radiography are modifications of digital radiography. • These modalities perform better than digital radiography in detection of parenchymal lesions in active pulmonary tuberculosis. • Digital tomosynthesis has a sensitivity of 100% in detection of cavities. • Centrilobular nodules seen on CT in active pulmonary tuberculosis, were also demonstrated on digital tomosynthesis in our study. • Digital tomosynthesis can be used for diagnosis and follow up of patients in pulmonary tuberculosis, thereby reducing the number of CT examinations. - Abstract: Objective: To assess the role of digital tomosynthesis (DTS) and dual energy subtraction digital radiography (DES-DR) in detection of parenchymal lesions in active pulmonary tuberculosis (TB) and to compare them with digital radiography (DR). Materials and methods: This prospective study was approved by our institutional review committee. DTS and DES-DR were performed in 62 patients with active pulmonary TB within one week of multidetector computed tomography (MDCT) study. Findings of active pulmonary TB, that is consolidation, cavitation and nodules were noted on digital radiography (DR), DTS and DES-DR in all patients. Sensitivity, specificity, positive and negative predictive values of all 3 modalities was calculated with MDCT as reference standard. In addition presence of centrilobular nodules was also noted on DTS. Results: Our study comprised of 62 patients (33 males, 29 females with age range 18–82 years). Sensitivity and specificity of DTS for detection of nodules and cavitation was better than DR and DES-DR. Sensitivity and specificity of DTS for detection of consolidation was comparable to DR and DES-DR. DES-DR performed better than DR in detection of nodules and cavitation. DTS was also able to detect centrilobular nodules with sensitivity and specificity of 57.4% and 86.5% respectively. Conclusion: DTS and DES-DR perform better

  6. Role of digital tomosynthesis and dual energy subtraction digital radiography in detection of parenchymal lesions in active pulmonary tuberculosis

    Highlights: • Digital tomosynthesis and dual energy subtraction digital radiography are modifications of digital radiography. • These modalities perform better than digital radiography in detection of parenchymal lesions in active pulmonary tuberculosis. • Digital tomosynthesis has a sensitivity of 100% in detection of cavities. • Centrilobular nodules seen on CT in active pulmonary tuberculosis, were also demonstrated on digital tomosynthesis in our study. • Digital tomosynthesis can be used for diagnosis and follow up of patients in pulmonary tuberculosis, thereby reducing the number of CT examinations. - Abstract: Objective: To assess the role of digital tomosynthesis (DTS) and dual energy subtraction digital radiography (DES-DR) in detection of parenchymal lesions in active pulmonary tuberculosis (TB) and to compare them with digital radiography (DR). Materials and methods: This prospective study was approved by our institutional review committee. DTS and DES-DR were performed in 62 patients with active pulmonary TB within one week of multidetector computed tomography (MDCT) study. Findings of active pulmonary TB, that is consolidation, cavitation and nodules were noted on digital radiography (DR), DTS and DES-DR in all patients. Sensitivity, specificity, positive and negative predictive values of all 3 modalities was calculated with MDCT as reference standard. In addition presence of centrilobular nodules was also noted on DTS. Results: Our study comprised of 62 patients (33 males, 29 females with age range 18–82 years). Sensitivity and specificity of DTS for detection of nodules and cavitation was better than DR and DES-DR. Sensitivity and specificity of DTS for detection of consolidation was comparable to DR and DES-DR. DES-DR performed better than DR in detection of nodules and cavitation. DTS was also able to detect centrilobular nodules with sensitivity and specificity of 57.4% and 86.5% respectively. Conclusion: DTS and DES-DR perform better

  7. Diagnosis of pulmonary tuberculosis by score system in children and adolescents: a trial in a reference center in Bahia, Brazil

    Clemax Couto Sant'Anna

    2004-08-01

    Full Text Available Since 2002, the Brazilian Ministry of Health has recommended a score system for tuberculosis diagnosis of children and adolescents that does not need bacteriological positivity, because most cases in this age group have few bacteria. An observational, transversal study was carried out at the outpatient health care service of the reference medical service in Salvador, Bahia, including 164 patients with pulmonary tuberculosis, with ages ranging between 1 and 15 years of age, who were treated from 1990 to 2001. The gold standard used to establish the diagnosis was clinical, radiological, epidemiological and based on follow-up data. The score system for diagnosis purposes was tested retrospectively. The median age and the average age of the 164 patients were 6 and 6.62 years (SD ± 4.33, respectively. About 65% of the sample reported a history of close contact with a tuberculous adult. The BCG vaccine coverage was 70.7% (116/164. It was found that 26% (43/164 of the patients had severe malnutrition. Out of this group, 26/43 (60.47% were < 5mm reactive to the tuberculin test. On the other hand, out of the 91 patients with tuberculin test < 5mm, 29% (26/ 91 had severe malnutrition. The use of the score gave the following distribution: a TB very likely in 81.7% (134/164 of the patients; b possible TB in 15.9% (26/164 and TB unlikely in 2.4% (4/164. Among patients who had been vaccinated more than 2 years before, there was a 9 times higher risk of finding a tuberculin test above 10 mm in individuals with probable TB in comparison with the patients with possible or unlikely TB.

  8. Tuberculosis 2004: Challenges and Opportunities

    Glassroth, Jeffrey

    2005-01-01

    Tuberculosis (TB) continues as a major public health challenge worldwide. HIV-TB coinfection is especially concerning as it accelerates progression of infection to active disease and amplifies spread of TB including drug resistant disease. Application of molecular biology and insights from classic microbiology to TB control have resulted in important innovations in diagnosis and treatment.

  9. A Multi-Country Non-Inferiority Cluster Randomized Trial of Frontloaded Smear Microscopy for the Diagnosis of Pulmonary Tuberculosis

    Cuevas, Luis Eduardo; Al-Sonboli, Najla; Lawson, Lovett; Yassin, Mohammed Ahmed; Arbide, Isabel; Al-Aghbari, Nasher; Bahadur Sherchand, Jeevan; Al-Absi, Amin; Emenyonu, Emmanuel Nnamdi; Merid, Yared; Okobi, Mosis Ifenyi; Onuoha, Juliana Olubunmi; Aschalew, Melkamsew; Aseffa, Abraham; Harper, Greg

    2011-01-01

    Editors' Summary Background Tuberculosis is a global public health problem. Every year, about 1.7 million people die from this contagious bacterial infection, and about 9 million new cases occur, mainly in low- and middle-income countries. Mycobacterium tuberculosis, which causes tuberculosis, is spread in airborne droplets when people with the disease cough or sneeze, and usually infects the lungs (pulmonary tuberculosis). Symptoms of tuberculosis include a persistent cough, weight loss, and...

  10. Programmatic Impact of QuantiFERON-TB Gold In-Tube Implementation on Latent Tuberculosis Diagnosis and Treatment in a Public Health Clinic

    Maunank Shah; Danielle DiPietro; Adena Greenbaum; Sherry Ketemepi; Maria Martins-Evora; Vincent Marsiglia; Dorman, Susan E.

    2012-01-01

    BACKGROUND: QuantiFERON-TB Gold In-Tube (QFT-GIT) is considered an alternative to the tuberculin skin test (TST) for the diagnosis of tuberculosis (TB) infection, but the programmatic impact of QFT-GIT implementation is largely unknown. In March, 2010, the Baltimore City Health Department (BCHD) introduced routine QFT-GIT testing for individuals referred to the TB program for suspected latent TB infection (LTBI). DESIGN: Retrospective study comparing LTBI diagnosis and treatment during the 13...

  11. Paratuberculosis vaccination causes only limited cross-reactivity in the skin test for diagnosis of bovine tuberculosis.

    Joseba M Garrido

    Full Text Available Although there is a wide consensus on the efficacy of paratuberculosis vaccination to limit economic losses, its use has been restricted because of its interference in the diagnosis of tuberculosis. Data from a vaccine clinical trial in the Basque Country (Spain has been evaluated in relationship with bovine tuberculosis intradermal test results. The trial included two herds applying a Test and Culling strategy and five applying an inactivated vaccine. The vaccine was applied to animals of all ages present in each vaccinated herd when joining the trial, and then to all the replacers within their first three months of life. Yearly testing done with the comparative intradermal test (CIT was applied to all animals older than 6 weeks. Between 2005 and 2011, the study generated 2,033 records from Vaccinated Herds (VH and 2,252 from Test and Cull herds (TC. Pre-vaccination positive results rate was 2.40% among the 7 herds in the single bovine intradermal tuberculin test (BSIT. Two years later it rose to 20.42% in the VH and remained below at 0.75% in the TC. Applying the CIT reduced these rates to only 0.58% in the VH and to 0.25% in the TC ons. Regarding time since each animal joined the program, the proportion of positives to BSIT was variable and, in some cases, significantly different between time points. With regard to the age of vaccination, no significant differences were found between vaccination within the first year of life and afterwards. Vaccinated animals showed seventeen times more reactions than the non-vaccinated in the BSIT, but only four times more in the CIT. In conclusion, comparative intradermal test can be a useful tool to differentiate paratuberculosis vaccine cross-reactions from specific bovine tuberculosis reactions according to the European and Spanish legislation.

  12. Utility value of a T-cell interferon-γ release assay based on recombinant Mycobacterium tuberculosis 11kD protein in the diagnosis of tuberculosis

    张丽帆

    2014-01-01

    Objective To evaluate the diagnostic efficiency of a T-cell interferon-γrelease assay based on recombinant Mycobacterium tuberculosis(MTB)11kD protein for diagnosing tuberculosis.Methods This prospective study enrolled inpatients with suspected tuberculosis at PUMCH to examine the diagnostic sensitivity,specificity,predictive value(PV)and likelihood ratio(LR)of T-cell interferon-γrelease assays based on recombinant MTB-11kD

  13. Genome-Based In Silico Identification of New Mycobacterium tuberculosis Antigens Activating Polyfunctional CD8+ T Cells in Human Tuberculosis

    Tang, Sheila Tuyet; van Meijgaarden, Krista E.; Caccamo, Nadia;

    2011-01-01

    Although CD8(+) T cells help control Mycobacterium tuberculosis infection, their M. tuberculosis Ag repertoire, in vivo frequency, and functionality in human tuberculosis (TB) remains largely undefined. We have performed genome-based bioinformatics searches to identify new M. tuberculosis epitopes...... presented by major HLA class I supertypes A2, A3, and B7 (covering 80% of the human population). A total of 432 M. tuberculosis peptides predicted to bind to HLA-A*0201, HLA-A*0301, and HLA-B*0702 (representing the above supertypes) were synthesized and HLA-binding affinities determined. Peptide-specific CD......8(+) T cell proliferation assays (CFSE dilution) in 41 M. tuberculosis-responsive donors identified 70 new M. tuberculosis epitopes. Using HLA/peptide tetramers for the 18 most prominently recognized HLA-A*0201-binding M. tuberculosis peptides, recognition by cured TB patients' CD8(+) T cells was...

  14. Pilot study of a rapid and minimally instrumented sputum sample preparation method for molecular diagnosis of tuberculosis.

    Ferguson, Tanya M; Weigel, Kris M; Lakey Becker, Annie; Ontengco, Delia; Narita, Masahiro; Tolstorukov, Ilya; Doebler, Robert; Cangelosi, Gerard A; Niemz, Angelika

    2016-01-01

    Nucleic acid amplification testing (NAAT) enables rapid and sensitive diagnosis of tuberculosis (TB), which facilitates treatment and mitigates transmission. Nucleic acid extraction from sputum constitutes the greatest technical challenge in TB NAAT for near-patient settings. This report presents preliminary data for a semi-automated sample processing method, wherein sputum is disinfected and liquefied, followed by PureLyse(®) mechanical lysis and solid-phase nucleic acid extraction in a miniaturized, battery-operated bead blender. Sputum liquefaction and disinfection enabled a >10(4) fold reduction in viable load of cultured Mycobacterium tuberculosis (M.tb) spiked into human sputum, which mitigates biohazard concerns. Sample preparation via the PureLyse(®) method and a clinically validated manual method enabled positive PCR-based detection for sputum spiked with 10(4) and 10(5) colony forming units (cfu)/mL M.tb. At 10(3) cfu/mL sputum, four of six and two of six samples amplified using the comparator and PureLyse(®) method, respectively. For clinical specimens from TB cases and controls, the two methods provided 100% concordant results for samples with 1 mL input volume (N = 41). The semi-automated PureLyse(®) method therefore performed similarly to a validated manual comparator method, but is faster, minimally instrumented, and can be integrated into TB molecular diagnostic platforms designed for near-patient low-resource settings. PMID:26785769

  15. Loss of receptor on tuberculin-reactive T-cells marks active pulmonary tuberculosis.

    Mathias Streitz

    Full Text Available BACKGROUND: Tuberculin-specific T-cell responses have low diagnostic specificity in BCG vaccinated populations. While subunit-antigen (e.g. ESAT-6, CFP-10 based tests are useful for diagnosing latent tuberculosis infection, there is no reliable immunological test for active pulmonary tuberculosis. Notably, all existing immunological tuberculosis-tests are based on T-cell response size, whereas the diagnostic potential of T-cell response quality has never been explored. This includes surface marker expression and functionality of mycobacterial antigen specific T-cells. METHODOLOGY/PRINCIPAL FINDINGS: Flow-cytometry was used to examine over-night antigen-stimulated T-cells from tuberculosis patients and controls. Tuberculin and/or the relatively M. tuberculosis specific ESAT-6 protein were used as stimulants. A set of classic surface markers of T-cell naïve/memory differentiation was selected and IFN-gamma production was used to identify T-cells recognizing these antigens. The percentage of tuberculin-specific T-helper-cells lacking the surface receptor CD27, a state associated with advanced differentiation, varied considerably between individuals (from less than 5% to more than 95%. Healthy BCG vaccinated individuals had significantly fewer CD27-negative tuberculin-reactive CD4 T-cells than patients with smear and/or culture positive pulmonary tuberculosis, discriminating these groups with high sensitivity and specificity, whereas individuals with latent tuberculosis infection exhibited levels in between. CONCLUSIONS/SIGNIFICANCE: Smear and/or culture positive pulmonary tuberculosis can be diagnosed by a rapid and reliable immunological test based on the distribution of CD27 expression on peripheral blood tuberculin specific T-cells. This test works very well even in a BCG vaccinated population. It is simple and will be of great utility in situations where sputum specimens are difficult to obtain or sputum-smear is negative. It will also help

  16. TUBERCULOSIS-A REVIEW OF CLINICAL FEATURES, DIFFERENTIAL DIAGNOSIS AND TREATMENTS AVAILABLE.

    Sravani.Kethireddy*

    2010-01-01

    Tuberculosis (TB) is a common deadly infectious disease usually affecting the lungs and also attacks other parts of the body. The disease often is fatal if not treated properly. The following review is aimed at discussing the transmission of the disease, its incidence globally, classification, its pathogenesis, risk factors, the various diagnostic methods available and the treatments used fordifferent types of patients with a note on different drugs used to treat along with a few brand detail...

  17. In vitro released antigens in diagnosis and immunomonitoring of filaria and tuberculosis

    Harinath, B. C.; Kumar, Satish; Reddy, M. V. R.

    1997-01-01

    In vitro released antigens by living parasites or bacteria underin vitro maintenance or short term culture showing specific humoral immune response have been explored in development of immunodiagnostics for infectious diseases such as filariasis and tuberculosis in our laboratory. ELISA usingB. malayi mf ES antigen has been explored for detecting IgG antibody by Indirect ELISA and antigen by Inhibition ELISA and in immunomonitoring of carriers as well as clinical filarial cases. A ten year fo...

  18. HIV testing, HIV status and outcomes of treatment for tuberculosis in a major diagnosis and treatment centre in Yaounde, Cameroon: a retrospective cohort study

    Yone Eric

    2012-08-01

    Full Text Available Abstract Background Human immuno-deficiency virus (HIV infection and tuberculosis are common and often co-occurring conditions in sub-Saharan Africa (SSA. We investigated the effects of HIV testing and HIV status on the outcomes of tuberculosis treatment in a major diagnosis and treatment centre in Yaounde, Cameroon. Methods Participants were 1647 adults with tuberculosis registered at the Yaounde Jamot’s Hospital between January and December 2009. Multinomial logistic regression models were used to relate HIV testing and HIV status to the outcomes of tuberculosis treatment during follow-up, with adjustment for potential covariates. Results Mean age of participants was 35.5 years (standard deviation: 13.2 and 938 (57% were men. Clinical forms of tuberculosis were: smear-positive (73.8%, smear-negative (9.4% and extra-pulmonary (16.8%. Outcomes of tuberculosis treatment were: cure/completion (68.1%, failure (0.4%, default (20.1%, death (5.2% and transfer (6.3%. Using cure/completion as reference, not testing for HIV was associated with adjusted odds ratio of 2.30 (95% confidence interval: 1.65-3.21, 2.26 (1.29-3.97 and 2.69 (1.62-4.46 for the risk of failure/default, death and transfer respectively. The equivalents for a positive test among those tested (1419 participants were 1.19 (0.88-1.59, 6.35 (3.53-11.45 and 1.14 (0.69-1.86. Conclusions Non-consent for HIV testing in this setting is associated with all unfavourable outcomes of tuberculosis treatment. However been tested positive was the strongest predictor of fatal outcome. Efforts are needed both to improve acceptance of HIV testing among patients with tuberculosis and optimise the care of those tested positive.

  19. Standing of nucleic acid testing strategies in veterinary diagnosis laboratories to uncover Mycobacterium tuberculosis complex members.

    Costa, Pedro; Botelho, Ana; Couto, Isabel; Viveiros, Miguel; Inácio, João

    2014-01-01

    Nucleic acid testing (NAT) designate any molecular approach used for the detection, identification, and characterization of pathogenic microorganisms, enabling the rapid, specific, and sensitive diagnostic of infectious diseases, such as tuberculosis. These assays have been widely used since the 90s of the last century in human clinical laboratories and, subsequently, also in veterinary diagnostics. Most NAT strategies are based in the polymerase chain reaction (PCR) and its several enhancements and variations. From the conventional PCR, real-time PCR and its combinations, isothermal DNA amplification, to the nanotechnologies, here we review how the NAT assays have been applied to decipher if and which member of the Mycobacterium tuberculosis complex is present in a clinical sample. Recent advances in DNA sequencing also brought new challenges and have made possible to generate rapidly and at a low cost, large amounts of sequence data. This revolution with the high-throughput sequencing (HTS) technologies makes whole genome sequencing (WGS) and metagenomics the trendiest NAT strategies, today. The ranking of NAT techniques in the field of clinical diagnostics is rising, and we provide a SWOT (Strengths, Weaknesses, Opportunities, and Threats) analysis with our view of the use of molecular diagnostics for detecting tuberculosis in veterinary laboratories, notwithstanding the gold standard being still the classical culture of the agent. The complementary use of both classical and molecular diagnostics approaches is recommended to speed the diagnostic, enabling a fast decision by competent authorities and rapid tackling of the disease. PMID:25988157

  20. A STUDY OF IMPACT OF DETERMINANTS OF PATIENTS AND HEALTH SYSTEM DELAY ON TUBERCULOSIS DIAGNOSIS AND TREATMENT IN BANGALORE

    Jagadish Siddalinga Devaru

    2013-01-01

    Full Text Available Setting: TU/DMCs of Bangalore city. India. All new sputum positive patients registered to the selected TU/DMCs were interviewed. A total of 468 patients aged above 20 years were enrolled. The study period was from January to June 2009. Objectives: To track the delay in diagnosis and treatment of patients reporting to tuberculosis units and microscopy centers. Design: A cross sectional study. TU/DMCs were randomly selected. A pretested questionnaire was administered to collect data. Results: The study population had 326 (69.7% males. The mean age of study population was 38.5 years. 74.4% were married, 20.7% were illiterates, 27.8% were daily wagers, 10.5% were unemployed. The median and mean total delays from development of cough to diagnosis were 41 days and 36.04 days; the median and mean patient delay was 24 days and 20.7 days, and health system delay was 18 and 15.31 days respectively. There was a significant difference among the different age group of patients with older people having longer patient delay (p<0.0001. Lower income, illiteracy, unemployment, showed significant association with patients delay (p<0.0001. Alcohol intake and smoking habit among the male patients had significant association for longer patient delay (p=0.00004. Health seeking behavior like self medication, also had longer patient delay. Other socio demographic factors had no significant influence on the patient delay. Longer health system delay was found among patients who visited general practitioners and Ayurvedic medicine. Conclusion: More specific and effective health education of the general public on tuberculosis and seeking of appropriate medical consultation are likely to improve case detection.

  1. Evaluation of Forty-Nine Patients with Abdominal Tuberculosis

    Murat Kilic

    2014-12-01

    Full Text Available Aim: Abdominal tuberculosis is an uncommon form of extrapulmonary infection. In this study, we aimed to highlight the nonspecific clinical presentations and diagnostic difficulties of abdominal tuberculosis. Material and Method: Clinical features, diagnostic methods, and the therapeutic outcomes of 49 patients diagnosed as abdominal tuberculosis between 2003 and 2014 were retrospectively analyzed. Results: The patients were classified into four subgroups including peritoneal (28, nodal (14, intestinal (5, and solid organ tuberculosis (2. The most frequent symptoms were abdominal pain, abdominal distention and fatique. Ascites appeared to be the most frequent clinical finding. Ascites and enlarged abdominal lymph nodes were the most frequent findings on ultrasonography and tomography. Diagnosis of abdominal tuberculosis was mainly depended on histopathology of ascitic fluid and biopsies from peritoneum, abdominal lymph nodes or colonoscopic materials. Forty patients healed with standart 6-month therapy while extended treatment for 9-12 months was needed in 8 whom had discontinued drug therapy and had persistent symptoms and signs. One patient died within the treatment period due to disseminated infection. Discussion: The diagnosis of abdominal tuberculosis is often difficult due to diverse clinical presentations. The presence of ascites, personal/familial/contact history of tuberculosis, and coexisting active extraabdominal tuberculosis are the most significant marks in diagnosis. Diagnostic laparoscopy and tissue sampling seem to be the best diagnostic approach for abdominal tuberculosis.

  2. [Health examination in future at the era of low tuberculosis incidence--from contacts examination toward active epidemiological studies].

    Maeda, Hideo; Shirai, Chika

    2013-03-01

    Japan is still "intermediate burden" country as medium-incidence of tuberculosis (TB). But the incidence of TB varies by public health units. The priority for TB control would be lowering in the areas where the incidence of TB is relatively low. In addition, younger age groups get low prevalence of TB infection than elderly persons. As a result, fewer experiences for TB diagnosis and treatment in the hospital and the medical facility would cause the delay in the detection of TB patients which eventually cause outbreaks. Although there are differences in population density and population mobility between urban and rural areas, the socially economic vulnerable patients and foreign patients are the common risks. Any public health units' policies of TB should correspond to the individual situation. At the era of low tuberculosis incidence, the infection risk is to be "From ubiquitous to the uneven distribution". This makes TB detection much more difficult. At this symposium, each speaker presented the case for actually experienced with QFT test and/or VNTR analysis. They mainly focused on the paradigm shift in TB control which is indispensable for resolving the gaps in regional differences and the differences in diagnostic capability. Although the cases in this symposium were not for the low incidence situation, the pioneering approaches presented here would boost the future application of QFT and VNTR analysis nationwide. The discussions also partially covered the technical infrastructure for molecular epidemiology which covers the whole country. By making full use of QFT test and VNTR analysis as a contact screening tool, we can appropriately understand the risk of TB infection in the region from a buildup of bacteria and patient information. Now is the time to prepare for. Active surveillance of TB by this way would clarify the risk of the disease and lead to the advocacy essential for the resolution. 1. Current situation and challenge of contact survey by using QFT

  3. Poor performance of serological tests in the diagnosis of pulmonary tuberculosis: evidence from a contact tracing field study.

    Sarman Singh

    Full Text Available BACKGROUND: Delayed or missed diagnosis of TB continues to fuel the global TB epidemic, especially in resource limited settings. Use of serology for the diagnosis of tuberculosis, commonly used in India, is another factor. In the present study a commercially available serodiagnostic assay was assessed for its diagnostic value in combination with smear, culture and clinical manifestations. METHODOLOGY/PRINCIPAL FINDINGS: A total of 2300 subjects were recruited for the study, but 1041 subjects were excluded for various reasons. Thus 1259 subjects were included in the study of which 470 were pulmonary tuberculosis cases (440 of 470 were culture-positive and 789 were their asymptomatic contacts. A house-to-house survey method was used. Blood samples were tested for IgM, IgA, and IgG antibodies using the Pathozyme Myco M (IgM, Myco A (IgA and Myco G (IgG enzyme immunoassay (EIA. Out of 470 PTB cases, BCG scar was positive in 82.34%. The Mantoux test and smear positivity rates in PTB cases were 94.3% (430/456, and 65.32% (307/470, respectively. Among the asymptomatic contacts, BCG scar was positive in 95.3% and Mantoux test was positive in 80.66% (442/548 contacts. No contact was found falsely smear positive. The sensitivity of IgM, IgA, and IgG EIA tests was 48.7%, 25.7% and 24.4%, respectively, while the specificity was 71.5%, 80.5%, 76.6%, respectively. Performance of EIAs was not affected by the previous BCG vaccination. However, prior BCG vaccination was statistically significantly (p = 0.005 associated with Mantoux test positivity in PTB cases but not in contacts (p = 0.127. The agreement between serology and Mantoux test was not significant. CONCLUSION: The commercial serological test evaluated showed poor sensitivity and specificity and suggests no utility for detection of pulmonary tuberculosis.

  4. Evaluation of the 2007 WHO guideline to improve the diagnosis of tuberculosis in ambulatory HIV-positive adults.

    Olivier Koole

    Full Text Available BACKGROUND: In 2007 WHO issued a guideline to improve the diagnosis of smear-negative and extrapulmonary tuberculosis (EPTB in HIV-positive patients. This guideline relies heavily on the acceptance of HIV-testing and availability of chest X-rays. METHODS AND FINDINGS: Cohort study of TB suspects in four tuberculosis (TB clinics in Phnom Penh, Cambodia. We assessed the operational performance of the guideline, the incremental yield of investigations, and the diagnostic accuracy for smear-negative tuberculosis in HIV-positive patients using culture positivity as reference standard. 1,147 (68.9% of 1,665 TB suspects presented with unknown HIV status, 1,124 (98.0% agreed to be tested, 79 (7.0% were HIV-positive. Compliance with the guideline for chest X-rays and sputum culture requests was 97.1% and 98.3% respectively. Only 35 of 79 HIV-positive patients (44.3% with a chest X-ray suggestive of TB started TB treatment within 10 days. 105 of 442 HIV-positive TB suspects started TB treatment (56.2% smear-negative pulmonary TB (PTB, 28.6% smear-positive PTB, 15.2% EPTB. The median time to TB treatment initiation was 5 days (IQR: 2-13 days, ranging from 2 days (IQR: 1-11.5 days for EPTB, over 2.5 days (IQR: 1-4 days for smear-positive PTB to 9 days (IQR: 3-17 days for smear-negative PTB. Among the 34 smear-negative TB patients with a confirmed diagnosis, the incremental yield of chest X-ray, clinical suspicion or abdominal ultrasound, and culture was 41.2%, 17.6% and 41.2% respectively. The sensitivity and specificity of the algorithm to diagnose smear-negative TB in HIV-positive TB suspects was 58.8% (95%CI: 42.2%-73.6% and 79.4% (95%CI: 74.8%-82.4% respectively. CONCLUSIONS: Pending point-of-care rapid diagnostic tests for TB disease, diagnostic algorithms are needed. The diagnostic accuracy of the 2007 WHO guideline to diagnose smear-negative TB is acceptable. There is, however, reluctance to comply with the guideline in terms of immediate treatment

  5. Tuberculose em pacientes com artrite reumatoide: a dificuldade no diagnóstico da forma latente Tuberculosis in rheumatoid arthritis patients: the difficulty in making the diagnosis of latent infection

    Daniela Graner Schuwartz Tannus Silva

    2010-04-01

    Full Text Available Desde o início do uso de drogas anti-TNF para o tratamento da artrite reumatoide e outras doenças inflamatórias, casos de tuberculose pulmonar e extrapulmonar vêm sendo notificados em pacientes submetidos a tal tratamento. Na maioria das vezes, a doença se desenvolve durante as seis primeiras infusões. Todo paciente deve ser avaliado para tuberculose latente antes do início do uso de um bloqueador de TNF; no entanto, o diagnóstico de tuberculose latente é um desafio. A prova tuberculínica, o único teste disponível para a detecção de tuberculose latente por quase um século, apresenta uma série de limitações. Testes baseados na detecção da produção de IFN-γ in vitro por células mononucleares ativadas por antígenos específicos parecem ser mais acurados e vêm sendo pesquisados em pacientes com artrite reumatoide.Since the beginning of the use of anti-TNF in the treatment of rheumatoid arthritis and other inflammatory diseases, cases of pulmonary tuberculosis and extrapulmonary tuberculosis have been reported in patients receiving such treatment. In most cases, the disease develops by the time the patient has received the sixth infusion. Every patient should be evaluated for latent tuberculosis infection prior to the use of a TNF inhibitor. However, the diagnosis of latent tuberculosis infection is a challenge. The tuberculin test, which was the only test available to detect latent tuberculosis infection for nearly a century, presents a number of limitations. Tests based on the detection of the in-vitro production of IFN-γ by mononuclear cells activated by specific antigens appear to be more accurate and have been studied in patients with rheumatoid arthritis.

  6. Release of interleukin-1 by peripheral blood mononuclear cells in patients with tuberculosis and active inflammation.

    Chensue, S. W.; Davey, M P; Remick, D. G.; Kunkel, S. L.

    1986-01-01

    Peripheral blood monocytes from patients with active tuberculosis and acute inflammatory disease showed spontaneous interleukin-1 production when compared with those from control patients or healthy controls. Moreover, interleukin-1 production appeared to be a more specific indicator of active disease than were other commonly used indices, such as the erythrocyte sedimentation rate and serum C-reactive protein levels.

  7. Rapid Diagnosis of Smear-Negative Tuberculosis Using Immunology and Microbiology with Induced Sputum in HIV-Infected and Uninfected Individuals

    Breen, R A M; Hardy, G. A. D.; Perrin, F. M. R.; Lear, S; Kinloch, S.; Smith, C. J.; Cropley, I.; Janossy, G.; Lipman, M. C. I.

    2007-01-01

    Rationale and Objectives. Blood-based studies have demonstrated the potential of immunological assays to detect tuberculosis. However lung fluid sampling may prove superior as it enables simultaneous microbiological detection of mycobacteria to be performed. Until now this has only been possible using the expensive and invasive technique of broncho-alveolar lavage. We sought to evaluate an immunoassay using non-invasive induced-sputum to diagnose active tuberculosis. Methods and Results. Pros...

  8. Strategic use of serology for the diagnosis of bovine tuberculosis after intradermal skin testing.

    Casal, Carmen; Díez-Guerrier, Alberto; Álvarez, Julio; Rodriguez-Campos, Sabrina; Mateos, Ana; Linscott, Richard; Martel, Edmond; Lawrence, John C; Whelan, Clare; Clarke, John; O'Brien, Amanda; Domínguez, Lucas; Aranaz, Alicia

    2014-06-01

    Diagnostic tests based on cell-mediated immunity are used in programmes for eradication of bovine tuberculosis (Mycobacterium bovis). Serological assays could be applied as ancillary methods to detect infected animals. Our objective was to evaluate two serological techniques: M. bovis Ab Test (IDEXX, USA) and Enferplex™ TB assay (Enfer, Ireland) in animals tested simultaneously with the single and comparative intradermal tests and the interferon-gamma assay. This work was performed at two stages. First, a preliminary panel of samples collected prior to intradermal tests from tuberculosis-free (n=60) and M. bovis-infected herds (n=78) was assayed, obtaining high specificity: 100% (M. bovis Ab Test) and 98.3% (Enferplex TB assay) but low sensitivity (detection of M. bovis infected animals): 23.9% (M. bovis Ab Test) and 32.6% (Enferplex TB assay). Subsequently, the use of serological techniques was further studied in two herds with M. bovis infection (n=77) using samples collected prior to, and 72 h and 15 days after PPD inoculation. The highest level of detection of infected animals for serology was achieved at 15 days post-intradermal tests taking advantage of the anamnestic effect: 70.4% and 85.2% in herd A, and 66.7% and 83.3% in herd B, using M. bovis Ab Test and Enferplex TB assay, respectively. Quantitative results (average values obtained with M. bovis Ab Test ELISA and degree of positivity obtained with Enferplex TB assay) were higher in animals showing lesions compatible with tuberculosis. No significant differences were observed in the number of confirmed infected animals detected with either serological technique. PMID:24679958

  9. Advances in the Diagnosis, Treatment and Control of HIV Associated Tuberculosis

    Bruce J. Kirenga; Chanda, Duncan M; Muwonge, Catherine M; Yimer, Getnet; Francis E Adatu; Onyebujoh, Philip C

    2012-01-01

    There has been an increase in the number of published tuberculosis/HIV (TB/HIV) research findings in recent times. The potential impact of these findings on routine care has informed this review which aims at discussing current concepts and practices underpinning TB/HIV care and control. Any HIV infected person with a cough of any duration is currently considered a TB suspect. Preliminary results also show that the diagnostic yield of same day sputum samples (front loading) is comparable to t...

  10. Successful diagnosis of hyperpyrexia induced by isoniazid in a child with suspected extra-pulmonary tuberculosis

    Qu, Caihong; Li, Xiaoyan; Zheng, Zhenda; Zhu, Jieming

    2015-01-01

    A 9-year-old boy received a rifampicin-isoniazid-ethambutol regimen for suspected extra-pulmonary tuberculosis, and glucurolactone and vitamin B6 to provide liver protection and decrease neurotoxicity associated with isoniazid. Baseline serum aminotransferase and total bilirubin levels were within normal limits before anti-tubercular treatment. After 4 days of treatment, the patient’s body temperature increased (from 38.0°C to 40.1°C) and on the 11th day of treatment, serum chemistry results ...

  11. Rapid, Semiquantitative Assay To Discriminate among Compounds with Activity against Replicating or Nonreplicating Mycobacterium tuberculosis.

    Gold, Ben; Roberts, Julia; Ling, Yan; Quezada, Landys Lopez; Glasheen, Jou; Ballinger, Elaine; Somersan-Karakaya, Selin; Warrier, Thulasi; Warren, J David; Nathan, Carl

    2015-10-01

    The search for drugs that can kill replicating and nonreplicating Mycobacterium tuberculosis faces practical bottlenecks. Measurement of CFU and discrimination of bacteriostatic from bactericidal activity are costly in compounds, supplies, labor, and time. Testing compounds against M. tuberculosis under conditions that prevent the replication of M. tuberculosis often involves a second phase of the test in which conditions are altered to permit the replication of bacteria that survived the first phase. False-positive determinations of activity against nonreplicating M. tuberculosis may arise from carryover of compounds from the nonreplicating stage of the assay that act in the replicating stage. We mitigate these problems by carrying out a 96-well microplate liquid MIC assay and then transferring an aliquot of each well to a second set of plates in which each well contains agar supplemented with activated charcoal. After 7 to 10 days-about 2 weeks sooner than required to count CFU-fluorometry reveals whether M. tuberculosis bacilli in each well have replicated extensively enough to reduce a resazurin dye added for the final hour. This charcoal agar resazurin assay (CARA) distinguishes between bacterial biomasses in any two wells that differ by 2 to 3 log10 CFU. The CARA thus serves as a pretest and semiquantitative surrogate for longer, more laborious, and expensive CFU-based assays, helps distinguish bactericidal from bacteriostatic activity, and identifies compounds that are active under replicating conditions, nonreplicating conditions, or both. Results for 14 antimycobacterial compounds, including tuberculosis (TB) drugs, revealed that PA-824 (pretomanid) and TMC207 (bedaquiline) are largely bacteriostatic. PMID:26239979

  12. Anti-Mycobacterium tuberculosis activity and cytotoxicity of Calophyllum brasiliense Cambess (Clusiaceae

    Claudia Terencio Agostinho Pires

    2014-06-01

    Full Text Available We evaluated the in vitro anti-Mycobacterium tuberculosis activity and the cytotoxicity of dichloromethane extract and pure compounds from the leaves of Calophyllum brasiliense. Purification of the dichloromethane extract yielded the pure compounds (- mammea A/BB (1, (- mammea B/BB (2 and amentoflavone (3. The compound structures were elucidated on the basis of spectroscopic and spectrometric data. The contents of bioactive compounds in the extracts were quantified using high performance liquid chromatography coupled to an ultraviolet detector. The anti-M. tuberculosis activity of the extracts and the pure compounds was evaluated using a resazurin microtitre assay plate. The cytotoxicity assay was performed in J774G.8 macrophages using the 3-(4,5-dimethyl thiazol-2-yl-2,5-diphenyl tetrazolium bromide colourimetric method. The quantification of the dichloromethane extract showed (1 and (2 at concentrations of 31.86 ± 2.6 and 8.24 ± 1.1 µg/mg of extract, respectively. The dichloromethane and aqueous extracts showed anti-M. tuberculosis H37Rv activity of 62.5 and 125 µg/mL, respectively. Coumarins (1 and (2 showed minimal inhibitory concentration ranges of 31.2 and 62.5 µg/mL against M. tuberculosis H37Rv and clinical isolates. Compound (3 showed no activity against M. tuberculosis H37Rv. The selectivity index ranged from 0.59-1.06. We report the activity of the extracts and coumarins from the leaves of C. brasiliense against M. tuberculosis.

  13. Drug-resistant tuberculosis--current dilemmas, unanswered questions, challenges, and priority needs.

    Zumla, Alimuddin; Abubakar, Ibrahim; Raviglione, Mario; Hoelscher, Michael; Ditiu, Lucica; McHugh, Timothy D; Squire, S Bertel; Cox, Helen; Ford, Nathan; McNerney, Ruth; Marais, Ben; Grobusch, Martin; Lawn, Stephen D; Migliori, Giovanni-Battista; Mwaba, Peter; O'Grady, Justin; Pletschette, Michel; Ramsay, Andrew; Chakaya, Jeremiah; Schito, Marco; Swaminathan, Soumya; Memish, Ziad; Maeurer, Markus; Atun, Rifat

    2012-05-15

    Tuberculosis was declared a global emergency by the World Health Organization (WHO) in 1993. Following the declaration and the promotion in 1995 of directly observed treatment short course (DOTS), a cost-effective strategy to contain the tuberculosis epidemic, nearly 7 million lives have been saved compared with the pre-DOTS era, high cure rates have been achieved in most countries worldwide, and the global incidence of tuberculosis has been in a slow decline since the early 2000s. However, the emergence and spread of multidrug-resistant (MDR) tuberculosis, extensively drug-resistant (XDR) tuberculosis, and more recently, totally drug-resistant tuberculosis pose a threat to global tuberculosis control. Multidrug-resistant tuberculosis is a man-made problem. Laboratory facilities for drug susceptibility testing are inadequate in most tuberculosis-endemic countries, especially in Africa; thus diagnosis is missed, routine surveillance is not implemented, and the actual numbers of global drug-resistant tuberculosis cases have yet to be estimated. This exposes an ominous situation and reveals an urgent need for commitment by national programs to health system improvement because the response to MDR tuberculosis requires strong health services in general. Multidrug-resistant tuberculosis and XDR tuberculosis greatly complicate patient management within resource-poor national tuberculosis programs, reducing treatment efficacy and increasing the cost of treatment to the extent that it could bankrupt healthcare financing in tuberculosis-endemic areas. Why, despite nearly 20 years of WHO-promoted activity and >12 years of MDR tuberculosis-specific activity, has the country response to the drug-resistant tuberculosis epidemic been so ineffectual? The current dilemmas, unanswered questions, operational issues, challenges, and priority needs for global drug resistance screening and surveillance, improved treatment regimens, and management of outcomes and prevention of DR

  14. LED Fluorescence Microscopy for the Diagnosis of Pulmonary Tuberculosis: A Multi-Country Cross-Sectional Evaluation

    Cuevas, Luis Eduardo; Yassin, Mohammed Ahmed; Al-Sonboli, Najla; Lawson, Lovett; Arbide, Isabel; Al-Aghbari, Nasher; Bahadur Sherchand, Jeevan; Al-Absi, Amin; Emenyonu, Emmanuel Nnamdi; Merid, Yared; Okobi, Mosis Ifenyi; Onuoha, Juliana Olubunmi; Aschalew, Melkamsew; Aseffa, Abraham; Harper, Greg

    2011-01-01

    Editors' Summary Background Every year, nearly 10 million people develop tuberculosis—a contagious bacterial infection that usually affects the lungs (pulmonary tuberculosis)—and about 1.7 million people die from the disease. Mycobacterium tuberculosis, which causes tuberculosis, is spread in airborne droplets when people with the disease cough or sneeze. Thus, to control tuberculosis, it is essential that infected individuals are rapidly identified and treated. The “gold standard” diagnostic...

  15. 13[C]-urea breath test as a novel point-of-care biomarker for tuberculosis treatment and diagnosis.

    Mandeep S Jassal

    Full Text Available BACKGROUND: Pathogen-specific metabolic pathways may be detected by breath tests based on introduction of stable isotopically-labeled substrates and detection of labeled products in exhaled breath using portable infrared spectrometers. METHODOLOGY/PRINCIPAL FINDINGS: We tested whether mycobacterial urease activity could be utilized in such a breath test format as the basis of a novel biomarker and diagnostic for pulmonary TB. Sensitized New-Zealand White Rabbits underwent bronchoscopic infection with either Mycobacterium bovis or Mycobacterium tuberculosis. Rabbits were treated with 25 mg/kg of isoniazid (INH approximately 2 months after infection when significant cavitary lung pathology was present. [(13C] urea was instilled directly into the lungs of intubated rabbits at selected time points, exhaled air samples analyzed, and the kinetics of delta(13CO(2 formation were determined. Samples obtained prior to inoculation served as control samples for background (13CO(2 conversion in the rabbit model. (13CO(2, from metabolic conversion of [(13C]-urea by mycobacterial urease activity, was readily detectable in the exhaled breath of infected rabbits within 15 minutes of administration. Analyses showed a rapid increase in the rate of (13CO(2 formation both early in disease and prior to treatment with INH. Following INH treatment, all evaluable rabbits showed a decrease in the rate of (13CO(2 formation. CONCLUSIONS/SIGNIFICANCE: Urea breath testing may provide a useful diagnostic and biomarker assay for tuberculosis and for treatment response. Future work will test specificity for M. tuberculosis using lung-targeted dry powder inhalation formulations, combined with co-administering oral urease inhibitors together with a saturating oral dose of unlabeled urea, which would prevent the delta(13CO(2 signal from urease-positive gastrointestinal organisms.

  16. Direct microscopy versus sputum cytology analysis and bleach sedimentation for diagnosis of tuberculosis: a prospective diagnostic study

    Hepple Pamela

    2010-09-01

    % CI 2.4-11.8, p = 0.016, respectively. Conclusions The combination of bleach sedimentation and SCA resulted in significantly increased microscopy positivity rates with a case definition of either one or two positive smears. Implementation of bleach sedimentation led to a significant increase in the diagnosis of smear-positive patients. Implementation of SCA did not result in significantly increased diagnosis of tuberculosis, but did result in improved sample quality. Requesting extra sputum samples based on SCA results, combined with bleach sedimentation, could significantly increase the detection of smear-positive patients if routinely implemented in resource-limited settings where gold standard techniques are not available. We recommend that a pilot phase is undertaken before routine implementation to determine the impact in a particular context.

  17. Radioiodinated DPA-713 imaging correlates with bactericidal activity of tuberculosis treatments in mice.

    Ordonez, Alvaro A; Pokkali, Supriya; DeMarco, Vincent P; Klunk, Mariah; Mease, Ronnie C; Foss, Catherine A; Pomper, Martin G; Jain, Sanjay K

    2015-01-01

    Current tools for monitoring response to tuberculosis treatments have several limitations. Noninvasive biomarkers could accelerate tuberculosis drug development and clinical studies, but to date little progress has been made in developing new imaging technologies for this application. In this study, we developed pulmonary single-photon emission computed tomography (SPECT) using radioiodinated DPA-713 to serially monitor the activity of tuberculosis treatments in live mice, which develop necrotic granulomas and cavitary lesions. C3HeB/FeJ mice were aerosol infected with Mycobacterium tuberculosis and administered either a standard or a highly active bedaquiline-containing drug regimen. Serial (125)I-DPA-713 SPECT imaging was compared with (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and standard microbiology. Ex vivo studies were performed to characterize and correlate DPA-713 imaging with cellular and cytokine responses. Pulmonary (125)I-DPA-713 SPECT, but not (18)F-FDG PET, was able to correctly identify the bactericidal activities of the two tuberculosis treatments as early as 4 weeks after the start of treatment (P < 0.03). DPA-713 readily penetrated the fibrotic rims of necrotic and cavitary lesions. A time-dependent decrease in both tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels was observed with treatments, with (125)I-DPA-713 SPECT correlating best with tissue TNF-α levels (ρ = 0.94; P < 0.01). (124)I-DPA-713 was also evaluated as a PET probe and demonstrated a 4.0-fold-higher signal intensity in the infected tuberculous lesions than uninfected controls (P = 0.03). These studies provide proof of concept for application of a novel noninvasive imaging biomarker to monitor tuberculosis treatments, with the potential for application for humans. PMID:25403669

  18. The in vitro activity of beta-lactamase inhibitors in combination with cephalosporins against M. tuberculosis.

    Chen, C H; Yang, M H; Lin, J S; Lee, Y C; Perng, R P

    1995-04-01

    Although there are reports that the addition of a beta-lactamase inhibitor to ampicillin or amoxicillin greatly improves their in vitro activity against M. tuberculosis, there are no written reports about the antituberculosis effects of beta-lactamase inhibitors in combination with cephalosporins against M. tuberculosis. In this report, we have determined the minimal inhibitory concentrations (MIC) of 5 cephalosporins with or without combination with beta-lactamase inhibitor against M. tuberculosis strains isolated from patients before antituberculosis treatment and checked the production of beta-lactamase by bacteria before this procedure. Four strains of M. tuberculosis were contaminated during the experiment, and all the other 16 strains hydrolyzed the nitrocefin disc, thus indicating a beta-lactamase producer. The MICs of cephalosporins alone against M. tuberculosis were 200-400 micrograms/ml for ceforanide, 100-400 micrograms/ml for cephapirin, 400-1600 micrograms/ml for cefamandole, 200-1600 micrograms/ml for cefotaxime, and 800-1600 micrograms/ml for ceftriaxone. After adding the equimolar concentrations of sulbactam, the MICs were reduced to 100-200 micrograms/ml for ceforanide, 12.5-100 micrograms/ml for cephapirin, 100-400 micrograms/ml for cefamandole, 25-200 micrograms/ml for cefotaxime, and 100-800 micrograms/ml for ceftriaxone. We concluded that sulbactam enhanced the antituberculosis effect of cephalosporins. PMID:7624446

  19. Improved rapid molecular diagnosis of multidrug-resistant tuberculosis using a new reverse hybridization assay, REBA MTB-MDR

    Bang, Hyeeun; Park, Sangjung; Hwang, Joohwan; Jin, Hyunwoo; Cho, Eunjin; Kim, Dae Yoon; Song, Taeksun; Shamputa, Isdore Chola; Via, Laura E.; Barry, Clifton E.; Cho, Sang-Nae

    2011-01-01

    Rapid diagnosis of multidrug-resistant tuberculosis (MDR-TB) is essential for the prompt initiation of effective second-line therapy to improve treatment outcome and limit transmission of this obstinate disease. A variety of molecular methods that enable the rapid detection of mutations implicated in MDR-TB have been developed. The sensitivity of the methods is dependent, in principle, on the repertoire of mutations being detected, which is typically limited to mutations in the genes rpoB, katG and the promoter region of inhA. In this study, a new reverse hybridization assay, REBA MTB-MDR (M&D), that probes mutations in the oxyR–ahpC intergenic region, in addition to those in rpoB, katG and the inhA promoter region, was evaluated. A set of 240 Mycobacterium tuberculosis clinical isolates from patients receiving retreatment regimens was subjected to conventional phenotypic drug-susceptibility testing (DST) and the REBA MTB-MDR assay. The nucleotide sequences of the loci known to be involved in drug resistance were determined for comparison. In brief, the results showed that the REBA MTB-MDR assay efficiently recognized nucleotide changes in the oxyR–ahpC intergenic region as well as those in rpoB, katG and the inhA promoter region with higher sensitivity, resulting in an 81.0 % detection rate for isoniazid resistance. Inclusion of the oxyR–ahpC intergenic region in the REBA MTB-MDR assay improved the overall sensitivity of molecular DST for MDR-TB from 73.1 to 79.9 %. PMID:21596910

  20. A molecular platform for the diagnosis of multidrug-resistant and pre-extensively drug-resistant tuberculosis based on single nucleotide polymorphism mutations present in Colombian isolates of Mycobacterium tuberculosis

    Martínez, Luz Maira Wintaco; Castro, Gloria Puerto; Guerrero, Martha Inírida

    2016-01-01

    Developing a fast, inexpensive, and specific test that reflects the mutations present in Mycobacterium tuberculosis isolates according to geographic region is the main challenge for drug-resistant tuberculosis (TB) control. The objective of this study was to develop a molecular platform to make a rapid diagnosis of multidrug-resistant (MDR) and extensively drug-resistant TB based on single nucleotide polymorphism (SNP) mutations present in therpoB, katG, inhA,ahpC, and gyrA genes from Colombian M. tuberculosis isolates. The amplification and sequencing of each target gene was performed. Capture oligonucleotides, which were tested before being used with isolates to assess the performance, were designed for wild type and mutated codons, and the platform was standardised based on the reverse hybridisation principle. This method was tested on DNA samples extracted from clinical isolates from 160 Colombian patients who were previously phenotypically and genotypically characterised as having susceptible or MDR M. tuberculosis. For our method, the kappa index of the sequencing results was 0,966, 0,825, 0,766, 0,740, and 0,625 forrpoB, katG, inhA,ahpC, and gyrA, respectively. Sensitivity and specificity were ranked between 90-100% compared with those of phenotypic drug susceptibility testing. Our assay helps to pave the way for implementation locally and for specifically adapted methods that can simultaneously detect drug resistance mutations to first and second-line drugs within a few hours. PMID:26841047

  1. Densely calcified tuberculous constrictive pericarditis with concurrent active pulmonary tuberculosis infection

    S Laudari

    2015-07-01

    Full Text Available Though pulmonary tuberculosis is a common chronic infection in the developing countries like Nepal, the incidence of tubercular constrictive pericarditis is very low. Here we report a patient of active pulmonary tuberculosis with sputum positive for acid fast bacilli along with densely calcified constrictive pericarditis which has been reported as a very rare presentation in the literature.DOI: http://dx.doi.org/10.3126/jcmsn.v10i2.12955 Journal of College of Medical Sciences-Nepal, 2014, Vol.10(2; 41-43

  2. Specific T-cell epitopes for immunoassay-based diagnosis of Mycobacterium tuberculosis infection

    Brock, I; Weldingh, K; Leyten, EM; Arend, SM; Ravn, Pernille; Andersen, P

    2004-01-01

    recently identified antigens (Rv2653, Rv2654, Rv3873, and Rv3878) from genomic regions that are lacking from the Mycobacterium bovis bacillus Calmette-Guerin (BCG) vaccine strains as well as from the most common nontuberculous mycobacteria. The fine specificity of potential epitopes in these molecules was...... evaluated by sensitive testing of the T-cell responses of peripheral blood mononuclear cells derived from M. bovis BCG-vaccinated healthy individuals to synthesized overlapping peptides. Three of the four molecules contained regions with significant specificity problems (Rv2653, Rv3873, and Rv3878). We...... selected and combined the specific peptide stretches from the four proteins not recognized by M. bovis BCG-vaccinated individuals. These peptide stretches were tested with peripheral blood mononuclear cells obtained from patients with microscopy- or culture-confirmed tuberculosis and from healthy M. bovis...

  3. QuantiFERON® TB Gold IT in the diagnosis of active pulmonary TB

    Clara Fabris

    2010-03-01

    Full Text Available The IGRAs (Interferon-γ Release Assays are commercial assays which measure T-cell-mediated response in vitro after specific stimulation, and represent the alternative to TST (Tuberculin Skin Test in the diagnosis of latent tuberculosis infection (ILTB and of active tuberculosis (TB. Among these we choose the assay QuantiFERON ®-TB Gold IT (Cellestis Ltd, Carnegie,Victoria, Australia (QFT in which interferon-γ (IFN-γ was measured after lymphocyte stimulation with 3 antigens of the RD1 region of M. tuberculosis: ESAT-6, CFP-10 and TB 7.7. We wanted to assess the sensitivity of the method in cases of pulmonary TB, using cultured isolates of M. tuberculosis as gold-standard. From August 2006 to July 2009 there were 54 suspected cases of pulmonary TB, confirmed by culture.The QFT was requested for 32 patients before any microbiological confirmation and therapy. Of these patients 14 aged 20-50 years, 6 aged 50-70 years and 12 were more than 70-year-old. The QFT was positive in 25 patients (INF-γ> 0.35 IU/mL and negative in 7 patients (INF-γ <0.35 IU/mL while 2 patients had an INF-γ value of 0.34 IU/mL. Susceptibility to pulmonary TB is very high in young subjects and decreases with increasing age. In elderly population it is frequent a TB reactivation due to a decline in T-cell-immune response.Therefore, a negative or borderline value of IFN-γ should be interpreted with care.

  4. Evaluation of Anti-TBGL Antibody in the Diagnosis of Tuberculosis Patients in China

    Jingge Zhao

    2015-01-01

    Full Text Available Tuberculous glycolipid (TBGL is a component of the Mycobacterium tuberculosis cell wall, and anti-TBGL antibodies are used for serodiagnosis of tuberculosis. Anti-TBGL IgG and IgA levels were measured in 45 pulmonary TB patients (PTB, 26 extra-pulmonary TB patients (ETB, 16 AIDS-TB patients, and 58 healthy controls (HC including 39 health care workers (HW and 19 newly enrolled students (ST. Anti-TBGL IgG measurements yielded 68.9% and 46.2% sensitivity in PTB and ETB, respectively, and 81.0% specificity. However, anti-TBGL IgA measurements were significantly less sensitive in detecting ETB than PTB (15.4% versus 46.7% sensitivity but showed up to 89.7% specificity. Samples from AIDS-TB patients exhibited low reaction of anti-TBGL IgG and IgA with 6.3% and 12.5% sensitivity, respectively. Unlike anti-lipoarabinomannan (LAM IgG that was found to elevate in sputum smearpositive subjects, anti-TBGL IgG and IgA elevated in those with cavitation and bronchiectasis, respectively. Anti-TBGL IgG in cavitary TB yielded 78.2% sensitivity compared to 57.1% in those otherwise. Meanwhile, higher anti-TBGL IgA titers were observed in HW than in ST, and increasing anti-TBGL IgG titers were observed in HW on follow-up. Therefore, higher anti-TBGL antibody titers are present in patients presenting cavities and bronchiectasis and subjects under TB exposure risk.

  5. Clinical, radiological and molecular diagnosis correlation in serum samples from patients with osteoarticular tuberculosis

    Guadalupe García-Elorriaga

    2014-07-01

    Conclusions: Nested PCR in serum samples is a rapid, highly sensitive and specific modality for OTB detection. PCR should be performed in addition to clinical evaluation, imaging studies, acid-fast bacilli staining, culture and histopathology diagnosis, if possible.

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

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Changes from activity in pulmonary tuberculosis pension cases. 3.378 Section 3.378 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity...

  7. Interferon Gamma Release Assays in active Tuberculosis: new medical insights

    Sandro Pierdomenico

    2011-09-01

    Full Text Available Since first presentation, Interferon γ Release Assays (IGRAs have had basic and wide application to LTBI, in accordance with international consensus and CDC recommendations, leaving their use in active TB to the field of study and research.We reviewed the results of 633 patients investigated from 2004 to 2008 targeting active TB, with the objective to highlight immunological data supporting test performances.We evaluated Quantiferon TB Gold (1st generation IGRA kit in association to Culture (MGIT 960 and Lowenstein Jensen and PCR (Probetec-ET having the positivity of culture plus clinical diagnosis as the standard true value to compare. QTB Gold was studied in 69 TB positive patients (42 pulmonary and 27 extra-pulmonary, with Sensitivity, Specificity, PPV and NPV average to 61.8%, 94.5%, 54.3% and 95.9% respectively, after indeterminate results discharging. Significant statistical differences didn’t emerge between pulmonary and extra-pulmonary infections (CI 95%.The overall indeterminate ratio arose up to 20.3% in patients with active TB vs 2.7% of global population (p<0.001. In 22% of patients with active pulmonary disease, IGRA conversed to positivity after 15 days in replicated tests, in spite of current treatment. 4 patients, with pulmonary TB and Quantiferon persistent negativities, underwent 18 months follow-up as not respondent although SIRE phenotypic susceptibilities and enough DOT compliance. Molecular DST documented hetero resistance for rpoB (MUT 1, MUT 3 plus wild lines and katG (MUT 1 plus wild in association to lack of inhA wild lines (Genotype MTBDR plus, Hain Lifescience. These reports suggest a mutational relationship between Rv3874 – 3875 cassette, encoding ESAT-6 / CFP-10, and rpoB, katG, inhA genes plausibly implying weak or absent selective clonal Th 1 activation to IGRA antigens. Our data seem to point out: 1 positive results are able to match true active TB in less than 50% of patients; 2 negative results could leave

  8. Access to Bacteriologic-Based Diagnosis in Smear Positive Retreatment Tuberculosis Patients in Rural China: A Cross-Sectional Study in Three Geographic Varied Provinces

    Zhou, Changming; Jiang, Weili; Yuan, Li; Lu, Wei; He, Jinge; Zhao, Qi; Xu, Biao

    2016-01-01

    Objective To determine factors influencing the utilization and accessibility to bacteriologic-based tuberculosis (TB) diagnosis among sputum smear positive (SS+) retreatment TB patients, and to develop strategies for improving the case detection rate of MDR-TB in rural China. Study Design and Setting A cross-sectional study of SS+ TB retreatment patients was conducted in eight counties from three provinces with different implementation period and strategy of MDR-TB program in China. Demograph...

  9. Differential diagnosis between Crohn’s disease and intestinal tuberculosis using integrated parameters including clinical manifestations, T-SPOT, endoscopy and CT enterography

    Zhang, Tianyu; Fan, Rong; Wang, Zhengting; Hu, Shurong; Zhang, Maochen; Lin, Yun; Tang, Yonghua; Zhong, Jie

    2015-01-01

    Background: The aim of the study was to evaluate clinical manifestations, T-SPOT, endoscopy and CT enterography to differentiate Crohn’s disease (CD) from intestinal tuberculosis (ITB). Methods: 128 in patients with suspected CD and ITB were prospectively enrolled in the study. Demographic, clinical, laboratory, endoscopic and CT enterographic data were collected. After treatment for 6 months, when a definite diagnosis was reached, the differential diagnostic value of each parameter was analy...

  10. Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in Hiv-positive adults

    Shah, Maunank; Hanrahan, Colleen; Wang, Zhuo Yu; Dendukuri, Nandini; Lawn, Stephen D; Denkinger, Claudia M; Steingart, Karen R

    2016-01-01

    Background Rapid detection of tuberculosis (TB) among people living with human immunodeficiency virus (HIV) is a global health priority. HIV-associated TB may have different clinical presentations and is challenging to diagnose. Conventional sputum tests have reduced sensitivity in HIV-positive individuals, who have higher rates of extrapulmonary TB compared with HIV-negative individuals. The lateral flow urine lipoarabinomannan assay (LF-LAM) is a new, commercially available point-of-care test that detects lipoarabinomannan (LAM), a lipopolysaccharide present in mycobacterial cell walls, in people with active TB disease. Objectives To assess the accuracy of LF-LAM for the diagnosis of active TB disease in HIV-positive adults who have signs and symptoms suggestive of TB (TB diagnosis).To assess the accuracy of LF-LAM as a screening test for active TB disease in HIV-positive adults irrespective of signs and symptoms suggestive of TB (TB screening). Search methods We searched the following databases without language restriction on 5 February 2015: the Cochrane Infectious Diseases Group Specialized Register; MEDLINE (PubMed,1966); EMBASE (OVID, from 1980); Science Citation Index Expanded (SCI-EXPANDED, from 1900), Conference Proceedings Citation Index-Science (CPCI-S, from 1900), and BIOSIS Previews (from 1926) (all three using the Web of Science platform; MEDION; LILACS (BIREME, from 1982); SCOPUS (from 1995); the metaRegister of Controlled Trials (mRCT); the search portal of the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP); and ProQuest Dissertations & Theses A&l (from 1861). Selection criteria Eligible study types included randomized controlled trials, cross-sectional studies, and cohort studies that determined LF-LAM accuracy for TB against a microbiological reference standard (culture or nucleic acid amplification test from any body site). A higher quality reference standard was one in which two or more specimen types were

  11. 儿童脊柱结核诊疗现状及进展%Current status and progress in diagnosis and treatment for children with spinal tuberculosis

    李晋; 宋文慧

    2015-01-01

    通过分析最近几年关于儿童脊柱结核诊疗方面的相关文献,从诊断和治疗两方面探讨儿童脊柱结核的特点;并评估各种诊疗手段的临床应用价值。目前认为早期诊断、及时解除压迫症状、维持脊柱的稳定、预防晚期脊柱畸形进一步加重是儿童脊柱结核诊疗的重点。在抗结核药物治疗基础上,采用个体化的手术干预及支具制动策略,可良好地缓解症状,控制疾病的进展,减少并发症的发生,提高患儿生存质量。基因诊断及微创治疗为儿童脊柱结核的诊疗提供了新的思路。%Through the analysis of literatures about the diagnosis and treatment of children's spinal tuberculosis in recent years, from two aspects of diagnosis and treatment to study the characteristics of spinal tuberculosis in children, and evaluate the clinical value of various diagnostic methods. Early diagnosis and timely removement of oppression symptoms, maintaining the stability of the spine, preventing further advanced spinal deformity are considered to be the key in diagnosis and treatment of children's spinal tuberculosis. On the basis of anti-tuberculosis drugs treatment, adopting the strategy of individualized operation and braking can be good to relieve symptoms, control the progress of the disease, reduce complications and improve the quality of life in children. Genetic diagnosis and minimally surgical treatment offer new ways for the diagnosis and treatment of spinal tuberculosis in children.

  12. Primary isolated hepatic tuberculosis

    Isolated hepatic tuberculosis without pulmonary or bowel involvement is a diagnostic challenge and can cause considerable morbidity. A young lady from Lahore presented with fever, pain in right hypochondria, nausea and weight loss. CT scan of abdomen showed multiple small hypodense non-enhancing lesions and a heterogeneous texture of liver. Biopsy confirmed the diagnosis of hepatic tuberculosis. It was concluded a case of isolated hepatic tuberculosis without evidence of other primary sites involvement. It is important to consider tuberculosis in the differential diagnosis when suspecting lymphoproliferative or metastatic diseases in a patient with vague symptoms and abnormal hepatic texture on CT. (author)

  13. A field evaluation of the Hardy TB MODS Kit™ for the rapid phenotypic diagnosis of tuberculosis and multi-drug resistant tuberculosis.

    Laura Martin

    Full Text Available Even though the WHO-endorsed, non-commercial MODS assay offers rapid, reliable TB liquid culture and phenotypic drug susceptibility testing (DST at lower cost than any other diagnostic, uptake has been patchy. In part this reflects misperceptions about in-house assay quality assurance, but user convenience of one-stop procurement is also important. A commercial MODS kit was developed by Hardy Diagnostics (Santa Maria, CA, USA with PATH (Seattle, WA, USA to facilitate procurement, simplify procedures through readymade media, and enhance safety with a sealing silicone plate lid. Here we report the results from a large-scale field evaluation of the MODS kit in a government service laboratory.2446 sputum samples were cultured in parallel in Lowenstein-Jensen (LJ, conventional MODS and in the MODS kit. MODS kit DST was compared with conventional MODS (direct DST and proportion method (indirect DST. 778 samples (31.8% were Mycobacterium tuberculosis culture-positive. Compared to conventional MODS the sensitivity, specificity, positive, and negative predictive values (95% confidence intervals of the MODS Kit were 99.3% (98.3-99.8%, 98.3% (97.5-98.8%, 95.8% (94.0-97.1%, and 99.7% (99.3-99.9%. Median (interquartile ranges time to culture-positivity (and rifampicin and isoniazid DST was 10 (9-13 days for conventional MODS and 8.5 (7-11 for MODS Kit (p<0.01. Direct rifampicin and isoniazid DST in MODS kit was almost universally concordant with conventional MODS (97.9% agreement, 665/679 evaluable samples and reference indirect DST (97.9% agreement, 687/702 evaluable samples.MODS kit delivers performance indistinguishable from conventional MODS and offers a convenient, affordable alternative with enhanced safety from the sealing silicone lid. The availability in the marketplace of this platform, which conforms to European standards (CE-marked, readily repurposed for second-line DST in the near future, provides a fresh opportunity for improving equity of

  14. Subdeltoid Bursa Tuberculosis with Rice Body Formation–A Case Report

    Santosh L. Munde

    2015-01-01

    Full Text Available Tuberculous tenosynovitis and bursitis account for approximately 1%. A 56 years old female presented with swelling in left shoulder, gradually increasing in size with slight restriction in movement since last three months. X-ray revealed no abnormality of humerus head. Histopathological examination showed granulomatous tissue with multiple rice bodies. A positive culture of mycobacterium tuberculosis confirmed the diagnosis of tuberculosis. We here report a case of subdeltoid bursitis with rice body formation and without active bone and joint tuberculosis.

  15. Rapid diagnosis of MDR and XDR tuberculosis with the MeltPro TB assay in China.

    Pang, Yu; Dong, Haiyan; Tan, Yaoju; Deng, Yunfeng; Cai, Xingshan; Jing, Hui; Xia, Hui; Li, Qiang; Ou, Xichao; Su, Biyi; Li, Xuezheng; Zhang, Zhiying; Li, Junchen; Zhang, Jiankang; Huan, Shitong; Zhao, Yanlin

    2016-01-01

    New diagnostic methods have provided a promising solution for rapid and reliable detection of drug-resistant TB strains. The aim of this study was to evaluate the performance of the MeltPro TB assay in identifying multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) patients from sputum samples. The MeltPro TB assay was evaluated using sputum samples from 2057 smear-positive TB patients. Phenotypic Mycobacterial Growth Indicator Tube (MGIT) 960 drug susceptibility testing served as a reference standard. The sensitivity of the MeltPro TB assay was 94.2% for detecting resistance to rifampicin and 84.9% for detecting resistance to isoniazid. For second-line drugs, the assay showed a sensitivity of 83.3% for ofloxacin resistance, 75.0% for amikacin resistance, and 63.5% for kanamycin resistance. However, there was a significant difference for detecting kanamycin resistance between the two pilot sites in sensitivity, which was 53.2% in Guangdong and 81.5% in Shandong (P = 0.015). Overall, the MeltPro TB assay demonstrated good performance for the detection of MDR- and XDR-TB, with a sensitivity of 86.7% and 71.4%, respectively. The MeltPro TB assay is an excellent alternative for the detection of MDR- and XDR-TB cases in China, with high accuracy, short testing turn-around time, and low unit price compared with other tests. PMID:27149911

  16. Mixed impact of Xpert® MTB/RIF on tuberculosis diagnosis in Cambodia

    Moore, B. K.; Kyle, R. P.; Eng, B.; Nong, K.; Pevzner, E. S.; Eam, K. K.; Eang, M. T.; Killam, W. P.

    2016-01-01

    Setting: National Tuberculosis (TB) Program sites in northwest Cambodia. Objective: To evaluate the impact of Xpert® MTB/RIF at point of care (POC) as compared to non-POC sites on the diagnostic evaluation of people living with the human immunodeficiency virus (PLHIV) with TB symptoms and patients with possible multidrug-resistant (MDR) TB. Design: Observational cohort of patients undergoing routine diagnostic evaluation for TB following the rollout of Xpert. Results: Between October 2011 and June 2013, 431 of 822 (52%) PLHIV with TB symptoms and 240/493 (49%) patients with possible MDR-TB underwent Xpert. Xpert was more likely to be performed when available as POC. A smaller proportion of PLHIV at POC sites were diagnosed with TB than at non-POC sites; however, at POC sites, a higher proportion of those diagnosed with TB were bacteriologically positive. There was poor agreement between Xpert and other tests such as smear microscopy and culture. Overall, the evaluation of patients with possible MDR-TB increased following Xpert rollout, yet for patients confirmed as having drug resistance on drug susceptibility testing, only 46% had rifampin resistance that would be identified with Xpert. Conclusion: Although utilization of Xpert was low, it may have contributed to an increase in evaluations for possible MDR-TB and a decline in empiric treatment for PLHIV when available as POC. PMID:27358807

  17. Blood or Urine IP-10 Cannot Discriminate between Active Tuberculosis and Respiratory Diseases Different from Tuberculosis in Children

    Linda Petrone

    2015-01-01

    Full Text Available Objectives. Interferon-γ inducible protein 10 (IP-10, either in blood or in urine, has been proposed as a tuberculosis (TB biomarker for adults. This study aims to evaluate the potential of IP-10 diagnostics in children from Uganda, a high TB-endemic country. Methods. IP-10 was measured in the blood and urine concomitantly taken from children who were prospectively enrolled with suspected active TB, with or without HIV infection. Clinical/microbiological parameters and commercially available TB-immune assays (tuberculin skin test (TST and QuantiFERON TB-Gold In-Tube (QFT-IT were concomitantly evaluated. Results. One hundred twenty-eight children were prospectively enrolled. The analysis was performed on 111 children: 80 (72% of them were HIV-uninfected and 31 (27.9% were HIV-infected. Thirty-three healthy adult donors (HAD were included as controls. The data showed that IP-10 is detectable in the urine and blood of children with active TB, independent of HIV status and age. However, although IP-10 levels were higher in active TB children compared to HAD, the accuracy of identifying “active TB” was low and similar to the TST and QFT-IT. Conclusion. IP-10 levels are higher in children with respiratory illness compared to controls, independent of “TB status” suggesting that the evaluation of this parameter can be used as an inflammatory marker more than a TB test.

  18. Blood or Urine IP-10 Cannot Discriminate between Active Tuberculosis and Respiratory Diseases Different from Tuberculosis in Children

    Petrone, Linda; Cannas, Angela; Aloi, Francesco; Nsubuga, Martin; Sserumkuma, Joseph; Nazziwa, Ritah Angella; Jugheli, Levan; Lukindo, Tedson; Girardi, Enrico; Reither, Klaus; Goletti, Delia

    2015-01-01

    Objectives. Interferon-γ inducible protein 10 (IP-10), either in blood or in urine, has been proposed as a tuberculosis (TB) biomarker for adults. This study aims to evaluate the potential of IP-10 diagnostics in children from Uganda, a high TB-endemic country. Methods. IP-10 was measured in the blood and urine concomitantly taken from children who were prospectively enrolled with suspected active TB, with or without HIV infection. Clinical/microbiological parameters and commercially available TB-immune assays (tuberculin skin test (TST) and QuantiFERON TB-Gold In-Tube (QFT-IT)) were concomitantly evaluated. Results. One hundred twenty-eight children were prospectively enrolled. The analysis was performed on 111 children: 80 (72%) of them were HIV-uninfected and 31 (27.9%) were HIV-infected. Thirty-three healthy adult donors (HAD) were included as controls. The data showed that IP-10 is detectable in the urine and blood of children with active TB, independent of HIV status and age. However, although IP-10 levels were higher in active TB children compared to HAD, the accuracy of identifying “active TB” was low and similar to the TST and QFT-IT. Conclusion. IP-10 levels are higher in children with respiratory illness compared to controls, independent of “TB status” suggesting that the evaluation of this parameter can be used as an inflammatory marker more than a TB test. PMID:26346028

  19. Coincident helminth infection modulates systemic inflammation and immune activation in active pulmonary tuberculosis.

    Parakkal Jovvian George

    Full Text Available Helminth infections are known to modulate innate and adaptive immune responses in active and latent tuberculosis (TB. However, the role of helminth infections in modulating responses associated with inflammation and immune activation (reflecting disease activity and/or severity in TB is not known.We measured markers of inflammation and immune activation in active pulmonary TB individuals (ATB with co-incidental Strongyloides stercoralis (Ss infection. These included systemic levels of acute phase proteins, matrix metalloproteinases and their endogenous inhibitors and immune activation markers. As a control, we measured the systemic levels of the same molecules in TB-uninfected individuals (NTB with or without Ss infection.Our data confirm that ATB is associated with elevated levels of the various measured molecules when compared to those seen in NTB. Our data also reveal that co-incident Ss infection in ATB individuals is associated with significantly decreased circulating levels of acute phase proteins, matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases as well as the systemic immune activation markers, sCD14 and sCD163. These changes are specific to ATB since they are absent in NTB individuals with Ss infection.Our data therefore reveal a profound effect of Ss infection on the markers associated with TB disease activity and severity and indicate that co-incidental helminth infections might dampen the severity of TB disease.

  20. Accuracy of the Bronchoalveolar Lavage Enzyme-Linked Immunospot Assay for the Diagnosis of Pulmonary Tuberculosis: A Meta-analysis.

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

    2016-03-01

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

  1. Tuberculosis peritonitis: gallium-67 scintigraphic appearance.

    Sumi, Y; Ozaki, Y; Hasegawa, H; Shindoh, N; Katayama, H; Tamamoto, F

    1999-06-01

    Tuberculosis peritonitis is a rare manifestation of extrapulmonary tuberculosis. The results of gallium-67 scintigraphy of three patients with tuberculosis peritonitis were reviewed to assess its usefulness in the diagnosis of this condition. Tuberculosis peritonitis was associated with diffuse or focal abdominal localization and decreased hepatic accumulation of gallium-67. These gallium-67 scan features of tuberculosis peritonitis may help to optimize the diagnosis and management of this disease. PMID:10435380

  2. Interpretation Criteria for Comparative Intradermal Tuberculin Test for Diagnosis of Bovine Tuberculosis in Cattle in Maroua Area of Cameroon

    Temwa, J.; Mouiche, M. M.; Iyawa, D.; Zoli, P. A.

    2016-01-01

    Intradermal tuberculin test (TST) is the choice method for diagnosis of bovine tuberculosis (Tb) in live animals. This work was done to assess the performance of single intradermal comparative cervical tuberculin (SICCT) test in randomly selected cattle in Maroua, Cameroon, against detection of Tb lesions and detection of Tb lesions plus acid fast bacilli in lesions. While 22.28% of slaughtered cattle presented Tb lesions at meat inspection, detection rates of anti-bovine-Tb antibody, Tb lesions, and Tb lesions plus acid fast bacilli were 68.57%, 32.95%, and 22.35%, respectively. SICCT-bovine-Tb positive cattle were 35.29%, 29.41%, 25.88%, 24.7%, and 21.18% at ≥2 mm, ≥2.5 mm, ≥3 mm, ≥3.5 mm, and ≥4 mm cut-offs, respectively. Higher sensitivity and predictive values were obtained at severe interpretations. The best performance was at ≥3 mm and ≥3.5 mm cut-offs. Against detection of Tb lesions, ≥3 mm and ≥3.5 mm showed sensitivity of 67.8% and specificity of 94.7% and 96.5%, respectively. For detection of Tb lesions accompanied with acid fast bacilli in lesions, ≥3 mm and ≥3.5 mm showed sensitivity of 89.4% and specificity of 92.4% and 93.9%, respectively. These findings revealed that interpretations of SICCT-bovine-Tb should be at ≥3 mm and/or ≥3.5 mm cut-offs. Severe interpretation of TST is essential for optimal diagnosis of bovine Tb in cattle in Maroua, Cameroon.

  3. Interpretation Criteria for Comparative Intradermal Tuberculin Test for Diagnosis of Bovine Tuberculosis in Cattle in Maroua Area of Cameroon.

    Awah-Ndukum, J; Temwa, J; Ngwa, V Ngu; Mouiche, M M; Iyawa, D; Zoli, P A

    2016-01-01

    Intradermal tuberculin test (TST) is the choice method for diagnosis of bovine tuberculosis (Tb) in live animals. This work was done to assess the performance of single intradermal comparative cervical tuberculin (SICCT) test in randomly selected cattle in Maroua, Cameroon, against detection of Tb lesions and detection of Tb lesions plus acid fast bacilli in lesions. While 22.28% of slaughtered cattle presented Tb lesions at meat inspection, detection rates of anti-bovine-Tb antibody, Tb lesions, and Tb lesions plus acid fast bacilli were 68.57%, 32.95%, and 22.35%, respectively. SICCT-bovine-Tb positive cattle were 35.29%, 29.41%, 25.88%, 24.7%, and 21.18% at ≥2 mm, ≥2.5 mm, ≥3 mm, ≥3.5 mm, and ≥4 mm cut-offs, respectively. Higher sensitivity and predictive values were obtained at severe interpretations. The best performance was at ≥3 mm and ≥3.5 mm cut-offs. Against detection of Tb lesions, ≥3 mm and ≥3.5 mm showed sensitivity of 67.8% and specificity of 94.7% and 96.5%, respectively. For detection of Tb lesions accompanied with acid fast bacilli in lesions, ≥3 mm and ≥3.5 mm showed sensitivity of 89.4% and specificity of 92.4% and 93.9%, respectively. These findings revealed that interpretations of SICCT-bovine-Tb should be at ≥3 mm and/or ≥3.5 mm cut-offs. Severe interpretation of TST is essential for optimal diagnosis of bovine Tb in cattle in Maroua, Cameroon. PMID:27563481

  4. Monitoring Therapeutic Response in a Case of Extrapulmonary Tuberculosis by Serial F 18 FDG PET/CT

    Due to the low yield of AFB smear and culture in extrapulmonary tuberculosis, therapeutic responses of patients with extrapulmonary tuberculosis are usually monitored clinically and/or radiographically. Such monitoring techniques, however, are not enough to provide effective diagnosis if a remnant lesion exists after treatment. Tuberculosis presents hypermetabolic activity on F 18 fluorodeoxyglucose positron emission tomography/computed tomography (F 18 FDG PET/CT) scanning. Reported herein is a case of extrapulmonary tuberculosis where the therapeutic response was useful for detecting the extent of extrapulmonary tuberculosis and for estimating the patient's therapeutic response

  5. Assessment of an indirect ELISA for the diagnosis of bovine tuberculosis

    The sensitivity and specificity of an ELISA for the detection of bovine IgG anti-Mycobacterium bovis (M. bovis) antibodies were 73.6% and 94.1% respectively, as determined in 53 bacteriologically confirmed tuberculous cattle and 101 healthy cattle from a tuberculosis-free area. In addition, the results of ELISA and tuberculin tests in 149 cattle were compared with those of subsequent necropsy studies. Both tests failed to detect 2 animals with tuberculous lesions and positive M. bovine culture. Three of 12 cattle, in which M. bovine was isolated but no lesions were found, reacted to tuberculin as did 2 of 7 cattle that had atypical mycobacterial infection. In none of these animals was it possible to detect antibody titres against M. bovis. In 128 cattle that had no lesions nor the presence of mycobacteria, 6 were tuberculin reactors and 7 others had antibody titres against M. bovis. Negative results were obtained by ELISA in 21 of 22 paratuberculous cattle. Antibody titres were not detected in 88.9% to 96.4% of 697 cattle in three tests from two tuberculin negative herds of an endemic area. In a herd with proven M. bovis infection, the distribution of seropositive animals in tuberculin and non-tuberculin reactors was similar. Antibody responses to cutaneous tuberculin stimuli were observed in 4 cattle experimentally infected with M. bovis, but only in 2 of 10 healthy controls after repeated PPD stimuli. Nine controls which had either received a single tuberculin dose or no inoculation showed no increase in antibody levels. The low sensitivity of this ELISA limits its usefulness as a diagnostic tool for identifying individual tuberculous animals in eradication campaigns. However, it could be helpful in epidemiological surveillance if further field testing indicates that infected herds can be identified by ELISA. (author). 21 refs, 2 figs, 2 tabs

  6. Incremental yield of submitting three sputum specimens for the diagnosis of pulmonary tuberculosis

    Objectives: To assess the efficacy and diagnostic yield of third sputum smear among pulmonary TB patients. Study type, settings and duration: This retrospective data analysis was done at PMRC TB Research Centre in collaboration with Institute of Chest Medicine, King Edward Medical University/Mayo Hospital Lahore, from January 2010 to December 2011. Materials and Methods: Patients presenting with respiratory symptoms, having abnormal chest X-rays and having a clinical suspicion of tuberculosis were asked to submit three sputum samples on two consecutive days (1st spot, 2nd early morning, 3rd spot) for acid-fast bacilli smear microscopy. Smears were prepared and stained by Ziehl-Neelsen method. Results: A total of 7785 TB suspects submitted three sputum samples making a total of 23,355 slides for checking acid-fast bacilli using smear microscopy examinations. The smear positivity rate was 11.8%. About 12% suspects fulfilled the case definition of having one positive smear confirmed by a second smear, while, only 2.5% suspects fulfilled the case definition based on third smear in combination with first or second. A total 1164(15%) suspects had at least one positive smear; of these 896(77%) were positive in first smear, 190(16%) were negative in first smear but positive in second and 78(6.7%) were positive in third smear after two negative smears. Conclusion: Recently changed WHO criteria for examination of two sputum smears is based on evidences collected from the globe however, for Pakistan the value of third smear which picked almost 7% cases is quite significant and should still be practiced. Policy message: Checking AFB using 3 sputum smears should still be practiced in Pakistan especially, for those who are initially negative on 2 smears. (author)

  7. Direct labeling of isoniazid with technetium-99m for diagnosis of tuberculosis

    Isonicotinic acid hydrazide (isoniazid) is one of the most effective agents in tuberculosis therapy. Hence it was chosen as ligand for 99mTc labeling and imaging in the developed animal model with a gamma camera. Direct labeling of isoniazid with technetium-99m was studied. Factors affecting the radiolabeling efficiency such as amount of reducing agent, pH and time of the reaction were studied. Biodistribution of the labeled compound was performed in Sprague-Dawley rats. The localization kinetics of the radiolabeled complex was also studied in the developed animal model by injecting 100-125 MBq 99mTc-isoniazid intravenously in the ear of rabbit and the images were taken with a gamma camera. Optimum conditions gave > 98% labeling efficiency of 99mTc-isoniazid. Biodistribution studies in rats revealed that the maximum uptake was in kidneys (15%, 8% and 2.5% at 0.5, 4 and 24 hours, respectively), indicating renal excretion of the 99mTc-isoniazid. High accumulation was obtained in liver (10%, 11% and 4% at 0.5, 4 and 24 hours, respectively) and significant radioactivity was also seen in the intestines (8%, 6% and 1% at 0.5, 4 and 24 hours, respectively), indicating hepatobiliary excretion of the complex. Less than 2% uptake in stomach until 24 hours confirmed good in vivo stability of the complex. 99mTc-isoniazid initially accumulated in infective lesions of S. aureus in rabbits due to hyper-vascularity, but because of its non specificity for S. aureus the residency of 99mTc-isoniazid was low and it showed rapid wash out from the lesion, whereas residency of tubercular lesion was high and it remained in the tubercular lesion in the delayed images also. The results suggest that 99mTc-isoniazid is a specific agent for localization of tubercular lesions. (orig.)

  8. Direct labeling of isoniazid with technetium-99m for diagnosis of tuberculosis

    Roohi, S.; Mushtaq, A.; Jehangir, M. [Isotope Production Div., Pakistan Inst. of Nuclear Science and Technology, P.O. Nilore, Islamabad (Pakistan); Malik, S.A. [Dept. of Biological Sciences, Quaid-e-Azam Univ., Islamabad (Pakistan)

    2006-07-01

    Isonicotinic acid hydrazide (isoniazid) is one of the most effective agents in tuberculosis therapy. Hence it was chosen as ligand for {sup 99m}Tc labeling and imaging in the developed animal model with a gamma camera. Direct labeling of isoniazid with technetium-99m was studied. Factors affecting the radiolabeling efficiency such as amount of reducing agent, pH and time of the reaction were studied. Biodistribution of the labeled compound was performed in Sprague-Dawley rats. The localization kinetics of the radiolabeled complex was also studied in the developed animal model by injecting 100-125 MBq {sup 99m}Tc-isoniazid intravenously in the ear of rabbit and the images were taken with a gamma camera. Optimum conditions gave > 98% labeling efficiency of {sup 99m}Tc-isoniazid. Biodistribution studies in rats revealed that the maximum uptake was in kidneys (15%, 8% and 2.5% at 0.5, 4 and 24 hours, respectively), indicating renal excretion of the {sup 99m}Tc-isoniazid. High accumulation was obtained in liver (10%, 11% and 4% at 0.5, 4 and 24 hours, respectively) and significant radioactivity was also seen in the intestines (8%, 6% and 1% at 0.5, 4 and 24 hours, respectively), indicating hepatobiliary excretion of the complex. Less than 2% uptake in stomach until 24 hours confirmed good in vivo stability of the complex. {sup 99m}Tc-isoniazid initially accumulated in infective lesions of S. aureus in rabbits due to hyper-vascularity, but because of its non specificity for S. aureus the residency of {sup 99m}Tc-isoniazid was low and it showed rapid wash out from the lesion, whereas residency of tubercular lesion was high and it remained in the tubercular lesion in the delayed images also. The results suggest that {sup 99m}Tc-isoniazid is a specific agent for localization of tubercular lesions. (orig.)

  9. Detección de la expresión génica in vivo de Mycobacterium tuberculosis durante la tuberculosis pulmonar activa Mycobacterium tuberculosis in vivo-expressed genes detection during active pulmonary tuberculosis

    Alejandra Otazo M; Ingrid Gutiérrez S; Víctor Acevedo F; Carlos Calderón A; Nancy P Maulén L

    2012-01-01

    El estudio de la expresión génica de Mycobacterium tuberculosis ha involucrado la experimentación "in vitro ", "ex vivo " e "in vivo " (modelos animales), pero aún sin el éxito esperado. Proponemos que revelar los factores clave de la tuberculosis humana requiere investigar la expresión génica de M. tuberculosis dentro del ser humano ("in vivo "). Para ello, aislamos el mRNA total de M. tuberculosis, desde muestras clínicas respiratorias de pacientes con diagnóstico de tuberculosis pulmonar; ...

  10. Cathepsin L maturation and activity is impaired in macrophages harboring M. avium and M. tuberculosis.

    Nepal, Rajeev M; Mampe, Stephanie; Shaffer, Brian; Erickson, Ann H; Bryant, Paula

    2006-06-01

    Mycobacterium tuberculosis-infected macrophages demonstrate diminished capacity to present antigens via class II MHC molecules. Since successful class II MHC-restricted antigen presentation relies on the actions of endocytic proteases, we asked whether the activities of cathepsins (Cat) B, S and L-three major lysosomal cysteine proteases-are modulated in macrophages infected with pathogenic Mycobacterium spp. Infection of murine bone marrow-derived macrophages with either Mycobacterium avium or M. tuberculosis had no obvious effect on Cat B or Cat S activity. In contrast, the activity of Cat L was altered in infected cells. Specifically, whereas the 24-kDa two-chain mature form of active Cat L predominated in uninfected cells, we observed an increase in the steady-state activity of the precursor single-chain (30 kDa) and 25-kDa two-chain forms of the enzyme in cells infected with either M. avium or M. tuberculosis. Pulse-chase analyses revealed that maturation of nascent, single-chain Cat L into the 25-kDa two-chain form was impaired in infected macrophages, and that maturation into the 24-kDa two-chain form did not occur. Consistent with these data, M. avium infection inhibited the IFNgamma-induced secretion of active two-chain Cat L by macrophages. Viable bacilli were not required to disrupt Cat L maturation, suggesting that a constitutively expressed mycobacterial component was responsible. The absence of the major active form of lysosomal Cat L in M. avium- and M. tuberculosis-infected macrophages may influence the types of T cell epitopes generated in these antigen-presenting cells, and/or the rate of class II MHC peptide loading. PMID:16636015

  11. [Imaging and Laboratory Diagnostics for Tuberculosis].

    Bauer, C M; Schmähl, A; Kreuter, M

    2016-05-01

    Diagnosis of tuberculosis (TB) is difficult, since symptoms are often very unspecific or lacking. However active, prompt and accurate diagnosis is the key element in the public health response to tuberculosis and the cornerstone of tuberculosis control. Different diagnostic methods for an assured diagnosis of TB are necessary. Chest radiography is a useful keystone to identify tuberculosis, but diagnosis of tuberculosis cannot be established by radiography alone. CT scanning is used in patients without pathological chest radiography but clinically suspected active TB and to differentiate TB from other diseases. Radiological appearance is primarily determined by the immune status of patients and caverns and disseminated disease foci are often observed. Laboratory diagnostic methods include microscopic identification of acid-fast mycobacteria from any body fluid (especially sputum), as well as isolation and characterisation of mycobacteria in culture. It is then possible to type the pathogens by the shape of their colony, their growth behavior and their biochemical characteristics. These methods are regarded as the gold standard in diagnosis of active TB. In patients who are highly suspected of having TB, but whose sputum specimens tested negative for mycobacteria, a nucleic acid amplification test is additionally performed. Moreover, sensitivity testing with first and second line antitubercular drugs is applied as standard. Laboratory diagnostic testing of cellular immunity against pathogenic mycobacteria employs the tuberculin skin test (TST, Mantoux tuberculin test) or the more specific interferon γ test to determine γ interferon released by T lymphocytes stimulated in vitro. The new ELISA and ELISPOT procedures exhibit higher test specificity and less cross reactivity to NTM (non-tuberculosis mycobacteria), are independent of BCG-vaccination status and correlate better with the degree of exposure than does the TST. PMID:27187878

  12. Screening and rapid molecular diagnosis of tuberculosis in prisons in Russia and Eastern Europe: a cost-effectiveness analysis.

    Daniel E Winetsky

    Full Text Available BACKGROUND: Prisons of the former Soviet Union (FSU have high rates of multidrug-resistant tuberculosis (MDR-TB and are thought to drive general population tuberculosis (TB epidemics. Effective prison case detection, though employing more expensive technologies, may reduce long-term treatment costs and slow MDR-TB transmission. METHODS AND FINDINGS: We developed a dynamic transmission model of TB and drug resistance matched to the epidemiology and costs in FSU prisons. We evaluated eight strategies for TB screening and diagnosis involving, alone or in combination, self-referral, symptom screening, mass miniature radiography (MMR, and sputum PCR with probes for rifampin resistance (Xpert MTB/RIF. Over a 10-y horizon, we projected costs, quality-adjusted life years (QALYs, and TB and MDR-TB prevalence. Using sputum PCR as an annual primary screening tool among the general prison population most effectively reduced overall TB prevalence (from 2.78% to 2.31% and MDR-TB prevalence (from 0.74% to 0.63%, and cost US$543/QALY for additional QALYs gained compared to MMR screening with sputum PCR reserved for rapid detection of MDR-TB. Adding sputum PCR to the currently used strategy of annual MMR screening was cost-saving over 10 y compared to MMR screening alone, but produced only a modest reduction in MDR-TB prevalence (from 0.74% to 0.69% and had minimal effect on overall TB prevalence (from 2.78% to 2.74%. Strategies based on symptom screening alone were less effective and more expensive than MMR-based strategies. Study limitations included scarce primary TB time-series data in FSU prisons and uncertainties regarding screening test characteristics. CONCLUSIONS: In prisons of the FSU, annual screening of the general inmate population with sputum PCR most effectively reduces TB and MDR-TB prevalence, doing so cost-effectively. If this approach is not feasible, the current strategy of annual MMR is both more effective and less expensive than strategies

  13. Immunology in Tuberculosis : Challenges in Monitoring of Disease Activity and Identifying Correlates of Protection

    van Altena, Richard; Duggirala, Sridevi; Groschel, Matthias I. P.; van der Werf, Tjip S.

    2011-01-01

    Humans have always lived with tubercle bacilli. Host susceptibility - both inherited and acquired - determines whether an individual infected with Mycobacterium tuberculosis will eventually fall ill and develop tuberculosis (TB). After infection with M. tuberculosis, a latent TB infection may ensue

  14. Sputum smear negative pulmonary tuberculosis: sensitivity and specificity of diagnostic algorithm

    Mugusi Ferdinand M

    2011-11-01

    Full Text Available Abstract 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

  15. Comparison of interferon-gamma release assays and adenosine deaminase of pleural fluid for the diagnosis of pleural tuberculosis

    刘菲

    2014-01-01

    Objective To compare the diagnostic performance of interferon gamma releasing assays(T-SPOT.TB)and adenosine deaminase(ADA)in pleural tuberculosis,and therefore to evaluate the value of T-SPOT.TB in a high tuberculosis burden country.Methods From June 2011to November 2012,111 patients with pleural fluid in Beijing Chest Hospital,Capital Medical University were

  16. Detección de la expresión génica in vivo de Mycobacterium tuberculosis durante la tuberculosis pulmonar activa Mycobacterium tuberculosis in vivo-expressed genes detection during active pulmonary tuberculosis

    Alejandra Otazo M

    2012-12-01

    Full Text Available El estudio de la expresión génica de Mycobacterium tuberculosis ha involucrado la experimentación "in vitro ", "ex vivo " e "in vivo " (modelos animales, pero aún sin el éxito esperado. Proponemos que revelar los factores clave de la tuberculosis humana requiere investigar la expresión génica de M. tuberculosis dentro del ser humano ("in vivo ". Para ello, aislamos el mRNA total de M. tuberculosis, desde muestras clínicas respiratorias de pacientes con diagnóstico de tuberculosis pulmonar; posteriormente, sintetizamos el dscDNA y lo analizamos mediante RT-PCR cualitativo. Detectamos la expresión de la secuencia de inserción IS6110 y de los genes "housekeeping " 16SrRNA y sigA en M. tuberculosis creciendo in vivo (tuberculosis pulmonar así como cultivado in vitro. La expresión de los genes mprA y mprB, que codifican el sistema de transducción de señales MprAB, sólo se detectó en M. tuberculosis crecido in vitro. Con nuestros resultados damos el primer paso hacia la implementación de un método no invasivo para el estudio del transcriptoma de M. tuberculosis, dentro de su único hospedero natural, con el fin de analizar la regulación "in vivo" de los determinantes genéticos requeridos para su virulencia y patogénesis.Mycobacterium tuberculosis gene expression studies have involved "in vitro", "ex vivo" and "in vivo" experiments (animal models, but without the expected success. We propose that key features of human tuberculosis could be discovered by studying the M. tuberculosis gene expression within the human host. Therefore, we isolated totalM. tuberculosis mRNA from human clinical respiratory specimens of patients diagnosed with pulmonary tuberculosis; after this, we synthesized the dscDNA and tested it by qualitative RT-PCR assays. We detected the expression of IS6110 insertion sequence and of the "housekeeping" genes 16SrRNA andsigA in M. tuberculosis grown in vivo (pulmonary tuberculosis as well as grown in vitro M

  17. Fluctuating Behavior and Influential Factors in the Performance of the QuantiFERON-TB Gold In-Tube Assay in the Diagnosis of Tuberculosis

    Lei Bao; Tao Li; Ni Diao; Yaojie Shen; Lingyun Shao; Ying Zhang; Shuihua Lu; Wenhong Zhang

    2015-01-01

    Background The QuantiFERON-TB Gold In-Tube (QFT-GIT) is a newly developed but widely used interferon-γ release assay for diagnosing tuberculosis (TB). However, research has not determined whether age or the use of an immune suppressive or anti-TB treatment influences this assay’s ability to detect TB. We assessed the QFT-GIT diagnostic performance for active tuberculosis (ATB) in children and adults in an endemic country and explored the effects of glucocorticoids and anti-TB therapy on the d...

  18. Population Health Impact and Cost-Effectiveness of Tuberculosis Diagnosis with Xpert MTB/RIF: A Dynamic Simulation and Economic Evaluation

    Menzies, Nicolas A.; Ted Cohen; Hsien-Ho Lin; Megan Murray; Salomon, Joshua A.

    2012-01-01

    Editors' Summary Background In 2010, about 9 million people developed tuberculosis (TB)—a contagious bacterial disease that usually infects the lungs—and about 1.5 million people died from the disease. Most of these deaths were in low- and middle-income countries, and a quarter were in HIV-positive individuals, who are particularly susceptible to TB. Mycobacterium tuberculosis, the bacterium that causes TB, is spread in airborne droplets when people with active disease cough or sneeze. The ch...

  19. Abdominal tuberculosis: Imaging features

    Radiological findings of abdominal tuberculosis can mimic those of many different diseases. A high level of suspicion is required, especially in high-risk population. In this article, we will describe barium studies, ultrasound (US) and computed tomography (CT) findings of abdominal tuberculosis (TB), with emphasis in the latest. We will illustrate CT findings that can help in the diagnosis of abdominal tuberculosis and describe imaging features that differentiate it from other inflammatory and neoplastic diseases, particularly lymphoma and Crohn's disease. As tuberculosis can affect any organ in the abdomen, emphasis is placed to ileocecal involvement, lymphadenopathy, peritonitis and solid organ disease (liver, spleen and pancreas). A positive culture or hystologic analysis of biopsy is still required in many patients for definitive diagnosis. Learning objectives:1.To review the relevant pathophysiology of abdominal tuberculosis. 2.Illustrate CT findings that can help in the diagnosis

  20. Testing Pooled Sputum with Xpert MTB/RIF for Diagnosis of Pulmonary Tuberculosis To Increase Affordability in Low-Income Countries

    Abdurrahman, Saddiq T.; Mbanaso, Omezikam; Lawson, Lovett; Oladimeji, Olanrewaju; Blakiston, Matthew; Obasanya, Joshua; Dacombe, Russell; Adams, Emily R.; Emenyonu, Nnamdi; Sahu, Suvanand; Creswell, Jacob

    2015-01-01

    Tuberculosis (TB) is a global public health problem, with the highest burden occurring in low-income countries. In these countries, the use of more sensitive diagnostics, such as Xpert MTB/RIF (Xpert), is still limited by costs. A cost-saving strategy to diagnose other diseases is to pool samples from various individuals and test them with single tests. The samples in positive pool samples are then retested individually to identify the patients with the disease. We assessed a pooled testing strategy to optimize the affordability of Xpert for the diagnosis of TB. Adults with presumptive TB attending hospitals or identified by canvassing of households in Abuja, Nigeria, were asked to provide sputum for individual and pooled (4 per pool) testing. The agreement of the results of testing of individual and pooled samples and costs were assessed. A total of 738 individuals submitted samples, with 115 (16%) being Mycobacterium tuberculosis positive. Valid Xpert results for individual and pooled samples were available for 718 specimens. Of these, testing of pooled samples detected 109 (96%) of 114 individual M. tuberculosis-positive samples, with the overall agreement being 99%. Xpert semiquantitative M. tuberculosis levels had a positive correlation with the smear grades, and the individual sample-positive/pooled sample-negative results were likely due to the M. tuberculosis concentration being below the detection limit. The strategy reduced cartridge costs by 31%. Savings were higher with samples from individuals recruited in the community, where the proportion of positive specimens was low. The results of testing of pooled samples had a high level of agreement with the results of testing of individual samples, and use of the pooled testing strategy reduced costs and has the potential to increase the affordability of Xpert in countries with limited resources. PMID:26019204

  1. Primary skeletal muscle tuberculosis at an unusual site

    Tuberculosis can involve virtually any organ and it manifests itself in various forms. The selective involvement of muscles by a tuberculous process without coexisting active skeletal or extra skeletal tuberculosis is very rarely seen. A case of isolated tuberculosis of the biceps brachii muscle without any evident primary focus revealed as an intramuscular mass in a 37 years old immunocompetent female is presented. Diagnosis was established by histology and acid fast stain culture. The patient showed marked improvement with a standard four drug regimen with no evidence of disease activity at the four year follow up. This rare case is presented with review of literature. (author)

  2. Utility of CT in the evaluation of pulmonary tuberculosis in patients without Aids

    Objective. To assess the utility of CT in the evaluation of pulmonary tuberculosis in patients without AIDS. Patients and methods. Thin-section CT scans for suspicion of pulmonary tuberculosis were obtained from 226 patients. A total of 38 patients were excluded; the reasons were unavailability of final results (n=18), patient unavailability for follow-up (n=13), and coexistence of tuberculosis and aspergilloma (n=7). The results from 188 patients were used for this study. After assessing the patterns of parenchymal lesion, involved segments, and presence of cavity, bronchiectases, and bronchogenic spread of the lesion with CT, tentative diagnosis and disease activity were recorded. Results. With CT, 133 of 146 patients (91%) with tuberculosis were correctly diagnosed as having pulmonary tuberculosis whereas 32 of 42 patients (76%) without tuberculosis were correctly excluded. CT diagnosis of lung cancer (n=8), bacterial pneumonia (n=2), pulmonary metastasis (n=1), chronic hypersensitivity pneumonia (n=1) and diffuse pan-bronchiolitis (n=1) turned out to be tuberculosis. Conversely CT diagnoses of tuberculosis appeared pathologically as lung cancer (n=5), bacterial pneumonia 71/89, 80%) and inactive state (51/57, 89%) of disease respectively could be correctly differentiated by CT. Conclusion. CT can be helpful in the diagnosis of pulmonary tuberculosis in most cases. On the basis of CT findings, distinction of active from inactive disease can be made in most cases. (authors)

  3. Ultrasound-guided biopsy of the thickened peritoneal reflections: efficacy and diagnostic role in the differential diagnosis of peritoneal tuberculosis and peritoneal carcinomatosis

    To evaluate the accuracy and safety of ultrasound-guided biopsy of the thickened peritoneal reflections and to determine the efficacy and diagnostic role of this procedure in the differential diagnosis of peritoneal tuberculosis and peritoneal carcinomatosis. Twenty-seven patients with only mildly thickened (25 mm or less) peritoneal reflections without apparent mass formations, and in whom imaging findings were not diagnostic, underwent ultrasound-guided biopsy. Five-MHz linear or convex linear array transducers were used for ultrasound guidance, and an automated gun with 18-gauge (n=3D23) or 20-gauge (n=3D4) needles for tissue sampling. biopsies were performed on the thickened parietal peritoneum (n=3D9), greater omentum (n=3D11), and small bowel mesentery (n=3D7), and the results were compared with the final diagnosis determined by radiologic/clinical follow-up (n=3D17) or laparoscopic biopsy (n=3D10). Complications and changes in hemoglobin and hematocrit levels after the procedure were evaluated. Specimens adequate for pathologic examination were obtained in all 27 patients. The histopathologic results were metastatic carcinomatosis (n=3D15), peritoneal tuberculosis (n=3D8), and chronic granulomatous inflammation (n=3D4). Specific pathologic diagnosis was obtained in all patients except the four with chronic granulomatous inflammation. Differentiation between benignancy and malignancy was possible in all patients and the histopathologic specific accuracy rate was 100%. No clinically significant complications were observed. In 24 patients with ascites at the site of the biopsy, transient bleeding was observed immediately after the procedure, but this stopped spontaneously within a few minutes. Post-procedural hemoglobin and hematocrit levels were only minimally lower (mean values of 0.9 g/dL and 3.0%, respectively) than pre-procedurally. Ultrasound-guided biopsy of thickened peritoneal reflections is a safe and effective diagnostic procedure and is useful in

  4. Comparative cytotoxic and anti-tuberculosis activity of Aplysina caissara marine sponge crude extracts.

    Azevedo, Luciana G; Muccillo-Baisch, Ana L; Filgueira, Daza de M V B; Boyle, Robert T; Ramos, Daniela F; Soares, Andrea D; Lerner, Clea; Silva, Pedro A; Trindade, Gilma S

    2008-01-01

    Three crude extracts of Aplysina caissara, a marine sponge endemic to Brazil, were tested against a hepatoma cell line and Mycobacterium tuberculosis. The results demonstrate that all extracts are toxic and capable of inhibiting cellular growth. Additionally, the extracts produced morphological aberrations and inhibited cell attachment to culture substrates. These effects were dose/time dependent. Our results also suggest that reactive oxygen species (ROS) production is not involved in the cytotoxic processes levied by the extracts employed in this study and that active metabolites are likely to be present in the polar fractions of the crude extracts. Finally, our results indicate that all three extracts exhibit a moderate anti-tuberculosis capacity, and that the removal of an extract's lipid fraction appears to diminish this activity. PMID:17826358

  5. Encapsulation of Anti-Tuberculosis Drugs within Mesoporous Silica and Intracellular Antibacterial Activities

    Xin Xia

    2014-09-01

    Full Text Available Tuberculosis is a major problem in public health. While new effective treatments to combat the disease are currently under development, they tend suffer from poor solubility often resulting in low and/or inconsistent oral bioavailability. Mesoporous materials are here investigated in an in vitro intracellular assay, for the effective delivery of compound PA-824; a poorly soluble bactericidal agent being developed against Tuberculosis (TB. Mesoporous materials enhance the solubility of PA-824; however, this is not translated into a higher antibacterial activity in TB-infected macrophages after 5 days of incubation, where similar values are obtained. The lack of improved activity may be due to insufficient release of the drug from the mesopores in the context of the cellular environment. However, these results show promising data for the use of mesoporous particles in the context of oral delivery with expected improvements in bioavailability.

  6. Tuberculosis Endometritis Presenting as A Leiomyoma

    Mahboobeh Shirazi

    2015-02-01

    Full Text Available Genitourinary tuberculosis is a common extrapulmonary manifestation of tuberculosis. Taking into consideration that genitourinary tuberculosis may be associated with a diversity of presentations, its diagnoses may be difficult. A young woman with an initial presumptive diagnosis of a uterine leiomyoma presented with abdominal pain and a pelvic mass that after further investigations, she was diagnosed with genital tuberculosis.

  7. Tuberculosis Endometritis Presenting as A Leiomyoma

    Mahboobeh Shirazi; Fatemeh Shahbaz; Leila Pirzadeh; Seyed Rahim Mohammadi; Parisa Ghaffari; Tahereh Eftekhar

    2015-01-01

    Genitourinary tuberculosis is a common extrapulmonary manifestation of tuberculosis. Taking into consideration that genitourinary tuberculosis may be associated with a diversity of presentations, its diagnoses may be difficult. A young woman with an initial presumptive diagnosis of a uterine leiomyoma presented with abdominal pain and a pelvic mass that after further investigations, she was diagnosed with genital tuberculosis.

  8. In vitro activity of amoxicillin in combination with clavulanic acid against Mycobacterium tuberculosis.

    Cynamon, M H; Palmer, G S

    1983-01-01

    The comparative in vitro activity of amoxicillin alone and in combination with clavulanic acid against 15 isolates of Mycobacterium tuberculosis was evaluated by broth dilution susceptibility testing. Amoxicillin inhibited 4 of 15 isolates at 8 micrograms/ml or less but was not bactericidal against any of the isolates at that concentration. Amoxicillin in combination with clavulanic acid was bactericidal for 14 of 15 isolates tested at an amoxicillin concentration of 4 micrograms/ml or less a...

  9. Active and latent tuberculosis in Brazilian correctional facilities: a cross-sectional study

    Carbone, Andrea da Silva Santos; Paião, Dayse Sanchez Guimarães; Sgarbi, Renata Viebrantz Enne; Lemos, Everton Ferreira; Cazanti, Renato Fernando; Ota, Marcos Massaki; Junior, Alexandre Laranjeira; Bampi, José Victor Bortolotto; Elias, Vanessa Perreira Fayad; Simionatto, Simone; Motta-Castro, Ana Rita Coimbra; Pompílio, Maurício Antonio; de Oliveira, Sandra Maria do Valle; Ko, Albert I; Andrews, Jason R.

    2015-01-01

    Background Tuberculosis (TB) rates among prisoners are more than 20 times that of the general population in Brazil, yet there are limited data available to facilitate the development of effective interventions in this high-transmission setting. We aimed to assess risk factors for TB infection and evaluate the yield of mass screening for active disease among inmates. Methods We administered a questionnaire and tuberculin skin test (TST) to a population-based sample of inmates from 12 prisons i...

  10. Diagnosis of tuberculosis in the wild boar (Sus scrofa: a comparison of methods applicable to hunter-harvested animals.

    Nuno Santos

    Full Text Available BACKGROUND: To obtain robust epidemiological information regarding tuberculosis (TB in wildlife species, appropriate diagnostic methods need to be used. Wild boar (Sus scrofa recently emerged as a major maintenance host for TB in some European countries. Nevertheless, no data is available to evaluate TB post-mortem diagnostic methods in hunter-harvested wild boar. METHODOLOGY/PRINCIPAL FINDINGS: Six different diagnostic methods for TB were evaluated in parallel in 167 hunter-harvested wild boar. Compared to bacteriological culture, estimates of sensitivity of histopathology was 77.8%, gross pathology 72.2%, PCR for the MPB70 gene 66.7%, detection of acid-fast bacilli (AFB in tissue contact smears 55.6% and in histopathology slides 16.7% (estimated specificity was 96.7%, 100%, 100%, 94.4% and 100%, respectively. Combining gross pathology with stained smears in parallel increased estimated sensitivity to 94.4% (94.4% specificity. Four probable bacteriological culture false-negative animals were identified by Discriminant Function Analysis. Recalculating the parameters considering these animals as infected generated estimated values for sensitivity of bacteriology and histopathology of 81.8%, gross pathology 72.7%, PCR for the MPB70 gene 63.6%, detection of AFB in tissue contact smears 54.5% and in histopathology slides 13.6% (estimated specificity was 100% for gross pathology, PCR, bacteriology and detection of AFB in histopathology slides, 96.7% for histopathology and 94.4% for stained smears. CONCLUSIONS/SIGNIFICANCE: These results show that surveys for TB in wild boar based exclusively on gross pathology considerably underestimate prevalence, while combination of tests in parallel much improves sensitivity and negative predictive values. This finding should thus be considered when planning future surveys and game meat inspection schemes. Although bacteriological culture is the reference test for TB diagnosis, it can generate false

  11. Nitric Oxide Generated from Isoniazid Activation by KatG: Source of Nitric Oxide and Activity against Mycobacterium tuberculosis

    Timmins, Graham S.; Master, Sharon; Rusnak, Frank; Deretic, Vojo

    2004-01-01

    Isonicotinic acid hydrazide (INH) is a frontline antituberculosis agent. Once taken up by Mycobacterium tuberculosis, INH requires activation by the catalase-peroxidase KatG, converting INH from its prodrug form into a range of bactericidal reactive species. Here we used 15N-labeled INH together with electron paramagnetic resonance spin trapping techniques to demonstrate that nitric oxide (NȮ) is generated from oxidation at the hydrazide nitrogens during the activation of INH by M. tuberculos...

  12. Perinatal tuberculosis: a diagnostic challenge

    Edna Lúcia S. de Souza

    2006-06-01

    Full Text Available Despite the high prevalence of tuberculosis in adults and children, the congenital and perinatal forms of tuberculosis are rare. In Brazil, there has been only one published case of congenital tuberculosis and two cases of the perinatal form of this disease. We report a case of perinatal tuberculosis presenting with pneumonia. Alcohol-acid-resistant bacilli were found in the gastric lavage. Diagnosis of this disease presentation requires a high index of suspicion.

  13. 女性生殖器结核的超声诊断%Ultrasonic diagnosis of female genital tuberculosis

    曹小娟; 黄林; 曹恒; 何小乔; 李荆

    2011-01-01

    目的 探讨女性生殖器结核的超声图像特征及诊断要点.方法 术前密切结合临床病史、症状及X线检查资料,对经腹壁、经阴道二维超声或经腹壁与经阴道联合超声检查的69例女性生殖器结核患者的盆腹腔病灶超声图像与手术病理检查结果进行综合分析.结果 69例患者中生育期58例(84.1%),来自农村41例(59.4%),主诉盆腔包块34例(49.3%).其中63例(91.3%)盆腹腔二维超声显示异常,其声图像特征:(1)盆腔肿块58例(92.1%),实性肿块21例,内部或周边均可见细小点状及斑状强回声,后方无明显声影.(2)腹水28例(44.4%),6例腹水内见带状回声呈广泛网格样分布.(3)包裹性积液22例(34.9%),6例积液内伴点状、带状强回声.(4)子宫内膜回声异常35例(55.6%),3例内膜回声在宫腔积液的衬托下呈锯齿状不规则增厚.(5)输卵管回声异常6例(9.5%).(6)大网膜回声异常14例(22.2%).(7)腹膜增厚中腹腔腹膜增厚16例、盆腔腹膜增厚14例,盆腔腹膜欠规则增厚呈锯齿状、粟粒样结节回声改变.盆腹腔病灶内见各超声图像多交织、伴随存在.69例中6例(8.7%)不孕患者盆腹腔超声图像未显示异常,术中发现6例均为粘连型结核性盆腔炎.结论 女性生殖器结核患者的盆腹腔超声图像呈多样性,熟悉其超声图像特征性表现,详细询问病史,密切结合临床并对患者行全面系统盆腹腔超声检查,可为临床早期积极干预治疗女性生殖器结核病提供诊断依据.%Objective To analyze the ultrasound manifestation feature and key diagnosis crinteria of female genital tuberculosis. Methods Combined with the clinical data, symptoms and X-ray examination before operation,69 cases of infertile patients were performed a complete inspection of abdominopelvic cavity by trans-abdo men ( and/or vaginal ) ultrasound , which were compared with the results of operation and pathology. Results Sixty-nine cases of patients includes

  14. A Bayesian Nonlinear Mixed-Effects Regression Model for the Characterization of Early Bactericidal Activity of Tuberculosis Drugs

    Burger, Divan Aristo; Schall, Robert

    2014-01-01

    Trials of the early bactericidal activity (EBA) of tuberculosis (TB) treatments assess the decline, during the first few days to weeks of treatment, in colony forming unit (CFU) count of Mycobacterium tuberculosis in the sputum of patients with smear-microscopy-positive pulmonary TB. Profiles over time of CFU data have conventionally been modeled using linear, bilinear, or bi-exponential regression. We propose a new biphasic nonlinear regression model for CFU data that comprises linear and bi...

  15. Sterilizing Activities of Novel Combinations Lacking First- and Second-Line Drugs in a Murine Model of Tuberculosis

    Williams, Kathy; Minkowski, Austin; Amoabeng, Opokua; Peloquin, Charles A.; Taylor, Dinesh; Andries, Koen; Wallis, Robert S.; Mdluli, Khisimuzi E.; Eric L Nuermberger

    2012-01-01

    Novel oral regimens composed of new drugs with potent activity against Mycobacterium tuberculosis and no cross-resistance with existing agents are needed to shorten and simplify treatment for both drug-susceptible and drug-resistant tuberculosis. As part of a continuing effort to evaluate novel drug combinations for treatment-shortening potential in a murine model, we performed two long-term, relapse-based experiments. In the first experiment, several 3- and 4-drug combinations containing new...

  16. Application of MSCT in the diagnosis of adult new-onset pulmonary tuberculosis%MSCT在成人新发肺结核诊断中的应用

    林栋; 冼秀玲; 石罗君; 包家福; 马自传; 黄家杰; 覃倪

    2014-01-01

    目的:探讨多层螺旋CT(MSCT)在成人新发肺结核诊断中的应用价值。方法98例成人新发肺结核患者作为研究对象。对所有患者分别应用X线平片及MSCT进行胸部扫描,根据影像学结果进行诊断及病情评价,判断MSCT应用在成人新发肺结核诊断中的临床价值。结果 MSCT检出新发肺结核89例(90.82%), X线平片检出75例(76.53%),两种方法比较差异有统计学意义(P<0.05);MSCT定位肺内病变患者71例,肺内隐蔽性病变18例,与X线平片结果比较差异有统计学意义(P<0.05)。结论 MSCT应用检查成人新发肺结核可提高其临床诊断正确率,明确病灶类型及定位,对在早期及时控制肺结核传播、防止患者肺结核病情进展具有重要意义。%Objective To investigate the application vaule of multi-slice CT (MSCT) in the diagnosis of adult new-onset pulmonary tuberculosis. Methods A total of 98 adult patients with new-onset pulmonary tuberculosis were selected as the study objects. All patients underwent X-ray and chest MSCT scans. Diagnosis and condition assessment were made by imaging results, then the clinical value of MSCT in diagnosis of adult new-onset pulmonary tuberculosis was determined. Results MSCT detected 89 cases of new-onset pulmonary tuberculosis (90.82%), and X-ray detected 75 cases (76.53%). The difference between the two methods was statistically significant (P<0.05). MSCT positioning showed 71 cases with lung lesions and 18 cases with pulmonary lesions concealment, which had significant difference from the X-ray results (P<0.05). Conclusion MSCT in checking adult new-onset pulmonary tuberculosis can improve the accuracy of clinical diagnosis, and clarify lesion type and location of the spread of tuberculosis. It is also important for timely control and prevention of disease progression in patients with pulmonary tuberculosis.

  17. Biomarkers for the detection, prognois and evaluation of active tuberculosis

    Shinimukundan, Harshini [Los Alamos National Laboratory

    2010-12-08

    The global TS surveillance workshop aims to address the problems with current methods for the detection of TB, and tracking emergence of resistant strains. The purpose of the attached presentation is to review the current methods in the detection of pathogen biomarkers for TB and if that technology has promise for diagnosis of TB. A summary of three biomarkers and some data on their detection strategies is presented. Some of the work is from LANL work but much of it is derived from literature references on the subject.

  18. The Importance of Implementation Strategy in Scaling Up Xpert MTB/RIF for Diagnosis of Tuberculosis in the Indian Health-Care System: A Transmission Model

    Salje, Henrik; Andrews, Jason R.; Deo, Sarang; Satyanarayana, Srinath; Sun, Amanda Y.; Pai, Madhukar; David W. Dowdy

    2014-01-01

    Background: India has announced a goal of universal access to quality tuberculosis (TB) diagnosis and treatment. A number of novel diagnostics could help meet this important goal. The rollout of one such diagnostic, Xpert MTB/RIF (Xpert) is being considered, but if Xpert is used mainly for people with HIV or high risk of multidrug-resistant TB (MDR-TB) in the public sector, population-level impact may be limited. Methods and Findings: We developed a model of TB transmission, care-seeking beha...

  19. Skeletal tuberculosis

    Tuberculosis remains a major cause of bone and joint infection, and its frequency has been increasing during recent years. Recent imaging methods, especially MR, are necessary for the early diagnosis of the disease, because conventional radiography may fail to reveal the initial osseous lesions. Spine is the most common site of infection, with relatively characteristic features; MR is the most suitable method for evaluation of bone involvement, paravertebral and epidural abscesses. Radiographic presentation of tuberculous osteitis and osteo-arthritis is less characteristic. The final diagnosis frequently needs histological studies and cultures of bone, synovial tissue or synovial fluid. (authors)., 13 figs., 35 refs

  20. [Pharyngeal tuberculosis: Case report].

    Spini, Roxana Gabriela; Bordino, Lucas; Cohen, Daniela; Martins, Andrea; Ramírez, Zaida; González, Norma E

    2015-08-01

    Pharyngeal tuberculosis is a rare extrapulmonary manifestation. In Argentina, the number of cases of tuberculosis reported in children under 19 years in 2012 was 1752. Only 12.15% had extrapulmonary manifestation. A case of a 17 year old girl with pharyngeal tuberculosis is reported. The patient presented intermittent fever and swallowing pain for 6 months, without response to conventional antibiotic treatment. Chest X-ray showedbilateral micronodular infiltrate, so hospitalization was decided to study and treat. The sputum examination for acid-fast resistant bacilli was positive and treatment with four antituberculous drugs was started, with good evolution and disappearance of symptoms. Diagnostic confirmation with the isolation of Mycobacterium tuberculosis in sputum culture was obtained. The main symptoms of pharyngeal tuberculosis are sore throat and difficulty in swallowing of long evolution. It is important to consider tuberculosis as differential diagnosis in patients with chronic pharyngitis unresponsive to conventional treatment. PMID:26172025

  1. Tuberculosis in HIV-infected infants, children, and adolescents in Latin America

    Margot R. Krauss

    2015-02-01

    Full Text Available Objective:To evaluate the occurrence, clinical presentations and diagnostic methods for tuberculosis in a cohort of HIV-infected infants, children and adolescents from Latin America.Methods:A retrospective analysis of children with tuberculosis and HIV was performed within a prospective observational cohort study conducted at multiple clinical sites in Latin America.Results:Of 1114 HIV-infected infants, children, and adolescents followed from 2002 to 2011, 69 that could be classified as having confirmed or presumed tuberculosis were included in this case series; 52.2% (95% CI: 39.8-64.4% had laboratory-confirmed tuberculosis, 15.9% (95% CI: 8.2-26.7% had clinically confirmed disease and 31.9% (95% CI: 21.2-44.2% had presumed tuberculosis. Sixty-six were perinatally HIV-infected. Thirty-two (61.5% children had a history of contact with an adult tuberculosis case; however information on exposure to active tuberculosis was missing for 17 participants. At the time of tuberculosis diagnosis, 39 were receiving antiretroviral therapy. Sixteen of these cases may have represented immune reconstitution inflammatory syndrome.Conclusions:Our study emphasizes the need for adequate contact tracing of adult tuberculosis cases and screening for HIV or tuberculosis in Latin American children diagnosed with either condition. Preventive strategies in tuberculosis-exposed, HIV-infected children should be optimized.

  2. Immune Responses to ESAT-6 and CFP-10 by FASCIA and Multiplex Technology for Diagnosis of M. tuberculosis Infection; IP-10 Is a Promising Marker

    Emilie Borgström; Peter Andersen; Fredrik Atterfelt; Inger Julander; Gunilla Källenius; Markus Maeurer; Ida Rosenkrands; Maria Widfeldt; Judith Bruchfeld; Hans Gaines

    2012-01-01

    BACKGROUND: There is a need for reliable markers to diagnose active and latent tuberculosis (TB). The interferon gamma release assays (IGRAs) are compared to the tuberculin skin test (TST) more specific, but cannot discriminate between recent or remote TB infection. Here the Flow-cytometric Assay for Specific Cell-mediated Immune-response in Activated whole blood (FASCIA), which quantifies expanded T-lymphoblasts by flow-cytometric analysis after long-term antigen stimulation of whole blood, ...

  3. FINANCIAL DIAGNOSIS OF A COMPANY’S ACTIVITIES

    SUCIU GHEORGHE

    2013-12-01

    Full Text Available Financial diagnosis consists of a number of instruments and methods which help to evaluate a company’s financial situation and performances. The financial diagnosis identifies the favourable and unfavourable factors which will affect the company’s future activity. The purpose of financial diagnosis is to draw a comparison with similar companies, in order to establish risk, profitability, and value parameters, by estimating the cost of capital (discount rate. The financial diagnosis helps to appreciate the past and present financial situation, and based on them to make projections for the future.

  4. Patient and community experiences of tuberculosis diagnosis and care within a community-based intervention in Ethiopia: a qualitative study

    Tulloch, Olivia; Theobald, Sally; Morishita, Fukushi; Datiko, Daniel G.; Asnake, Girum; Tesema, Tadesse; Jamal, Habiba; Markos, Paulos; Cuevas, Luis E.; Yassin, Mohammed A.

    2015-01-01

    Background The Ethiopian TB control programme relies on passive case finding of TB cases. The predominantly rural-based population in Ethiopia has limited access to health facilities creating barriers to TB services. An intervention package aimed to bring TB diagnosis and treatment services closer to communities has been implemented through partnership with health extension workers (HEWs). They undertook advocacy, communication and social mobilization (ACSM) activities, identified symptomatic...

  5. Serial interferon-gamma release assays during treatment of active tuberculosis in young adults

    Lee Choon-Taek

    2010-10-01

    Full Text Available Abstract Background The role of interferon-γ release assay (IGRA in monitoring responses to anti-tuberculosis (TB treatment is not clear. We evaluated the results of the QuantiFERON-TB Gold In-tube (QFT-GIT assay over time during the anti-TB treatment of adults with no underlying disease. Methods We enrolled soldiers who were newly diagnosed with active TB and admitted to the central referral military hospital in South Korea between May 1, 2008 and September 30, 2009. For each participant, we preformed QFT-GIT assay before treatment (baseline and at 1, 3, and 6 months after initiating anti-TB medication. Results Of 67 eligible patients, 59 (88.1% completed the study protocol. All participants were males who were human immunodeficiency virus (HIV-negative and had no chronic diseases. Their median age was 21 years (range, 20-48. Initially, 57 (96.6% patients had positive QFT-GIT results, and 53 (89.8%, 42 (71.2%, and 39 (66.1% had positive QFT-GIT results at 1, 3, and 6 months, respectively. The IFN-γ level at baseline was 5.31 ± 5.34 IU/ml, and the levels at 1, 3, and 6 months were 3.95 ± 4.30, 1.82 ± 2.14, and 1.50 ± 2.12 IU/ml, respectively. All patients had clinical and radiologic improvements after treatment and were cured. A lower IFN-γ level, C-reactive protein ≥ 3 mg/dl, and the presence of fever (≥ 38.3°C at diagnosis were associated with negative reversion of the QFT-GIT assay. Conclusion Although the IFN-γ level measured by QFT-GIT assay decreased after successful anti-TB treatment in most participants, less than half of them exhibited QFT-GIT reversion. Thus, the reversion to negativity of the QFT-GIT assay may not be a good surrogate for treatment response in otherwise healthy young patients with TB.

  6. Clinical features of active tuberculosis that developed during anti-tumor necrosis factor therapy in patients with inflammatory bowel disease

    Lee, Jang Wook; Park, Ji Hoon; Kim, Jeong Wook; Kang, Sang Bum; Koo, Ja Seol; Kim, Young-Ho; Kim, You Sun; Joo, Young Eun; Chang, Sae Kyung

    2016-01-01

    Background/Aims Anti-tumor necrosis factor (TNF) therapy for active ulcerative colitis (UC) and Crohn's disease (CD) is associated with increased risks of tuberculosis (TB) infection. We analyzed the incidence and clinical features of Korean patients with inflammatory bowel disease (IBD) who developed active TB during anti-TNF therapy. Methods Ten cases of active TB developed in patients treated with infliximab (n=592) or adalimumab (n=229) for UC (n=160) or CD (n=661) were reviewed. We analyzed demographics, interval between start of anti-TNF therapy and active TB development, tests for latent TB infection (LTBI), concomitant medications, and the details of diagnosis and treatments for TB. Results The incidence of active TB was 1.2% (10/821): 1.5% (9/592) and 0.4% (1/229) in patients receiving infliximab and adalimumab, respectively. The median time to the development of active TB after initiation of anti-TNF therapy was three months (range: 2–36). Three patients had past histories of treatment for TB. Positive findings in a TB skin test (TST) and/or interferon gamma releasing assay (IGRA) were observed in three patients, and two of them received anti-TB prophylaxis. Two patients were negative by both TST and IGRA. The most common site of active TB was the lungs, and the active TB was cured in all patients. Conclusions Active TB can develop during anti-TNF therapy in IBD patients without LTBI, and even in those with histories of TB treatment or LTBI prophylaxis. Physicians should be aware of the potential for TB development during anti-TNF therapy, especially in countries with a high prevalence of TB.

  7. Diagnostic potential of IS6110, 38kDa, 65kDa and 85B sequence-based polymerase chain reaction in the diagnosis of Mycobacterium tuberculosis in clinical samples

    Negi S

    2007-01-01

    Full Text Available Purpose: The correlation between the presence of specific gene sequence of M. tuberculosis and specific diagnosis of clinical tuberculosis is not known. This study compared the results of polymerase chain reaction (PCR amplification of M . tuberculosis specific DNA sequences (IS6110, 65kDa, 38kDa and mRNA coding for 85 B protein from different clinical samples of pulmonary and extrapulmonary tuberculosis. Methods: One hundred and seventy-two clinical samples from suspected tuberculosis patients were tested for smear examination, culture (LJ and rapid BACTEC 460 TB system and PCR. PCR was performed with specific primers for the targets: IS6110, 65kDa, 38kDa and 85B. Results: Each PCR test was found to have a much higher positivity than conventional test and BACTEC culture ( P < 0.05. Smear positive samples (56 and the samples (36 showing positive results by conventional methods (smear and LJ medium culture and BACTEC were found to be positive by all PCR protocols. No significant difference was found between the four PCR protocols ( P >0.05. The primer specific for amplifying the 123bp IS6110 fragment gave the highest positivity (83%, followed by 65kDa, 38kDa and 85B RT-PCR in descending order. Conclusions: These data suggest that the presence of IS6110 correlates more closely with the diagnosis of clinical tuberculosis than that of 65kDa, 38kDa and 85B proteins.

  8. Mefloquine and its oxazolidine derivative compound are active against drug-resistant Mycobacterium tuberculosis strains and in a murine model of tuberculosis infection.

    Rodrigues-Junior, Valnês S; Villela, Anne D; Gonçalves, Raoni S B; Abbadi, Bruno Lopes; Trindade, Rogério Valim; López-Gavín, Alexandre; Tudó, Griselda; González-Martín, Julian; Basso, Luiz Augusto; de Souza, Marcus V N; Campos, Maria Martha; Santos, Diógenes Santiago

    2016-08-01

    Repurposing of drugs to treat tuberculosis (TB) has been considered an alternative to overcome the global TB epidemic, especially to combat drug-resistant forms of the disease. Mefloquine has been reported as a potent drug to kill drug-resistant strains of Mycobacterium tuberculosis. In addition, mefloquine-derived molecules have been synthesised and their effectiveness against mycobacteria has been assessed. In this work, we demonstrate for the first time the activities of mefloquine and its oxazolidine derivative compound 1E in a murine model of TB infection following administration of both drugs by the oral route. The effects of associations between mefloquine or 1E with the clinically used antituberculosis drugs isoniazid, rifampicin, ethambutol, moxifloxacin and streptomycin were also investigated. Importantly, combination of mefloquine with isoniazid and of 1E with streptomycin showed a two-fold decrease in their minimum inhibitory concentrations (MICs). Moreover, no tested combinations demonstrated antagonist interactions. Here we describe novel evidence on the activity of mefloquine and 1E against a series of quinolone-resistant M. tuberculosis strains. These data show MICs against quinolone-resistant strains (0.5-8 µg/mL) similar to or lower than those previously reported for multidrug-resistant strains. Taking these results together, we can suggest the use of mefloquine or 1E in combination with clinically available drugs, especially in the case of resistant forms of TB. PMID:27364701

  9. Cerebrospinal fluid adenosine deaminase activity: A complimentary tool in the early diagnosis of tuberculous meningitis

    Taori Girdhar M

    2006-03-01

    Full Text Available Abstract Background Tuberculous meningitis (TBM is the commonest form of neurotuberculosis caused by Mycobacterium tuberculosis bacilli (MTB. The diagnosis of TBM is often difficult. A reliable, cost-effective and rapid diagnostic test, which can be performed in any standard pathology laboratory, could be of help in the diagnosis of TBM. In the present study we measured the adenosine deaminase (ADA activity in cerebrospinal fluid (CSF of TBM and non-TBM patients. Method ADA activity in CSF was determined according to a method based on the Berthlot reaction, which is the formation of a colored indophenol complex from ammonia liberated from adenosine, and quantified spectrophotometrically. Results The CSF ADA activity from TBM patients was compared with CSF ADA from non-TBM infectious meningitis patients, and from patients with non-infectious neurological disorders. The mean CSF ADA activity was found to be significantly higher in CSF of TBM patients, 14.31 ± 3.87 (2.99–26.94, mean ± SD with range, than in the CSF from non-TBM infectious meningitis, 9.25 ± 2.14 (4.99–13.96 and from the non-infectious neurological disorders group, 2.71 ± 1.96 (0.00–7.68, P Conclusion This study demonstrated that ADA activity in the CSF of TBM patients, using a cut-off value 11.39 U/L/min, can be useful for the early differential diagnosis of TBM. This test can be performed in any pathology laboratory where more sophisticated methods are not available.

  10. Identification and Characterization of Lipase Activity and Immunogenicity of LipL from Mycobacterium tuberculosis.

    Jun Cao

    Full Text Available Lipids and lipid-metabolizing esterases/lipases are highly important for the mycobacterial life cycle and, possibly, for mycobacterial virulence. In this study, we expressed 10 members of the Lip family of Mycobacterium tuberculosis. Among the 10 proteins, LipL displayed a significantly high enzymatic activity for the hydrolysis of long-chain lipids. The optimal temperature for the lipase activity of LipL was demonstrated to be 37°C, and the optimal pH was 8.0. The lipase active center was not the conserved motif G-x-S-x-G, but rather the S-x-x-K and GGG motifs, and the key catalytic amino acid residues were identified as G50, S88, and K91, as demonstrated through site-directed mutagenesis experiments. A three-dimensional modeling structure of LipL was constructed, which showed that the GGG motif was located in the surface of a pocket structure. Furthermore, the subcellular localization of LipL was demonstrated to be on the mycobacterial surface by Western blot analysis. Our results revealed that the LipL protein could induce a strong humoral immune response in humans and activate a CD8+ T cell-mediated response in mice. Overall, our study identified and characterized a novel lipase denoted LipL from M. tuberculosis, and demonstrated that LipL functions as an immunogen that activates both humoral and cell-mediated responses.

  11. NLRP3 Activation Was Regulated by DNA Methylation Modification during Mycobacterium tuberculosis Infection

    Wei, Meili; Wang, Lu; Wu, Tao; Xi, Jun; Han, Yuze; Yang, Xingxiang; Zhang, Ding; Fang, Qiang

    2016-01-01

    Mycobacterium tuberculosis (Mtb) infection activates the NLRP3 inflammasome in macrophages and dendritic cells. Much attention has been paid to the mechanisms for regulation of NLRP3 against Mtb. However, whether epigenetic mechanisms participated in NLRP3 activation is still little known. Here we showed that NLRP3 activation was regulated by DNA methylation modification. Mtb infection promoted NLRP3 activation and inflammatory cytokines expression. NLRP3 promoter was cloned and subsequently identified by Dual-Luciferase Reporter System. The results showed that NLRP3 promoter activity was decreased after methylation by DNA methylase Sss I in vitro. Meanwhile, DNA methyltransferases inhibitor DAC could upregulate the expression of NLRP3. Furthermore, promoter region of NLRP3 gene was demethylated after Mtb H37Rv strain infection. These data revealed that DNA methylation was involved in NLRP3 inflammasome activation during Mtb infection and provided a new insight into the relationship between host and pathogens. PMID:27366746

  12. Discrimination between Active and Latent Tuberculosis Based on Ratio of Antigen-Specific to Mitogen-Induced IP-10 Production

    Jeong, Yun Hee; Hur, Yun-Gyoung; Lee, Hyejon; Kim, Sunghyun; Cho, Jang-Eun; Chang, Jun; Shin, Sung Jae; Lee, Hyeyoung; Kang, Young Ae; Cho, Sang-Nae; Ha, Sang-Jun

    2014-01-01

    Mycobacterium tuberculosis is the major causative agent of tuberculosis (TB). The gamma interferon (IFN-γ) release assay (IGRA) has been widely used to diagnose TB by testing cell-mediated immune responses but has no capacity for distinguishing between active TB and latent TB infection (LTBI). This study aims to identify a parameter that will help to discriminate active TB and LTBI. Whole-blood samples from 33 active TB patients, 20 individuals with LTBI, and 26 non-TB controls were applied t...

  13. Activity against Mycobacterium smegmatis and M. tuberculosis by extract of South African medicinal plants.

    Mativandlela, Sannah Patience Nkami; Meyer, Jacob Jacobus Marion; Hussein, Ahmed A; Houghton, Peter J; Hamilton, Chris J; Lall, Namrita

    2008-06-01

    Seven ethnobotanically selected medicinal plants were screened for their antimycobacterial activity. The minimum inhibitory concentration (MIC) of four plants namely Artemisia afra, Dodonea angustifolia, Drosera capensis and Galenia africana ranged from 0.781 to 6.25 mg/mL against Mycobacterium smegmatis. G. africana showed the best activity exhibiting an MIC of 0.78 mg/mL and a minimum bactericidal concentration (MBC) of 1.56 mg/mL. The MICs of ethanol extracts of D. angustifolia and G. africana against M. tuberculosis were found to be 5.0 and 1.2 mg/mL respectively. The mammalian cytotoxicity IC(50) value of the most active antimycobacterial extract, from G. africana, was found to be 101.3 microg/mL against monkey kidney Vero cells. Since the ethanol G. africana displayed the best antimycobacterial activity, it was subjected to fractionation which led to the isolation of a flavone, 5,7,2'-trihydroxyflavone. The MIC of this compound was found to be 0.031 mg/mL against M. smegmatis and 0.10 mg/mL against M. tuberculosis. This study gives some scientific basis to the traditional use of these plants for TB-related symptoms. PMID:18412151

  14. Synthesis and Anti-Tuberculosis Activity of the Marine Natural Product Caulerpin and Its Analogues

    Cristina I. Canché Chay

    2014-03-01

    Full Text Available Caulerpin (1a, a bis-indole alkaloid from the marine algal Caulerpa sp., was synthesized in three reaction steps with an overall yield of 11%. The caulerpin analogues (1b–1g were prepared using the same synthetic pathway with overall yields between 3% and 8%. The key reaction involved a radical oxidative aromatic substitution involving xanthate (3 and 3-formylindole compounds (4a–4g. All bis-indole compounds synthesized were evaluated against the Mycobacterium tuberculosis strain H37Rv, and 1a was found to display excellent activity (IC50 0.24 µM.

  15. Impact of Diabetes Mellitus on Treatment Outcomes of Patients with Active Tuberculosis

    Dooley, Kelly E.; Tang, Tania; Golub, Jonathan E.; Dorman, Susan E.; Cronin, Wendy

    2009-01-01

    Diabetes mellitus (DM) is an emerging chronic health condition of developed and developing countries. We conducted a retrospective cohort study of patients with active, culture-confirmed tuberculosis (TB) in Maryland to determine the impact of DM on TB treatment outcomes. Of 297 TB patients, 42 (14%) had DM. Patients with diabetes had 2.0 times higher odds of death than patients without diabetes (95% confidence interval [CI] 0.74–5.2, P = 0.18). Adjusting for human immunodeficiency virus (HIV...

  16. Soluble Urokinase Plasminogen Activator Receptor Levels in Tuberculosis Patients at High Risk for Multidrug Resistance

    Tri Yudani Mardining Raras; Triwahju Astuti; Iin Noor Chozin

    2012-01-01

    The soluble urokinase plasminogen activator receptor (suPAR) has been shown to be a strong prognostic biomarker for tuberculosis (TB). In the present study, the profiles of plasma suPAR levels in pulmonary TB patients at high risk for multidrug resistance were analyzed and compared with those in multidrug resistant (MDR)-TB patients. Forty patients were prospectively included, consisting of 10 MDR-TB patients and 30 TB patients at high risk for MDR, underwent clinical assesment. Plasma suPAR ...

  17. Characterization of the Helicase Activity and Substrate Specificity of Mycobacterium tuberculosis UvrD▿

    Curti, Elena; Smerdon, Stephen J; Davis, Elaine O.

    2006-01-01

    UvrD is a helicase that is widely conserved in gram-negative bacteria. A uvrD homologue was identified in Mycobacterium tuberculosis on the basis of the homology of its encoded protein with Escherichia coli UvrD, with which it shares 39% amino acid identity, distributed throughout the protein. The gene was cloned, and a histidine-tagged form of the protein was expressed and purified to homogeneity. The purified protein had in vitro ATPase activity that was dependent upon the presence of DNA. ...

  18. Chest wall tuberculosis; CT findings in 14 patients

    To present CT findings of chest wall tuberculosis. CT scans were obtained in 14 patients with proven chest wall tuberculosis. Diagnosis was confirmed by means of right open thoracostomy with abscess evacuation (n=1), excision and curettage (n=11) or excision and curettage along with resection of the involved lung (n=2). The images were assessed with emphasis for the extrapleural, pleural, and pulmonary lesions. All patients showed juxtacostal soft tissue mass with central low attenuation and peripheral rim enhancement. The lesions were located in the left hemithorax in eight patients and in the right in six. Multiple lesions were found in three patients (two in one and three in two). Rib destruction was observed in four patients. Intercostal muscle involvement of thickening and enhancement were shown in all patients. Thirteen patients (93%) had evidence of pulmonary tuberculosis: active pulmonary tuberculosis in nine and stable tuberculosis in four. Pleural lesions, including empyema necessitatis in six, were observed in eleven (79%). On CT scan, chest wall tuberculosis is characterized by juxtacostal soft tissue lesion with central low attenuation and peripheral rim enhancement. Rib destruction may be associated. Additionally, enhancing intercostal muscle suggest direct inflammatory process of tuberculosis and spread channel to the chest wall involvement of pleuropulmonary tuberculosis

  19. CT appearances of abdominal tuberculosis

    Lee, W.-K., E-mail: leewk33@hotmail.com [Department of Medical Imaging, St Vincent' s Hospital, University of Melbourne, Fitzroy, Victoria (Australia); Van Tonder, F.; Tartaglia, C.J.; Dagia, C. [Department of Medical Imaging, St Vincent' s Hospital, University of Melbourne, Fitzroy, Victoria (Australia); Cazzato, R.L. [Department of Radiology, Universita Campus Bio-Medico di Roma, Rome (Italy); Duddalwar, V.A. [Department of Radiology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California (United States); Chang, S.D. [Department of Medical Imaging, Vancouver General Hospital, University of British Columbia, British Columbia (Canada)

    2012-06-15

    The purpose of this article is to review and illustrate the spectrum of computed tomography (CT) appearances of abdominal tuberculosis. Tuberculosis can affect any organ or tissue in the abdomen, and can be mistaken for other inflammatory or neoplastic conditions. The most common sites of tuberculosis in the abdomen include lymph nodes, genitourinary tract, peritoneal cavity and gastrointestinal tract. The liver, spleen, biliary tract, pancreas and adrenals are rarely affected, but are more likely in HIV-seropositive patients and in miliary tuberculosis. This article should alert the radiologist to consider abdominal tuberculosis in the correct clinical setting to ensure timely diagnosis and enable appropriate treatment.

  20. CT appearances of abdominal tuberculosis

    The purpose of this article is to review and illustrate the spectrum of computed tomography (CT) appearances of abdominal tuberculosis. Tuberculosis can affect any organ or tissue in the abdomen, and can be mistaken for other inflammatory or neoplastic conditions. The most common sites of tuberculosis in the abdomen include lymph nodes, genitourinary tract, peritoneal cavity and gastrointestinal tract. The liver, spleen, biliary tract, pancreas and adrenals are rarely affected, but are more likely in HIV-seropositive patients and in miliary tuberculosis. This article should alert the radiologist to consider abdominal tuberculosis in the correct clinical setting to ensure timely diagnosis and enable appropriate treatment.

  1. The Sensitivity and Specificity of Loop-Mediated Isothermal Amplification (LAMP) Assay for Tuberculosis Diagnosis in Adults with Chronic Cough in Malawi

    Nliwasa, Marriott; MacPherson, Peter; Chisala, Palesa; Kamdolozi, Mercy; Khundi, McEwen; Kaswaswa, Kruger; Mwapasa, Mphatso; Msefula, Chisomo; Sohn, Hojoon; Flach, Clare; Corbett, Elizabeth L.

    2016-01-01

    Background Current tuberculosis diagnostics lack sensitivity, and are expensive. Highly accurate, rapid and cheaper diagnostic tests are required for point of care use in low resource settings with high HIV prevalence. Objective To investigate the sensitivity and specificity, and cost of loop-mediated isothermal amplification (LAMP) assay for tuberculosis diagnosis in adults with chronic cough compared to Xpert® MTB/RIF, fluorescence smear microscopy. Methods Between October 2013 and March 2014, consecutive adults at a primary care clinic were screened for cough, offered HIV testing and assessed for tuberculosis using LAMP, Xpert® MTB/RIF and fluorescence smear microscopy. Sensitivity and specificity (with culture as reference standard), and costs were estimated. Results Of 273 adults recruited, 44.3% (121/273) were HIV-positive and 19.4% (53/273) had bacteriogically confirmed tuberculosis. The sensitivity of LAMP compared to culture was 65.0% (95% CI: 48.3% to 79.4%) with 100% (95% CI: 98.0% to 100%) specificity. The sensitivity of Xpert® MTB/RIF (77.5%, 95% CI: 61.5% to 89.2%) was similar to that of LAMP, p = 0.132. The sensitivity of concentrated fluorescence smear microscopy with routine double reading (87.5%, 95% CI: 73.2% to 95.8%) was higher than that of LAMP, p = 0.020. All three tests had high specificity. The lowest cost per test of LAMP was at batch size of 14 samples (US$ 9.98); this was lower than Xpert® MTB/RIF (US$ 13.38) but higher than fluorescence smear microscopy (US$ 0.65). Conclusion The sensitivity of LAMP was similar to Xpert® MTB/RIF but lower than fluorescence smear microscopy; all three tests had high specificity. These findings support the Malawi policy that recommends a combination of fluorescence smear microscopy and Xpert® MTB/RIF prioritised for people living with HIV, already found to be smear-negative, or being considered for retreatment of tuberculosis. PMID:27171380

  2. The Sensitivity and Specificity of Loop-Mediated Isothermal Amplification (LAMP Assay for Tuberculosis Diagnosis in Adults with Chronic Cough in Malawi.

    Marriott Nliwasa

    Full Text Available Current tuberculosis diagnostics lack sensitivity, and are expensive. Highly accurate, rapid and cheaper diagnostic tests are required for point of care use in low resource settings with high HIV prevalence.To investigate the sensitivity and specificity, and cost of loop-mediated isothermal amplification (LAMP assay for tuberculosis diagnosis in adults with chronic cough compared to Xpert® MTB/RIF, fluorescence smear microscopy.Between October 2013 and March 2014, consecutive adults at a primary care clinic were screened for cough, offered HIV testing and assessed for tuberculosis using LAMP, Xpert® MTB/RIF and fluorescence smear microscopy. Sensitivity and specificity (with culture as reference standard, and costs were estimated.Of 273 adults recruited, 44.3% (121/273 were HIV-positive and 19.4% (53/273 had bacteriogically confirmed tuberculosis. The sensitivity of LAMP compared to culture was 65.0% (95% CI: 48.3% to 79.4% with 100% (95% CI: 98.0% to 100% specificity. The sensitivity of Xpert® MTB/RIF (77.5%, 95% CI: 61.5% to 89.2% was similar to that of LAMP, p = 0.132. The sensitivity of concentrated fluorescence smear microscopy with routine double reading (87.5%, 95% CI: 73.2% to 95.8% was higher than that of LAMP, p = 0.020. All three tests had high specificity. The lowest cost per test of LAMP was at batch size of 14 samples (US$ 9.98; this was lower than Xpert® MTB/RIF (US$ 13.38 but higher than fluorescence smear microscopy (US$ 0.65.The sensitivity of LAMP was similar to Xpert® MTB/RIF but lower than fluorescence smear microscopy; all three tests had high specificity. These findings support the Malawi policy that recommends a combination of fluorescence smear microscopy and Xpert® MTB/RIF prioritised for people living with HIV, already found to be smear-negative, or being considered for retreatment of tuberculosis.

  3. Different screening strategies (single or dual for the diagnosis of suspected latent tuberculosis: a cost effectiveness analysis

    Rook Graham

    2010-02-01

    Full Text Available Abstract Background Previous health economic studies recommend either a dual screening strategy [tuberculin skin test (TST followed by interferon-γ-release assay (IGRA] or a single one [IGRA only] for latent tuberculosis infection (LTBI, the former largely based on claims that it is more cost-effective. We sought to examine that conclusion through the use of a model that accounts for the additional costs of adverse drug reactions and directly compares two commercially available versions of the IGRA: the Quantiferon-TB-Gold-In-Tube (QFT-GIT and T-SPOT.TB. Methods A LTBI screening model directed at screening contacts was used to perform a cost-effectiveness analysis, from a UK healthcare perspective, taking into account the risk of isoniazid-related hepatotoxicity and post-exposure TB (2 years post contact using the TST, QFT-GIT and T-SPOT.TB IGRAs. Results Examining costs alone, the TST/IGRA dual screening strategies (TST/T-SPOT.TB and TST/QFT-GIT; £162,387 and £157,048 per 1000 contacts, respectively cost less than their single strategy counterparts (T-SPOT.TB and QFT-GIT; £203,983 and £202,921 per 1000 contacts which have higher IGRA test costs and greater numbers of persons undergoing LTBI treatment. However, IGRA alone strategies direct healthcare interventions and costs more accurately to those that are truly infected. Subsequently, less contacts need to be treated to prevent an active case of TB (T-SPOT.TB and QFT-GIT; 61.7 and 69.7 contacts in IGRA alone strategies. IGRA single strategies also prevent more cases of post-exposure TB. However, this greater effectiveness does not outweigh the lower incremental costs associated with the dual strategies. Consequently, when these costs are combined with effectiveness, the IGRA dual strategies are more cost-effective than their single strategy counterparts. Comparing between the IGRAs, T-SPOT.TB-based strategies (single and dual; £39,712 and £37,206 per active TB case prevented

  4. Active and latent tuberculosis in prisoners in the Central-West Region of Brazil

    Anderson Oliveira Estevan

    2013-07-01

    Full Text Available Introduction Jailed populations exhibit high rates of tuberculosis (TB infection and active disease. Methods A cross-sectional study was performed to estimate the prevalence of latent and active TB and to identify factors associated with latent infection in inmates. Results The prevalence of latent TB was 49%, and the prevalence of active TB was 0.4%. The presence of a Bacille Calmette-Guérin (BCG scar (prevalence ratio (PR=1.65; 95% confidence interval (CI: 1.09-2.50; p=0.0162 and the World Health Organization (WHO score for active TB in prisons (PR=1.07; 95% CI: 1.01-1.14; p=0.0181 were correlated with infection. Conclusions The identification of associated factors and the prevalence of latent and active TB allows the development of plans to control this disease in jails.

  5. Tuberculosis and nutrition

    Gupta Krishna

    2009-01-01

    Full Text Available Malnutrition and tuberculosis are both problems of considerable magnitude in most of the underdeveloped regions of the world. These two problems tend to interact with each other. Tuberculosis mortality rates in different economic groups in a community tend to vary inversely with their economic levels. Similarly, nutritional status is significantly lower in patients with active tuberculosis compared with healthy controls. Malnutrition can lead to secondary immunodeficiency that increases the host′s susceptibility to infection. In patients with tuberculosis, it leads to reduction in appetite, nutrient malabsorption, micronutrient malabsorption, and altered metabolism leading to wasting. Both, protein-energy malnutrition and micronutrients deficiencies increase the risk of tuberculosis. It has been found that malnourished tuberculosis patients have delayed recovery and higher mortality rates than well-nourished patients. Nutritional status of patients improves during tuberculosis chemotherapy. High prevalence of human immunodeficiency (HIV infection in the underdeveloped countries further aggravates the problem of malnutrition and tuberculosis. Effect of malnutrition on childhood tuberculosis and tuberculin skin test are other important considerations. Nutritional supplementation may represent a novel approach for fast recovery in tuberculosis patients. In addition, raising nutritional status of population may prove to be an effective measure to control tuberculosis in underdeveloped areas of world.

  6. Monocyte Signal Transduction Receptors in Active and Latent Tuberculosis

    Magdalena Druszczynska

    2013-01-01

    Full Text Available The mechanisms that promote either resistance or susceptibility to TB disease remain insufficiently understood. Our aim was to compare the expression of cell signaling transduction receptors, CD14, TLR2, CD206, and β2 integrin LFA-1 on monocytes from patients with active TB or nonmycobacterial lung disease and healthy individuals with M.tb latency and uninfected controls to explain the background of the differences between clinical and subclinical forms of M.tb infection. A simultaneous increase in the expression of the membrane bound mCD14 receptor and LFA-1 integrin in patients with active TB may be considered a prodrome of breaking immune control by M.tb bacilli in subjects with the latent TB and absence of clinical symptoms.

  7. Breathe Analysis in Tuberculosis Disease Recognition in New Millennium

    Ranabir Pal

    2013-06-01

    Full Text Available To control the tuberculosis pandemic we need rapid, inexpensive finding tool. To assess the worth of exhaled breath analysis in tuberculosis case detection. A wide-ranging exploration of documents was done in indexed literatures and website-based research reports. Thirty-eight studies were identified on more than 200 potentially relevant articles related to breath analysis on tuberculosis. A broad criterion was formed in the absence of universally accepted method by the researchers on exhaled breathe analysis, irrespective of their criteria for diagnosis of tuberculosis. Wide differences in samples, primary outcome variables, lack of uniformity in criteria for positive diagnosis, and study instruments confounded the outcome variables. These non-invasive breathe tests of tuberculosis and exploring factual and surrogate markers in primary bacterial activity as well as during interventions. Prospective utility of breath analysis by varied methods deserve their proportional weightage. The study reviewed non-judgmentally on the ongoing work in the field of breath analysis that may be worth developing and evaluating as a cost-effective entrant in diagnostic and prognostic algorithms of tuberculosis. Time has come to explore this to the fullest extent for a superior conceptual design of the factors for a futuristic model of non-invasive direct point-of-care diagnostic understanding of the factors influencing diagnosis and prognosis.

  8. Towards establishing a rhinoceros-specific interferon-gamma (IFN-y) assay for diagnosis of tuberculosis

    Morar, D.; Schreuder, J.; Meny, M.; Kooten, P.J.; Tijhaar, E.; Michel, A.L.; Rutten, V.P.M.G.

    2013-01-01

    Mycobacterium bovis is the causal agent of bovine tuberculosis (BTB), with a diverse host range, extending from livestock to domestic and captive wild animals as well as free-ranging wildlife species. In South Africa, BTB is endemic in the Kruger National Park (KNP) and the Hluluwe iMfolozi National

  9. Evaluation of Ethanol Extracted Surface Antigens of Mycobacterium bovis for Diagnosis of Bovine Tuberculosis in Livestock Cattle and Wild Deer

    Background: Bovine tuberculosis (TB), caused by Mycobacterium bovis, is a zoonotic disease resulting in chronic granulomatous lymphadenitis, particularly in the lungs and lung-associated lymph nodes. Although bovine TB has been nearly eradicated in many developed countries, the disease persists pri...

  10. Lung surfactant dysfunction in tuberculosis: effect of mycobacterial tubercular lipids on dipalmitoylphosphatidylcholine surface activity.

    Chimote, G; Banerjee, R

    2005-11-10

    In pulmonary tuberculosis, Mycobacterium tuberculosis bacteria reside in the alveoli and are in close proximity with the alveolar surfactant. Mycolic acid in its free form and as cord factor, constitute the major lipids of the mycobacterial cell wall. They can detach from the bacteria easily and are known to be moderately surface active. We hypothesize that these surface-active mycobacterial cell wall lipids could interact with the pulmonary surfactant and result in lung surfactant dysfunction. In this study, the major phospholipid of the lung surfactant, dipalmitoylphosphatidylcholine (DPPC) and binary mixtures of DPPC:phosphatidylglycerol (PG) in 9:1 and 7:3 ratios were modelled as lung surfactant monolayers and the inhibitory potential of mycolic acid and cord factor on the surface activity of DPPC and DPPC:PG mixtures was evaluated using Langmuir monolayers. The mycobacterial lipids caused common profile changes in all the isotherms: increase in minimum surface tension, compressibility and percentage area change required for change in surface tension from 30 to 10 mN/m. Higher minimum surface tension values were achieved in the presence of mycolic acid (18.2+/-0.7 mN/m) and cord factor (13.28+/-1.2 mN/m) as compared to 0 mN/m, achieved by pure DPPC film. Similarly higher values of compressibility (0.375+/-0.005 m/mN for mycolic acid:DPPC and 0.197+/-0.003 m/mN for cord factor:DPPC monolayers) were obtained in presence of mycolic acid and cord factor. Thus, mycolic acid and cord factor were said to be inhibitory towards lung surfactant phospholipids. Higher surface tension and compressibility values in presence of tubercular lipids are suggestive of an unstable and fluid surfactant film, which will fail to achieve low surface tensions and can contribute to alveolar collapse in patients suffering from pulmonary tuberculosis. In conclusion a biophysical inhibition of lung surfactant may play a role in the pathogenesis of tuberculosis and may serve as a target for

  11. Moxifloxacin (BAY12-8039), a New 8-Methoxyquinolone, Is Active in a Mouse Model of Tuberculosis

    Miyazaki, Eishi; Miyazaki, Miki; Chen, Jong Min; Chaisson, Richard E.; Bishai, William R.

    1999-01-01

    Moxifloxacin (BAY12-8039) is a new 8-methoxyquinolone shown to be active against Mycobacterium tuberculosis in vitro. We tested moxifloxacin for activity in mice against M. tuberculosis CSU93, a highly virulent, recently isolated clinical strain. The MIC of moxifloxacin for the CSU93 strain was 0.25 μg/ml. The serum moxifloxacin concentration after oral administration in mice peaked within 0.25 h, reaching 7.8 μg/ml with doses of 100 mg/kg of body weight; the maximum concentration and the ana...

  12. The ligase chain reaction as a primary screening tool for the detection of culture positive tuberculosis.

    O'Connor, T M

    2012-02-03

    BACKGROUND: The ligase chain reaction Mycobacterium tuberculosis assay uses ligase chain reaction technology to detect tuberculous DNA sequences in clinical specimens. A study was undertaken to determine its sensitivity and specificity as a primary screening tool for the detection of culture positive tuberculosis. METHODS: The study was conducted on 2420 clinical specimens (sputum, bronchoalveolar lavage fluid, pleural fluid, urine) submitted for primary screening for Mycobacterium tuberculosis to a regional medical microbiology laboratory. Specimens were tested in parallel with smear, ligase chain reaction, and culture. RESULTS: Thirty nine patients had specimens testing positive by the ligase chain reaction assay. Thirty two patients had newly diagnosed tuberculosis, one had a tuberculosis relapse, three had tuberculosis (on antituberculous therapy when tested), and three had healed tuberculosis. In the newly diagnosed group specimens were smear positive in 21 cases (66%), ligase chain reaction positive in 30 cases (94%), and culture positive in 32 cases (100%). Using a positive culture to diagnose active tuberculosis, the ligase chain reaction assay had a sensitivity of 93.9%, a specificity of 99.8%, a positive predictive value of 83.8%, and a negative predictive value of 99.9%. CONCLUSIONS: This study is the largest clinical trial to date to report the efficacy of the ligase chain reaction as a primary screening tool to detect Mycobacterium tuberculosis infection. The authors conclude that ligase chain reaction is a useful primary screening test for tuberculosis, offering speed and discrimination in the early stages of diagnosis and complementing traditional smear and culture techniques.

  13. Ion Channel Blockers as Antimicrobial Agents, Efflux Inhibitors, and Enhancers of Macrophage Killing Activity against Drug Resistant Mycobacterium tuberculosis.

    Diana Machado

    Full Text Available Given the ability of M. tuberculosis to survive as an intracellular pathogen and its propensity to develop resistance to the existing antituberculosis drugs, its treatment requires new approaches. Here the antimycobacterial properties of verapamil, thioridazine, chlorpromazine, flupenthixol and haloperidol were investigated against a panel of drug resistant M. tuberculosis strains, both in vitro and on human-infected macrophages. These compounds are efflux inhibitors that share among them the characteristic of being ion channel blockers. In vitro, all compounds exhibited synergistic inhibitory activities when combined with isoniazid and rifampicin, and were able to inhibit active efflux, demonstrating their role as efflux inhibitors. Gene expression analysis showed that M. tuberculosis efflux genes were overexpressed in response to antibiotic exposure, in vitro and within macrophages, irrespective of their resistance pattern. These compounds displayed a rapid and high killing activity against M. tuberculosis, associated with a decrease in intracellular ATP levels demonstrating that the bactericidal action of the ion channel blockers against M. tuberculosis clinical strains is associated with their interference with energy metabolism. The compounds led to a decrease in the intracellular mycobacterial load by increasing phagosome acidification and activating lysosomal hydrolases. The results presented in this study enable us to propose the following mechanism of action for these compounds: a in the bacteria, the compounds generate a cascade of events involving the inhibition of the respiratory chain complexes and energy production for efflux activity. Indirectly, this reduce the resistance level to antituberculosis drugs potentiating their activity; b on the host cell, the treatment with the ion channel blockers increases phagosome acidification and induces the expression of phagosomal hydrolases, leading to bacterial growth restriction

  14. Ion Channel Blockers as Antimicrobial Agents, Efflux Inhibitors, and Enhancers of Macrophage Killing Activity against Drug Resistant Mycobacterium tuberculosis.

    Machado, Diana; Pires, David; Perdigão, João; Couto, Isabel; Portugal, Isabel; Martins, Marta; Amaral, Leonard; Anes, Elsa; Viveiros, Miguel

    2016-01-01

    Given the ability of M. tuberculosis to survive as an intracellular pathogen and its propensity to develop resistance to the existing antituberculosis drugs, its treatment requires new approaches. Here the antimycobacterial properties of verapamil, thioridazine, chlorpromazine, flupenthixol and haloperidol were investigated against a panel of drug resistant M. tuberculosis strains, both in vitro and on human-infected macrophages. These compounds are efflux inhibitors that share among them the characteristic of being ion channel blockers. In vitro, all compounds exhibited synergistic inhibitory activities when combined with isoniazid and rifampicin, and were able to inhibit active efflux, demonstrating their role as efflux inhibitors. Gene expression analysis showed that M. tuberculosis efflux genes were overexpressed in response to antibiotic exposure, in vitro and within macrophages, irrespective of their resistance pattern. These compounds displayed a rapid and high killing activity against M. tuberculosis, associated with a decrease in intracellular ATP levels demonstrating that the bactericidal action of the ion channel blockers against M. tuberculosis clinical strains is associated with their interference with energy metabolism. The compounds led to a decrease in the intracellular mycobacterial load by increasing phagosome acidification and activating lysosomal hydrolases. The results presented in this study enable us to propose the following mechanism of action for these compounds: a) in the bacteria, the compounds generate a cascade of events involving the inhibition of the respiratory chain complexes and energy production for efflux activity. Indirectly, this reduce the resistance level to antituberculosis drugs potentiating their activity; b) on the host cell, the treatment with the ion channel blockers increases phagosome acidification and induces the expression of phagosomal hydrolases, leading to bacterial growth restriction irrespective of their

  15. Ion Channel Blockers as Antimicrobial Agents, Efflux Inhibitors, and Enhancers of Macrophage Killing Activity against Drug Resistant Mycobacterium tuberculosis

    Perdigão, João; Couto, Isabel; Portugal, Isabel; Martins, Marta; Amaral, Leonard; Anes, Elsa; Viveiros, Miguel

    2016-01-01

    Given the ability of M. tuberculosis to survive as an intracellular pathogen and its propensity to develop resistance to the existing antituberculosis drugs, its treatment requires new approaches. Here the antimycobacterial properties of verapamil, thioridazine, chlorpromazine, flupenthixol and haloperidol were investigated against a panel of drug resistant M. tuberculosis strains, both in vitro and on human-infected macrophages. These compounds are efflux inhibitors that share among them the characteristic of being ion channel blockers. In vitro, all compounds exhibited synergistic inhibitory activities when combined with isoniazid and rifampicin, and were able to inhibit active efflux, demonstrating their role as efflux inhibitors. Gene expression analysis showed that M. tuberculosis efflux genes were overexpressed in response to antibiotic exposure, in vitro and within macrophages, irrespective of their resistance pattern. These compounds displayed a rapid and high killing activity against M. tuberculosis, associated with a decrease in intracellular ATP levels demonstrating that the bactericidal action of the ion channel blockers against M. tuberculosis clinical strains is associated with their interference with energy metabolism. The compounds led to a decrease in the intracellular mycobacterial load by increasing phagosome acidification and activating lysosomal hydrolases. The results presented in this study enable us to propose the following mechanism of action for these compounds: a) in the bacteria, the compounds generate a cascade of events involving the inhibition of the respiratory chain complexes and energy production for efflux activity. Indirectly, this reduce the resistance level to antituberculosis drugs potentiating their activity; b) on the host cell, the treatment with the ion channel blockers increases phagosome acidification and induces the expression of phagosomal hydrolases, leading to bacterial growth restriction irrespective of their

  16. DD neutron yield diagnosis by indium activation

    The measurement of DD neutron yield by activation is presented. This method is based on the inelastic scattering reaction of 115In with DD neutron, and the activated γ spectrum is counted by HPGe detector. The relation between the counts of detected y rays and the neutron yield is analyzed. The optimal thickness of sample is given by Monte Carlo simulation, which is 1 cm. The entire counting system has been calibrated on the K-400 accelerator. The result shows that the DD neutron measurement by indium activation can be used in the ICF experiment when the neutron yield is above 2 × 109. The total error of the system is below 10% in this condition. The total error will reduce when the neutron yield is larger. (authors)

  17. Tuberculosis latente Latent tuberculosis

    Juan C Rodríguez D

    2012-01-01

    La tuberculosis continúa siendo un problema enorme en salud pública. Se ha estimado que anualmente en todo el mundo 9 millones de personas contraen esta enfermedad y que 2 millones de muertes se deben a la tuberculosis. La exposición al M. tuberculosis causa la enfermedad en cerca del 10% de la población expuesta. En el 90% restante de los expuestos la respuesta inmune inhibe la multiplicación del M. tuberculosis. En una parte de las personas expuestas (~40%) algunos bacilos no son muertos pe...

  18. High Affinity Inha Inhibitors with Activity Against Drug-Resistant Strains of Mycobacterium Tuberculosis

    Sullivan,T.; Truglio, J.; Boyne, M.; Novichenok, P.; Zhang, X.; Stratton, C.; Li, H.; Kaur, T.; Amin, A.; et al.

    2006-01-01

    Novel chemotherapeutics for treating multidrug-resistant (MDR) strains of Mycobacterium tuberculosis (MTB) are required to combat the spread of tuberculosis, a disease that kills more than 2 million people annually. Using structure-based drug design, we have developed a series of alkyl diphenyl ethers that are uncompetitive inhibitors of InhA, the enoyl reductase enzyme in the MTB fatty acid biosynthesis pathway. The most potent compound has a Ki{prime} value of 1 nM for InhA and MIC{sub 99} values of 2-3 {micro}g mL{sup -1} (6-10 {micro}M) for both drug-sensitive and drug-resistant strains of MTB. Overexpression of InhA in MTB results in a 9-12-fold increase in MIC{sub 99}, consistent with the belief that these compounds target InhA within the cell. In addition, transcriptional response studies reveal that the alkyl diphenyl ethers fail to upregulate a putative efflux pump and aromatic dioxygenase, detoxification mechanisms that are triggered by the lead compound triclosan. These diphenyl ether-based InhA inhibitors do not require activation by the mycobacterial KatG enzyme, thereby circumventing the normal mechanism of resistance to the front line drug isoniazid (INH) and thus accounting for their activity against INH-resistant strains of MTB.

  19. LTBI: latent tuberculosis infection or lasting immune responses to M. tuberculosis? A TBNET consensus statement

    Mack, U; Migliori, G B; Sester, M;

    2009-01-01

    Tuberculosis control relies on the identification and preventive treatment of individuals who are latently infected with Mycobacterium tuberculosis. However, direct identification of latent tuberculosis infection is not possible. The diagnostic tests used to identify individuals latently infected...... improved, if we were to gain a better understanding on M. tuberculosis latency and reactivation. This statement by the TBNET summarises knowledge and limitations of the currently available tests used in adults and children for the diagnosis of latent tuberculosis infection. In summary, the main issue...

  20. Endobronchial ultrasound-guided transbronchial needle aspiration for the diagnosis of intrathoracic lymphadenopathy in patients with extrathoracic malignancy: A study in a tuberculosis-endemic country

    M Akif Özgül

    2013-01-01

    Full Text Available Background: Mediastinal lymphadenopathy in patients with malignancy is a common clinical problem in tuberculosis-endemic countries. The recently developed endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA procedure enables direct and real-time aspiration of mediastinal and hilar lymph nodes. The aim of the study was to determine the efficacy of EBUS-TBNA results in the evaluation of mediastinal lymph nodes in patients with extrathoracic malignancy. Materials and Methods: Retrospective analysis was performed in 40 patients with proven (n = 38 or suspected metastasis of unknown origin (n = 2 who underwent EBUS-TBNA between July 2007 and August 2011. Results: All 40 patients successfully underwent EBUS-TBNA and no complications were observed. EBUS-TBNA diagnosed metastasis from extrathoracic malignancy in 16 (40% patients, new lung cancer in 2 (5%, reactive lymph node in 9 (22.5%, sarcoidosis in 5 (12.5%, anthracosis in 5 (12.5% and tuberculosis in 3 (7.5%. The diagnostic sensitivity, specificity, positive predictive value (PPV, negative predictive value (NPV and accuracy of EBUS-TBNA based on the number of patients were 90.0%, 100%, 100%, 90.9% and 95.0%, respectively. In 33 patients with available data of fluorodeoxyglucose positron emission tomography (PET/computed tomography (CT scans, the diagnostic sensitivity, specificity, PPV, NPV and accuracy of PET/CT scan based on the number of patients were 94.7%, 35.7%, 66.6%, 83.3%, and 69.6%, respectively. The association between larger lymph node size on EBUS and malignancy of lymph node sample on pathological examination was statistically significant (P = 0.018. Conclusions: EBUS-TBNA is a sensitive, specific, minimally invasive and a safe procedure for the diagnosis of mediastinal and hilar metastasis from extrapulmonary malignancy in a tuberculosis-endemic country.

  1. Imaging of musculoskeletal tuberculosis

    Purpose and methods. To perform an illustrated and educational review of musculoskeletal tuberculosis. Results. As the incidence of musculoskeletal tuberculosis still increases, a review appears justified. The following four main presentations are detailed and illustrated, by emphasizing the value of both CT and MR imaging: a) spine tuberculosis (∼ 50 %/) commonly involves two adjacent vertebral bodies with usual large paravertebral abscesses. The following lesions are highly suggestive of tuberculosis: solitary vertebral involvement, solitary epidural abscess with or without erosive spondylitis; b) osteo-arthritis: peripherally located erosions at synovial insertions with gradual narrowing of the joint space are highly suggestive; c) osteomyelitis: unusual, may involve any bones; d) tenosynovitis and bursitis. Conclusion. Imaging studies are essential for diagnosis and to assess the extent of musculo-skeletal tuberculosis. (author)

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

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

    2016-07-01

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

  3. Evaluation of the role of ascitic fluid polymerase chain reaction targeting IS6110 of Mycobacterium tuberculosis in the diagnosis of tuberculous intestinal obstruction

    Sanjay Kumar Yadav

    2015-01-01

    Full Text Available Introduction: We evaluated if ascitic fluid sample could be used for the diagnosis of tuberculosis intestinal obstruction (TBIO by a nested polymerase chain reaction (PCR assay and analyzed the clinical and laboratory findings in 33 patients with confirmed intestinal tuberculosis (TB compared to 54 patients with other pathologies of intestinal obstruction. Methods: We tested ascitic fluid sample by Ziehl-Neelson staining; Löwenstein-Jensen (L-J culture method was used for the culture and PCR was performed for targeting the IS6110 sequence. Results: We found that 87.9% (29/33 of cases with intestinal TB and 0% (0/54 with other causes who had positive results with the nested PCR assay. PCR, in principle, is a highly sensitive technique that detects DNA from a single to a few microorganisms with the overall sensitivity, specificity, and positive predictive value (PPV of 87.87%, 100%, and 100%, respectively. Acid-fast bacillus (AFB staining alone has positivity of only 24% and histology alone has positivity of 88%. Conclusion: PCR has a potentially important role in improving the diagnostic accuracy.

  4. Diagnostic accuracy of the genotype MTBDRsl assay for rapid diagnosis of extensively drug-resistant tuberculosis in HIV-coinfected patients.

    Kontsevaya, Irina; Ignatyeva, Olga; Nikolayevskyy, Vladyslav; Balabanova, Yanina; Kovalyov, Alexander; Kritsky, Andrey; Matskevich, Olesya; Drobniewski, Francis

    2013-01-01

    The Russian Federation is a high-tuberculosis (TB)-burden country with high rates of Mycobacterium tuberculosis multidrug resistance (MDR) and extensive drug resistance (XDR), especially in HIV-coinfected patients. Rapid and reliable diagnosis for detection of resistance to second-line drugs is vital for adequate patient management. We evaluated the performance of the GenoType MTBDRsl (Hain Lifescience GmbH, Nehren, Germany) assay on smear-positive sputum specimens obtained from 90 HIV-infected MDR TB patients from Russia. Test interpretability was over 98%. Specificity was over 86% for all drugs, while sensitivity varied, being the highest (71.4%) for capreomycin and lowest (9.4%) for kanamycin, probably due to the presence of mutations in the eis gene. The sensitivity of detection of XDR TB was 13.6%, increasing to 42.9% if kanamycin (not commonly used in Western Europe) was excluded. The assay is a highly specific screening tool for XDR detection in direct specimens from HIV-coinfected TB patients but cannot be used to rule out XDR TB. PMID:23152552

  5. Immunodiagnosis of tuberculosis: new questions, new tools conference 2008

    Gennaro Maria L

    2010-12-01

    Full Text Available Abstract Human infection with Mycobacterium tuberculosis exists as a spectrum of conditions ranging from asymptomatic infection to active disease. Novel, accurate tuberculosis immunodiagnostics have been introduced over the last decade, but it remains challenging to timely diagnose active disease and to accurately distinguish asymptomatic M. tuberculosis infection from immune memory resulting from a prior infection eradicated by the host response. The conference titled Immunodiagnosis of Tuberculosis: New Questions, New Tools, which was held on September 21-23, 2008 in Virginia Beach, Virginia, United States, brought together basic scientists and clinical experts to discuss recent progress in tuberculosis research and diagnosis. Global analyses of M. tuberculosis biology and the host immune response, with emphasis on systems approaches to the study of host-pathogen interactions, were presented. Moreover, conference participants discussed new tests in the pipeline and reviewed new technologies leading to novel assay formats. The discussion included technologies ranging from simple, inexpensive point-of-care tests to automated molecular platforms for detection of multiple infections based on the “lab on a chip” concept. It was also recognized that the utility of any new diagnostic relies on laboratory capacity, accessibility, costs, and test deployment. The conference included lessons from the field. For example, the application of existing technologies to neglected areas, such as diagnosis in children and HIV+ populations, was discussed.

  6. A high-resolution computed tomography-based scoring system to differentiate the most infectious active pulmonary tuberculosis from community-acquired pneumonia in elderly and non-elderly patients

    Yeh, Jun-Jun [Ditmanson Medical Foundation Chia-Yi Christian Hospital, Section of Thoracic Imaging, Department of Chest Medicine and Family Medicine, Chiayi City (China); Chia Nan University of Pharmacy and Science, Tainan (China); Meiho University, Pingtung (China); Pingtung Christian Hospital, Pingtung (China); Chen, Solomon Chih-Cheng; Chen, Cheng-Ren [Ditmanson Medical Foundation Chia-Yi Christian Hospital, Department of Medical Research, Chiayi City (China); Yeh, Ting-Chun; Lin, Hsin-Kai; Hong, Jia-Bin; Wu, Bing-Tsang [Ditmanson Medical Foundation Chia-Yi Christian Hospital, Department of Family Medicine, Chiayi City (China); Wu, Ming-Ting [Department of Radiology, Kaohsiung Veterans General Hospital, Section of Thoracic and Circulation Imaging, Kaohsiung (China); School of Medicine, National Yang Ming University, Faculty of Medicine, Taipei (China)

    2014-10-15

    The objective of this study was to use high-resolution computed tomography (HRCT) imaging to predict the presence of smear-positive active pulmonary tuberculosis (PTB) in elderly (at least 65 years of age) and non-elderly patients (18-65 years of age). Patients with active pulmonary infections seen from November 2010 through December 2011 received HRCT chest imaging, sputum smears for acid-fast bacilli and sputum cultures for Mycobacterium tuberculosis. Smear-positive PTB was defined as at least one positive sputum smear and a positive culture for M. tuberculosis. Multivariate logistic regression analyses were performed to determine the HRCT predictors of smear-positive active PTB, and a prediction score was developed on the basis of receiver operating characteristic curve analysis. Of 1,255 patients included, 139 were diagnosed with smear-positive active PTB. According to ROC curve analysis, the sensitivity, specificity, positive predictive value, negative predictive value, false positive rates and false negative rates were 98.6 %, 95.8 %, 78.5 %, 99.8 %, 4.2 % and 1.4 %, respectively, for diagnosing smear-positive active PTB in elderly patients, and 100.0 %, 96.9 %, 76.5 %, 100.0 %, 3.1 % and 0.0 %, respectively, for non-elderly patients. HRCT can assist in the early diagnosis of the most infectious active PTB, thereby preventing transmission and minimizing unnecessary immediate respiratory isolation. (orig.)

  7. A high-resolution computed tomography-based scoring system to differentiate the most infectious active pulmonary tuberculosis from community-acquired pneumonia in elderly and non-elderly patients

    The objective of this study was to use high-resolution computed tomography (HRCT) imaging to predict the presence of smear-positive active pulmonary tuberculosis (PTB) in elderly (at least 65 years of age) and non-elderly patients (18-65 years of age). Patients with active pulmonary infections seen from November 2010 through December 2011 received HRCT chest imaging, sputum smears for acid-fast bacilli and sputum cultures for Mycobacterium tuberculosis. Smear-positive PTB was defined as at least one positive sputum smear and a positive culture for M. tuberculosis. Multivariate logistic regression analyses were performed to determine the HRCT predictors of smear-positive active PTB, and a prediction score was developed on the basis of receiver operating characteristic curve analysis. Of 1,255 patients included, 139 were diagnosed with smear-positive active PTB. According to ROC curve analysis, the sensitivity, specificity, positive predictive value, negative predictive value, false positive rates and false negative rates were 98.6 %, 95.8 %, 78.5 %, 99.8 %, 4.2 % and 1.4 %, respectively, for diagnosing smear-positive active PTB in elderly patients, and 100.0 %, 96.9 %, 76.5 %, 100.0 %, 3.1 % and 0.0 %, respectively, for non-elderly patients. HRCT can assist in the early diagnosis of the most infectious active PTB, thereby preventing transmission and minimizing unnecessary immediate respiratory isolation. (orig.)

  8. Diagnosis of Tuberculosis in the Wild Boar (Sus scrofa): A Comparison of Methods Applicable to Hunter-Harvested Animals

    Santos, Nuno Gonçalo Carvalho Caroço dos; Geraldes, Margarida; Afonso, Andreia Fernandes; Almeida, Virgílio; Neves, Margarida Correia

    2010-01-01

    Background To obtain robust epidemiological information regarding tuberculosis (TB) in wildlife species, appropriate diagnostic methods need to be used. Wild boar (Sus scrofa) recently emerged as a major maintenance host for TB in some European countries. Nevertheless, no data is available to evaluate TB post-mortem diagnostic methods in hunter-harvested wild boar. Methodology/Principal Findings Six different diagnostic methods for TB were evaluated in parallel in 167 hunter-harvested wild bo...

  9. Comparison of DNA Extraction Protocols for Mycobacterium Tuberculosis in Diagnosis of Tuberculous Meningitis by Real-time Polymerase Chain Reaction

    Rajeev Thakur; Smita Sarma; Renu Goyal

    2011-01-01

    Background: Several nucleic acid amplification techniques are available for detection of Mycobacterium tuberculosis (MTB) in pulmonary and extrapulmonary samples, but insufficient data are available on the diagnostic utility of these techniques in tubercular meningitis where bacilli load is less. The success of final amplification and detection of nucleic acid depends on successful extraction of DNA from the organism. Aims: We performed this study to compare four methods of extraction of MTB ...

  10. Rapid Diagnosis of Extensively Drug-Resistant Tuberculosis by Use of a Reverse Line Blot Hybridization Assay▿†

    Ajbani, Kanchan; Shetty,Anjali; Mehta, Ajita; Rodrigues, Camilla

    2011-01-01

    Drug resistance in tuberculosis (TB) is a matter of grave concern for TB control programs, as there is currently no cure for some extensively drug-resistant (XDR) strains. There is concern that this resistance could transmit, stressing the need for additional control measures, rapid diagnostic methods, and newer drugs for treatment. We developed an in-house assay that can rapidly detect resistance to drugs involved in the definition of XDR-TB directly from smear-positive specimens. Two hundre...

  11. A national audit of the laboratory diagnosis of tuberculosis and other mycobacterial diseases within the United Kingdom.

    Drobniewski, F. A.; Watt, B; Smith, E. G.; Magee, J G; Williams, R.; Holder, J.; Ostrowski, J.

    1999-01-01

    In order to audit United Kingdom laboratory diagnostic and reference services including novel molecular methods for tuberculosis, a questionnaire was sent to laboratories submitting specimens to the PHLS Mycobacterium Reference Unit (MRU) and regional centres and to the Scottish Mycobacteria Reference Laboratory (SMRL) in 1996-7. Nationally, 67.2% of laboratories responded. Most UK laboratories were fully or conditionally CPA accredited and take part in the NEQAS proficiency scheme. On averag...

  12. Implementation and effect of intensified case finding on diagnosis of tuberculosis in a large urban HIV clinic in Uganda: a retrospective cohort study.

    Hermans Sabine

    2012-08-01

    Full Text Available Abstract Background Increased detection of tuberculosis (TB using intensified or active case finding (ICF is one of the cornerstones of the Stop TB Strategy, and contrasts with passive case finding (PCF which relies on self-reported symptoms. There is no clear guidance on implementation strategies. We implemented ICF in addition to ongoing PCF in our large urban HIV clinic in July 2010 using a twice-daily announcement screen method by a trained peer educator, asking waiting patients to self-refer to a trained peer supporter for screening of TB symptoms. We sought to determine the associated effect on TB case detection. Methods Suspects were investigated by sputum smear, chest X-ray and ultrasound, if indicated. Routinely collected clinical and laboratory data were merged with the ICF register and TB clinic data for patients attending the clinic in 2010. We compared the yield of TB cases (defined as the prevalence of newly diagnosed TB cases in the screened population, the type of TB diagnosed and the total cost per TB case identified (in United States Dollars [USD] for the period before and after ICF implementation. Results Of the 20,456 patients who visited the clinic in 2010, 614 were identified as TB suspects, 220 pre-ICF and 394 post-ICF (229 via PCF and 165 via ICF. The proportion diagnosed with TB dropped from 66% to 48% (60% in suspects identified through PCF and 31% through ICF. During the post-ICF period, TB suspects identified through ICF compared to PCF identification were more likely to be female, older, on ART and to have been enrolled in HIV care for a longer duration. The yield of combined PCF and ICF screening was 1.4% pre-ICF and 1.7% post-ICF with a cost per TB case identified of 12.29 USD and 21.80 USD, respectively. Conclusions Implementation of ICF in a large HIV clinic yielded more TB suspects and cases, but substantially increased costs and was unable to capture the majority of TB suspects who were referred for diagnosis

  13. Evidence for the generation of active oxygen by isoniazid treatment of extracts of Mycobacterium tuberculosis H37Ra.

    Shoeb, H A; Bowman, B U; Ottolenghi, A C; Merola, A J

    1985-01-01

    Crude extracts of Mycobacterium tuberculosis H37Ra, an isonicotinic acid hydrazide (isoniazid) (INH)-susceptible strain which has peroxidase activity, catalyzed the production of catechol from phenol in the presence of INH and H2O2 as shown by the development of the 444-nm absorption peak of oxidized catechol product. Extracts of the INH-resistant strain of M. tuberculosis H37Ra, which has no peroxidase, did not catalyze the reaction. The rate of development of the 444-nm peak increased propo...

  14. A mathematical representation of the development of Mycobacterium tuberculosis active, latent and dormant stages.

    Magombedze, Gesham; Mulder, Nicola

    2012-01-01

    The majority of individuals infected with Mycobacterium tuberculosis (Mtb) bacilli develop latent infection. Mtb becomes dormant and phenotypically drug resistant when it encounters multiple stresses within the host, and expresses a set of genes, known as the dormancy regulon, in vivo. These genes are expressed in vitro in response to nitric oxide (NO), hypoxia (oxygen deprivation), and nutrient starvation. The occurrence and reactivation of latent tuberculosis (TB) is not clearly understood. The ability of the pathogen to enter and exit from different states is associated with its ability to cause persistent infection. During infection it is not known whether the organism is in a persistent slow replicating state or a dormant non-replicating state, with the latter ultimately causing a latent infection with the potential to reactivate to active disease. We collected gene expression data for Mtb bacilli under different stress conditions that simulate latency or dormancy. Time course experiments were selected and differentially expressed gene profiles were determined at each time point. A mathematical model was then developed to show the dynamics of Mtb latency based on the profile of differentially expressed genes. Analysis of the time course data show the dynamics of latency occurrence in vitro and the mathematical model reveals all possible scenarios of Mtb latency development with respect to the different conditions that may be produced by the immune response in vivo. The mathematical model provides a biological explanation of how Mtb latency occurs based on observed gene expression changes in in vitro latency models. PMID:21968442

  15. Loop mediated isothermal amplification assay using hydroxy naphthol blue, conventional polymerase chain reaction and real-time PCR in the diagnosis of intraocular tuberculosis

    P K Balne

    2015-01-01

    Full Text Available This study is a comparative evaluation (Chi-square test of a closed tube loop mediated isothermal amplification assay using hydroxy naphthol blue dye (HNB-LAMP, real-time polymerase chain reaction (PCR and conventional PCR in the diagnosis of intraocular tuberculosis. Considering clinical presentation as the gold standard in 33 patients, the sensitivity of HNB-LAMP assay (75.8% was higher (not significant, P value 0.2 than conventional PCR (57.6% and lower than real-time PCR (90.9%. Specificity was 100% by all three methods. No amplification was observed in negative controls (n = 20 by all three methods. The cost of the HNB-LAMP assay was Rs. 500.00 and it does not require thermocycler, therefore, it can be used as an alternative to conventional PCR in resource-poor settings.

  16. Pesquisa de IgA contra o antígeno recombinante HspX de Mycobacterium tuberculosis no diagnóstico de tuberculose pleural Determination of levels of specific IgA to the HspX recombinant antigen of Mycobacterium tuberculosis for the diagnosis of pleural tuberculosis

    Loanda Carvalho Sant' Ana Limongi

    2011-06-01

    Full Text Available OBJETIVO: Avaliar a acurácia da dosagem de IgA contra o antígeno recombinante HspX no líquido pleural e no soro de pacientes com derrame pleural para o diagnóstico de tuberculose pleural. MÉTODOS: Estudo transversal de teste diagnóstico. Amostras de líquido pleural e de soro de pacientes com derrame pleural e suspeita de tuberculose pleural foram avaliadas para a determinação da densidade óptica de IgA contra HspX utilizando ELISA indireto. RESULTADOS: Foram avaliadas amostras de líquido pleural e de soro de 132 pacientes: 97 com tuberculose pleural (grupo de estudo e 35 com derrame pleural por outras causas (grupo controle. A dosagem de IgA em líquido pleural foi capaz de discriminar os pacientes com tuberculose pleural dos controles. A sensibilidade do teste em líquido pleural e em soro foi, respectivamente, de 69% e 30%, enquanto a especificidade foi de 83% e 84%, respectivamente. CONCLUSÕES: Os dados sugerem o potencial da utilização deste teste no diagnóstico de tuberculose pleural. Estudos com amostras maiores e em diferentes cenários epidemiológicos são necessáriosOBJECTIVE: To evaluate the accuracy of determining specific IgA to HspX recombinant antigen in pleural fluid and serum samples for the diagnosis of pleural tuberculosis in patients with pleural effusion. METHODS: This was a cross-sectional study. Serum and pleural fluid samples of patients with pleural effusion and suspected of having pleural tuberculosis were tested with indirect ELISA in order to determine the optical density of specific IgA to HspX. RESULTS: We evaluated serum and pleural fluid samples from 132 patients: 97 diagnosed with pleural tuberculosis (study group and 35 diagnosed with pleural effusion due to other causes (control group. The determination of IgA in pleural fluid satisfactorily discriminated between pleural tuberculosis patients and control patients. The sensitivity of the test in pleural fluid and in serum was 69% and 30

  17. Evaluation of anti-Mycobacterium tuberculosis activity of Campomanesia adamantium (Myrtaceae

    Fernando Rogério Pavan

    2009-01-01

    Full Text Available The anti-Mycobacterium tuberculosis activity of Campomanesia adamantium fruits extracts were evaluated. Six compounds, identified as flavanones and chalcones were quantified by HPLC-DAD-UV. Promising antitubercular activity was observed with ethyl acetate extract (MIC 62.5 µg/mL and their fractions (MIC values ranging from 39 to above 250 µg/mL. The better MIC result of 39 µg/mL was associated with two fractions that contain bigger amounts of 5,7-dihydroxy-6, 8-di-C-methylflavanone and 2',4'-dihydroxy-3',5'-dimethyl-6'-methoxychalcone. These compounds exhibited MICs >250 and 62.5 µg/mL, respectively, while their mixtures showed values ranging from 62.5 to 7.8 µg/mL, demonstrating a synergism between them.

  18. Evaluation of anti-Mycobacterium tuberculosis activity of Campomanesia adamantium (Myrtaceae)

    Pavan, Fernando Rogerio; Leite, Clarice Queico Fujimura [UNESP, Araraquara, SP (Brazil). Faculdade de Ciencias Farmaceuticas. Dept. de Ciencias Biologicas], e-mail: pavanfer@yahoo.com.br; Coelho, Roberta Gomes; Coutinho, Isabel Duarte; Honda, Neli Kika [Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, MS (Brazil). Dept. de Quimica; Cardoso, Claudia Andrea Lima [Universidade Estadual de Mato Grosso do Sul, Dourados, MS (Brazil). Curso de Quimica; Vilegas, Wagner; Leite, Sergio Roberto de Andrade [UNESP, Araraquara, SP (Brazil). Inst. de Quimica. Dept. de Quimica; Sato, Daisy Nakamura [Instituto Adolfo Lutz de Ribeirao Preto, SP (Brazil)

    2009-07-01

    The anti-Mycobacterium tuberculosis activity of Campomanesia adamantium fruits extracts were evaluated. Six compounds, identified as flavanones and chalcones were quantified by HPLC-DAD-UV. Promising antitubercular activity was observed with ethyl acetate extract (MIC 62.5 {mu}g/mL) and their fractions (MIC values ranging from 39 to above 250 {mu}g/mL). The better MIC result of 39 {mu}g/mL was associated with two fractions that contain bigger amounts of 5,7-dihydroxy-6, 8-di-C-methylflavanone and 2',4'-dihydroxy-3',5'-dimethyl-6'-methoxychalcone. These compounds exhibited MICs >250 and 62.5 {mu}g/mL, respectively, while their mixtures showed values ranging from 62.5 to 7.8 {mu}g/mL, demonstrating a synergism between them. (author)

  19. Evaluation of anti-Mycobacterium tuberculosis activity of Campomanesia adamantium (Myrtaceae)

    The anti-Mycobacterium tuberculosis activity of Campomanesia adamantium fruits extracts were evaluated. Six compounds, identified as flavanones and chalcones were quantified by HPLC-DAD-UV. Promising antitubercular activity was observed with ethyl acetate extract (MIC 62.5 μg/mL) and their fractions (MIC values ranging from 39 to above 250 μg/mL). The better MIC result of 39 μg/mL was associated with two fractions that contain bigger amounts of 5,7-dihydroxy-6, 8-di-C-methylflavanone and 2',4'-dihydroxy-3',5'-dimethyl-6'-methoxychalcone. These compounds exhibited MICs >250 and 62.5 μg/mL, respectively, while their mixtures showed values ranging from 62.5 to 7.8 μg/mL, demonstrating a synergism between them. (author)

  20. Phytoconstituents from Alpinia purpurata and their in vitro inhibitory activity against Mycobacterium tuberculosis

    Oliver B Villaflores

    2010-01-01

    Full Text Available Alpinia purpurata or red ginger was studied for its phytochemical constituents as part of our growing interest on Philippine Zingiberaceae plants that may exhibit antimycobacterial activity. The hexane and dichloromethane subextracts of the leaves were fractionated and purified using silica gel chromatography to afford a mixture of C 28 -C 32 fatty alcohols, a 3-methoxyflavone and two steroidal glycosides. The two latter metabolites were spectroscopically identified as kumatakenin (1, sitosteryl-3-O-6-palmitoyl-b-D-glucoside (2 and b-sitosteryl galactoside (3 using ultraviolet (UV, infrared (IR, electron impact mass spectrometer (EIMS and nuclear magnetic resonance (NMR experiments, and by comparison with literature data. This study demonstrates for the first time the isolation of these constituents from A. purpurata. In addition to the purported anti-inflammatory activity, its phytomedicinal potential to treat tuberculosis is also described.

  1. Differential diagnosis between Crohn’s disease and intestinal tuberculosis using integrated parameters including clinical manifestations, T-SPOT, endoscopy and CT enterography

    Zhang, Tianyu; Fan, Rong; Wang, Zhengting; Hu, Shurong; Zhang, Maochen; Lin, Yun; Tang, Yonghua; Zhong, Jie

    2015-01-01

    Background: The aim of the study was to evaluate clinical manifestations, T-SPOT, endoscopy and CT enterography to differentiate Crohn’s disease (CD) from intestinal tuberculosis (ITB). Methods: 128 in patients with suspected CD and ITB were prospectively enrolled in the study. Demographic, clinical, laboratory, endoscopic and CT enterographic data were collected. After treatment for 6 months, when a definite diagnosis was reached, the differential diagnostic value of each parameter was analyzed. Multivariable logistic regression was used to analyze further, parameters of statistical significance to establish a mathematical regression equation. Receiver operating characteristic curves were plotted. Results: Clinical parameters helpful in differentiating CD from ITB included diarrhea, night sweat and perianal disease. Endoscopic parameters were useful in differentiating CD from ITB including transverse ulcers, longitudinal ulcers, rodent-like ulcers and patulous ileocecal valve. CT enterographic parameters aided the identification of the two conditions. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of a mathematical regression model established for 6 parameters of clinical endoscopy and CT enterography were 97.8%, 96.8%, 97.6%, 98.9% and 93.7% respectively, whereas those for T-SPOT were 96.8%, 91.3%, 92.7%, 78.9% and 98.8% respectively. Conclusions: T-SPOT is useful to exclude a diagnosis of ITB. Differentiating CD from ITB is a difficult clinical problem that requires a consideration of clinical, T-SPOT, endoscopic and CT enterographic parameters for accurate diagnosis. PMID:26770348

  2. Pancreatic tuberculosis: MDCT features and differential diagnosis%胰腺结核九例的MDCT特征和误诊分析

    梁宗辉; 窦娅芳; 唐颖; 汤伟军; 冯晓源

    2011-01-01

    Objective To study the multi-detector spiral CT (MDCT) features of pancreatic tuberculosis to improve the awareness and correct diagnosis. Methods Imaging features of MDCT were retrospectively reviewed on 9 cases with pancreatic tuberculosis that were diagnosed from 2003 to 2009, among them two patients underwent MDCT angiography, the features were compared with those of operative and pathological findings. Results One case of pancreatic cancer, 2 cases of cystadenocarcinoma and 1 case of pseudocyst, 2 cases of pancreatic cancer with retroperitoneal lymph node metastasis, 2 cases of lymphoma were diagnosed by MDCT, and all the lesions were diagnosed as pancreatic tuberculosis pathologically, and the misdiagnosis rate was 100%. Pancreatic tuberculosis often presented as pancreatic head mass, sometimes pancreatic body and tail were involved. MDCT showed isopycnic or low density solid-cyst mass, occasionally calcification was present, with slightly or moderate ring-like enhancement after contrast injection. There was no enlargement of the pancreatic duct. The retroperitoneal and adjacent lymph nodes were always enlarged with ring-like enhancement. Sometimes there was evidence of tuberculosis of other abdominal organs. Conclusions Ring-like enhanced lesions with ring-like enhanced lymph nodes without enlargement of pancreatic duct are characteristic MDCT features of pancreatic tuberculosis.%目的 分析胰腺结核(pancreatic tuberculoses,PT)的多层螺旋CT(MDCT)征象,以期提高对该病的认识和诊断正确率.方法 收集2003年至2009年行MDCT检查并最终确诊为PT的9例患者,其中2例行MDCT血管成像.分析PT的MDCT特征性表现,并与手术及病理结果进行比较.结果 MDCT诊断为胰腺癌1例、囊腺癌1例、囊腺瘤2例、假性囊肿1例、胰腺癌伴后腹膜淋巴结转移2例、淋巴瘤2例.通过病理证实,9例均为PT,误诊率达100%.PT常表现为胰头肿块,亦可累及体尾部或整个胰腺.MDCT呈现等或略

  3. The presence of a booster phenomenon among contacts of active pulmonary tuberculosis cases: a retrospective cohort

    Queiroz-Mello Fernanda C

    2007-03-01

    Full Text Available Abstract Background Assuming a higher risk of latent tuberculosis (TB infection in the population of Rio de Janeiro, Brazil, in October of 1998 the TB Control Program of Clementino Fraga Filho Hospital (CFFH routinely started to recommend a two-step tuberculin skin test (TST in contacts of pulmonary TB cases in order to distinguish a boosting reaction due to a recall of delayed hypersensitivity previously established by infection with Mycobacterium tuberculosis (M.tb or BCG vaccination from a tuberculin conversion. The aim of this study was to assess the prevalence of boosted tuberculin skin tests among contacts of individuals with active pulmonary tuberculosis (TB. Methods Retrospective cohort of TB contacts ≥ 12 years old who were evaluated between October 1st, 1998 and October 31st 2001. Contacts with an initial TST ≤ 4 mm were considered negative and had a second TST applied after 7–14 days. Boosting reaction was defined as a second TST ≥ 10 mm with an increase in induration ≥ 6 mm related to the first TST. All contacts with either a positive initial or repeat TST had a chest x-ray to rule out active TB disease, and initially positive contacts were offered isoniazid preventive therapy. Contacts that boosted did not receive treatment for latent TB infection and were followed for 24 months to monitor the development of TB. Statistical analysis of dichotomous variables was performed using Chi-square test. Differences were considered significant at a p Results Fifty four percent (572/1060 of contacts had an initial negative TST and 79% of them (455/572 had a second TST. Boosting was identified in 6% (28/455. The mean age of contacts with a boosting reaction was 42.3 ± 21.1 and with no boosting was 28.7 ± 21.7 (p = 0.01. Fifty percent (14/28 of individuals whose test boosted met criteria for TST conversion on the second TST (increase in induration ≥ 10 mm. None of the 28 contacts whose reaction boosted developed TB disease within

  4. Active Fault Diagnosis in Sampled-data Systems

    Niemann, Hans Henrik; Poulsen, Niels Kjølstad

    2015-01-01

    The focus in this paper is on active fault diagnosis (AFD) in closed-loop sampleddata systems. Applying the same AFD architecture as for continuous-time systems does not directly result in the same set of closed-loop matrix transfer functions. For continuous-time systems, the LFT (linear fractional...

  5. Diagnosis of chronic active hepatitis in a miniature schnauzer

    Hendrix, Alana D.

    2004-01-01

    A 12-year-old male castrated miniature schnauzer was presented with a history of abdominal distension. Serum biochemical analysis and abdominal ultrasonography indicated hepatic disease. A wedge biopsy provided a diagnosis of chronic active hepatitis. A therapeutic regime was initiated to improve the quality of life and slow the progression of this disease is described.

  6. Characterization of Antibacterial and Hemolytic Activity of Synthetic Pandinin 2 Variants and Their Inhibition against Mycobacterium tuberculosis

    Rodríguez, Alexis; Villegas, Elba; Montoya-Rosales, Alejandra; Rivas-Santiago, Bruno; Corzo, Gerardo

    2014-01-01

    The contention and treatment of Mycobacterium tuberculosis and other bacteria that cause infectious diseases require the use of new type of antibiotics. Pandinin 2 (Pin2) is a scorpion venom antimicrobial peptide highly hemolytic that has a central proline residue. This residue forms a structural “kink” linked to its pore-forming activity towards human erythrocytes. In this work, the residue Pro14 of Pin2 was both substituted and flanked using glycine residues (P14G and P14GPG) based on the low hemolytic activities of antimicrobial peptides with structural motifs Gly and GlyProGly such as magainin 2 and ponericin G1, respectively. The two Pin2 variants showed antimicrobial activity against E. coli, S. aureus, and M. tuberculosis. However, Pin2 [GPG] was less hemolytic (30%) than that of Pin2 [G] variant. In addition, based on the primary structure of Pin2 [G] and Pin2 [GPG], two short peptide variants were designed and chemically synthesized keeping attention to their physicochemical properties such as hydrophobicity and propensity to adopt alpha-helical conformations. The aim to design these two short antimicrobial peptides was to avoid the drawback cost associated to the synthesis of peptides with large sequences. The short Pin2 variants named Pin2 [14] and Pin2 [17] showed antibiotic activity against E. coli and M. tuberculosis. Besides, Pin2 [14] presented only 25% of hemolysis toward human erythrocytes at concentrations as high as 100 µM, while the peptide Pin2 [17] did not show any hemolytic effect at the same concentration. Furthermore, these short antimicrobial peptides had better activity at molar concentrations against multidrug resistance M. tuberculosis than that of the conventional antibiotics ethambutol, isoniazid and rifampicin. Therefore, Pin2 [14] and Pin2 [17] have the potential to be used as an alternative antibiotics and anti-tuberculosis agents with reduced hemolytic effects. PMID:25019413

  7. In Vivo Molecular Dissection of the Effects of HIV-1 in Active Tuberculosis.

    Lucy C K Bell

    2016-03-01

    Full Text Available Increased risk of tuberculosis (TB associated with HIV-1 infection is primarily attributed to deficient T helper (Th1 immune responses, but most people with active TB have robust Th1 responses, indicating that these are not sufficient to protect against disease. Recent findings suggest that favourable outcomes following Mycobacterium tuberculosis infection arise from finely balanced inflammatory and regulatory pathways, achieving pathogen control without immunopathology. We hypothesised that HIV-1 and antiretroviral therapy (ART exert widespread changes to cell mediated immunity, which may compromise the optimal host protective response to TB and provide novel insights into the correlates of immune protection and pathogenesis. We sought to define these effects in patients with active TB by transcriptional profiling of tuberculin skin tests (TST to make comprehensive molecular level assessments of in vivo human immune responses at the site of a standardised mycobacterial challenge. We showed that the TST transcriptome accurately reflects the molecular pathology at the site of human pulmonary TB, and used this approach to investigate immune dysregulation in HIV-1/TB co-infected patients with distinct clinical phenotypes associated with TST reactivity or anergy and unmasking TB immune reconstitution inflammatory syndrome (IRIS after initiation of ART. HIV-1 infected patients with positive TSTs exhibited preserved Th1 responses but deficient immunoregulatory IL10-inducible responses. Those with clinically negative TSTs revealed profound anergy of innate as well as adaptive immune responses, except for preservation of type 1 interferon activity, implicated in impaired anti-mycobacterial immunity. Patients with unmasking TB IRIS showed recovery of Th1 immunity to normal levels, but exaggerated Th2-associated responses specifically. These mechanisms of immune dysregulation were localised to the tissue microenvironment and not evident in peripheral

  8. In Vivo Molecular Dissection of the Effects of HIV-1 in Active Tuberculosis.

    Bell, Lucy C K; Pollara, Gabriele; Pascoe, Mellissa; Tomlinson, Gillian S; Lehloenya, Rannakoe J; Roe, Jennifer; Meldau, Richard; Miller, Robert F; Ramsay, Alan; Chain, Benjamin M; Dheda, Keertan; Noursadeghi, Mahdad

    2016-03-01

    Increased risk of tuberculosis (TB) associated with HIV-1 infection is primarily attributed to deficient T helper (Th)1 immune responses, but most people with active TB have robust Th1 responses, indicating that these are not sufficient to protect against disease. Recent findings suggest that favourable outcomes following Mycobacterium tuberculosis infection arise from finely balanced inflammatory and regulatory pathways, achieving pathogen control without immunopathology. We hypothesised that HIV-1 and antiretroviral therapy (ART) exert widespread changes to cell mediated immunity, which may compromise the optimal host protective response to TB and provide novel insights into the correlates of immune protection and pathogenesis. We sought to define these effects in patients with active TB by transcriptional profiling of tuberculin skin tests (TST) to make comprehensive molecular level assessments of in vivo human immune responses at the site of a standardised mycobacterial challenge. We showed that the TST transcriptome accurately reflects the molecular pathology at the site of human pulmonary TB, and used this approach to investigate immune dysregulation in HIV-1/TB co-infected patients with distinct clinical phenotypes associated with TST reactivity or anergy and unmasking TB immune reconstitution inflammatory syndrome (IRIS) after initiation of ART. HIV-1 infected patients with positive TSTs exhibited preserved Th1 responses but deficient immunoregulatory IL10-inducible responses. Those with clinically negative TSTs revealed profound anergy of innate as well as adaptive immune responses, except for preservation of type 1 interferon activity, implicated in impaired anti-mycobacterial immunity. Patients with unmasking TB IRIS showed recovery of Th1 immunity to normal levels, but exaggerated Th2-associated responses specifically. These mechanisms of immune dysregulation were localised to the tissue microenvironment and not evident in peripheral blood. TST

  9. Multifunctional CD4 T Cell Responses in Patients with Active Tuberculosis

    Qiu, Zhengang; Zhang, Mingxia; Zhu, Yuzhen; Zheng, Feiqun; Lu, Puxuan; Liu, Haiying; Michael W Graner; Zhou, Boping; Chen, Xinchun

    2012-01-01

    The roles of multifunctional CD4 T cells in human tuberculosis are not well defined. In this study, we found that patients with tuberculosis had decreased PMA/ionomycin stimulated multifunctional CD4 T cells, and increased Mycobacterium tuberculosis antigen-specific multifunctional CD4 T cells, when compared to individuals with latent tuberculosis infection and healthy controls. PMA/ionomycin stimulated IFN-γ+IL-2+TNF-α+ CD4 T cell responses were decreased in patients with smear-positive tube...

  10. Tuberculosis: medico-legal aspects.

    Vetrugno, G; De-Giorgio, F; D'Alessandro, F; Scafetta, I; Berloco, F; Buonsenso, D; Abbate, F; Scalise, G; Pascali, V L; Valentini, P

    2014-01-01

    Tuberculosis is a diffusive infectious disease whose typical behaviour differentiates it from other infectious diseases spread by human-to-human transmission (flu, chicken pox, cholera, etc.) that follow a classic epidemic pattern. Indeed, in the presence of a known source of Koch bacilli that is capable of spreading the bacteria by air, not all exposed individuals inhale the bacteria, not all those who inhale them absorb them, not all those who absorb the bacteria are unable to eliminate them, not all who are able to eliminate them do so using delayed hypersensitivity, not all those who react with delayed hypersensitivity suffer lasting tissue damage (among other things, minor), not all who suffer tissue damage have anatomical sequelae, and not all those who have anatomical sequelae, however minimal, become carriers of bacilli in the latent period. The vast majority (90-95%) of the latter - which are in any case a portion, not the totality of those exposed - remain asymptomatic throughout their lives and never develop active tuberculosis. Based on these biological characteristics and the legal concepts of "epidemic" and "disease," it becomes highly problematic, if not impossible, to assert both that tuberculosis can cause events of sufficient magnitude to be associated with the crime of "epidemic," and that the mere diagnosis of a latent tuberculosis infection is sufficient to assume the presence of an illness legally prosecutable in criminal proceedings or a disability prosecutable in civil proceedings. Furthermore, clinically apparent tuberculosis is a temporarily-and in some cases permanently-disabling condition, and in certain work environments, even with the difficulties caused by the lack of available effective diagnostic tools and the insidious behaviour of the disease in the early stages, targeted monitoring to identify other persons who may become ill is appropriate. PMID:24804006

  11. TUBERCULOSIS: MEDICO-LEGAL ASPECTS

    Giuseppe Vetrugno

    2014-04-01

    Full Text Available Tuberculosis is a diffusive infectious disease whose typical behavior differentiates it from other infectious diseases spread by human-to-human transmission (flu, chicken pox, cholera, etc. which follow a classically epidemic pattern. Indeed, in the presence of a known source of Koch bacilli capable of spreading them by air, not all exposed individuals inhale the bacteria, not all those who inhale them absorb them, not all those who absorb them are unable to eliminate them, not all who are able to eliminate them do so using delayed hypersensitivity, not all those who react with delayed hypersensitivity suffer lasting tissue damage (among other things, minor, not all who suffer tissue damage have anatomical sequelae, not all those who have anatomical sequelae, however minimal, become carriers of bacilli in the latent period. The vast majority (90-95% of the latter – which are in any case a portion, not the totality of those exposed – remain asymptomatic throughout their lives and never develop active tuberculosis. Based on these biological characteristics and the legal concepts of “epidemic” and “disease,” it becomes highly problematic, if not impossible, to assert both that tuberculosis can cause events of sufficient magnitude to be associated with the crime of “epidemic,” and that the mere diagnosis of a latent tuberculosis infection is sufficient to assume the presence of an illness legally prosecutable in criminal proceedings or a disability prosecutable in civil proceedings. Further, clinically apparent tuberculosis is a temporarily—in some cases permanently—disabling condition, and in certain work environments, even with the difficulties caused by the lack of available effective diagnostic tools and the insidious behavior of the disease in the early stages, it appears appropriate to engage in targeted monitoring, also for the early identification of persons who may become ill.

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

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

    2011-09-01

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

  13. Early imaging diagnosis of multi-drug resistant pulmonary tuberculosis%耐多药肺结核的影像学早期诊断

    曾令延; 陈根铭; 黄福城; 朱少乾

    2013-01-01

    目的收集经药物敏感试验证实的耐多药肺结核病例,探索耐多药肺结核的早期影像学诊断。方法收集2011年1月-2012年9月380例疑似肺结核患者在本院诊治过程中病灶恶化者,所有胸片由两名经验丰富的影像科医生诊断为耐多药肺结核,与最终经药物敏感试验证实的耐多药肺结核病例比较。结果380例中经影像学诊断与药物敏感试验诊断的耐多药肺结核病例数分别为101例、90例,二者的差异无显著性(p>0.05),其中经影像学误诊为耐多药肺结核的病例分别是:肺结核合并肺炎3例,肺非结核分枝杆菌感染4例,肺癌3例,卡式肺囊虫肺炎1例。结论影像学诊断与药物敏感试验诊断可疑耐多药肺结核的准确率无显著性差异,影像学诊断可对耐多药肺结核作出早期诊断。%Objective To explore early imaging diagnosis of collected multi-drug resistant Pulmonary tuberculosis(MDR-PTB) patients whose diagnosis were confirmed by drug sensitivity test. Methods 380 suspected MDR-PTB patients who received treatment in our hospital from january 2011 to september 2012 had progressing lesions, MDR-PTB was diagnosed by two experienced radiologists through reading and interpreting all the chest x-ray fims . And then comparing with the cases of MDR-PTB confirmed by drug sensitivity test. Results OF 380 cases , the number of MDR-PTB diagnosed by imaging diagnostic methods and drug sensitivity test was 101, 90, respectively; There was no significant difference between the two diagnostic methods(p>0.05). Of all cases misdiagnosed to MDR-PTB, there were 3 cases of pulmonary tuberculosis complicated pneumonia, 4 cases of pulmonary non-tuberculosis mycobacteria infection , 3 cases of lung cancers, 1 case of pneumocystis carinii pneumonia, respectively; Conclusion There was no significant difference between the accuracy of imaging diagnosis and drug sensitivity test in diagnosing MDR-PTB, Imaging

  14. Imaging of pulmonary tuberculosis

    Tuberculosis, more than any other infectious disease, has always been a challenge, since it has been responsible for a great amount of morbidity and mortality in humans. After a steady decline in the number of new cases during the twentieth century, due to improved social and environmental conditions, early diagnosis, and the development of antituberculous medication, a stagnation and even an increase in the number of new cases was noted in the mid-1980s. The epidemiological alteration is multifactorial: global increase in developing countries; minority groups (HIV and other immunocompromised patients); and elderly patients due to an altered immune status. Other factors that may be responsible are a delayed diagnosis, especially in elderly patients, incomplete or inadequate therapy, and the emergence of multidrug-resistant tuberculosis. The course of the disease and its corresponding clinicoradiological pattern depends on the interaction between the organism and the host response. Classically, pulmonary tuberculosis has been classified in primary tuberculosis, which occurred previously in children, and postprimary tuberculosis, occurring in adult patients. In industrialized countries, however, there seems to be a shift of primary tuberculosis towards adults. Furthermore, due to an altered immunological response in certain groups, such as immunocompromised and elderly patients, an atypical radioclinical pattern may occur. The changing landscape, in which tuberculosis occurs, as well as the global resurgence, and the changed spectrum of the clinical and radiological presentation, justify a renewed interest of radiologists for the imaging features of pulmonary tuberculosis. This article deals with the usual imaging features of pulmonary tuberculosis as well as the atypical patterns encountered in immunodepressed and elderly patients. (orig.)

  15. PENILE TUBERCULOSIS PRESENTING AS PHIMOSIS

    Mahalakshmi

    2015-03-01

    Full Text Available We report a case of penile tuberculosis presenting as phimosis . A dorsal slit revealed an ulceroproliferative growth which resembled Carcinoma. The diagnosis of tuberculosis was based on histopathology. Successful treatment was achieved by Antituberculosis therapy. We report this case because of its unsual presentati on and its rarity

  16. PENILE TUBERCULOSIS PRESENTING AS PHIMOSIS

    Mahalakshmi; Yuwarani; Narayanan; Sudha

    2015-01-01

    We report a case of penile tuberculosis presenting as phimosis . A dorsal slit revealed an ulceroproliferative growth which resembled Carcinoma. The diagnosis of tuberculosis was based on histopathology. Successful treatment was achieved by Antituberculosis therapy. We report this case because of its unsual presentati on and its rarity

  17. TUBERCULOSIS IN AFRICA - ANY NEWS

    VANDERWERF, TS

    1994-01-01

    The tuberculosis situation in Africa in the AIDS era has become bleak. The tuberculosis incidence has increased in most sub-Saharan African countries, diagnosis has become more difficult, response to treatment, though initially good, is eventually less effective, and patient compliance, which has be

  18. Pancreatic Tuberculosis or Autoimmune Pancreatitis

    Ayesha Salahuddin; Muhammad Wasif Saif

    2014-01-01

    Introduction. Isolated pancreatic and peripancreatic tuberculosis is a challenging diagnosis due to its rarity and variable presentation. Pancreatic tuberculosis can mimic pancreatic carcinoma. Similarly, autoimmune pancreatitis can appear as a focal lesion resembling pancreatic malignancy. Endoscopic ultrasound-guided fine needle aspiration provides an effective tool for differentiating between benign and malignant pancreatic lesions. The immune processes involved in immunoglobulin G4 relate...

  19. Diagnosis of mucoviscidosis by neutron activation analysis. Part 1

    Symptoms pathology, incidence, and gravity of the inherent syndrome called mucoviscidosis, or cystic fibrosis are described in this Part I. The analytical methods used for its diagnosis, both the conventional chemical ones and by neutron activation analysis are also summarised. Finally, an analytical method to study the incidence of mucoviscidosis in Brazil is presented. This , essentially, consists in bromine determination, in fingernails, by resonance neutron activation analysis. (author)

  20. In vitro activities of the newly synthesised ER-2 against clinical isolates of Mycobacterium tuberculosis susceptible or resistant to antituberculosis drugs.

    Rao, Shilpakala Sainath; Raghunathan, Raghavachari; Ekambaram, Ramesh; Raghunathan, Malathi

    2009-11-01

    Two hundred isolates of Mycobacterium tuberculosis were evaluated for their susceptibility to a newly synthesised quinolone derivative, ER-2, compared with ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin. ER-2 and moxifloxacin showed the greatest activity [MIC for 90% of strains tested (MIC(90))=0.5 microg/mL], although levofloxacin and ciprofloxacin showed good activity with an MIC(90) of 1 microg/mL. More importantly, ER-2 showed excellent activity against M. tuberculosis H37Rv both in the lungs and spleen of mice, indicating the potential therapeutic value of ER-2 against M. tuberculosis. PMID:19625168

  1. Current features of primary tuberculosis on medical imaging based on a series of fourteen cases

    Active pulmonary tuberculosis, a source of contamination, is currently undergoing a recrudescence in developed countries, particularly in clinical contexts of immuno-depression. The authors report a retrospective series of 14 cases of primary tuberculosis in a paediatric population (7 girls and 7 boys) with a mean age of 3.5 years (range: 4 months - 16 years) observed over a 3-year period. After reviewing the current radiological features of patent primary tuberculosis, the authors emphasize the contribution of chest CT scan in latent forms with a normal chest x-ray and a difficult bacteriological diagnosis. Imaging remains an essential tool in early diagnosis, therapeutic management and active surveillance of this form. The authors propose a decisional flow-chart in the case of suspected primary tuberculosis in children. (authors). 20 refs., 8 figs

  2. New classes of alanine racemase inhibitors identified by high-throughput screening show antimicrobial activity against Mycobacterium tuberculosis.

    Karen G Anthony

    Full Text Available BACKGROUND: In an effort to discover new drugs to treat tuberculosis (TB we chose alanine racemase as the target of our drug discovery efforts. In Mycobacterium tuberculosis, the causative agent of TB, alanine racemase plays an essential role in cell wall synthesis as it racemizes L-alanine into D-alanine, a key building block in the biosynthesis of peptidoglycan. Good antimicrobial effects have been achieved by inhibition of this enzyme with suicide substrates, but the clinical utility of this class of inhibitors is limited due to their lack of target specificity and toxicity. Therefore, inhibitors that are not substrate analogs and that act through different mechanisms of enzyme inhibition are necessary for therapeutic development for this drug target. METHODOLOGY/PRINCIPAL FINDINGS: To obtain non-substrate alanine racemase inhibitors, we developed a high-throughput screening platform and screened 53,000 small molecule compounds for enzyme-specific inhibitors. We examined the 'hits' for structural novelty, antimicrobial activity against M. tuberculosis, general cellular cytotoxicity, and mechanism of enzyme inhibition. We identified seventeen novel non-substrate alanine racemase inhibitors that are structurally different than any currently known enzyme inhibitors. Seven of these are active against M. tuberculosis and minimally cytotoxic against mammalian cells. CONCLUSIONS/SIGNIFICANCE: This study highlights the feasibility of obtaining novel alanine racemase inhibitor lead compounds by high-throughput screening for development of new anti-TB agents.

  3. Primer Parotid Tuberculosis in Two Siblings

    Baylan, Muzeyyen Yildirim; Ozmen, Cihan Akgul; Samanci, Baver

    2013-01-01

    Tuberculosis of the parotid gland is an uncommon disease. In this study, we present primary parotid tuberculosis in two siblings. Two female siblings, of 16 and 14 years of age, presented with unilateral masses in the parotid region. Acid-fast bacilli were found in the aspiration fluid of the lesion. After the tuberculosis treatment, the patients were doing well. In this study, we discussed clinical presentation, diagnosis, treatment of primary parotid tuberculosis, and noteworthiness the tra...

  4. Specificity and sensitivity of chest radiographs in the diagnosis of paediatric pulmonary tuberculosis and the value of additional high-kilovolt radiographs

    Tuberculosis (TB) remains the most common notifiable infectious disease in South Africa. The diagnosis of pulmonary TB in children is often very difficult because of the non-specific radiological signs and inter-observer variation in the interpretation of radiographs. The frontal high-kilovolt (kV) radiograph has been used to assess the effect of TB adenopathy on the tracheobronchial tree and to detect endobronchial lesions. The aims of the present study were to assess the specificity and sensitivity of chest radiographs in the diagnosis of pulmonary TB and to assess whether the addition of the high-kV radiograph affects these parameters. The study group consisted of paediatric patients suspected of having pulmonary TB over a 6-year period. These patients had clinical, bacteriological and radiographic examinations. Radiographs were examined by one experienced radiologist in two sittings separated by a 6-week interval. On the first sitting, only standard radiographs were examined and, on the second sitting, these were supplemented with high-kV radiographs. Differences in the detection of each recognized radiological feature of pulmonary TB before and after the addition of the high-kV film were analysed for statistical significance. The frequency of radiographic findings in our study compared favourably with other reports. No statistically significant differences for the detection of radiographic features consistent with pulmonary TB, or for the diagnosis of pulmonary TB, were demonstrated between the two sittings. Specificity increased from 74.4% to 86.6% with the addition of the high-kV view and sensitivity remained constant at 38.8%. The present study does not support the routine use of the frontal high-kV radiograph for the diagnosis of pulmonary TB. This paper also confirms the findings of others, that standard chest radiographs are a poor indicator of pulmonary TB in children Copyright (2004) Blackwell Publishing Asia Pty Ltd

  5. Analysis of Curative Effect of Diagnosis and Treatment of Silicosis Patients Complicated with Pulmonary Tuberculosis%矽肺合并肺结核患者的诊断及治疗疗效分析

    郭利强

    2015-01-01

    目的:研究矽肺合并肺结核的临床特点和诊疗方法,提高治愈率。方法对2009年2月~2013年11月确诊的80例矽肺合并肺结核患者的临床资料进行分析。结果矽肺合并肺结核患者临床特点与矽肺分期有关,玉期矽肺患者结核中毒症状相对多见,Ⅱ、芋期矽肺患者临床症状较玉期矽肺患者严重。治愈率玉期矽肺跃Ⅱ期矽肺跃芋期矽肺。结论矽肺合并肺结核经抗结核治疗疗效比单纯肺结核差,疗程和治疗效果与矽肺分期有关系。%Objective To study the clinical characteristics of silicosis amalgamative tuberculosis and diagnosis methods,improve the cure rate.Methods From February 2009 to November 2013 confirmed the clinical data of 80 cases of silicosis amalgamative tuberculosis patients were analyzed.Results The patients with silicosis amalgamative tuberculosis clinical features associated with silicosis in instal ment,Ⅰphase silicosis tuberculosis poisoning symptoms relatively more people see,II Ⅲ phase silicosis,clinical symptom is玉phase silicosis seriously.The cure rateⅠphase silicosis>II phase silicosis>Ⅲ stage of silicosis.Conclusion Silicosis amalgamative tuberculosis by anti-tuberculosis treatment curative ef ect than pure tuberculosis,treatment and treatment ef ect with silicosis stage.

  6. Structural analysis of the dodecameric proteasome activator PafE in Mycobacterium tuberculosis.

    Bai, Lin; Hu, Kuan; Wang, Tong; Jastrab, Jordan B; Darwin, K Heran; Li, Huilin

    2016-04-01

    The human pathogen Mycobacterium tuberculosis (Mtb) requires a proteasome system to cause lethal infections in mice. We recently found that proteasome accessory factor E (PafE, Rv3780) activates proteolysis by the Mtb proteasome independently of adenosine triphosphate (ATP). Moreover, PafE contributes to the heat-shock response and virulence of Mtb Here, we show that PafE subunits formed four-helix bundles similar to those of the eukaryotic ATP-independent proteasome activator subunits of PA26 and PA28. However, unlike any other known proteasome activator, PafE formed dodecamers with 12-fold symmetry, which required a glycine-XXX-glycine-XXX-glycine motif that is not found in previously described activators. Intriguingly, the truncation of the PafE carboxyl-terminus resulted in the robust binding of PafE rings to native proteasome core particles and substantially increased proteasomal activity, suggesting that the extended carboxyl-terminus of this cofactor confers suboptimal binding to the proteasome core particle. Collectively, our data show that proteasomal activation is not limited to hexameric ATPases in bacteria. PMID:27001842

  7. HIV prevalence and diabetes prevalence among tuberculosis patients in Antananarivo city: a descriptive study

    Julio Rakotonirina; Herilala Razanakoto; Laurence Rasolofomanana; Lala Rasoamialy-Sola Razanakolona

    2014-01-01

    Background: In developing countries, HIV infection is the main disease leads to tuberculosis (TB) active. Each tuberculosis (TB) patient of TB diagnosis and treatment centers in Antananarivo city should receive HIV serology counseling. The TB-diabetes association is rarely considered. In general population in Madagascar HIV was 0.37% in 2010 and Diabetes affects about 3% of the population. This study aims to estimate the prevalence of HIV infection and diabetes among TB patients. Methods: ...

  8. Tuberculosis in Older Adults.

    Rajagopalan, Shobita

    2016-08-01

    Tuberculosis (TB) remains one of the world's most lethal infectious diseases. Preventive and control strategies among other high-risk groups, such as the elderly population, continues to be a challenge. Clinical features of TB in older adults may be atypical and confused with age-related diseases. Diagnosis and management of TB in the elderly person can be difficult; treatment can be associated with adverse drug reactions. This article reviews the current global epidemiology, pathogenesis, clinical characteristics, diagnosis, management, and prevention of Mycobacterium tuberculosis infection in community-dwelling and institutionalized aging adults. PMID:27394018

  9. Global Chemical Composition and Antioxidant and Anti-Tuberculosis Activities of Various Extracts of Globularia alypum L. (Globulariaceae Leaves

    François Couderc

    2011-12-01

    Full Text Available In this work, an evaluation of the biological activities of Globularia alypum L. extracts and their global chemical composition was realized. Extracts from G. alypum were obtained by two extraction methods. The composition of polyphenols (8.5–139.95 g gallic acid equivalent/Kg of dry mass, tannins (1.39–18.65 g catechin equivalent/Kg of dry mass, anthocyanins (8.17–70.69 mg cyanidin equivalent/Kg of dry mass and flavonoids (0.31–19.28 g quercetin equivalent/Kg of dry mass was evaluated. The samples were subjected to a screening for their antioxidant activities using the DPPH· and ABTS·+ assays. For the first time, the anti-tuberculosis activity (H37Rv for G. alypum was tested against Mycobacterium tuberculosis. The strongest antioxidant activity was obtained for the methanol extract (IC50 = 15.58 ± 0.168 mg/L and the best anti-tuberculosis activity was obtained for the petroleum ether extract (IC50 = 77 mg/L. We have found a positive correlation between the total phenolics content and the antioxidant activity R2 = 0.88 (DPPH· and R2 = 0.97 (ABTS·+. We have found also a positive correlation between the flavonoid content and the antioxidant activity R2 = 0.91 (DPPH· and R2 = 0.91 (ABTS·+.

  10. Activity of Medicinal Plant Extracts on Multiplication of Mycobacterium tuberculosis under Reduced Oxygen Conditions Using Intracellular and Axenic Assays.

    Bhatter, Purva D; Gupta, Pooja D; Birdi, Tannaz J

    2016-01-01

    Aim. Test the activity of selected medicinal plant extracts on multiplication of Mycobacterium tuberculosis under reduced oxygen concentration which represents nonreplicating conditions. Material and Methods. Acetone, ethanol and aqueous extracts of the plants Acorus calamus L. (rhizome), Ocimum sanctum L. (leaf), Piper nigrum L. (seed), and Pueraria tuberosa DC. (tuber) were tested on Mycobacterium tuberculosis H37Rv intracellularly using an epithelial cell (A549) infection model. The extracts found to be active intracellularly were further studied axenically under reducing oxygen concentrations. Results and Conclusions. Intracellular multiplication was inhibited ≥60% by five of the twelve extracts. Amongst these 5 extracts, in axenic culture, P. nigrum (acetone) was active under aerobic, microaerophilic, and anaerobic conditions indicating presence of multiple components acting at different levels and P. tuberosa (aqueous) showed bactericidal activity under microaerophilic and anaerobic conditions implying the influence of anaerobiosis on its efficacy. P. nigrum (aqueous) and A. calamus (aqueous and ethanol) extracts were not active under axenic conditions but only inhibited intracellular growth of Mycobacterium tuberculosis, suggesting activation of host defense mechanisms to mediate bacterial killing rather than direct bactericidal activity. PMID:26941797

  11. Activity of Medicinal Plant Extracts on Multiplication of Mycobacterium tuberculosis under Reduced Oxygen Conditions Using Intracellular and Axenic Assays

    Purva D. Bhatter

    2016-01-01

    Full Text Available Aim. Test the activity of selected medicinal plant extracts on multiplication of Mycobacterium tuberculosis under reduced oxygen concentration which represents nonreplicating conditions. Material and Methods. Acetone, ethanol and aqueous extracts of the plants Acorus calamus L. (rhizome, Ocimum sanctum L. (leaf, Piper nigrum L. (seed, and Pueraria tuberosa DC. (tuber were tested on Mycobacterium tuberculosis H37Rv intracellularly using an epithelial cell (A549 infection model. The extracts found to be active intracellularly were further studied axenically under reducing oxygen concentrations. Results and Conclusions. Intracellular multiplication was inhibited ≥60% by five of the twelve extracts. Amongst these 5 extracts, in axenic culture, P. nigrum (acetone was active under aerobic, microaerophilic, and anaerobic conditions indicating presence of multiple components acting at different levels and P. tuberosa (aqueous showed bactericidal activity under microaerophilic and anaerobic conditions implying the influence of anaerobiosis on its efficacy. P. nigrum (aqueous and A. calamus (aqueous and ethanol extracts were not active under axenic conditions but only inhibited intracellular growth of Mycobacterium tuberculosis, suggesting activation of host defense mechanisms to mediate bacterial killing rather than direct bactericidal activity.

  12. Improvement in Plasma Drug Activity during the Early Treatment Interval among Tanzanian Patients with Multidrug-Resistant Tuberculosis

    Ndusilo, Norah D.; Scott K. Heysell; Mpagama, Stellah G.; Gratz, Jean; Segesela, Farida H.; Pazia, Saumu J.; Wang, Xin-Qun; Houpt, Eric R.; Kibiki, Gibson S

    2015-01-01

    Background Individual pharmacokinetic variability may be common in patients treated for multidrug-resistant tuberculosis (MDR-TB) but data are sparse from resource-limited settings and across the early treatment interval. Methods Plasma drug activity, as measured by the TB Drug Activity (TDA) assay at 2 and 4 weeks of treatment with a standardized MDR-TB regimen was performed in patients with pulmonary MDR-TB from Tanzania. TDA values were correlated with measures of early treatment outcome i...

  13. Sterilizing activity of second-line regimens containing TMC207 in a murine model of tuberculosis.

    Nicolas Veziris

    Full Text Available RATIONALE: The sterilizing activity of the regimen used to treat multidrug resistant tuberculosis (MDR TB has not been studied in a mouse model. OBJECTIVE AND METHODS: Swiss mice were intravenously inoculated with 6 log10 of Mycobacterium tuberculosis (TB strain H37Rv, treated with second-line drug combinations with or without the diarylquinoline TMC207, and then followed without treatment for 3 more months to determine relapse rates (modified Cornell model. MEASUREMENTS: Bactericidal efficacy was assessed by quantitative lung colony-forming unit (CFU counts. Sterilizing efficacy was assessed by measuring bacteriological relapse rates 3 months after the end of treatment. MAIN RESULTS: The relapse rate observed after 12 months treatment with the WHO recommended MDR TB regimen (amikacin, ethionamide, pyrazinamide and moxifloxacin was equivalent to the relapse rate observed after 6 months treatment with the recommended drug susceptible TB regimen (rifampin, isoniazid and pyrazinamide. When TMC207 was added to this MDR TB regimen, the treatment duration needed to reach the same relapse rate dropped to 6 months. A similar relapse rate was also obtained with a 6-month completely oral regimen including TMC207, moxifloxacin and pyrazinamide but excluding both amikacin and ethionamide. CONCLUSIONS: In this murine model the duration of the WHO MDR TB treatment could be reduced to 12 months instead of the recommended 18-24 months. The inclusion of TMC207 in the WHO MDR TB treatment regimen has the potential to further shorten the treatment duration and at the same time to simplify treatment by eliminating the need to include an injectable aminoglycoside.

  14. Evaluation of the Xpert MTB/RIF assay for diagnosis of tuberculosis and rifampin resistance in county-level laboratories in Hunan province, China

    Hu Peilei; Bai Liqiong; Liu Fengping; Ou Xichao; Zhang Zhiying; Yi Songlin; Chen Zhongnan

    2014-01-01

    Background The Xpert MTB/RIF showed high sensitivity and specificity in previous studies carried out in different epidemiological and geographical settings and patient populations in high-burden tuberculosis (TB) countries.However,there were little data obtained by validation or demonstration study of the assay in China.In this study,the performance of Xpert MTB/RIF was investigated in two county-level laboratories in Hunan Province,China.Methods Consecutive patients with suspected pulmonary tuberculosis (PTB) and suspicion for multidrug-resistant tuberculosis (MDR-TB) were enrolled.For each patient suspected to have PTB,three sputum specimens (one spot sputum,one night sputum,and one morning sputum) were collected and each sputum was tested with smear microscopy,L(o)wenstein-Jensen (LJ) culture,and Xpert MTB/RIF test.For comparison across subgroups and testing methods,95% confidence intervals were calculated.All analyses were done with SPSS 16.0,and P <0.05 was regarded as significant.Results For case detection,the sensitivity of Xpert MTB/RIF was 100% for smear-and culture-positive TB and 88.6% for smear-negative and culture-positive TB; the overall sensitivity was 94.5% for all culture-positive patients.The specificity was 99.8%.The sensitivity of Xpert MTB/RIF assay was 22.0% in clinical TB patients and the specificity reached 100.0% in the group of patients who are infected with nontuberculous mycobacteria.For the detection of rifampin resistance,the sensitivity of MTB/RIF RIF-resistance detection was 92.9%,and the specificity was 98.7%.Of the 26 Xpert MTB/RIF-positive and RIF-resistant patients confirmed by LJ proportion tests,20 (76.9%) patients were infected by MDR-TB.Conclusions The Xpert MTB/RIF assay is a highly sensitive and specific method for diagnosis of TB and RIF resistance,which will enable it to have the potential to be used in county-level laboratories and lead to the reduction of the infectious pool and improvements in TB

  15. Clinical characteristic, diagnosis and effectiveness of treatment of tuberculosis in HIV-infected patients in the Saratov region

    T. I. Morozova

    2016-01-01

    Full Text Available Aim: evaluate the clinical manifestations, efficacy of microbiologicaldiagnosis and results of treatment of patients with tuberculosis (TB in combination with HIV (TB/HIV, residing in the territory of the Saratov region.Materials and methods: analyzed the medical records (hospital records, medical history, personal record cards TB/HIV, 130 patients coinfected with TB/HIV who were on treatment in TB facilities of Saratov region in 2014.Results: it was found that the combination of TB and HIV infection was more common in men (71,5% aged 30–39 years, mostly (75,4% residents of large cities. TB in 64,6% of cases develop on the background of existing HIV infection with disease duration from 1 to 18 years. The dominant forms of TB were infiltrative – 50,8% and disseminated – 25,4% with high levels of multidrug resistance (MDR – 25% and polyresistance – 17,3%. Efficiency a course of treatment of ТВ which was completed in 2014 year amounted to 41,5% and was higher in the group of patients in which treatment with anti-tuberculosis therapy is used antiretroviral therapy (ARVT – 49,3% versus 30,9% without ARVT, p = 0,0416. It was found increase of CD4 cell counts after treatment in patients TB/HIV, which, together with anti-tuberculosis therapy received ARVT 301 ± 45 cells/microliter vs. 202,3 ± 32 cells/microliter in patients without ARVT, p=0,0416.Conclusion: determined that TB in patients with HIV infection characterized by severe course of the process with low efficiency of treatment and high MDR, which requires the strengthening of measures to control the spread of TB in these patients. 

  16. High resolution computed tomography(HRCT) findings of a solitary pulmonary nodule : differential diagnosis of cancer and tuberculosis

    To evaluate the role of HRCT in the differentiation of Pulmonary tuberculosis and lung cancer, where the manifestation of disease is a solitary pulmonary nodule(SPN). Forty eight SPNs including 29 cancers proven by surgery(n=10), by bronchoscopic biopsy(n=7) and by fine needle aspiration biopsy(n=12), and 19 tuberculous nodules proven by surgery(n=4), by bronchoscopic biopsy(n=4), by fine needle aspiration biopsy(n=5), by a positive result in AFB culture without evidence of malignant cells(n=3), and by a decrease in size on serial plain chests despite negative AFB culture(n=3) were included. Scanning parameters for HRCT were 140 KVp, 170 mA, 1.5 mm collimation, 3 sec scanning time, and a high spatial frequency algorithm was used. With regard to the marginal features of nodules, the findings more commonly observed in malignant nodules were greater average length of the longest spicule(5.35 ± 3.19 mm versus 2.75 ± 1.56 mm), and more commonspiculated nodules greater than 3 cm in diameter, 16(55%) versus 2(10.5%)(p<0.05). Regarding the internal characteristics of nodules and perinodular parenchymal changes, the findings more commonly observed in cases of cancer were air-bronchograms within nodules(14 ; 48.3%) and interlobar fissure puckering (6 ; 20.7%), whereas in tuberculosis cases the most common findings were low density of nodule(16 ; 84.2%), cavitation(12 ; 63.1%), and perinodular focal lung hypodensity(5 ; 26.3%), (p<0.05). no statstically significant difference was observed between the incidence of satellite lesion of tuberculous(73.7%) and of malignant nodules(34.5%). However, perilobular nodules or bronchovascular bundle thickening s were more commonly observed in the satellite lesions of malignant nodules(9 ; 90%), whereas centrilobular nodules or lobular consolidation were more commonly observed in those of tuberculous nodules(12 ; 85.7%), (p<0.05). HRCT provides detailed information concerning perinodular parenchymal changes and characteristics of

  17. Activity against Mycobacterium tuberculosis with concomitant induction of cellular immune responses by a tetraaza-macrocycle with acetate pendant arms.

    David, S; Ordway, D; Arroz, M J; Costa, J; Delgado, R

    2001-01-01

    The novel tetraaza-macrocyclic compound 3,7,11-tris(carboxymethyl)-3,7,11,17-tetraaza-bicyclo[11.3.1]heptadeca-1(17),13,15-triene, abbreviated as ac3py14, was investigated for its activity against Mycobacterium tuberculosis and for induction of protective cellular immune responses. Perspective results show that ac3py14 and its Fe3+ 1:1 complex, [Fe(ac3py14)], inhibited radiometric growth of several strains of M. tuberculosis. Inhibition with 25 microg/mL varied from 99% for H37Rv to 80% and above for multiple drug-resistant clinical isolates. The capacity of ac3py14 to elicit a beneficial immune response without cellular apoptosis was assessed and compared to the effects of virulent M. tuberculosis. The present study produces evidence that after stimulation with ac3py14 there was significant production of interferon gamma (IFN-gamma), whereas the production of interleukin-5 (IL-5) remained low, and there was development of a memory population (CD45RO). The level of binding of Annexin V, a marker of apoptosis, was not sufficient to result in toxic effects toward alphabeta and gammadelta T cells and CD14+ macrophages. This preliminary study is the first report of a compound that simultaneously exerts an inhibitory effect against M. tuberculosis and induces factors associated with protective immune responses. PMID:11501675

  18. Tuberculosis Endometrial Polyp

    Julien Seror

    2013-01-01

    Full Text Available Tuberculosis can cause infertility when it infects the genital tract (e.g., endometritis. A 31-year-old woman (origin: Algeria was referred to our academic gynecological institute for unexplained primary infertility. The patient presented with no complaint. Hysteroscopy showed a 10 mm sized endometrial polyp. The polyp was removed. Pathology showed lymphocytic and plasmacytic chronic inflammatory modification, granulomatous modification, and gigantocellular modification,which lead to the diagnosis of tuberculosis. No acid fast organism was seen on Ziehl-Neelsen staining. A chest thorax X-ray revealed no sign of pulmonary tuberculosis. The patient underwent antituberculosis therapy during one year. Posttreatment hysteroscopy revealed no abnormality. This is the first reported case of endometrial tuberculosis diagnosed following removal of a polyp with classical benign appearance.

  19. Update on cutaneous tuberculosis.

    Dias, Maria Fernanda Reis Gavazzoni; Bernardes Filho, Fred; Quaresma, Maria Victória; Nascimento, Leninha Valério do; Nery, José Augusto da Costa; Azulay, David Rubem

    2014-01-01

    Tuberculosis continues to draw special attention from health care professionals and society in general. Cutaneous tuberculosis is an infection caused by M. tuberculosis complex, M. bovis and bacillus Calmette-Guérin. Depending on individual immunity, environmental factors and the type of inoculum, it may present varied clinical and evolutionary aspects. Patients with HIV and those using immunobiological drugs are more prone to infection, which is a great concern in centers where the disease is considered endemic. This paper aims to review the current situation of cutaneous tuberculosis in light of this new scenario, highlighting the emergence of new and more specific methods of diagnosis, and the molecular and cellular mechanisms that regulate the parasite-host interaction. PMID:25387498

  20. Update on cutaneous tuberculosis*

    Dias, Maria Fernanda Reis Gavazzoni; Bernardes Filho, Fred; Quaresma, Maria Victória; do Nascimento, Leninha Valério; Nery, José Augusto da Costa; Azulay, David Rubem

    2014-01-01

    Tuberculosis continues to draw special attention from health care professionals and society in general. Cutaneous tuberculosis is an infection caused by M. tuberculosis complex, M. bovis and bacillus Calmette-Guérin. Depending on individual immunity, environmental factors and the type of inoculum, it may present varied clinical and evolutionary aspects. Patients with HIV and those using immunobiological drugs are more prone to infection, which is a great concern in centers where the disease is considered endemic. This paper aims to review the current situation of cutaneous tuberculosis in light of this new scenario, highlighting the emergence of new and more specific methods of diagnosis, and the molecular and cellular mechanisms that regulate the parasite-host interaction. PMID:25387498

  1. Peritonitis due to genital tuberculosis

    Svendsen, Jesper Hastrup; Mikkelsen, A L; Siemssen, O J

    1985-01-01

    A case of genital tuberculosis is presented. The diagnosis was made by laparotomy and histological examination of biopsies from peritoneum and the Fallopian tube. The literature is reviewed and the diagnostic approach and treatment discussed.......A case of genital tuberculosis is presented. The diagnosis was made by laparotomy and histological examination of biopsies from peritoneum and the Fallopian tube. The literature is reviewed and the diagnostic approach and treatment discussed....

  2. Role of alpha-crystallin, early-secreted antigenic target 6-kDa protein and culture filtrate protein 10 as novel diagnostic markers in osteoarticular tuberculosis

    Nazia Rizvi

    2016-07-01

    Full Text Available Osteoarticular tuberculosis constitutes about 3% of all tuberculosis cases. Early and accurate diagnosis of tuberculosis is a challenging problem especially in the case of osteoarticular tuberculosis owing to the lower number of bacilli. However, an accurate and timely diagnosis of the disease results in an improved efficacy of the given treatment. Besides the limitations of conventional methods, nowadays molecular diagnostic techniques have emerged as a major breakthrough for the early diagnosis of tuberculosis with high sensitivity and specificity. Alpha-crystallin is a dominantly expressed protein responsible for the long viability of the pathogen during the latent phase under certain stress conditions such as hypoxia and nitric oxide stress. Two other proteins—early secreted antigenic target-6 and culture filtrate protein-10—show high expression in the active infective phase of Mycobacterium tuberculosis. In this article, we focus on the different proteins expressed dominantly in latent/active tuberculosis, and which may be further used as prognostic biomarkers for diagnosing tuberculosis, both in latent and active phases.

  3. Performance of the Genotype® MTBDRPlus assay in the diagnosis of tuberculosis and drug resistance in Samara, Russian Federation

    Fedorin Ivan

    2009-03-01

    Full Text Available Abstract Background Russia is a high tuberculosis (TB burden country with a high prevalence of multidrug resistant tuberculosis (MDRTB. Molecular assays for detection of MDRTB on clinical specimens are not widely available in Russia. Results We performed an evaluation of the GenoType® MTBDRplus assay (HAIN Lifescience GmbH, Germany on a total of 168 sputum specimens from individual patients at a public health laboratory in Central Russia, as a model of a middle income site in a region with high levels of drug resistance. Phenotypic drug resistance tests (DST were performed on cultures derived from the same sputum specimens using the BACTEC 960 liquid media system. Interpretable GenoType® MTBDRplus results were obtained for 154(91.7% specimens with readability rates significantly higher in sputum specimens graded 2+ and 3+ compared to 1+ (RR = 1.17 95%CI 1.04–1.32. The sensitivity and specificity of the assay for the detection of rifampicin (RIF and isoniazid (INH resistance and MDR was 96.2%, 97.4%, 97.1% and 90.7%, 83.3%, 88.9% respectively. Mutations in codon 531 of the rpoB gene and codon 315 of the katG gene dominated in RIF and INH resistant strains respectively. Disagreements between phenotypical and molecular tests results (12 samples could be explained by the presence of rare mutations in strains circulating in Russia and simultaneous presence of resistant and sensitive bacilli in sputum specimens (heteroresistance. Conclusion High sensitivity, short turnaround times and the potential for screening large numbers of specimens rapidly, make the GenoType® MTBDRplus assay suitable as a first-line screening assay for drug resistant TB.

  4. Fault Diagnosis in a Centrifugal Pump Using Active Magnetic Bearings

    Nordmann Rainer; Aenis Martin

    2004-01-01

    The number of rotors running in active magnetic bearings (AMBs) has increased over the last few years. These systems offer a great variety of advantages compared to conventional systems. The aim of this article is to use the AMBs together with a developed built-in software for identification, fault detection, and diagnosis in a centrifugal pump. A single-stage pump representing the turbomachines is investigated. During full operation of the pump, the AMBs are used as actuators to generate def...

  5. Tuberculous Enteritis: A Rare Complication of Miliary Tuberculosis.

    Figueroa, Danisha; Guzman, Nilmarie; Isache, Carmen

    2016-01-01

    Tuberculous enteritis is a clinical rarity even in immunocompromised patients. We present a case of miliary tuberculosis with gastrointestinal involvement. A 47-year-old homosexual male from Philippines with no significant medical history presented with productive cough, night sweats, subjective fevers, shortness of breath, watery diarrhea, and 25-pound weight loss in past one year. On physical exam he was afebrile, mildly hypotensive, tachycardic, and tachypneic, but saturating well on room air. He was cachectic with oral thrush and bilateral fine rales. Chest X-ray revealed a miliary pattern. His sputum AFB smear was strongly positive. PCR and sputum culture were positive for Mycobacterium tuberculosis. He was started on Rifampin, Isoniazid, Ethambutol, and Pyrazinamide. He was found to be HIV positive with an absolute CD4 count of 4 cells/μL. Due to persistent diarrhea, stool was sent for AFB culture and grew M. tuberculosis. He responded well to treatment with resolution of symptoms. Tuberculous enteritis occurs in about 2% of the patients with pulmonary tuberculosis. Although it is uncommon, it should be considered in patients with active pulmonary tuberculosis and abdominal complaints. A presumptive diagnosis of tuberculous enteritis can be made in the setting of active pulmonary tuberculosis with suggestive clinical, endoscopic, and/or radiographic findings. PMID:27022494

  6. Imaging of Esophageal Tuberculosis

    Purpose: To evaluate the various radiological abnormalities in patients with proven esophageal tuberculosis. Material and Methods: The case records of 23 patients with proven esophageal tuberculosis were evaluated retrospectively for various radiological abnormalities. Twenty-two patients had secondary involvement of esophagus in the form of direct extension of mediastinal and pulmonary tuberculosis or spinal tuberculosis. Only 1 patient had primary involvement of the esophagus with no evidence of disease elsewhere. The diagnosis was confirmed by endoscopic and CT-guided biopsy/aspiration cytology in 7 and 6 cases, respectively. Diagnosis was made on the basis of surgical biopsy of lymph node and autopsy in 1 patient each. In the remaining 8 patients the diagnosis was based on radiological and endoscopic findings and the response to antituberculous treatment. Results: Chest radiography (CXR) was abnormal in 65% patients. While the findings were non-conclusive for esophageal tuberculosis, characteristic lesions of tuberculosis in lungs or spine were suggestive of tuberculous etiology. In 15 patients, CT of the chest confirmed the corresponding CXR findings and also showed additional findings of mediastinal lymphadenopathy when CXR was normal. Fourteen patients showed mediastinal lymphadenopathy on CT of the chest. In all these patients, more than one group of lymph nodes was involved. The characteristic hypodense center of lymph nodes suggestive of tuberculosis was seen in 12 patients. Radiological abnormalities seen in barium swallow examination were extrinsic compression, traction diverticula, strictures, sinus/fistulous tracts, kinking and pseudotumor mass of esophagus in decreasing order of frequency. The middle third of the esophagus was found to be the most frequent site of involvement

  7. Serial counts of Mycobacterium tuberculosis in sputum as surrogate markers of the sterilising activity of rifampicin and pyrazinamide in treating pulmonary tuberculosis

    Mitchison Denis

    2001-11-01

    Full Text Available Abstract Background Since the sterilising activity of new antituberculosis drugs is difficult to assess by conventional phase III studies, surrogate methods related to eventual relapse rates are required. Methods A suitable method is suggested by a retrospective analysis of viable counts of Mycobacterium tuberculosis in 12-hr sputum collections from 122 newly diagnosed patients with pulmonary tuberculosis in Nairobi, done pretreatment and at 2, 7, 14 and 28 days. Treatment was with isoniazid and streptomycin, supplemented with either thiacetazone (SHT or rifampicin + pyrazinamide (SHRZ. Results During days 0–2, a large kill due to isoniazid occurred, unrelated to treatment or HIV status; thereafter it decreased exponentially. SHRZ appeared to have greater sterilising activity than SHT during days 2–7 (p = 0.044, due to rifampicin, and during days 14–28, probably due mainly to pyrazinamide. The greatest discrimination between SHRZ and SHT treatments was found between regression estimates of kill over days 2–28 (p = 0.0005 in patients who remained positive up to 28 days with homogeneous kill rates. No associations were found between regression estimates and the age, sex, and extent of disease or cavitation. An increased kill in HIV seropositive patients, unrelated to the treatment effect, was evident during days 2–28 (p = 0.007, mainly during days 2–7. Conclusions Surrogate marker studies should either be in small groups treated with monotherapy during days 2 to about 7 or as add-ons or replacements in isoniazid-containing standard regimens from days 2 to 28 in large groups.

  8. Population-level impact of active tuberculosis case finding in an Asian megacity.

    David W Dowdy

    Full Text Available BACKGROUND: The potential population-level impact of private-sector initiatives for tuberculosis (TB case finding in Southeast Asia remains uncertain. In 2011, the Indus Hospital TB Control Program in Karachi, Pakistan, undertook an aggressive case-finding campaign that doubled notification rates, providing an opportunity to investigate potential population-level effects. METHODS: We constructed an age-structured compartmental model of TB in the intervention area. We fit the model using field and literature data, assuming that TB incidence equaled the estimated nationwide incidence in Pakistan (primary analysis, or 1.5 times greater (high-incidence scenario. We modeled the intervention as an increase in the rate of formal-sector TB diagnosis and evaluated the potential impact of sustaining this rate for five years. RESULTS: In the primary analysis, the five-year intervention averted 24% (95% uncertainty range, UR: 18-30% of five-year cumulative TB cases and 52% (95% UR: 45-57% of cumulative TB deaths. Corresponding reductions in the high-incidence scenario were 12% (95% UR: 8-17% and 27% (95% UR: 21-34%, although the absolute number of lives saved was higher. At the end of five years, TB notification rates in the primary analysis were below their 2010 baseline, incidence had dropped by 45%, and annual mortality had fallen by 72%. About half of the cumulative impact on incidence and mortality could be achieved with a one-year intervention. CONCLUSIONS: Sustained, multifaceted, and innovative approaches to TB case-finding in Asian megacities can have substantial community-wide epidemiological impact.

  9. Palladium(II) complexes with thiosemicarbazones: syntheses, characterization and cytotoxicity against breast cancer cells and Anti-Mycobacterium tuberculosis activity

    Maia, Pedro I. da S.; Deflon, Victor M., E-mail: deflon@iqsc.usp.b [Universidade de Sao Paulo (USP), Sao Carlos, SP (Brazil). Inst. de Quimica; Graminha, Angelica; Batista, Alzir A. [Universidade Federal de Sao Carlos (UFSCar), SP (Brazil). Dept. de Quimica; Pavan, Fernando R.; Leite, Clarice Q.F. [UNESP, Araraquara, SP (Brazil). Faculdade de Ciencias Farmaceuticas; Back, Davi F.; Lang, Ernesto S. [Universidade Federal de Santa Maria (UFSM), RS (Brazil). Dept. de Quimica; Ellena, Javier [Universidade de Sao Paulo (USP), Sao Carlos, SP (Brazil). Inst. de Fisica; Lemos, Sebastiao de S. [Universidade de Brasilia (UnB), DF (Brazil). Inst. de Quimica; Salistre-de-Araujo, Heloisa S. [Universidade Federal de Sao Carlos (UFSCAR), SP (Brazil). Dept. de Ciencias Fisiologicas

    2010-07-01

    Three Pd{sup II} complexes were prepared from N(4)-substituted thiosemicarbazones: [Pd(aptsc)(PPh{sub 3})](NO{sub 3}) centre dot H{sub 2}O, 1, [Pd(apmtsc)(PPh{sub 3})](NO{sub 3}), 2, and [Pd(apptsc)(PPh{sub 3})](NO{sub 3}) centre dot H{sub 2}O, 3, where PPh{sub 3} = triphenylphosphine; Haptsc 2-acetylpyridine-thiosemicarbazone; Hapmtsc 2-acetylpyridine-N(4)-methyl-thiosemicarbazone and Happtsc 2-acetylpyridine-N(4)-phenyl-thiosemicarbazone. All complexes were characterized by elemental analysis, IR, UV-Vis, {sup 1}H and {sup 31}P{l_brace}{sup 1}H{r_brace} NMR spectroscopies, and had their crystalline structures determined by X-ray diffractometry from single crystals. The monoanionic thiosemicarbazonate ligands act in a tridentate mode, binding to the metal through the pyridine nitrogen, the azomethine nitrogen and the sulfur atoms. The cytotoxic activity against the breast cancer cell line MDA-MB231 and the anti-Mycobacterium tuberculosis H{sub 37}Rv ATCC 27294 activity were evaluated for the compounds. All Pd{sup II} complexes were highly active against the studied cell line, presenting similar values of IC{sub 50}, around 5 mumol L{sup -1}, while the clinically applied antitumor agent cisplatin was inactive. The compounds show remarkable anti-M. tuberculosis activities, presenting MIC values comparable or better than some commercial anti-M tuberculosis drugs. (author)

  10. Palladium(II) complexes with thiosemicarbazones: syntheses, characterization and cytotoxicity against breast cancer cells and Anti-Mycobacterium tuberculosis activity

    Three PdII complexes were prepared from N(4)-substituted thiosemicarbazones: [Pd(aptsc)(PPh3)](NO3) · H2O, 1, [Pd(apmtsc)(PPh3)](NO3), 2, and [Pd(apptsc)(PPh3)](NO3) · H2O, 3, where PPh3 = triphenylphosphine; Haptsc 2-acetylpyridine-thiosemicarbazone; Hapmtsc 2-acetylpyridine-N(4)-methyl-thiosemicarbazone and Happtsc 2-acetylpyridine-N(4)-phenyl-thiosemicarbazone. All complexes were characterized by elemental analysis, IR, UV-Vis, 1H and 31P{1H} NMR spectroscopies, and had their crystalline structures determined by X-ray diffractometry from single crystals. The monoanionic thiosemicarbazonate ligands act in a tridentate mode, binding to the metal through the pyridine nitrogen, the azomethine nitrogen and the sulfur atoms. The cytotoxic activity against the breast cancer cell line MDA-MB231 and the anti-Mycobacterium tuberculosis H37Rv ATCC 27294 activity were evaluated for the compounds. All PdII complexes were highly active against the studied cell line, presenting similar values of IC50, around 5 μmol L-1, while the clinically applied antitumor agent cisplatin was inactive. The compounds show remarkable anti-M. tuberculosis activities, presenting MIC values comparable or better than some commercial anti-M tuberculosis drugs. (author)

  11. Aberrant Inflammasome Activation Characterizes Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome.

    Tan, Hong Yien; Yong, Yean Kong; Shankar, Esaki M; Paukovics, Geza; Ellegård, Rada; Larsson, Marie; Kamarulzaman, Adeeba; French, Martyn A; Crowe, Suzanne M

    2016-05-15

    Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) complicates combination antiretroviral therapy (cART) in up to 25% of patients with HIV/TB coinfection. Monocytes and IL-18, a signature cytokine of inflammasome activation, are implicated in TB-IRIS pathogenesis. In this study, we investigated inflammasome activation both pre- and post-cART in TB-IRIS patients. HIV/TB patients exhibited higher proportions of monocytes expressing activated caspase-1 (casp1) pre-cART, compared with HIV patients without TB, and patients who developed TB-IRIS exhibited the greatest increase in casp1 expression. CD64(+) monocytes were a marker of increased casp1 expression. Furthermore, IL-1β, another marker of inflammasome activation, was also elevated during TB-IRIS. TB-IRIS patients also exhibited greater upregulation of NLRP3 and AIM2 inflammasome mRNA, compared with controls. Analysis of plasma mitochondrial DNA levels showed that TB-IRIS patients experienced greater cell death, especially pre-cART. Plasma NO levels were lower both pre- and post-cART in TB-IRIS patients, providing evidence of inadequate inflammasome regulation. Plasma IL-18 levels pre-cART correlated inversely with NO levels but positively with monocyte casp1 expression and mitochondrial DNA levels, and expression of IL-18Rα on CD4(+) T cells and NK cells was higher in TB-IRIS patients, providing evidence that IL-18 is a marker of inflammasome activation. We propose that inflammasome activation in monocytes/macrophages of HIV/TB patients increases with ineffective T cell-dependent activation of monocytes/macrophages, priming them for an excessive inflammatory response after cART is commenced, which is greatest in patients with TB-IRIS. PMID:27076678

  12. Study of the insertion sequence IS6110 in Mycobacterium tuberculosis Beijing strains and its promoter activity

    Alonso Ezcurra, María Henar; Otal gil Isabel

    2012-01-01

    Mycobacterium tuberculosis es el agente causal de la tuberculosis (TB). Esta enfermedad ha acompañado a la raza humana a lo largo de su historia y hoy en día sigue siendo una de las enfermedades infecciosas que causa mayor número de muertes en el mundo. Aunque se han realizado grandes avances en la lucha contra esta enfermedad, sigue siendo un problema de salud mundial. En la actualidad, una de las familias de M. tuberculosis que más atención atrae en todo el mundo es la familia Beijing, debi...

  13. Tuberculosis extrapulmonar Extrapulmonary tuberculosis

    P. Fanlo

    2007-01-01

    Full Text Available A pesar de que el pulmón es el órgano diana por excelencia de la tuberculosis, cualquier otro órgano y sistema puede verse afectado. En este trabajo se revisan las formas de tuberculosis extrapulmonar a excepción de la pleural que requieren del facultativo, en ocasiones, su más valiosa pericia diagnóstica. Desde la temida meningitis tuberculosa, pasando por la afectación insidiosa de la espondilodiscitis, la llamativa afectación ganglionar, la afectación genitourinaria, la pericarditis, para terminar las formas menos frecuentes como la ocular o la cutánea. En cada apartado indicaremos lo más característico con la finalidad de que pueda servir de orientación diagnóstica y terapéutica.In spite of the lung being the target organ par excellence of tuberculosis, any other organ and system can be affected. In this article we review the forms of extrapulmonary tuberculosis, with the exception of the pleural form that requires the use of good diagnostic skills. From the dreaded tuberculous meningitis, by way of the insidious affectation of the spondylodiscitis, the so-called ganglionary affectation , the genitourinary affectation, pericarditis, and ending with less frequent forms such as ocular and cutaneous tuberculosis. In each section we will indicate what is most characteristic with the aim of providing a diagnostic and therapeutic orientation.

  14. Diagnóstico imunológico da tuberculose: problemas e estratégias para o sucesso Immunological diagnosis of tuberculosis: problems and strategies for success

    Henrique Couto Teixeira

    2007-06-01

    prophylactically, does not impede the progression of the disease, which usually manifests as decreased cellular immunity. Early diagnosis, together with polychemotherapy, can control the dissemination of the tuberculosis infection. The current diagnostic methods present certain problems. Such problems include the low sensitivity of sputum smear microscopy, the fact that performing microbiological cultures is quite time-consuming, and the low specificity of the skin test with the purified protein derivative of M. tuberculosis. New diagnostic methods, which use specific antigens such as the early secreted antigenic target 6-kDa and culture filtrate protein 10kDa, are being evaluated. The genes that encode these antigens are located in the DNA region of difference 1 of M. tuberculosis, M. africanum and M. bovis. However, they are absent from the M. bovis (BCG and from most environmental mycobacteria. Diagnostic methods such as QuantiFERON-TB® and T SPOT.TB®, which are based on the production of interferon-gamma by T lymphocytes, in response to those antigens, are being tested and have been found to outstrip the purified protein derivative skin test in the following characteristics: greater sensitivity; lower cross-reactivity due to BCG vaccination or infection with environmental mycobacteria; and execution time. The introduction of diagnostic methods that are more specific and sensitive, together with gaining a better understanding of the molecular and cellular mechanisms that regulate the parasite-host interaction, can increase the efficiency of strategies devised to combat tuberculosis.

  15. Tuberculose e silicose: epidemiologia, diagnóstico e quimioprofilaxia Tuberculosis and silicosis: epidemiology, diagnosis and chemoprophylaxis

    Carlos Eduardo Galvão Barboza

    2008-11-01

    Full Text Available A silicose, a mais prevalente das pneumoconioses, é provocada pela inalação de partículas de sílica cristalina. Indivíduos expostos à sílica, com ou sem silicose, apresentam risco aumentado de tuberculose e de micobacterioses não-tuberculosas. O risco de silicóticos desenvolverem tuberculose em relação a controles sadios varia de 2,8 a 39 vezes, em conformidade com a gravidade da doença de base. Têm sido estudados diferentes esquemas de quimioprofilaxia para tuberculose em silicóticos, todos com eficácia semelhante e com redução final de risco para cerca da metade em relação ao uso de placebo. São, no entanto, esquemas de longa duração, o que, acrescido dos possíveis efeitos colaterais (particularmente hepatotoxicidade, podem prejudicar a aderência. As diretrizes atuais recomendam a realização de prova tuberculínica e, se positiva, a instituição de quimioprofilaxia. São vários os esquemas possíveis, tanto em termos de drogas quanto de duração. Nossa recomendação é de que se use isoniazida na dose de 300 mg/dia (ou 10 mg/kg/dia por seis meses para os indivíduos com silicose ou sadios com exposição superior a 10 anos, se forem reatores fortes à prova tuberculínica (induração > 10 mm. São necessários, no entanto, novos estudos para que indicações, drogas, doses e duração da profilaxia sejam definidas mais apropriadamente.Silicosis, the most prevalent of the pneumoconioses, is caused by inhalation of crystalline silica particles. Silica-exposed workers, with or without silicosis, are at increased risk for tuberculosis and nontuberculous mycobacteria-related diseases. The risk of a patient with silicosis developing tuberculosis is higher (2.8 to 39 times higher, depending on the severity of the silicosis than that found for healthy controls. Various regimens for tuberculosis chemoprophylaxis in patients with silicosis have been studied, all of which present similar efficacy and overall risk reduction

  16. Inhibition of nuclear factor-kappa B activation decreases survival of Mycobacterium tuberculosis in human macrophages.

    Xiyuan Bai

    Full Text Available Nuclear factor-kappa B (NFκB is a ubiquitous transcription factor that mediates pro-inflammatory responses required for host control of many microbial pathogens; on the other hand, NFκB has been implicated in the pathogenesis of other inflammatory and infectious diseases. Mice with genetic disruption of the p50 subunit of NFκB are more likely to succumb to Mycobacterium tuberculosis (MTB. However, the role of NFκB in host defense in humans is not fully understood. We sought to examine the role of NFκB activation in the immune response of human macrophages to MTB. Targeted pharmacologic inhibition of NFκB activation using BAY 11-7082 (BAY, an inhibitor of IκBα kinase or an adenovirus construct with a dominant-negative IκBα significantly decreased the number of viable intracellular mycobacteria recovered from THP-1 macrophages four and eight days after infection. The results with BAY were confirmed in primary human monocyte-derived macrophages and alveolar macrophages. NFκB inhibition was associated with increased macrophage apoptosis and autophagy, which are well-established killing mechanisms of intracellular MTB. Inhibition of the executioner protease caspase-3 or of the autophagic pathway significantly abrogated the effects of BAY. We conclude that NFκB inhibition decreases viability of intracellular MTB in human macrophages via induction of apoptosis and autophagy.

  17. A novel molecule with notable activity against multi-drug resistant tuberculosis.

    Nair, Vasu; Okello, Maurice O; Mangu, Naveen K; Seo, Byung I; Gund, Machhindra G

    2015-03-15

    Multi-drug resistant tuberculosis (MDR-TB) is emerging as a serious global health problem, which has been elevated through co-infection involving HIV and MDR-Mtb. The discovery of new compounds with anti-MDR TB efficacy and favorable metabolism profiles is an important scientific challenge. Using computational biology and ligand docking data, we have conceived a multifunctional molecule, 2, as a potential anti-MDR TB agent. This compound was produced through a multi-step synthesis. It exhibited significant in vitro activity against MDR-TB (MIC 1.56μg/mL) and its half-life (t1/2) in human liver microsomes was 14.4h. The metabolic profiles of compound 2 with respect to human cytochrome P450 (CYP) and uridine 5'-diphospho-glucuronosyltransferase (UGT) isozymes were favorable. Compound 2 also had relatively low in vitro cytotoxicity in uninfected macrophages. It displayed synergistic behavior against MDR-TB in combination with PA-824. Interestingly, compound 2 also displayed in vitro anti-HIV activity. PMID:25677656

  18. Serological markers of hepatitis B and C in patients with HIV/AIDS and active tuberculosis.

    Araújo-Mariz, Carolline; Lopes, Edmundo Pessoa; Ximenes, Ricardo A A; Lacerda, Heloísa R; Miranda-Filho, Demócrito B; Montarroyos, Ulisses R; Barreto, Silvana; Salustiano, Daniela Medeiros; Albuquerque, Maria Fátima Pessoa Militão

    2016-06-01

    Infection with hepatitis B virus (HBV) and C virus (HCV) are common in patients with HIV/AIDS and tuberculosis (TB). This is a cross-sectional study with patients infected with HIV/AIDS and active TB in Recife, Brazil, aiming to verify the prevalence of markers for HBV: antibody to hepatitis B core antigen (anti-HBc); and HCV: antibody to hepatitis C virus (anti-HCV) by chemiluminescence, and to identify the frequency of associated factors. Data were collected through questionnaires, and blood was drawn from patients for analysis. We used the chi-square test and the Fisher exact test when necessary. We conducted a bivariate logistic regression analysis and the magnitude of the associations was expressed as odds ratio (OR) with a confidence interval of 95%. Among 166 patients studied with HIV/AIDS and active TB, anti-HBc was positive in 61 patients [36.7%; 95%CI (29.4-44.6%)] and anti-HCV in 11[6.6%; 95%CI (3.4-11.5%)]. In the logistic regression analysis, male sex, and age ≥40 years were independent factors associated with the occurrence of anti-HBc. In conclusion, we verified a high frequency of HBV contact marker and a low frequency of HCV markers in patients with HIV/AIDS and TB in Recife. J. Med. Virol. 88:996-1002, 2016. © 2015 Wiley Periodicals, Inc. PMID:26580855

  19. UvrD2 is essential in Mycobacterium tuberculosis, but its helicase activity is not required.

    Williams, Alan; Güthlein, Carolin; Beresford, Nicola; Böttger, Erik C; Springer, Burkhard; Davis, Elaine O

    2011-09-01

    UvrD is an SF1 family helicase involved in DNA repair that is widely conserved in bacteria. Mycobacterium tuberculosis has two annotated UvrD homologues; here we investigate the role of UvrD2. The uvrD2 gene at its native locus could be knocked out only in the presence of a second copy of the gene, demonstrating that uvrD2 is essential. Analysis of the putative protein domain structure of UvrD2 shows a distinctive domain architecture, with an extended C terminus containing an HRDC domain normally found in SF2 family helicases and a linking domain carrying a tetracysteine motif. Truncated constructs lacking the C-terminal domains of UvrD2 were able to compensate for the loss of the chromosomal copy, showing that these C-terminal domains are not essential. Although UvrD2 is a functional helicase, a mutant form of the protein lacking helicase activity was able to permit deletion of uvrD2 at its native locus. However, a mutant protein unable to hydrolyze ATP or translocate along DNA was not able to compensate for lack of the wild-type protein. Therefore, we concluded that the essential role played by UvrD2 is unlikely to involve its DNA unwinding activity and is more likely to involve DNA translocation and, possibly, protein displacement. PMID:21725019

  20. Early diagnosis of tuberculosis in the health services in different regions of Brazil El diagnóstico oportuno de la tuberculosis en los servicios de salud de varias regiones de Brasil Diagnóstico oportuno da tuberculose nos serviços de saúde de diversas regiões do Brasil

    Tereza Cristina Scatena Villa; Maria Amélia Zanon Ponce; Anneliese Domingues Wysocki; Rubia Laine de Paula Andrade; Tiemi Arakawa; Beatriz Estuque Scatolin; Maria Eugenia Firmino Brunello; Aline Ale Beraldo; Lucia Marina Scatena; Aline Aparecida Monroe; Reinaldo Antonio da Silva Sobrinho; Lenilde Duarte de Sá; Jordana Almeida Nogueira; Marluce Maria Araújo Assis; Roxana Isabel Cardozo-Gonzales

    2013-01-01

    OBJECTIVE: To analyze the infected person's first contact with the health services, for the early diagnosis of tuberculosis (TB) in different regions of Brazil. METHOD: a cross-sectional study undertaken in 6 municipalities in the South-east, South and North-east regions of Brazil. Data collection involved secondary sources and interviews with the patients. The data was analyzed using descriptive techniques and multiple correspondence factor analysis. RESULTS: Primary Health Care (PHC) presen...

  1. HIV Infection Does Not Affect Active Case Finding of Tuberculosis in South African Gold Miners

    Lewis, James J.; Charalambous, Salome; Day, John H.; Katherine L Fielding; Alison D. Grant; Hayes, Richard J; Corbett, Elizabeth L.; CHURCHYARD, Gavin J

    2009-01-01

    Rationale: Gold miners in South Africa undergo annual radiological screening for tuberculosis in an occupational health center of a gold mining company, but the optimal screening algorithm is unclear.

  2. The effects of HIV on the sensitivity of a whole blood IFN-gamma release assay in Zambian adults with active tuberculosis.

    Edward Raby

    Full Text Available BACKGROUND: Interferon gamma release assays (IGRA are replacing the tuberculin skin test (TST as a diagnostic tool for Mycobacterium tuberculosis infection. However research into the test's performance in the high HIV-TB burden setting is scarce. This study aimed to define the sensitivity of an IGRA, QuantiFERON-TB Gold In-Tube (QGIT, in adult Zambian patients with active smear-positive tuberculosis. Secondary outcomes focussed on the effect of HIV on the test's performance. PRINCIPAL FINDINGS: Patients attending government health clinics were recruited within 1 month of starting treatment for TB. Subjects were tested with QGIT and TST. T lymphocyte counts were estimated (CD3(+, CD4(+, CD8(+. QGIT was performed for 112 subjects. 83/112 were QGIT positive giving an overall sensitivity of 74% [95%CI: 66,82]. A marked decrease in sensitivity was observed in HIV positive patients with 37/59 (63% being QGIT positive compared to 31/37 (84% HIV negative patients [chi(2 p = 0.033]. Low CD4(+ count was associated with increases in both indeterminate and false-negative results. Low CD4(+ count in combination with high/normal CD8(+ count was associated with false-negative results. TST was recorded for 92 patients, 62/92 were positive, giving a sensitivity of 67% [95%CI: 58,77]. Although there was little difference in the overall sensitivities, agreement between TST and QGIT was poor. CONCLUSIONS: QGIT was technically feasible with results in HIV negative subjects comparable to those achieved elsewhere. However, where under-treated HIV is prevalent, an increased proportion of both indeterminate and false-negative QGIT results can be expected in patients with active TB. The implications of this for the diagnosis of LTBI by QGIT is unclear. The diagnostic and prognostic relevance of IGRAs in high burden settings needs to be better characterised.

  3. In Vitro Activity of Rifampicin and Verapamil Combination in Multidrug-Resistant Mycobacterium tuberculosis

    Demitto, Fernanda de Oliveira; do Amaral, Renata Claro Ribeiro; Maltempe, Flaviane Granero; Siqueira, Vera Lúcia Dias; Scodro, Regiane Bertin de Lima; Lopes, Mariana Aparecida; Caleffi-Ferracioli, Katiany R.; Canezin, Pedro Henrique; Cardoso, Rosilene Fressatti

    2015-01-01

    The aim of the present study was to evaluate the effect of the combination of rifampicin (RIF) and verapamil (VP) against the Mycobacterium tuberculosis H37Rv reference strain and six multidrug-resistant (MDR) M. tuberculosis clinical isolates by determining Time-Kill Curves and the ability to efflux drug by fluorometry. The RIF+VP combination showed synergism in one MDR clinical isolate. For the other five MDR clinical isolates, the drug combination showed no interaction. The MDR clinical is...

  4. Radioiodine uptake in inactive pulmonary tuberculosis

    Radioiodine may accumulate at sites of inflammation or infection. We have seen such accumulation in six thyroid cancer patients with a history of previously treated pulmonary tuberculosis. We also review the causes of false-positive radioiodine uptake in lung infection/inflammation. Eight foci of radioiodine uptake were seen on six iodine-123 diagnostic scans. In three foci, the uptake was focal and indistinguishable from thyroid cancer pulmonary metastases from thyroid cancer. In the remaining foci, the uptake appeared nonsegmental, linear or lobar, suggesting a false-positive finding. The uptake was unchanged, variable in appearance or non-persistent on follow-up scans and less extensive than the fibrocystic changes seen on chest radiographs. In the two patients studied, thyroid hormone level did not affect the radioiodine lung uptake and there was congruent gallium-67 uptake. None of the patients had any evidence of thyroid cancer recurrence or of reactivation of tuberculosis and only two patients had chronic intermittent chest symptoms. Severe bronchiectasis, active tuberculosis, acute bronchitis, respiratory bronchiolitis, rheumatoid arthritis-associated lung disease and fungal infection such as Allescheria boydii and aspergillosis can lead to different patterns of radioiodine chest uptake mimicking pulmonary metastases. Pulmonary scarring secondary to tuberculosis may predispose to localized radioiodine accumulation even in the absence of clinically evident active infection. False-positive radioiodine uptake due to pulmonary infection/inflammation should be considered in thyroid cancer patients prior to the diagnosis of pulmonary metastases. (orig.)

  5. Diagnostics for pulmonary tuberculosis

    Cudahy, Patrick

    2016-01-01

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

  6. Diagnostics for pulmonary tuberculosis

    Cudahy, Patrick; Shenoi, Sheela

    2016-01-01

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

  7. QUANTITATIVE REAL-TIME PCR (Q-PCR FOR SPUTUM SMEAR DIAGNOSIS OF PULMONARY TUBERCULOSIS AMONG PEOPLE WITH HIV/AIDS

    Yvana Maria Maia de Albuquerque

    2014-04-01

    Full Text Available Objective: To assess quantitative real-time polymerase chain reaction (q-PCR for the sputum smear diagnosis of pulmonary tuberculosis (PTB in patients living with HIV/AIDS with a clinical suspicion of PTB. Method: This is a prospective study to assess the accuracy of a diagnostic test, conducted on 140 sputum specimens from 140 patients living with HIV/AIDS with a clinical suspicion of PTB, attended at two referral hospitals for people living with HIV/AIDS in the city of Recife, Pernambuco, Brazil. A Löwenstein-Jensen medium culture and 7H9 broth were used as gold standard. Results: Of the 140 sputum samples, 47 (33.6% were positive with the gold standard. q-PCR was positive in 42 (30% of the 140 patients. Only one (0.71% did not correspond to the culture. The sensitivity, specificity and accuracy of the q-PCR were 87.2%, 98.9% and 95% respectively. In 39 (93% of the 42 q-PCR positive cases, the CT (threshold cycle was equal to or less than 37. Conclusion: q-PCR performed on sputum smears from patients living with HIV/AIDS demonstrated satisfactory sensitivity, specificity and accuracy, and may therefore be recommended as a method for diagnosing PTB.

  8. High resolution chest CT in patients with pulmonary tuberculosis: Characteristic findings before and after antituberculous therapy

    Objective: The purpose of this study was (a) to describe HRCT findings for pulmonary tuberculosis before and after treatment, and (b) to evaluate the possible use of HRCT to assess disease activity. Patients and methods: We prospectively studied 52 patients with newly diagnosed pulmonary tuberculosis that was proven bacteriologically. HRCT scans were performed before and after treatment. Results: Micronodules, nodules, tree-in-bud appearance, consolidation, and cavities were the most common HRCT findings seen in active pulmonary tuberculosis. The disappearance of tree-in-bud appearance, pleural effusion and the presence of fibrotic change appear to be indications of the effectiveness of treatment. HRCT can differentiate old fibrotic lesions from newly active tuberculous lesions. Conclusions: HRCT may be helpful in the diagnosis of pulmonary tuberculosis and may be useful in the assessment of the efficacy of anti-tuberculous treatment

  9. Mycobacterial Bacilli Are Metabolically Active during Chronic Tuberculosis in Murine Lungs: Insights from Genome-Wide Transcriptional Profiling

    Chronic tuberculosis represents a major health problem for one third of the world’s population today. A key question relevant to chronic tuberculosis is the physiological status of Mycobacterium tuberculosis during this important stage of infection. Previous work on chronic tuberculosis revealed t...

  10. Value of Clinical Application of 7 Kinds of Experimental Methods in the Diagnosis of Tuberculosis%7种实验方法诊断结核病的临床应用价值

    张子胜

    2016-01-01

    目的:对7种实验方法诊断结核病的临床应用价值进行分析。方法结合某医院肺结核患者与健康体检者的痰标本,对7种实验方法的临床应用进行了检测。结果不同实验方法的检测阳性率有着较大的差异。结论涂片法操作简单,价格低廉,但是阳性率低;结核抗体法操作简单,但是无法区分感染与发病,SAT法较为灵敏,其一般作为辅助诊断方法。7种实验方法诊断结核病有着不同的临床应用价值。%Objective To analyze value of the clinical application of 7 kinds of experimental methods in the diagnosis of tuberculosis.Methods The clinical application of 7 kinds of experimental methods in combination with sputum samples from patients with pulmonary tuberculosis and healthy physical examination in a hospital were detected.ResultsThere were statisticaly significant differences in the positive rates of different experimental methods. Conclusion The smear method is simple and cheap, but the positive rate is low, the tuberculosis antibody method is simple, but which can not distinguish between infection and disease, SAT method is more sensitive, and it is generaly used as an auxiliary diagnosis method. The 7 kinds of experimental methods have different clinical application value in the diagnosis of tuberculosis.

  11. Prospective study of SEVA TB peroxidase assay for cocktail antigen and antibody in the diagnosis of Tuberculosis in suspected patients attending a tertiary care hospital located in rural area

    Anindita Majumdar; Pranita D Kamble; CM Badole; BC Harinath

    2010-01-01

    Objective:To evaluate inhouse developed SEVA TB peroxidase enzyme immunoassay using cocktail of mycobacterial excretory-secretory antigens (ES-31, ES-43&EST-6) for antibody detection and their affinity purified antibodies for antigen detection in tuberculosis suspected patients. Methods:Inhouse developed SEVA TB peroxidase enzyme immunoassay was evaluated prospectively in 73 suspected pulmonary and 46 extra-pulmonary tuberculosis patients during November 2008~March 2009 in a tertiary hospital located in rural area. Results: Assay on prospective analysis showed 100% correlation of pulmonary tuberculosis (PTB) and extra-pulmonary tuberculosis (EPTB) acid fast bacilli positivity and antitubercular treatment in 11 cases. Thirty nine PTB and 12 EPTB cases showed negative for ELISA test and were also not given antitubercular therapy. However 30 PTB and 27 EPTB cases showing ELISA positivity were neither acid fast bacilli positive nor antitubercular therapy treated. These cases may possibly have dormant infection and need further diagnosis. In EPTB cases ELISA was observed to be more useful than AFB smear test. Conclusions:This inhouse developed user-friendly peroxidase ELISA can be used as an adjunct test of smear microscopy or culture techniques for routine screening of patients suspected of PTB or EPTB.

  12. Intestinal tuberculosis sometimes mimics Crohn's disease.

    Esfandiar Shojaei

    2013-11-01

    Full Text Available Intestinal tuberculosis is an uncommon presentation of tuberculosis (TB and has clinicopathological similarities with Crohn's disease. In regions where TB is endemic clinicians must aware of this condition and fully evaluate their patients when Crohn's disease is diagnosed. We recommend all pathologic specimens be evaluate effectively for TB.Smear,culture and PCR for Mycobacterium.tuberculosis from samples aside the pathological reviews help for better diagnosis. Here we present a case of intestinal tuberculosis which initially diagnosed as Crohn's disease but after starting immunosuppressive agents he presented with disseminated tuberculosis.

  13. Detection activity assessment and diagnosis of dental caries lesions

    Braga, Mariana M; Mendes, Fausto M; Ekstrand, Kim R

    2010-01-01

    This article reviews the current methods for detection and assessment of caries lesions focusing on applicability for daily clinical practice. The end point is to arrive at a diagnosis for each caries lesion. Visual inspection aided by a ball-ended probe is essential for caries lesions assessment...... process, additional methods could aid the dentist in reaching a more appropriate treatment decision in some cases. The ICDAS, including the activity assessment system or the Nyvad system, seems to be the best option to reach final diagnoses for managing lesions. The radiographic method is the most...

  14. Tuberculosis (TB)

    ... infectious, immunologic, and allergic diseases NIAID Home Health & Research Topics Labs & Scientific Resources Funding About NIAID News & Events Volunteer NIAID > Health & Research Topics > Tuberculosis > Research Tuberculosis Understanding TB Research Research Goals ...

  15. Tuberculosis (TB)

    ... Skip Content Marketing Share this: Main Content Area Tuberculosis (TB) Overview In developed countries, such as the ... thought to be infected with TB bacteria, Mycobacterium tuberculosis ( Mtb ). TB is a chronic bacterial infection. It ...

  16. Tuberculosis Prevention

    ... Skip Content Marketing Share this: Main Content Area Tuberculosis (TB) Prevention TB is an airborne disease and ... patients. Many people who are infected with Mycobacterium tuberculosis ( Mtb ) do not get sick or spread the ...

  17. Kinetics of T cell-activation molecules in response to Mycobacterium tuberculosis antigens

    Antas Paulo RZ

    2002-01-01

    Full Text Available The phenotypic features acquired subsequent to antigen-specific stimulation in vitro were evaluated by means of the kinetic expressions of CD69 and CD25 activation molecules on T lymphocytes and assayed by flow cytometry in response to PPD, Ag85B, and ferritin in PPD-positive healthy control individuals. In response to PHA, CD69 staining on both CD4+ and CD8+ T cells became initially marked after 4 h, peaked at 24 h, and quickly decreased after 120 h. For CD25, a latter expression was detected around 8 h, having increased after 96 h. As expected, the response rate to the mycobacterial antigens was much lower than that to the mitogen. Positive staining was high after 96 h for CD25 and after 24 h for CD69. CD69 expression was significantly enhanced (p < 0.05 on CD8+ as compared to CD4+ T cells. High levels were also found between 96-120 h. Regarding Ag85B, CD25+ cells were mostly CD4+ instead of CD8+ T cells. Moreover, in response to ferritin, a lower CD25 expression was noted. The present data will allow further characterization of the immune response to new mycobacterial-specific antigens and their evaluation for possible inclusion in developing new diagnostic techniques for tuberculosis as well in a new vaccine to prevent the disease.

  18. Impact of socioeconomic status and living condition on latent tuberculosis diagnosis among the tribal population of Melghat: A cohort study

    Kashyap, Rajpal S; Nayak, Amit R; Husain, Aliabbas A; Shekhawat, Seema D; Satav, Ashish R; Jain, Ruchika K; Raje, Dhananjay V; Daginawala, Hatim F; Taori, Girdhar M

    2016-01-01

    Aims: To study socioeconomic status (SES) and living conditions (LC) as risk factors for latent tuberculosis infection (LTBI) and their impact on QuantiFERON-TB gold (QFT-G) and tuberculin skin test (TST) outcome for determining a better diagnostic test for LTBI in the malnourished tribal population of Melghat. Settings and Design: Six hundred sixty nine participants matching the inclusion criteria were recruited from 10 tribal villages of Melghat region, India. Subjects and Methods: Complete information related to various risk factors and test outcome was obtained on 398 participants, which was analyzed as per predefined conceptual framework. Factors were classified based on their relevance either at individual or household level, and subsequently based on the possibility of intervention. Data were partitioned into concordant and discordant sets depending on test agreement. Results: In concordant set, the two tests revealed that LTBI was significantly associated with smoking (adjusted odds ratio [aOR]: 2.64 [95% confidence interval [CI]: 1.03–6.79]), tobacco usage (aOR: 2.74 [95% CI: 1.50–4.99]), and malnourishment (aOR: 1.97 [95% CI: 1.12–3.48]) after basic adjustment. Inclusion of latent variable SES and LC in the model has mediating effect on the association of above factors with LTBI. Further, the association of SES and LC with LTBI in concordant set was unaltered in presence of other cofactors. From discordant set, results of QFT-G corroborated with that of concordant set. Conclusions: Poor SES and LC can be considered as strong risk factors linked with LTBI as compared to malnourishment, which is often targeted in such communities. Further, our study showed QFT-G test as a reliable tool in screening of LTBI in the tribal population of Melghat, India.

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

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

    2016-06-01

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

  20. Oral vaccination with heat inactivated Mycobacterium bovis activates the complement system to protect against tuberculosis.

    Beatriz Beltrán-Beck

    Full Text Available Tuberculosis (TB remains a pandemic affecting billions of people worldwide, thus stressing the need for new vaccines. Defining the correlates of vaccine protection is essential to achieve this goal. In this study, we used the wild boar model for mycobacterial infection and TB to characterize the protective mechanisms elicited by a new heat inactivated Mycobacterium bovis vaccine (IV. Oral vaccination with the IV resulted in significantly lower culture and lesion scores, particularly in the thorax, suggesting that the IV might provide a novel vaccine for TB control with special impact on the prevention of pulmonary disease, which is one of the limitations of current vaccines. Oral vaccination with the IV induced an adaptive antibody response and activation of the innate immune response including the complement component C3 and inflammasome. Mycobacterial DNA/RNA was not involved in inflammasome activation but increased C3 production by a still unknown mechanism. The results also suggested a protective mechanism mediated by the activation of IFN-γ producing CD8+ T cells by MHC I antigen presenting dendritic cells (DCs in response to vaccination with the IV, without a clear role for Th1 CD4+ T cells. These results support a role for DCs in triggering the immune response to the IV through a mechanism similar to the phagocyte response to PAMPs with a central role for C3 in protection against mycobacterial infection. Higher C3 levels may allow increased opsonophagocytosis and effective bacterial clearance, while interfering with CR3-mediated opsonic and nonopsonic phagocytosis of mycobacteria, a process that could be enhanced by specific antibodies against mycobacterial proteins induced by vaccination with the IV. These results suggest that the IV acts through novel mechanisms to protect against TB in wild boar.

  1. High-resolution CT for identify patients with smear-positive, active pulmonary tuberculosis

    Purpose: This study evaluates the use of high-resolution computed tomography (HRCT) to differentiate smear-positive, active pulmonary tuberculosis (PTB) from other pulmonary infections in the emergency room (ER) setting. Methods: One hundred and eighty-three patients diagnosed with pulmonary infections in an ER were divided into an acid fast bacillus (AFB) smear-positive, active PTB group (G1 = 84) and a non-AFB smear-positive, pulmonary infection group (G2 = 99). HRCT images from a 64-Multidetector CT were analyzed, retrospectively, for the morphology, number, and segmental distribution of pulmonary lesions. Results: Utilizing multivariate analysis, five variables were found to be independent risk factors predictive of G1: (1) consolidation involving the apex segment of right upper lobe, posterior segment of the right upper lobe, or apico-posterior segment of the left upper lobe; (2) consolidation involving the superior segment of the right or left lower lobe; (3) presence of a cavitary lesion; (4) presence of clusters of nodules; (5) absence of centrilobular nodules. A G1 prediction score was generated based on these 5 criteria to help differentiate G1 from G2. The area under the receiver operating characteristic (ROC) curve was 0.96 ± 0.012 in our prediction model. With an ideal cut-off point score of 3, the specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) are 90.9%, 96.4%, 90.0% and 96.8%, respectively. Conclusion: The use of this AFB smear-positive, active PTB prediction model based on 5 key HRCT findings may help ER physicians determine whether or not isolation is required while awaiting serial sputum smear results in high risk patients.

  2. Angiotensin-Converting Enzyme Inhibitors and Active Tuberculosis: A Population-Based Study.

    Wu, Jiunn-Yih; Lee, Meng-Tse Gabriel; Lee, Si-Huei; Lee, Shih-Hao; Tsai, Yi-Wen; Hsu, Shou-Chien; Chang, Shy-Shin; Lee, Chien-Chang

    2016-05-01

    Numerous epidemiological data suggest that the use of angiotensin-converting enzyme inhibitors (ACEis) can improve the clinical outcomes of pneumonia. Tuberculosis (TB) is an airborne bacteria like pneumonia, and we aimed to find out whether the use of ACEis can decrease the risk of active TB.We conducted a nested case-control analysis by using a 1 million longitudinally followed cohort, from Taiwan national health insurance research database. The rate ratios (RRs) for TB were estimated by conditional logistic regression, and adjusted using a TB-specific disease risk score (DRS) with 71 TB-related covariates.From January, 1997 to December, 2011, a total of 75,536 users of ACEis, and 7720 cases of new active TB were identified. Current use (DRS adjusted RR, 0.87 [95% CI, 0.78-0.97]), but not recent and past use of ACEis, was associated with a decrease in risk of active TB. Interestingly, it was found that chronic use (>90 days) of ACEis was associated with a further decrease in the risk of TB (aRR, 0.74, [95% CI, 0.66-0.83]). There was also a duration response effect, correlating decrease in TB risk with longer duration of ACEis use. The decrease in TB risk was also consistent across all patient subgroups (age, sex, heart failure, cerebrovascular diseases, myocardial infraction, renal diseases, and diabetes) and patients receiving other cardiovascular medicine.In this large population-based study, we found that subjects with recent and chronic use of ACEis were associated with decrease in TB risk. PMID:27175655

  3. Quantitative structure-activity relationship of molecules constituent of different essential oils with antimycobacterial activity against Mycobacterium tuberculosis and Mycobacterium bovis

    Andrade-Ochoa, Sergio; Nevárez-Moorillón, Guadalupe Virginia; Sánchez-Torres, Luvia E; Villanueva-García, Manuel; Sánchez-Ramírez, Blanca E.; Rodríguez-Valdez, Luz María; Rivera-Chavira, Blanca E.

    2015-01-01

    Background Essential oils and their constituents are commonly known for their antibacterial, antifungal and antiparasitic activity, and there are also reports on the antimycobacterial properties, but more experimental data are needed for the description of the mechanism of action or structural (and molecular) properties related to the antimicrobial activity. Methods Twenty-five constituents of essential oils were evaluated against Mycobacterium tuberculosis H37Rv and Mycobacterium bovis AN5 b...

  4. Prevalence of patients with respiratory symptoms through active case finding and diagnosis of pulmonary tuberculosis among prisoners and related predictors in a jail in the city of Carapicuíba, Brazil Prevalência de sintomáticos respiratórios através da busca ativa, diagnóstico de tuberculose pulmonar entre pessoas privadas de liberdade e fatores associados em uma cadeia pública no município de Carapicuíba, Brasil

    Amadeu A. Vieira

    2010-12-01

    Full Text Available BACKGROUND: Prisons offer a fertile setting for the transmission of tuberculosis due to the presence of many classic risk factors for both infection and disease: overcrowding, poor ventilation, and little sunlight. Prisoners are often malnourished and have poor hygiene and are more likely to have a background of alcohol and drug abuse. OBJECTIVES: To determine the prevalence of prisoners with respiratory symptoms and pulmonary tuberculosis (PTB through active case finding in a prisoner population of the county jail of Carapicuíba, and to study possible related variables. METHODS: This was a cross-sectional study, and respiratory symptomatic individuals (RSI were detected through active case finding. Socio-demographic data were collected from inmates' judicial history using a specific questionnaire. The RSI provided sputum specimens for detection of acid fast bacilli and culture for mycobacterium identification. RESULTS: Among the 397 prisoners studied, 154 reported respiratory symptoms for more than three weeks, and were considered RSI; the variables associated with RSI were: having already been tried and incarcerated for more than six months and seven were diagnosed as PTB (1,763 cases/ 100,000 inhabitants. CONCLUSIONS: The prevalence of RSI and PTB cases were respectively 39 and 35 times greater than the general population.INTRODUÇÃO: Estabelecimentos prisionais são um campo favorável para a transmissão de tuberculose (TB, devido a presença de vários fatores de risco clássicos, tanto para a infecção como para a doença: aglomeração, falta de ventilação e de iluminação, como também o fato de os detentos receberem uma nutrição deficitária e os locais possuí-rem condições de higiene precárias; uma grande proporção dos detentos apresentam história pregressa de alcoolismo e uso de drogas ilícitas nas dependências desses estabelecimentos. OBJETIVOS: Determinar a prevalência de sintomáticos respiratórios (RSI e casos

  5. Study of Avian Tuberculosis in a Zoo at the Bogota savannah through Tuberculin Testing and Active Epidemiologic Surveillance

    Germán Rodríguez Martínez

    2011-06-01

    Full Text Available The flow of wild birds is a weakness in epidemiologic surveillance because of its unknown potential as a source of disease dissemination. The investigation focused on an epidemiological tracking of the mixed wild bird population in a zoo in the Bogota Savannah, where three birds died with a presumptive diagnosis of tuberculosis. In order to verify the presence of Mycobacterium avium and to plan the required measures to avoid risk factors, a control group of five poultry birds of the Hy Line Brown variety that had already been exposed was used, as well as a sentinel group of the poultry birds from the same batch as the control group, and an external control group of 102 birds from cages near the area of the problem. Retrospective and prospective studies were carried out through histopathological, microbiological, epidemiological and molecular analysis. One hundred percent (100% of the birds from the original cages that died were genotypically diagnosed with tuberculosis caused by Mycobacterium avium. Thirty-five percent (35.5% of the sentinel group was affected by Mycobacterium avium, 28.6% by Mycobacterium gordonae, 14.3% by Mycobacterium chelonae and 21.4% by a mycobacterium that is very difficult to classify. The other animals outside the cage showed no evidence of infection. It is concluded that the problematic enclosure is affected by avian tuberculosis, which is of high risk both for birds and for humans. The poultry used as sentinels are excellent infective agent detectors, particularly of mycobacteria present in the environment, and the tuberculin test is a good indicator of infection with this type of microorganisms in poultry.

  6. 结核分枝杆菌RD1区编码蛋白ELISPOT辅助诊断活动性结核病的应用价值%The Diagnostic Value of Enzyme-linked immunosorbent assay by RD1 of Mycobacterium tuberculosis encoded protein in Detection of Active Tuberculosis

    杜凤娇; 傅瑜; 吴雪琼; 李亮; 高静韬; 张宗德

    2012-01-01

    Objective To compare T-SPOT. TB and Enzyme-linked immunosorbent assay(ELISPOT) using ESAT-6/CFP-10 fusion proteinas( E/C) and Rv3879c as antigens,and explore their roles in the auxiliary diagnosis of active tuberculosis. Methods Totally 106 patients with initial pulmonary tuberculosis(tuberculosis group) and 48 healthy person(healthy control group) and 43 patients with non-tuberculosis pulmonary disease(disease control group) were enrolled. The peripheral blood mononuclear cells of all participants were detected by ELISPOT and T-SPOT. TB, Then enumerated the spot forming cells(SFCs). All participants were also performed TST simultaneously. Results The sensitivity of ELISPOT and T-SPOT. TB were 90.6% and 93.4% in tuberculosis group and specificity were 91.5% in TST negative control group. The positive rate were 18. 8% and 16.7% in healthy person by these two methods, There wre not statistically significance difference between two methods(P >0.05). Conclusions Enzyme-linked immunosorbent assay( ELISPOT) using ESAT-6/CFP-10 fusion proteinas( E/C) and Rv3879c as antigens can be a assistant to diagnosis active tuberculosis. It offers certain diagnostic evidences for latent tuberculosis infection.%目的 比较E/C联合Rv3879c蛋白作为抗原的ELISPOT和T-SPOT.TB试剂盒,探讨其在活动性结核病诊断中的应用价值.方法 选取初治结核病患者106例作为结核组,43例肺部其它疾病患者做为疾病对照组和48例健康者做为健康对照组,应用T-SPOT.TB和ELISPOT检测受试者外周血单个核细胞的斑点形成细胞数量,同时对受试者行T研.结果 T-SPOT.TB和ELISPOT在结核病组中的敏感度分别为92.5%和93.4%,TST阴性对照组中的特异度均为91.5%,在健康者中的阳性率分别为18.8%和16.7%,且两种方法差异无统计学意义(均P>0.05).结论 E/C联合Rv3879c蛋白作为抗原的ELISPOT能够诊断活动性结核病,并为结核感染诊断提供一定的依据.

  7. Decreased C3 Activation by the devR Gene-Disrupted Mycobacterium tuberculosis Strain in Comparison to the Wild-Type Strain

    V. Narayan Rao

    2013-01-01

    Full Text Available Activation of the complement component C3 is an important step in the complement cascade, contributing to inflammatory mechanisms. Considerable research on gene-disrupted mycobacterial strains using animal models of tuberculosis infection has reported the roles of some of the mycobacterial genes during tuberculosis infection. The aim of the present study was to assess the pattern of complement activation by the devR gene-disrupted Mycobacterium tuberculosis H37Rv strain and compare with that by its wild-type strain. In vitro complement activation at the level of C3 by the gene-disrupted strain, its complemented strain, and wild-type strain was performed using solid-phase ELISA. It was observed that the ability of devR gene-disrupted M. tuberculosis H37Rv to activate C3 was significantly reduced in comparison to its wild-type strain (P<0.05. In addition, C3 activation by the complemented devR mutant strain was almost similar to that of the wild strain, which indicated that the reduced ability to activate C3 could potentially be due to the deletion of devR gene. These findings indicate that the gene devR probably aids in complement activation and contributes to the inflammatory processes during tuberculosis infection.

  8. IL-10 dependent suppression of type 1, type 2 and type 17 cytokines in active pulmonary tuberculosis.

    Nathella Pavan Kumar

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

  9. Activity of phosphino palladium(II) and platinum(II) complexes against HIV-1 and Mycobacterium tuberculosis.

    Gama, Ntombenhle H; Elkhadir, Afag Y F; Gordhan, Bhavna G; Kana, Bavesh D; Darkwa, James; Meyer, Debra

    2016-08-01

    Treatment of human immunodeficiency virus (HIV) is currently complicated by increased prevalence of co-infection with Mycobacterium tuberculosis. The development of drug candidates that offer the simultaneous management of HIV and tuberculosis (TB) would be of great benefit in the holistic treatment of HIV/AIDS, especially in sub-Saharan Africa which has the highest global prevalence of HIV-TB coinfection. Bis(diphenylphosphino)-2-pyridylpalladium(II) chloride (1), bis(diphenylphosphino)-2-pyridylplatinum(II) chloride (2), bis(diphenylphosphino)-2-ethylpyridylpalladium(II) chloride (3) and bis(diphenylphosphino)-2-ethylpyridylplatinum(II) (4) were investigated for the inhibition of HIV-1 through interactions with the viral protease. The complexes were subsequently assessed for biological potency against Mycobacterium tuberculosis H37Rv by determining the minimal inhibitory concentration (MIC) using broth microdilution. Complex (3) showed the most significant and competitive inhibition of HIV-1 protease (p = 0.014 at 100 µM). Further studies on its in vitro effects on whole virus showed reduced viral infectivity by over 80 % at 63 µM (p < 0.05). In addition, the complex inhibited the growth of Mycobacterium tuberculosis at an MIC of 5 µM and was non-toxic to host cells at all active concentrations (assessed by tetrazolium dye and real time cell electronic sensing). In vitro evidence is provided here for the possibility of utilizing a single metal-based compound for the treatment of HIV/AIDS and TB. PMID:27246555

  10. Activity calibration in breath test for diagnosis of Helicobacter pylori

    Some technical and measurement problems of the breath test for diagnosis of Helicobacter pylori are briefly discussed. Calibrated results obtained for population of 108 cases indicate difference between HP+ (infected with Helicobacter pylori) and HP- (non infected with Helicobacter pylori) in exhaled 14C activity not less than 3.9 kBq while the lower limit for HP+ cases was set at 6.8 kBq at the detection limit: 0.9 Bq/mmol of CO2. It was estimated that in exhalation way up to 29% of the taken activity was removed in HP+ cases during first 35 minutes. Radiation hazard for the patient system is negligibly small - dose equipment not exceeds 0.29% of the natural (environmental) yearly exposure. (author)

  11. Factors associated with patient and provider delays for tuberculosis diagnosis and treatment in Asia: a systematic review and meta-analysis.

    Jing Cai

    Full Text Available Delays in tuberculosis (TB diagnosis and treatment is a major barrier to effective management of the disease. Determining the factors associated with patient and provider delay of TB diagnosis and treatment in Asia may contribute to TB prevention and control.We searched the PubMed, EMBASE and Web of Science for studies that assessed factors associated with delays in care-seeking, diagnosis, or at the beginning of treatment, which were published from January 1992 to September 2014. Two reviewers independently identified studies that were related to our meta-analysis and extracted data from each study. Independent variables were categorized in separate tables for patient and provider delays.Among 45 eligible studies, 40 studies assessed patient delay whereas 30 assessed provider delay. Cross-sectional surveys were used in all but two articles, which included 17 countries and regions. Socio-demographic characteristics, TB-related symptoms and medical examination, and conditions of seeking medical care in TB patients were frequently reported. Male patients and long travel time/distance to the first healthcare provider led to both shorter patient delays [odds ratio (OR (95% confidence intervals, CI = 0.85 (0.78, 0.92; 1.39 (1.08, 1.78] and shorter provider delays [OR (95%CI = 0.96 (0.93, 1.00; 1.68 (1.12, 2.51]. Unemployment, low income, hemoptysis, and positive sputum smears were consistently associated with patient delay [ORs (95%CI = 1.18 (1.07, 1.30, 1.23 (1.02, 1.49, 0.64 (0.40, 1.00, 1.77 (1.07, 2.94, respectively]. Additionally, consultation at a public hospital was associated with provider delay [OR (95%CI = 0.43 (0.20, 0.91].We propose that the major opportunities to reduce delays involve enabling socio-demographic factors and medical conditions. Male, unemployed, rural residence, low income, hemoptysis, positive sputum smear, and long travel time/distance significantly correlated with patient delay. Male, long travel time/distance and

  12. Access to Bacteriologic-Based Diagnosis in Smear Positive Retreatment Tuberculosis Patients in Rural China: A Cross-Sectional Study in Three Geographic Varied Provinces.

    Changming Zhou

    Full Text Available To determine factors influencing the utilization and accessibility to bacteriologic-based tuberculosis (TB diagnosis among sputum smear positive (SS+ retreatment TB patients, and to develop strategies for improving the case detection rate of MDR-TB in rural China.A cross-sectional study of SS+ TB retreatment patients was conducted in eight counties from three provinces with different implementation period and strategy of MDR-TB program in China. Demographic and socioeconomic parameters were collected by self-reporting questionnaires. Sputum samples were collected and cultured by the laboratory of county-designated TB clinics and delivered to prefectural Centers for Disease Prevention and Control (CDC labs for DST with 4 first-line anti-TB drugs.Among the 196 SS+ retreatment patients, 61.22% received culture tests during current treatment. Patients from more developed regions (OR = 24.0 and 3.6, 95% CI: 8.6-67.3 and 1.1-11.6, with better socio-economic status (OR = 3. 8, 95% CI: 1.3-10.7, who had multiple previous anti-TB treatments (OR = 5.0, 95% CI: 1.6-15.9, and who failed in the most recent anti-TB treatment (OR = 2.6, 95% CI: 1.0-6.4 were more likely to receive culture tests. The percentage of isolates resistant to any of first-line anti-TB drugs and MDR-TB were 50.0% (95% CI: 39.8%-60.2% and 30.4% (95% CI: 21.0%-39.8% respectively.Retreatment SS+ TB patients, high risk MDR-TB population, had poor utilization of access to bacteriologic-based TB diagnosis, which is far from optimal. The next step of anti-TB strategy should be focused on how to make bacteriological-based diagnosis cheaper, safer and more maneuverable, and how to assure the DST-guided treatment for these high-risk TB patients.

  13. Multidrug-resistant tuberculosis

    McNerney Ruth

    2008-01-01

    Full Text Available Abstract Background With almost 9 million new cases each year, tuberculosis remains one of the most feared diseases on the planet. Led by the STOP-TB Partnership and WHO, recent efforts to combat the disease have made considerable progress in a number of countries. However, the emergence of mutated strains of Mycobacterium tuberculosis that are resistant to the major anti-tuberculosis drugs poses a deadly threat to control efforts. Multidrug-resistant tuberculosis (MDR-TB has been reported in all regions of the world. More recently, extensively drug resistant-tuberculosis (XDR-TB that is also resistant to second line drugs has emerged in a number of countries. To ensure that adequate resources are allocated to prevent the emergence and spread of drug resistance it is important to understand the scale of the problem. In this article we propose that current methods of describing the epidemiology of drug resistant tuberculosis are not adequate for this purpose and argue for the inclusion of population based statistics in global surveillance data. Discussion Whereas the prevalence of tuberculosis is presented as the proportion of individuals within a defined population having disease, the prevalence of drug resistant tuberculosis is usually presented as the proportion of tuberculosis cases exhibiting resistance to anti-tuberculosis drugs. Global surveillance activities have identified countries in Eastern Europe, the former Soviet Union and regions of China as having a high proportion of MDR-TB cases and international commentary has focused primarily on the urgent need to improve control in these settings. Other regions, such as sub-Saharan Africa have been observed as having a low proportion of drug resistant cases. However, if one considers the incidence of new tuberculosis cases with drug resistant disease in terms of the population then countries of sub-Saharan Africa have amongst the highest rates of transmitted MDR-TB in the world. We propose

  14. The effect of diagnostic delays on the drop-out rate and the total delay to diagnosis of tuberculosis.

    Stephen J Millen

    Full Text Available BACKGROUND: Numerous patient and healthcare system-related delays contribute to the overall delay experienced by patients from onset of TB symptoms to diagnosis and treatment. Such delays are critical as infected individuals remain untreated in the community, providing more opportunities for transmission of the disease and adversely affecting the epidemic. METHODOLOGY/PRINCIPAL FINDINGS: We present an analysis of the factors that contribute to the overall delay in TB diagnosis and treatment, in a resource-poor setting. Impact on the distribution of diagnostic delay times was assessed for various factors, the sensitivity of the diagnostic method being found to be the most significant. A linear relationship was found between the sensitivity of the test and the predicted mean delay time, with an increase in test sensitivity resulting in a reduced mean delay time and a reduction in the drop-out rate. CONCLUSIONS/SIGNIFICANCE: The results show that in a developing country a number of delay factors, particularly the low sensitivity of the initial sputum smear microscopy test, potentially increase total diagnostic delay times experienced by TB patients significantly. The results reinforce the urgent need for novel diagnostic methods, both for smear positive and negative TB, that are highly sensitive, accessible and point of care, in order to reduce mean delay times.

  15. Standardization of natural mycolic acid antigen composition and production for use in biomarker antibody detection to diagnose active tuberculosis.

    Ndlandla, F L; Ejoh, V; Stoltz, A C; Naicker, B; Cromarty, A D; van Wyngaardt, S; Khati, M; Rotherham, L S; Lemmer, Y; Niebuhr, J; Baumeister, C R; Al Dulayymi, J R; Swai, H; Baird, M S; Verschoor, J A

    2016-08-01

    Mycobacterium tuberculosis, the causative agent of tuberculosis, is characterized by the abundance of species specific, antigenic cell wall lipids called mycolic acids. These wax-like molecules all share an identical, amphiphilic mycolic motif, but have different functional groups in a long hydrophobic hydrocarbon mero-chain that divide them into three main classes: alpha-, keto- and methoxy-mycolic acids. Whereas alpha-mycolic acids constitutively maintain an abundance of around 50%, the ratio of methoxy- to keto-mycolic acid types may vary depending on, among other things, the growth stage of M. tuberculosis. In human patients, antibodies to mycolic acids have shown potential as diagnostic serum biomarkers for active TB. Variations in mycolic acid composition affect the antigenic properties and can potentially compromise the precision of detection of anti-mycolic acids antibodies in patient sera to natural mixtures. We demonstrate this here with combinations of synthetic mycolic acid antigens, tested against TB patient and control sera. Combinations of methoxy- and α-mycolic acids are more antigenic than combinations of keto- and α-mycolic acids, showing the former to give a more sensitive test for TB biomarker antibodies. Natural mixtures of mycolic acids isolated from mature cultures of M. tuberculosis H37Rv give the same sensitivity as that with synthetic methoxy- and α-mycolic acids in combination, in a surface plasmon resonance inhibition biosensor test. To ensure that the antigenic activity of isolates of natural mycolic acids is reproducible, we cultured M. tuberculosis H37Rv on Middlebrook 7H10 solid agar plates to stationary growth phase in a standardized, optimal way. The proportions of mycolic acid classes in various batches of the isolates prepared from these cultures were compared to a commercially available natural mycolic acid isolate. LC-MS/MS and NMR data for quantitation of mycolic acids class compositions show that the variation in batches

  16. Colorectal tuberculosis

    Our objective was to evaluate the incidence of colorectal tuberculosis in our series and to study its radiological spectrum. A total of 684 cases of proven gastrointestinal tuberculosis with positive barium contrast findings seen over a period of more than one decade were evaluated. The study did not include cases where colon was involved in direct contiguity with ileo-caecal tuberculosis. Seventy-four patients (10.8%) had colorectal tuberculosis. Commonest site involved was transverse colon, closely followed by rectum and ascending colon. Radiological findings observed were in the form of strictures (54%), colitis (39%) and polypoid lesions (7%). Complications noted were in the form of perforations and fistulae in 18.9% of cases. Colorectal tuberculosis is a very common site for gastrointestinal tuberculosis. Typical findings of colorectal tuberculosis are strictures, signs of colitis and polypoid lesions. Common complications are perforation and fistulae. (orig.)

  17. Sputum smear negative pulmonary tuberculosis: sensitivity and specificity of diagnostic algorithm

    Mugusi Ferdinand M; Swai Hedwiga F; Mbwambo Jessie K

    2011-01-01

    Abstract 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 u...

  18. Comparative Study of a Real-Time PCR Assay Targeting senX3-regX3 versus Other Molecular Strategies Commonly Used in the Diagnosis of Tuberculosis.

    Rocio Sanjuan-Jimenez

    Full Text Available Nucleic acid amplification tests are increasingly used for the rapid diagnosis of tuberculosis. We undertook a comparative study of the efficiency and diagnostic yield of a real-time PCR senX3-regX3 based assay versus the classical IS6110 target and the new commercial methods.This single-blind prospective comparative study included 145 consecutive samples: 76 from patients with culture-confirmed tuberculosis (86.8% pulmonary and 13.2% extrapulmonary tuberculosis: 48.7% smear-positive and 51.3% smear-negative and 69 control samples (24 from patients diagnosed with non-tuberculous mycobacteria infections and 45 from patients with suspected tuberculosis which was eventually ruled out. All samples were tested by two CE-marked assays (Xpert®MTB/RIF and AnyplexTM plus MTB/NTM and two in-house assays targeting senX3-regX3 and the IS6110 gene.The detection limit ranged from 1.00E+01 fg for Anyplex, senX3-regX3 and IS6110 to 1.00E+04 fg for Xpert. All three Xpert, senX3-regX3 and IS6110 assays detected all 37 smear-positive cases. Conversely, Anyplex was positive in 34 (91.9% smear-positive cases. In patients with smear-negative tuberculosis, differences were observed between the assays; Xpert detected 22 (56.41% of the 39 smear-negative samples, Anyplex 24 (61.53%, senX3-regX3 28 (71.79% and IS6110 35 (89.74%. Xpert and senX3-regX3 were negative in all control samples; however, the false positive rate was 8.7% and 13% for Anyplex and IS6110, respectively. The overall sensitivity was 77.6%, 85.7%, 77.3% and 94.7% and the specificity was 100%, 100%, 90.8% and 87.0% for the Xpert, senX3-regX3, Anyplex and IS6110 assays, respectively.Real-time PCR assays targeting IS6110 lack the desired specificity. The Xpert MTB/RIF and in-house senX3-regX3 assays are both sensitive and specific for the detection of MTBC in both pulmonary and extrapulmonary samples. Therefore, the real time PCR senX3-regX3 based assay could be a useful and complementary tool in the

  19. On Combining Multiple-Instance Learning and Active Learning for Computer-Aided Detection of Tuberculosis.

    Melendez, Jaime; van Ginneken, Bram; Maduskar, Pragnya; Philipsen, Rick H H M; Ayles, Helen; Sanchez, Clara I

    2016-04-01

    The major advantage of multiple-instance learning (MIL) applied to a computer-aided detection (CAD) system is that it allows optimizing the latter with case-level labels instead of accurate lesion outlines as traditionally required for a supervised approach. As shown in previous work, a MIL-based CAD system can perform comparably to its supervised counterpart considering complex tasks such as chest radiograph scoring in tuberculosis (TB) detection. However, despite this remarkable achievement, the uncertainty inherent to MIL can lead to a less satisfactory outcome if analysis at lower levels (e.g., regions or pixels) is needed. This issue may seriously compromise the applicability of MIL to tasks related to quantification or grading, or detection of highly localized lesions. In this paper, we propose to reduce uncertainty by embedding a MIL classifier within an active learning (AL) framework. To minimize the labeling effort, we develop a novel instance selection mechanism that exploits the MIL problem definition through one-class classification. We adapt this mechanism to provide meaningful regions instead of individual instances for expert labeling, which is a more appropriate strategy given the application domain. In addition, and contrary to usual AL methods, a single iteration is performed. To show the effectiveness of our approach, we compare the output of a MIL-based CAD system trained with and without the proposed AL framework. The task is to detect textural abnormalities related to TB. Both quantitative and qualitative evaluations at the pixel level are carried out. Our method significantly improves the MIL-based classification. PMID:26660889

  20. Inflammatory pseudotumour of the spleen associated with splenic tuberculosis

    Maria; Isabel; Prieto-Nieto; Juan; Pedro; Pérez-Robledo; Beatriz; Díaz-San; Andrés; Manuel; Nistal; José; Antonio; Rodríguez-Montes

    2014-01-01

    Inflammatory pseudotumor(IPT) of the spleen is an uncommon entity with an uncertain aetiology. Inflammatory pseudotumors present diagnostic difficulties because the clinical and radiological findings tend to suggest a malignancy. The symptoms include weight loss, fever, and abdominal pain. Most cases of splenic IPT present solitary relatively large well circumscribed masses on imaging. The diagnosis in the majority of the cases is made after histopathologic study of splenectomy specimens. The IPTs that occur in the spleen and liver are typically associated with Epstein-Barr virus. Thirtyseven percent of all new cases of active tuberculosis infection are extrapulmonary tuberculosis and tuberculous lymphadenitis the most commonly occurring form of extrapulmonary tuberculosis. We report the case of an inflammatory pseudotumor of the spleen associated with splenic tuberculous lymphadenitis in a 50-year-old female patient who was preoperatively diagnosed with a malignant spleen tumour based on her history of breast of carcinoma.