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Sample records for suspected active tuberculosis

  1. Evaluation of quantitative IFN-gamma response for risk stratification of active tuberculosis suspects.

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    Metcalfe, John Z; Cattamanchi, Adithya; Vittinghoff, Eric; Ho, Christine; Grinsdale, Jennifer; Hopewell, Philip C; Kawamura, L Masae; Nahid, Payam

    2010-01-01

    The contribution of interferon-gamma release assays (IGRAs) to appropriate risk stratification of active tuberculosis suspects has not been studied. To determine whether the addition of quantitative IGRA results to a prediction model incorporating clinical criteria improves risk stratification of smear-negative-tuberculosis suspects. Clinical data from tuberculosis suspects evaluated by the San Francisco Department of Public Health Tuberculosis Control Clinic from March 2005 to February 2008 were reviewed. We excluded tuberculosis suspects who were acid fast-bacilli smear-positive, HIV-infected, or under 10 years of age. We developed a clinical prediction model for culture-positive disease and examined the benefit of adding quantitative interferon (IFN)-gamma results measured by QuantiFERON-TB Gold (Cellestis, Carnegie, Australia). Of 660 patients meeting eligibility criteria, 65 (10%) had culture-proven tuberculosis. The odds of active tuberculosis increased by 7% (95% confidence interval [CI], 3-11%) for each doubling of IFN-gamma level. The addition of quantitative IFN-gamma results to objective clinical data significantly improved model performance (c-statistic 0.71 vs. 0.78; P added clinical value to a prediction model incorporating conventional risk factors. Although this benefit may be attenuated within highly experienced centers, the predictive accuracy of quantitative IFN-gamma levels should be evaluated in other settings.

  2. Smear positive pulmonary tuberculosis among suspected patients ...

    African Journals Online (AJOL)

    Background: Tuberculosis is a major public health problem throughout the world. Nearly one third of the world's population is infected with Mycobacterium tuberculosis (MTB) and hence at risk of developing active disease. Tuberculosis is a major cause of morbidity and mortality in Ethiopia, and the country belongs to one of ...

  3. Seasonal variation among tuberculosis suspects in four countries

    DEFF Research Database (Denmark)

    Mabaera, Biggie; Naranbat, Nymadawa; Katamba, Achilles

    2009-01-01

    The objective of the study was to analyze monthly trends across a calendar year in tuberculosis suspects and sputum smear-positive cases based on nationally representative samples of tuberculosis laboratory registers from Moldova, Mongolia, Uganda and Zimbabwe. Out of the 47 140 suspects registered...... in the tuberculosis laboratory registers, 13.4% (6312) were cases. The proportion varied from country to country, Moldova having the lowest (9%) and Uganda the highest (21%). From the monthly proportion of suspects and cases among total suspects and cases, seasonal variations were most marked in Mongolia which, among...... attendance to diagnostic laboratory services, evidenced by the contrasting findings of Mongolia (extreme continental northern climate) compared to Uganda (equatorial climate). A combination of external and possibly endogenous factors seems to determine whether tuberculosis suspects and cases present...

  4. Use of a T cell interferon gamma release assay in the investigation for suspected active tuberculosis in a low prevalence area

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    Norén Ann

    2009-07-01

    Full Text Available Abstract Background In settings with low background prevalence of tuberculosis (TB infection, interferon-γ release assays (IGRA could be useful for diagnosing active TB. This study aims to evaluate the performance of QuantiFERON®-TB Gold (QFT-G in the investigation for suspected active TB, with particular attention to patients originating in high-incidence countries. Furthermore, factors associated with QFT-G results in patients with active TB were assessed. Methods From patients investigated for clinically suspected active TB, blood was obtained for QFT-G testing, in addition to routine investigations. Positive (PPV and negative (NPV predictive values for QFT-G were calculated, comparing patients with confirmed TB and those with other final diagnoses. QFT-G results in TB patients originating from countries with intermediate or high TB incidence were compared with QFT-G results from a control group of recently arrived asymptomatic immigrants from high-incidence countries. Factors associated with QFT-G outcome in patients with confirmed TB were assessed. Results Among 141 patients, 41/70 (58.6% with confirmed TB had a positive QFT-G test, compared to 16/71 (22.6% patients with other final diagnoses, resulting in overall PPV of 71.9% and NPV of 67.6%. For patients with pulmonary disease, PPV and NPV were 61.1% and 67.7%, respectively, and 90.5% and 66.7% for subjects with extrapulmonary manifestations. Comparing patients from high-incidence countries with controls yielded a PPV for active TB of 76.7%, and a NPV of 82.7%. Patients with confirmed TB and positive QFT-G results were characterized by a lower median peripheral white blood cell count (5.9 × 109/L vs. 8.8 × 109/L; P P = 0.043 as compared to QFT-G-negative TB patients. Conclusion The overall PPV and NPV of QFT-G for identifying active TB were unsatisfactory, especially for pulmonary disease. Thus, the usefulness of QFT-G for this purpose is questionable. However, a high PPV was

  5. Smear positive pulmonary tuberculosis and associated risk factors among tuberculosis suspects attending spiritual holy water sites in Northwest Ethiopia.

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    Derseh, Dejene; Moges, Feleke; Tessema, Belay

    2017-01-26

    Tuberculosis (TB) remains one of the world's deadliest communicable diseases. In Ethiopia, tuberculosis patients have different pattern of health care seeking behavior. They usually adopt other approaches like traditional healers and spiritual holy water sites before consulting public health facilities. This study was aimed to assess the prevalence of smear positive pulmonary tuberculosis and associated risk factors among tuberculosis suspects attending spiritual holy water sites. A cross-sectional study was conducted from February 01, 2015 to March 30, 2015 in seven selected holy water sites in Northwest Ethiopia. During the study period, a total of 1384 adult holy water users were screened for PTB symptoms. A total of 382 pulmonary tuberculosis suspects participated in the study. Socio-demographic data were collected using a semi-structured questionnaire. Spot-morning-spot sputum specimens were collected and examined for acid fast bacilli using Auramine O fluorescence staining technique. Smear positive sputum samples were tested by GeneXpert MTB/RIF assay for rifampicin resistance. Descriptive statistics, binary and multivariate logistic regression analysis were employed using SPSS-16 software. The prevalence of smear positive pulmonary tuberculosis was 2.9% with point prevalence of 795/100, 000 holy water users. History of contact with tuberculosis patient (AOR = 9.174, 95% C.I = 2.195-38.34) and the number of family members > 5 per household (AOR = 9.258, 95% C.I = 1.14-74.97) were significantly associated with smear positive pulmonary tuberculosis. Rifampicin resistance was not detected from all smear positives by GeneXpert MTB/RIF assay. The prevalence of smear positive pulmonary tuberculosis in spiritual holy water sites was 7.4 fold higher than the general population. History of contact with active tuberculosis patients and increased family size were significantly associated with smear positive pulmonary TB. The national tuberculosis

  6. Frequency of rapid growing mycobacteria among tuberculosis suspected patients in Basra-Iraq

    National Research Council Canada - National Science Library

    Sulami, Amin A. Al; Taee, Asaad Al; Hasan, Zainab A

    2016-01-01

    Objective: The purpose of this study was to estimate the frequency of rapid growing mycobacteria among tuberculosis suspected patients in Basra governorate and study their resistance to drugs. Methods...

  7. Clinical application of T-spot test of Mycobacterium tuberculosis infection for diagnosis of suspected pulmonary tuberculosis patients

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    Xue-ping SHI

    2017-11-01

    Full Text Available Objective To explore the application value of T-spot test of Mycobacterium tuberculosis infection (T-SPOT.TB on diagnosis and differential diagnosis of pulmonary tuberculosis. Methods From Apr. 2014 to Dec. 2016, 700 patients with suspected pulmonary tuberculosis were collected, venous blood (5ml was drawn off and sputum was collected from each patient separately for T-SPOT.TB and pathogens identification (including TB. Chest CT, bronchoscopy brush or biopsy histopathological examination were followed up, cultivation of My. tuberculosis and of common bacteria with sputum or lavage fluid when needed. T-SPOT.TB test was performed according to the kit instruction operation. 2.5×105 peripheral blood mononuclear cells (PBMCs were added into the pre- coated anti- human γ- interferon antibody, and co-incubated separately with two specific My. tuberculosis antigens, namely early secretory targeting 6 (ESAT-6 and culture filtration protein 10 (CFP-10, and then the spot forming cells (SFCs were counted. The gold standard for present study were set as follows: 1 My. tuberculosis smear positive or culture positive; 2 Clinical diagnosis (meet any one is positive. The efficacy of T-SPOT.TB on diagnosing active TB was observed, and then the optimal critical value for diagnosing active TB was determined. Patients diagnosed as active TB were divided into 4 subgroups: initial treatment group, retreatment group, smear or culture positive group, and smear or culture negative group. T-SPOT.TB was carried out to detect A and B antigen, and the difference of formed SFCs was then compared. The present study was approved by the Ethics Committee of Xinjiang Uygur Autonomous Region Chest Hospital. Results Of 700 cases suspected of pulmonary tuberculosis enrolled in present study, 528 out of 624 definite cases (84.6% were finally diagnosed as active tuberculosis (active TB group and 96 cases (15.4% were as without TB infection (non-TB group. Positive results of T

  8. Shortening Isolation of Patients With Suspected Tuberculosis by Using Polymerase Chain Reaction Analysis

    DEFF Research Database (Denmark)

    Fløe, Andreas; Hilberg, Ole; Thomsen, Vibeke Østergaard

    2015-01-01

    Background. Isolation of patients suspected for pulmonary tuberculosis is guided by serial sputum smears. This can result in isolation for days for patients with noncontagious tuberculosis. To determine whether a single sample negative for Mycobacterium tuberculosis complex at polymerase chain re......-positive/PCR-negative cases underlines the importance of increasing the quantity and quality of samples. Moreover, it is important that samples analyzed with PCR are cultured, owing to higher-sensitivity drug susceptibility testing, differential diagnosis, and surveillance....

  9. Clinical utility of 18 Fluorodeoxyglucose (FDG-PET/CT scans in patients with suspect ocular tuberculosis

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    Salil Mehta

    2013-01-01

    Full Text Available Systemic imaging of patients with suspect ocular tuberculosis include chest X-rays and computed tomography (CT scans. Reports have suggested a role for 18 fluorodeoxyglucose-positron emission tomography/CT (FDG-PET/CT scans. We report on the clinical utility of 18 FDG PET/CT in two patients. Case 1: A 38-year-old female patient presented with recurrent anterior uveitis. A 18 FDG-PET scan revealed metabolically active supraclavicular and chest lymph nodes. An aspiration cytology of the cervical lymph node revealed caseating granulomas suggestive of tuberculosis. Case 2: A 58-year-old female patient presented with recurrent anterior uveitis. A 18 FDG-PET scan revealed metabolically active lymph nodes in the neck. A biopsy of the cervical lymph node revealed epithelioid granulomas suggestive of tuberculosis. Both patients were started on standard antitubercular therapy with a subsequent marked reduction of activity. PET/CT scans may suggest the sites of safe high-yield biopsies.

  10. [Suspected tuberculosis at a refugee center: 79 referred cases in 2 years at St. Loup Hospital].

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    Rieder, Philippe; Zwahlen, André

    2003-02-01

    The recent opening, close to the hospital of Saint-Loup, of an application centre for foreigners who ask for a status of refugee in Switzerland gave us the opportunity, over the last two years, to evaluate 79 patients with suspected tuberculosis. Of them 67% came from sub-Saharan Africa and 25% from Eastern Europe. A bacillary tuberculosis was found in 19 cases (24%), requiring immediate treatment and a respiratory isolation of a mean duration of 18 days. In addition, 11 cases (14%) had non-bacillary tuberculosis with negative sputum smear but positive culture. This new situation led us to implement a specific strategy of hospital hygiene.

  11. Factors associated with late presentation of suspected tuberculosis cases to tuberculosis management facilities: The case in Dagoretti district, Nairobi, Kenya

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    Njau, Irene Wambui; Karanja, Simon Muturi; Wanzala, Peter; Omolo, Jared Odhiambo

    2012-01-01

    Background Tuberculosis is a highly contagious disease accounting for a high number of deaths in the developing countries; its control can be effectively achieved if individuals with the disease receive adequate and timely treatment. The objective of this study was to determine the factors associated with late presentation of suspects to tuberculosis management facilities in Dagoretti district in Nairobi, Kenya. Method A cross sectional study was conducted on patients aged 18 years and above attending TB clinics in Dagoretti District, Nairobi Kenya. A total of 426 TB suspects were interviewed. The study covered 8 clinics in Dagoretti district. Analysis was done using SPSS version 16.0 and Epi info version 6, this included Chi Square for Bivariate analysis and Binary Logistic Regression for Multivariate Analysis. Results Out of the 426 tuberculosis suspects, 248 (58.2%) suspects had delayed in seeking medical care. In Bivariate analysis male gender (P = 0.039, O.R = 1.51; 95% Confidence Interval; 1.00- 2.27), level of education (Primary class 5-8) (P = 0.001, O.R= 2.06; 95% C.I 1.34-3.19) and place of first medical care (drug store) (P= 0.013, O.R = 1.63; 95% C.I 1.09-2.46) were all significantly associated with late presentation. After multivariate logistic regression, gender (P = 0,019, OR = 1.6), level of education (p = 0.029, OR = 1.26) and place of first medical care (P= 0.01 OR = 1.27), were found to be significantly associated with late presentation. Conclusion This study shows that age, level of education and place of first medical care are the factors associated with late presentation of suspects to tuberculosis management facilities. PMID:23077714

  12. Nontuberculous Mycobacteria Isolated from Tuberculosis Suspects in Ibadan, Nigeria

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    Simeon Idowu Cadmus

    2016-01-01

    Full Text Available In Nigeria, one of the highest tuberculosis (TB burdened nations, sputum smear microscopy is routinely employed for TB diagnosis at Directly Observed Treatment Short-Course (DOTS Centers. This diagnostic algorithm does not differentiate Mycobacterium tuberculosis complex (MTC from nontuberculous mycobacteria (NTM. Between December 2008 and January 2009, consecutive patients diagnosed with TB were screened for inclusion at 10 DOTS centers in Ibadan, Nigeria. To verify Mycobacterium species in patients diagnosed, we cultured and identified mycobacterial isolates using PCR, line probe assay, and spoligotyping techniques. From 48 patients screened, 23 met the inclusion criteria for the study. All the 23 study patients had a positive culture. Overall, we identified 11/23 patients (48% with MTC only, 9/23 (39% with NTM only, and 3/23 (13% with evidence of both MTC and NTM. Strains of MTC identified were Latin American Mediterranean (LAM genotype (n=12, M. africanum (n=1, and the genotype family T (n=1. Four M. avium-intracellulare-M. scrofulaceum complexes, one M. chelonae complex, one M. abscessus, and one M. intracellulare were identified. Our findings underscore the need to incorporate molecular techniques for more precise diagnosis of TB at DOTS centers to improve clinical outcomes and safe guard public health, particularly in TB endemic countries.

  13. Comparison of cortisol and thyroid hormones between tuberculosis-suspect and healthy elephants of Nepal.

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    Paudel, Sarad; Brown, Janine L; Thapaliya, Sharada; Dhakal, Ishwari P; Mikota, Susan K; Gairhe, Kamal P; Shimozuru, Michito; Tsubota, Toshio

    2016-12-01

    We compared cortisol and thyroid hormone (T3 and T4) concentrations between tuberculosis (TB)-suspected (n=10) and healthy (n=10) elephants of Nepal. Whole blood was collected from captive elephants throughout Nepal, and TB testing was performed using the ElephantTB STAT-PAK® and DPP VetTB® serological assays that detect antibodies against Mycobacterium tuberculosis and M. bovis in elephant serum. Cortisol, T3 and T4 were quantified by competitive enzyme immunoassays, and the results showed no significant differences in hormone concentrations between TB-suspect and healthy elephants. These preliminary data suggest neither adrenal nor thyroid function is altered by TB disease status. However, more elephants, including those positively diagnosed for TB by trunk wash cultures, need to be evaluated over time to confirm results.

  14. The Knowledge of Lung Tuberculosis Suspects for Sputum Examination Attitude In The Kamoning Primary Health Care

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    Puteri Febriana Arivany

    2017-04-01

    Full Text Available Tuberculosis is an infectious disease caused by the Mycobacterium tuberculosis. Tuberculosis (TB is an infectious disease mostly attacks the lungs TB disease is transmitted by smear positive TB patients through the air when an infected person coughs or sneezes in the form of droplets. Sputum examination is an effort to enforce TB diagnose and to determine the potential of this transmission. The aims was conducted to determine the relationship between the respondents’ knowledge andthe sputum examination in the health center Kamoning Sampang. This research used analytic observational study with survey method using cross sectional. The research performed in 60 patients and sampling method used is imple random sampling. The independent variabel consist of education, occupation, income respondents, education and attitude of the respondent in conducting sputum examination. The strength of correlation was measured by Contingency Coefficient and Odd Ratio (OR were analyzed using chi-square test. Contingency Coefficient of respondents knowledge knowledge suspected pulmonary tuberculosis in sputum examination is 0,253 and OR = 3,600. The conclusion is there was a weak correlation between the respondents knowledge and sputum examination. Symptoms and treatment of pulmonary TB can be identified if the health workers in collaboration with religious leaders and community leaders to provide the Information according to age and education of the respondents. Keywords: knowledge, attitude, TB suspect, sputum examination

  15. Prevalence of Intestinal Parasites and Associated Factors among Pulmonary Tuberculosis Suspected Patients Attending University of Gondar Hospital, Gondar, Northwest Ethiopia

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    Yalewayker Tegegne

    2018-01-01

    Full Text Available Introduction. Intestinal parasitic infections are among the major public health problems in developing countries. Hence, it is significant to explore coinfection with intestinal parasites and pulmonary tuberculosis because coinfection increases the complexity of control and prevention of pulmonary tuberculosis and parasitic diseases. Objective. To assess the prevalence of intestinal parasites among pulmonary tuberculosis suspected patients. Method. Institutional based cross-sectional study was conducted at University of Gondar Hospital from March to May, 2017. Stool samples were taken from each participant and examined by direct microscopy and concentration technique. Descriptive statistics was performed and chi-square test was used to show the association between variables. P values of <0.05 were considered statistically significant. Results. Intestinal parasites were detected in 50 (19.6% among a total of 256 pulmonary tuberculosis suspected patients who were included in the study, whereas the prevalence of pulmonary tuberculosis was 16.8% (43/256. Pulmonary tuberculosis and intestinal parasite coinfection was detected in 5 (2.0% of the participants. The most prevalent intestinal parasites infection in this study was Ascaris lumbricoides, 15 (5.85%, followed by Entamoeba histolytica/dispar, 14 (5.46%, and Hookworm, 13 (5.1%. Conclusion. The prevalence of intestinal parasites and their coinfection rate with pulmonary tuberculosis among pulmonary tuberculosis suspected patients were considerable.

  16. Mycobacterium tuberculosis Complex and HIV Co-Infection among Extrapulmonary Tuberculosis Suspected Cases at the University of Gondar Hospital, Northwestern Ethiopia.

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    Alemu Fanosie

    Full Text Available Extrapulmonary Tuberculosis (EPTB and Human Immunodeficiency Virus (HIV infection are interrelated as a result of immune depression. The aim of this study was to determine the prevalence of Mycobacterium tuberculosis complex isolates and the burden of HIV co-infection among EPTB suspected patients.An institution based cross-sectional study was conducted among EPTB suspected patients at the University of Gondar Hospital. Socio-demographic characteristics and other clinical data were collected using a pretested questionnaire. GeneXpert MTB/RIF assay was performed to diagnosis Mycobacterium tuberculosis complex and Rifampicin resistance. All samples were also investigated by cytology and culture. The HIV statuses of all patients were screened initially by KHB, and all positive cases were further re-tested by STAT-pack. Data was analyzed using SPSS version 20 computer software and a P-value of < 0.05 was taken as statistically significant.A total of 141 extrapulmonary suspected patients were enrolled in this study. The overall prevalence of culture confirmed extrapulmonary tuberculosis infection was 29.8%, but the GeneXpert result showed a 26.2% prevalence of Mycobacterium tuberculosis complex infection. The 78.4% prevalence of extrapulmonary tuberculosis infection was found to be higher among the adult population. The prevalence of HIV infection among EPTB suspected patients was 14.1%, while it was 32.4% among GeneXpert-confirmed extrapulmonary TB cases (12/37. Tuberculosis lymphadenitis was the predominant (78.4% type of EPTB infection followed by tuberculosis cold abscess (10.7%. Adult hood, previous history of contact with known pulmonary tuberculosis patients, and HIV co-infection showed a statistically significant association with extrapulmonary tuberculosis infection (P<0.013.The prevalence of culture confirmed-EPTB infection was high, and a higher EPTB-HIV co-infection was also observed.

  17. Cost-benefit analysis of Xpert MTB/RIF for tuberculosis suspects in German hospitals.

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    Diel, Roland; Nienhaus, Albert; Hillemann, Doris; Richter, Elvira

    2016-02-01

    Our objective was to assess the cost-benefit of enhancing or replacing the conventional sputum smear with the real-time PCR Xpert MTB/RIF method in the inpatient diagnostic schema for tuberculosis (TB).Recent data from published per-case cost studies for TB/multidrug-resistant (MDR)-TB and from comparative analyses of sputum microscopy, mycobacterial culture, Xpert MTB/RIF and drug susceptibility testing, performed at the German National Reference Center for Mycobacteria, were used. Potential cost savings of Xpert MTB/RIF, based on test accuracy and multiple cost drivers, were calculated for diagnosing TB/MDR-TB suspects from the hospital perspective.Implementing Xpert MTB/RIF as an add-on in smear-positive and smear-negative TB suspects saves on average €48.72 and €503, respectively, per admitted patient as compared with the conventional approach. In smear-positive and smear-negative MDR-TB suspects, cost savings amount to €189.56 and €515.25 per person, respectively. Full replacement of microscopy by Xpert MTB/RIF saves €449.98. In probabilistic Monte-Carlo simulation, adding Xpert MTB/RIF is less costly in 46.4% and 76.2% of smear-positive TB and MDR-TB suspects, respectively, but 100% less expensive in all smear-negative suspects. Full replacement by Xpert MTB/RIF is also consistently cost-saving.Using Xpert MTB/RIF as an add-on to and even as a replacement for sputum smear examination may significantly reduce expenditures in TB suspects. Copyright ©ERS 2016.

  18. Mycobacterium tuberculosis Complex and HIV Co-Infection among Extrapulmonary Tuberculosis Suspected Cases at the University of Gondar Hospital, Northwestern Ethiopia.

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    Fanosie, Alemu; Gelaw, Baye; Tessema, Belay; Tesfay, Wogahta; Admasu, Aschalew; Yitayew, Gashaw

    2016-01-01

    Extrapulmonary Tuberculosis (EPTB) and Human Immunodeficiency Virus (HIV) infection are interrelated as a result of immune depression. The aim of this study was to determine the prevalence of Mycobacterium tuberculosis complex isolates and the burden of HIV co-infection among EPTB suspected patients. An institution based cross-sectional study was conducted among EPTB suspected patients at the University of Gondar Hospital. Socio-demographic characteristics and other clinical data were collected using a pretested questionnaire. GeneXpert MTB/RIF assay was performed to diagnosis Mycobacterium tuberculosis complex and Rifampicin resistance. All samples were also investigated by cytology and culture. The HIV statuses of all patients were screened initially by KHB, and all positive cases were further re-tested by STAT-pack. Data was analyzed using SPSS version 20 computer software and a P-value of tuberculosis infection was 29.8%, but the GeneXpert result showed a 26.2% prevalence of Mycobacterium tuberculosis complex infection. The 78.4% prevalence of extrapulmonary tuberculosis infection was found to be higher among the adult population. The prevalence of HIV infection among EPTB suspected patients was 14.1%, while it was 32.4% among GeneXpert-confirmed extrapulmonary TB cases (12/37). Tuberculosis lymphadenitis was the predominant (78.4%) type of EPTB infection followed by tuberculosis cold abscess (10.7%). Adult hood, previous history of contact with known pulmonary tuberculosis patients, and HIV co-infection showed a statistically significant association with extrapulmonary tuberculosis infection (P<0.013). The prevalence of culture confirmed-EPTB infection was high, and a higher EPTB-HIV co-infection was also observed.

  19. Endoscopic ultrasound-guided fine-needle aspiration cytology in the evaluation of suspected tuberculosis in patients with isolated mediastinal lymphadenopathy

    DEFF Research Database (Denmark)

    Puri, R.; Vilmann, P.; Sud, R.

    2010-01-01

    Patients with suspected tuberculosis without pulmonary lesions and with mediastinal lymphadenopathy often pose a diagnostic challenge. Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) cytology is an established modality to evaluate mediastinal and abdominal lesions. The aim...... of the present study was to evaluate the role of EUS-FNA in isolated mediastinal lymphadenopathy in patients suspected of having tuberculosis....

  20. Audit of the practice of sputum smear examination for patients with suspected pulmonary tuberculosis in Fiji.

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    Gounder, Shakti; Tayler-Smith, Katherine; Khogali, Mohammed; Raikabula, Maopa; Harries, Anthony D

    2013-07-01

    In Fiji, patients with suspected pulmonary tuberculosis (PTB) currently submit three sputum specimens for smear microscopy for acid-fast bacilli, but there is little information about how well this practice is carried out. A cross-sectional retrospective review was carried out in all four TB diagnostic laboratories in Fiji to determine among new patients presenting with suspected PTB in 2011: the quality of submitted sputum; the number of sputum samples submitted; the relationship between quality and number of submitted samples to smear-positivity; and positive yield from first, second and third samples. Of 1940 patients with suspected PTB, 3522 sputum samples were submitted: 997 (51.4%) patients submitted one sample, 304 (15.7%) patients submitted two samples and 639 (32.9%) submitted three samples. Sputum quality was recorded in 2528 (71.8%) of samples, of which 1046 (41.4%) were of poor quality. Poor quality sputum was more frequent in females, inpatients and children (0-14 years). Good quality sputum and a higher number of submitted samples positively correlated with smear-positivity for acid-fast bacilli. There were 122 (6.3%) patients with suspected PTB who were sputum smear positive. Of those, 89 had submitted three sputum samples: 79 (89%) were diagnosed based on the first sputum sample, 6 (7%) on the second sample and 4 (4%) on the third sample. This study shows that there are deficiencies in the practice of sputum smear examination in Fiji with respect to sputum quality and recommended number of submitted samples, although the results support the continued use of three sputum samples for TB diagnosis. Ways to improve sputum quality and adherence to recommended guidelines are needed.

  1. Knowledge, health seeking behavior and perceived stigma towards tuberculosis among tuberculosis suspects in a rural community in southwest Ethiopia.

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    Gemeda Abebe

    Full Text Available BACKGROUND: Perceived stigma and lack of awareness could contribute to the late presentation and low detection rate of tuberculosis (TB. We conducted a study in rural southwest Ethiopia among TB suspects to assess knowledge about and stigma towards TB and their health seeking behavior. METHODS: A community based cross sectional survey was conducted from February to March 2009 in the Gilgel Gibe field research area. Any person 15 years and above with cough for at least 2 weeks was considered a TB suspect and included in the study. Data were collected by trained personnel using a pretested structured questionnaire. Logistic regression analysis was done using SPSS 15.0 statistical software. RESULTS: Of the 476 pulmonary TB suspects, 395 (83.0% had ever heard of TB; "evil eye" (50.4% was the commonly mentioned cause of TB. Individuals who could read and write were more likely to be aware about TB [(crude OR = 2.98, (95%CI: 1.25, 7.08] and more likely to know that TB is caused by a microorganism [(adjusted OR = 3.16, (95%CI: 1.77, 5.65] than non-educated individuals. Males were more likely to know the cause of TB [(adjusted OR = 1.92, (95%CI: 1.22, 3.03] than females. 51.3% of TB suspects perceived that other people would consider them inferior if they had TB. High stigma towards TB was reported by 199(51.2%. 220 (46.2% did not seek help for their illness. Individuals who had previous anti-TB treatment were more likely to have appropriate health seeking behavior [(adjusted OR = 3.65, (95%CI: 1.89, 7.06] than those who had not. CONCLUSION: There was little knowledge about TB in the Gilgel Gibe field research area. We observed inappropriate health seeking behavior and stigma towards TB. TB control programs in Ethiopia should educate rural communities, particularly females and non-educated individuals, about the cause and the importance of early diagnosis and treatment of TB.

  2. Evaluation of polymerase chain reaction using primer MPB 64 for diagnosis of clinically suspected cases of extrapulmonary tuberculosis

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    Dnyaneshwari P. Ghadage

    2014-01-01

    Full Text Available Background: Pulmonary tuberculosis can be easily diagnosed by simple techniques such as microscopy. However, extrapulmonary tuberculosis (EPTB often presents a diagnostic dilemma. Microscopy and culture have proved to be insensitive techniques for diagnosis of EPTB. There is an urgent need for rapid and sensitive diagnostic methods. Aim: The present study was conducted to evaluate the role of polymerase chain reaction (PCR in the early diagnosis of clinically suspected cases of EPTB. Materials and Methods: A total of 80 clinical specimens comprising pleural fluid, cerebrospinal fluid, ascitic fluid, fine-needle aspiration biopsy, and pus and biopsy from clinically suspected EPTB cases were processed and followed up by conventional methods and PCR using MPB64 primer. Results: Tuberculous pleural effusion (71% was found to be the most common clinical presentation of EPTB. Overall, PCR could detect EPTB in 61.2% cases. Microscopy and culture could detect 18.7% and 22.5% EPTB cases, respectively. PCR was positive in all tissue samples suggestive of tuberculosis on histopathological examination. Of the 62 EPTB patients who responded to antituberculosis treatment (ATT, 49 patients were PCR positive. Conclusion: PCR using MPB64 had a significant advantage over the conventional methods to detect the presence of M. tuberculosis in specimens of clinically suspected EPTB patients for early diagnosis of tuberculosis.

  3. Distribution of non-tuberculosis mycobacteria strains from suspected tuberculosis patients by heat shock protein 65 PCR–RFLP

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    Ali Nour-Neamatollahie

    2017-09-01

    Full Text Available The genus Mycobacterium contains more than 150 species. Non-tuberculosis mycobacteria (NTM often cause extrapulmonary and pulmonary disease. Mycobacteria detection at species level is necessary and provides useful information on epidemiology and facilitates successful treatment of patients. This retrospective study aimed to determine the incidence of the NTM isolates and Mycobacterium tuberculosis (Mtb in clinical specimens collected from Iranian patients during February 2011–December 2013, by PCR–restriction fragment length polymorphism analysis (PRA of the hsp65 gene. We applied conventional biochemical test and hsp65–PRA identification assay to identify species of mycobacteria in specimens from patients suspected of having mycobacterial isolates. This method was a sensitive, specific and effective assay for detecting mycobacterial species and had a 100% sensitivity and specificity for Mtb and Mycobacterium avium complex (MAC species. Using PRA for 380 mycobacterial selected isolates, including 317 Mtb, four Mycobacterium bovis and of the 59 clinical isolates, the most commonly identified organism was Mycobacterium kansasii (35.6%, followed by Mycobacterium simiae (16.9%, Mycobacterium gordonae (16.9%, Mycobacterium fortuitum (5.1%, Mycobacterium intracellulare (5.1%, Mycobacterium avium (5.1%, Mycobacterium scrofulaceum (3.4%, Mycobacterium gastri (3.4%, Mycobacterium flavescens (3.4%, Mycobacterium chelonae (3.4% and Mycobacterium nonchromogenicum (1.7%. PRA method, in comparison with classical methods, is rapid, useful and sensitive for the phylogenetic analysis and species detection of mycobacterial strains. Mycobacterium kansasii is the most common cause of infection by NTM in patients with non-HIV and HIV which demonstrated a high outbreak and diversity of NTM strains in our laboratory.

  4. [Investigation of the presence of Mycobacterium tuberculosis in the lymph node aspirates of the suspected tularemia lymphadenitis cases].

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    Albayrak, Nurhan; Celebi, Bekir; Kavas, Semra; Simşek, Hülya; Kılıç, Selçuk; Sezen, Figen; Arslantürk, Ahmet

    2014-01-01

    Recently reports of cervical tuberculous lymphadenitis and oropharyngeal tularemia which are the most common infectious causes of granulomatous lymphadenitis, have been significantly increased in Turkey. The differentiation of cervical tuberculous lymphadenitis and oropharyngeal tularemia is usually confusing on the basis of clinical and histopathological findings. Thus, in tularemia endemic areas, the patients are more commonly evaluated in terms of tularemia lymphadenitis leaving tuberculosis out. The aim of this study was to investigate the presence of Mycobacterium tuberculosis in cervical lymph node aspirates, obtained from tularemia suspected cases. A total of 105 oropharyngeal tularemia-suspected cases which were found negative for Francisella tularensis by bacteriological (culture), molecular (PCR) and serological (microagglutination) methods, were included in the study. The samples had been previously studied at National Tularemia Reference Laboratory, Turkish Public Health Institution, between 2009-2011. The study samples were evaluated in terms of M.tuberculosis by culture and real-time PCR (rtPCR) methods in the National Tuberculosis Reference Laboratory. Both Lowenstein-Jensen (LJ) medium and liquid-based MGIT (BD, USA) automated culture system were used for mycobacterial culture. Samples that yielded mycobacterial growth were identified as M.tuberculosis by immunochromotographic test (BD, USA). The lymph node aspirates of 65 patients who were F.tularensis PCR negative but antibody positive, were used as the control group. As a result, M.tuberculosis was found to be positive in 9 (8.6%) of 105 tularemia-negative lymph node aspirates, sent to our laboratory from different geographic regions for the investigation of tularemia. Six of the M.tuberculosis positive cases were male and the age range of the patients was 26-85 years. The presence of M.tuberculosis was detected only by culture in two samples, only by rtPCR in five samples and both by culture and

  5. Patient delay determinants for patients with suspected tuberculosis in Yogyakarta province, Indonesia.

    Science.gov (United States)

    Lock, Willem A; Ahmad, Riris A; Ruiter, Robert A C; van der Werf, Marieke J; Bos, Arjan E R; Mahendradhata, Yodi; de Vlas, Sake J

    2011-12-01

    Indonesia has a high incidence of tuberculosis (TB), despite the successful introduction of the directly observed treatment short-course strategy (DOTS strategy). DOTS depends on passive case finding. It is therefore important to identify determinants of patient delay and reasons for visiting a DOTS healthcare provider when seeking care. The aim of this study was to assess these determinants in TB suspects (coughing for at least 2 weeks). Cross-sectional data were gathered with a structured questionnaire in which psychosocial determinants were based on an extended version of the theory of planned behaviour (TPB). The study was conducted in five governmental lung clinics of Yogyakarta province. In total, 194 TB suspects that registered at the lung clinics were interviewed. The median patient delay was 14 days (range 0-145). Ordinal regression analyses showed that visiting a private healthcare provider when first seeking health care, reporting travel distance/travel time as reason for choosing a certain healthcare provider when first seeking health care, discussing the symptoms with family and a reported short travel time, but no factors of TPB, were significantly associated with a shorter patient delay. An important factor negatively associated with visiting a DOTS clinic was the reported travel time. Accessibility of the healthcare provider was the main determinant of patient delay, but the role of psychosocial factors cannot be fully excluded. Urban and suburban areas have relatively good access to (private) health care, hence the short delay. Thus, future studies should be focussed on extending the DOTS strategy to the private sector. © 2011 Blackwell Publishing Ltd.

  6. Evaluation of Xpert MTB/RIF Versus AFB Smear and Culture to Identify Pulmonary Tuberculosis in Patients With Suspected Tuberculosis From Low and Higher Prevalence Settings.

    Science.gov (United States)

    Luetkemeyer, Anne F; Firnhaber, Cynthia; Kendall, Michelle A; Wu, Xingye; Mazurek, Gerald H; Benator, Debra A; Arduino, Roberto; Fernandez, Michel; Guy, Elizabeth; Johnson, Pamela; Metchock, Beverly; Sattler, Fred; Telzak, Edward; Wang, Yun F; Weiner, Marc; Swindells, Susan; Sanne, Ian M; Havlir, Diane V; Grinsztejn, Beatriz; Alland, David

    2016-05-01

    The Xpert MTB/RIF (Xpert) assay is a rapid nucleic acid amplification test widely used in settings of high tuberculosis prevalence to detect tuberculosis as well asrpoBmutations associated with rifampin resistance. Data are needed on the diagnostic performance of Xpert in lower-prevalence settings to inform appropriate use for both tuberculosis detection and the need for respiratory isolation. Xpert was compared to 2 sputum samples, each evaluated with acid-fast bacilli (AFB) smear and mycobacterial culture using liquid and solid culture media, from participants with suspected pulmonary tuberculosis from the United States, Brazil, and South Africa. Of 992 participants enrolled with evaluable results, 22% had culture-confirmed tuberculosis. In 638 (64%) US participants, 1 Xpert result demonstrated sensitivity of 85.2% (96.7% in participants with AFB smear-positive [AFB(+)] sputum, 59.3% with AFB smear-negative [AFB(-)] sputum), specificity of 99.2%, negative predictive value (NPV) of 97.6%, and positive predictive value of 94.9%. Results did not differ between higher- and low-prevalence settings. A second Xpert assay increased overall sensitivity to 91.1% (100% if AFB(+), 71.4% if AFB(-)), with specificity of 98.9%. In US participants, a single negative Xpert result predicted the absence of AFB(+)/culture-positive tuberculosis with an NPV of 99.7%; NPV of 2 Xpert assays was 100%, suggesting a role in removing patients from airborne infection isolation. Xpert detected tuberculosis DNA and mutations associated with rifampin resistance in 5 of 7 participants with rifampin-resistant, culture-positive tuberculosis. Specificity for rifampin resistance was 99.5% and NPV was 98.9%. In the United States, Xpert testing performed comparably to 2 higher-tuberculosis-prevalence settings. These data support the use of Xpert in the initial evaluation of tuberculosis suspects and in algorithms assessing need for respiratory isolation. © The Author 2016. Published by Oxford

  7. HIV Infection Is Associated with Shortened Telomere Length in Ugandans with Suspected Tuberculosis.

    Science.gov (United States)

    Auld, Elizabeth; Lin, Jue; Chang, Emily; Byanyima, Patrick; Ayakaka, Irene; Musisi, Emmanuel; Worodria, William; Davis, J Lucian; Segal, Mark; Blackburn, Elizabeth; Huang, Laurence

    HIV infection is a risk factor for opportunistic pneumonias such as tuberculosis (TB) and for age-associated health complications. Short telomeres, markers of biological aging, are also associated with an increased risk of age-associated diseases and mortality. Our goals were to use a single cohort of HIV-infected and HIV-uninfected individuals hospitalized with pneumonia to assess whether shortened telomere length was associated with HIV infection, TB diagnosis, and 2-month mortality. This was a sub-study of the IHOP Study, a prospective observational study. Participants consisted of 184 adults admitted to Mulago Hospital in Kampala, Uganda who underwent evaluation for suspected TB and were followed for 2 months. Standardized questionnaires were administered to collect demographic and clinical data. PBMCs were isolated and analyzed using quantitative PCR to determine telomere length. The association between HIV infection, demographic and clinical characteristics, and telomere length was assessed, as were the associations between telomere length, TB diagnosis and 2-month mortality. Variables with a P≤0.2 in bivariate analysis were included in multivariate models. No significant demographic or clinical differences were observed between the HIV-infected and HIV-uninfected subjects. Older age (Paging and that shorter telomeres may be involved in age-associated health complications seen in this population. The findings indicate a need to further research the impact of HIV on aging.

  8. Novel method for sputum induction using the Lung Flute in patients with suspected pulmonary tuberculosis.

    Science.gov (United States)

    Fujita, Akira; Murata, Kengo; Takamori, Mikio

    2009-08-01

    The Lung Flute is a small self-powered audio device that generates sound waves, which vibrate in tracheobronchial secretions. This was a preliminary trial to evaluate the usefulness of the Lung Flute for sputum sampling in patients suspected of pulmonary tuberculosis (TB). Thirty-four patients who were not expectorating sputum, but for whom sputum examination was required for the differential diagnosis of TB or other diseases, were enrolled in the study. Patients were instructed to blow out fast and hard through the Lung Flute and to repeat this for a total 20 sets of two blows each. Using the Lung Flute, sputum samples were collected within 10 or 20 min from 30 of 34 patients (88%). The device permitted a rapid diagnosis of TB in seven of 15 confirmed TB cases. In three patients acid-fast bacillus smears were positive. In four patients acid-fast bacillus smears were negative, but PCR tests for TB were positive. Hyperventilation-related symptoms occurred in three patients. The application of the Lung Flute may represent a promising technique for the rapid diagnosis of pulmonary TB.

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

    Science.gov (United States)

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

    2016-01-01

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

  10. Endoscopic ultrasound-guided fine-needle aspiration cytology in the evaluation of suspected tuberculosis in patients with isolated mediastinal lymphadenopathy

    DEFF Research Database (Denmark)

    Puri, R.; Vilmann, P.; Sud, R.

    2010-01-01

    Patients with suspected tuberculosis without pulmonary lesions and with mediastinal lymphadenopathy often pose a diagnostic challenge. Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) cytology is an established modality to evaluate mediastinal and abdominal lesions. The aim...

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

    Directory of Open Access Journals (Sweden)

    Guillermo Madico

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

  12. HIV Infection Is Associated with Shortened Telomere Length in Ugandans with Suspected Tuberculosis.

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    Elizabeth Auld

    Full Text Available HIV infection is a risk factor for opportunistic pneumonias such as tuberculosis (TB and for age-associated health complications. Short telomeres, markers of biological aging, are also associated with an increased risk of age-associated diseases and mortality. Our goals were to use a single cohort of HIV-infected and HIV-uninfected individuals hospitalized with pneumonia to assess whether shortened telomere length was associated with HIV infection, TB diagnosis, and 2-month mortality.This was a sub-study of the IHOP Study, a prospective observational study. Participants consisted of 184 adults admitted to Mulago Hospital in Kampala, Uganda who underwent evaluation for suspected TB and were followed for 2 months. Standardized questionnaires were administered to collect demographic and clinical data. PBMCs were isolated and analyzed using quantitative PCR to determine telomere length. The association between HIV infection, demographic and clinical characteristics, and telomere length was assessed, as were the associations between telomere length, TB diagnosis and 2-month mortality. Variables with a P≤0.2 in bivariate analysis were included in multivariate models.No significant demographic or clinical differences were observed between the HIV-infected and HIV-uninfected subjects. Older age (P<0.0001, male gender (P = 0.04, total pack-years smoked (P<0.001, alcohol consumption in the past year (P = 0.12, and asthma (P = 0.08 were all associated (P≤0.2 with shorter telomere length in bivariate analysis. In multivariate analysis adjusting for these five variables, HIV-positive participants had significantly shorter telomeres than HIV-negative participants (β = -0.0621, 95% CI -0.113 to -0.011, P = 0.02. Shortened telomeres were not associated with TB or short-term mortality.The association between HIV infection and shorter telomeres suggests that HIV may play a role in cellular senescence and biological aging and that shorter telomeres may be

  13. Evaluation of an interferon-gamma release assay in children with suspected tuberculosis in Papua New Guinea.

    Science.gov (United States)

    Uluk, Tarcisius; Allison, Waridibo E; Vince, John; Wand, Handan; Tefuarani, Nakapi; Causer, Louise M; Ripa, Paulus; Kariko, Maylene; Kaminiel, Oscillah; Cunningham, Philip; Graham, Steve M; Kaldor, John M

    2013-02-01

    There are few data from tuberculosis (TB) endemic settings of the performance and outcome predictors of the QuantiFERON-TB Gold in Tube assay (QFT) in children with suspected TB. A prospective cross-sectional study was conducted in Papua New Guinea children with suspected TB evaluated at Port Moresby General Hospital (Port Moresby, Papua New Guinea). Two hundred sixteen children were enrolled including 106 probable TB, 87 possible TB and 23 without TB. Concordance between QFT and tuberculin skin test results was 86% (P < 0.001, κ = 0.70). QFT was significantly more likely to be positive than tuberculin skin test, overall and within the probable or possible TB categories, with no difference in prevalence of positivity between these 2 categories. The role of QFT in supporting the clinical diagnosis of TB in endemic settings, where resources are limited, remains uncertain especially as cost and technical requirements remain considerable.

  14. Differential Expression of Host Biomarkers in Saliva and Serum Samples from Individuals with Suspected Pulmonary Tuberculosis

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    Khutso G. Phalane

    2013-01-01

    Full Text Available The diagnosis of tuberculosis remains challenging in individuals with difficulty in providing good quality sputum samples such as children. Host biosignatures of inflammatory markers may be valuable in such cases, especially if they are based on more easily obtainable samples such as saliva. To explore the potential of saliva as an alternative sample in tuberculosis diagnostic/biomarker investigations, we evaluated the levels of 33 host markers in saliva samples from individuals presenting with pulmonary tuberculosis symptoms and compared them to those obtained in serum. Of the 38 individuals included in the study, tuberculosis disease was confirmed in 11 (28.9% by sputum culture. In both the tuberculosis cases and noncases, the levels of most markers were above the minimum detectable limit in both sample types, but there was no consistent pattern regarding the ratio of markers in serum/saliva. Fractalkine, IL-17, IL-6, IL-9, MIP-1β, CRP, VEGF, and IL-5 levels in saliva and IL-6, IL-2, SAP, and SAA levels in serum were significantly higher in tuberculosis patients (P<0.05. These preliminary data indicate that there are significant differences in the levels of host markers expressed in saliva in comparison to those expressed in serum and that inflammatory markers in both sample types are potential diagnostic candidates for tuberculosis disease.

  15. Phenotyping and genotyping identification of non-tuberculosis mycobacterium isolated from pulmonary tuberculosis suspected patients in Basrah Governorate

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    Z A Hasan

    2015-01-01

    Conclusions: This study emphasizes that NTM is present at high frequency, especially among TB-suspected patients, and this requires confirmation on a follow-up basis, along with the examination of patterns of sensitivity, and is an absolute necessity rather than the current hour in a health center in Iraq.

  16. Respiratory microbes present in the nasopharynx of children hospitalised with suspected pulmonary tuberculosis in Cape Town, South Africa

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    Felix S. Dube

    2016-10-01

    Full Text Available Abstract Background Lower respiratory tract infection in children is increasingly thought to be polymicrobial in origin. Children with symptoms suggestive of pulmonary tuberculosis (PTB may have tuberculosis, other respiratory tract infections or co-infection with Mycobacterium tuberculosis and other pathogens. We aimed to identify the presence of potential respiratory pathogens in nasopharyngeal (NP samples from children with suspected PTB. Method NP samples collected from consecutive children presenting with suspected PTB at Red Cross Children’s Hospital (Cape Town, South Africa were tested by multiplex real-time RT-PCR. Mycobacterial liquid culture and Xpert MTB/RIF was performed on 2 induced sputa obtained from each participant. Children were categorised as definite-TB (culture or qPCR [Xpert MTB/RIF] confirmed, unlikely-TB (improvement of symptoms without TB treatment on follow-up and unconfirmed-TB (all other children. Results Amongst 214 children with a median age of 36 months (interquartile range, [IQR] 19–66 months, 34 (16 % had definite-TB, 86 (40 % had unconfirmed-TB and 94 (44 % were classified as unlikely-TB. Moraxella catarrhalis (64 %, Streptococcus pneumoniae (42 %, Haemophilus influenzae spp (29 % and Staphylococcus aureus (22 % were the most common bacteria detected in NP samples. Other bacteria detected included Mycoplasma pneumoniae (9 %, Bordetella pertussis (7 % and Chlamydophila pneumoniae (4 %. The most common viruses detected included metapneumovirus (19 %, rhinovirus (15 %, influenza virus C (9 %, adenovirus (7 %, cytomegalovirus (7 % and coronavirus O43 (5.6 %. Both bacteria and viruses were detected in 73, 55 and 56 % of the definite, unconfirmed and unlikely-TB groups, respectively. There were no significant differences in the distribution of respiratory microbes between children with and without TB. Using quadratic discriminant analysis, human metapneumovirus, C. pneumoniae, coronavirus 043

  17. Prevalence of Non-Tuberculosis Mycobacterial Infections among Tuberculosis Suspects in Iran: Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Nasiri, Mohammad Javad; Dabiri, Hossein; Darban-Sarokhalil, Davood; Hashemi Shahraki, Abdolrazagh

    2015-01-01

    The infections due to Non-Tuberculosis Mycobacteria (NTM) are becoming an important health problem in many countries in the world. Globally, an increase in NTM infections has been reported from many countries around the world. However, limited information is available about the prevalence of NTM infections in Iran. The data of the prevalence of NTM infections were collected from databases such as PubMed, Web of science, Cochrane Library, Embase, Scopus, Iranmedex, and Scientific Information Database. Comprehensive Meta-Analysis (V2.0, Biostat) software was used to analyze the data. The meta-analyses showed that the prevalence of NTM infections was 10.2% (95% confidence interval [95% CI] 6.3-15.9) among culture-positive cases of tuberculosis (TB) in Iran. The further stratified analyses indicated that the prevalence of NTM was higher in studies that were done after year 2000. Additionally, M. simiae (43.3% [95% CI 36.8-50.0]), M. intracellucar (27.3% [95% CI 0.7-95.5]) and M. fortuitum (22.7% [95% CI 16.1-30.9]) were the most prevalent NTM species, respectively. The relatively high prevalence of NTM infections (10.2%) among culture positive cases for TB underlines the need for greater enforcement of infection control strategies. Establishment of appropriate diagnostic criteria and management guidelines for NTM diseases and expanding the number and quality of regional reference laboratories may facilitate more accurate action for prevention and control of NTM infections in Iran.

  18. SEVA TB ELISA - Multi antigen and antibody assays for serodiagnosis of suspected cases of pulmonary and extra pulmonary tuberculosis in tertiary care hospital -A retrospective study

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    Pranita J Waghmare

    2012-10-01

    Full Text Available Objective: To assess the usefulness of in-house developed multiantigen and antibody assays, in diagnosis of both pulmonary and extra-pulmonary tuberculosis. Method: Clinically suspected cases of 31 pulmonary and 171 extra-pulmonary tuberculosis (TB were screened by ELISA using cocktail (ES-31 + EST-6 antigen and their specific antibodies (anti ES-31 + anti EST-6 IgG for detection of antibody and and antigen (circulating antigen and immune complexed antigen respectively and correlated with antituberculosis therapy in retrospective study. Results: Out of 31 cases of pulmonary TB screened, 15 patients showed ELISA positivity out of which five cases were given antituberculosis therapy. Out of 171 cases of EPTB screened, 76 cases showed ELISA positivity out of which 18 were given antituberculosis therapy. Further 4 EPTB cases which showed AFB negativity were given ATT. The data was further analyzed based on PTB & EPTB, adults and children, OPD and IPD patients to understand false positivity in clinically suspected PTB and EPTB cases. There was significant correlation (108/202 cases with ELISA negativity and no ATT advised in clinically suspected PTB and EPTB patients. Conclusions: In house developed multi antigen and antibody assays have been observed to be quite useful as adjunct test in serodiagnosis of suspected cases of tuberculosis in particular extrapulmonary tuberculosis.

  19. Prevalence of non-tuberculous mycobacterial infections among tuberculosis suspects in Nigeria.

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    Gambo Aliyu

    Full Text Available Nigeria is ranked in the top five countries for tuberculosis deaths worldwide. This study investigated the mycobacterial agents associated with presumptive clinical pulmonary tuberculosis (TB in Nigeria and evaluated the pattern and frequency of mycobacterial infections over twelve calendar months period.Sputum samples from 1,603 consecutive new cases with presumptive diagnosis of TB were collected from August 2010 to July 2011. All sputum samples were incubated for detection of mycobacterial growth and those with positive acid fast bacilli (AFB growth were tested to detect mycobacterium tuberculosis (MTB complex and characterized to differentiate between MTB complex species. Cultures suggestive of Non-tuberculous mycobacterial infections (NTM were sub-cultured and characterized.Of the 1,603 patients screened, 444 (28% culture-positive cases of pulmonary tuberculosis were identified. Of these, 375 (85% were due to strains of MTB complex (354 cases of M. tuberculosis, 20 M. africanum and one case of M. bovis and 69 (15% were due to infection with NTM. In contrast to the MTB complex cases, the NTM cases were more likely to have been diagnosed during the calendar months of the Harmattan dust season (OR = 2.34, 1.28-4.29; p = 0.01, and aged older than 35 years (OR = 2.77, 1.52-5.02, p = 0.0007, but less likely to have AFB identified on their sputum smear (OR = 0.06, 0.02-0.14, p<0.0001. Among those with NTM infection, cases 35 years or younger were more likely to have co-infection with HIV (3.76, 1.72-8.22; p = 0.0009 compared to those older than 35 years.The high proportion of younger patients with clinical pulmonary TB due to NTM and co-infection with HIV and the likely role of the seasonal dust exposure in the occurrence of the disease, present novel public health challenges for prevention and treatment.

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

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    Eshetu Haileselassie Engeda

    2016-01-01

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

  1. Use of a molecular diagnostic test in AFB smear positive tuberculosis suspects greatly reduces time to detection of multidrug resistant tuberculosis.

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    Nestani Tukvadze

    Full Text Available The WHO has recommended the implementation of rapid diagnostic tests to detect and help combat M/XDR tuberculosis (TB. There are limited data on the performance and impact of these tests in field settings.The performance of the commercially available Genotype MTBDRplus molecular assay was compared to conventional methods including AFB smear, culture and drug susceptibility testing (DST using both an absolute concentration method on Löwenstein-Jensen media and broth-based method using the MGIT 960 system. Sputum specimens were obtained from TB suspects in the country of Georgia who received care through the National TB Program.Among 500 AFB smear-positive sputum specimens, 458 (91.6% had both a positive sputum culture for Mycobacterium tuberculosis and a valid MTBDRplus assay result. The MTBDRplus assay detected isoniazid (INH resistance directly from the sputum specimen in 159 (89.8% of 177 specimens and MDR-TB in 109 (95.6% of 114 specimens compared to conventional methods. There was high agreement between the MTBDRplus assay and conventional DST results in detecting MDR-TB (kappa = 0.95, p<0.01. The most prevalent INH resistance mutation was S315T (78% in the katG codon and the most common rifampicin resistance mutation was S531L (68% in the rpoB codon. Among 13 specimens from TB suspects with negative sputum cultures, 7 had a positive MTBDRplus assay (3 with MDR-TB. The time to detection of MDR-TB was significantly less using the MTBDRplus assay (4.2 days compared to the use of standard phenotypic tests (67.3 days with solid media and 21.6 days with broth-based media.Compared to conventional methods, the MTBDRplus assay had high accuracy and significantly reduced time to detection of MDR-TB in an area with high MDR-TB prevalence. The use of rapid molecular diagnostic tests for TB and drug resistance should increase the proportion of patients promptly placed on appropriate therapy.

  2. T-Cell Immunophenotyping Distinguishes Active From Latent Tuberculosis

    Science.gov (United States)

    Pollock, Katrina M.; Whitworth, Hilary S.; Montamat-Sicotte, Damien J.; Grass, Lisa; Cooke, Graham S.; Kapembwa, Moses S.; Kon, Onn M.; Sampson, Robert D.; Taylor, Graham P.; Lalvani, Ajit

    2013-01-01

    Background. Changes in the phenotype and function of Mycobacterium tuberculosis (M. tuberculosis)-specific CD4+ and CD8+ T-cell subsets in response to stage of infection may allow discrimination between active tuberculosis and latent tuberculosis infection. Methods. A prospective comparison of M. tuberculosis-specific cellular immunity in subjects with active tuberculosis and latent tuberculosis infection, with and without human immunodeficiency virus (HIV) coinfection. Polychromatic flow cytometry was used to measure CD4+ and CD8+ T-cell subset phenotype and secretion of interferon γ (IFN-γ), interleukin 2 (IL-2), and tumor necrosis factor α (TNF-α). Results. Frequencies of CD4+ and CD8+ cells secreting IFN-γ-only, TNF-α-only and dual IFN-γ/TNF-α were greater in active tuberculosis vs latent tuberculosis infection. All M. tuberculosis-specific CD4+ subsets, with the exception of IL-2-only cells, switched from central to effector memory phenotype in active tuberculosis vs latent tuberculosis infection, accompanied by a reduction in IL-7 receptor α (CD127) expression. The frequency of PPD-specific CD4+ TNF-α-only-secreting T cells with an effector phenotype accurately distinguished active tuberculosis from latent tuberculosis infection with an area under the curve of 0.99, substantially more discriminatory than measurement of function alone. Conclusions. Combined measurement of T-cell phenotype and function defines a highly discriminatory biomarker of tuberculosis disease activity. Unlocking the diagnostic and monitoring potential of this combined approach now requires validation in large-scale prospective studies. PMID:23966657

  3. Arginine Adjunctive Therapy in Active Tuberculosis

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    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. Mathematical Modeling of Tuberculosis Granuloma Activation

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    Steve M. Ruggiero

    2017-12-01

    Full Text Available Tuberculosis (TB is one of the most common infectious diseases worldwide. It is estimated that one-third of the world’s population is infected with TB. Most have the latent stage of the disease that can later transition to active TB disease. TB is spread by aerosol droplets containing Mycobacterium tuberculosis (Mtb. Mtb bacteria enter through the respiratory system and are attacked by the immune system in the lungs. The bacteria are clustered and contained by macrophages into cellular aggregates called granulomas. These granulomas can hold the bacteria dormant for long periods of time in latent TB. The bacteria can be perturbed from latency to active TB disease in a process called granuloma activation when the granulomas are compromised by other immune response events in a host, such as HIV, cancer, or aging. Dysregulation of matrix metalloproteinase 1 (MMP-1 has been recently implicated in granuloma activation through experimental studies, but the mechanism is not well understood. Animal and human studies currently cannot probe the dynamics of activation, so a computational model is developed to fill this gap. This dynamic mathematical model focuses specifically on the latent to active transition after the initial immune response has successfully formed a granuloma. Bacterial leakage from latent granulomas is successfully simulated in response to the MMP-1 dynamics under several scenarios for granuloma activation.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    of isoniazid for treatment of LTBI, with an estimated median (range) uptake of 55% (5-92.5%). Symptoms and sputum examination could be used more widely when screening for active tuberculosis. Treatment of latent tuberculosis infection might be better focused by targeted use of interferon-gamma release assays...

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

    DEFF Research Database (Denmark)

    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...

  7. In vitro anti-tuberculosis activity of azole drugs against Mycobacterium tuberculosis clinical isolates.

    Science.gov (United States)

    Imperiale, Belén R; Cataldi, Ángel A; Morcillo, Nora S

    Latent tuberculosis has been associated with the persistence of dormant Mycobacterium tuberculosis in the organism of infected individuals, who are reservoirs of the bacilli and the source for spreading the disease in the community. New active anti-TB drugs exerting their metabolic action at different stages and on latent/dormant bacilli are urgently required to avoid endogenous reactivations and to be part of treatments of multi- and extensively-drug resistant tuberculosis (M/XDR-TB). It was previously reported that azole drugs are active against M. tuberculosis. For that reason, the aims of this study were to determine the in vitro activity of azole drugs, imidazole (clotrimazole, CLO and econazole, ECO) and nitroimidazole (metronidazole, MZ and ipronidazole, IPZ), against a collection of MDR M. tuberculosis clinical isolates; and to analyze their potential use in both the LTB and the active forms of M/XDR-TB treatments. A total of 55 MDR M. tuberculosis isolates and H37Rv were included. MZ and IPZ activity against M. tuberculosis isolates were tested using anaerobic culture conditions. The activity of ECO and CLO was measured by the minimal inhibitory concentration (MIC) using a microdilution colorimetric method. MZ and IPZ showed bacteriostatic activity against M. tuberculosis strains. MIC50 and MIC90 to ECO was 4.0μg/ml, while MIC50 to CLO was 4.0μg/ml and MIC90 was 8.0μg/ml respectively. All azole compounds tested in the study showed inhibitory activity against MDR M. tuberculosis clinical isolates. Copyright © 2017 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

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

    DEFF Research Database (Denmark)

    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 confi......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...

  9. Evaluation of a directly observed six months fully intermittent treatment regimen for tuberculosis in patients suspected of poor compliance.

    Science.gov (United States)

    Caminero, J A; Pavón, J M; Rodríguez de Castro, F; Díaz, F; Julià, G; Caylá, J A; Cabrera, P

    1996-11-01

    Although a priority for tuberculosis control is to achieve the maximum cure rate, compliance with chemotherapy in specific high risk groups (homeless, intravenous drug abusers, chronic alcoholics) is usually poor. From January 1990 to December 1994 102 patients with tuberculosis (96 pulmonary, six extrapulmonary) who were poorly compliant with treatment were treated with a six month fully intermittent (twice weekly) directly observed regimen. They comprised 71 homeless subjects, 50 chronic alcoholics, 23 intravenous drug abusers, nine infected with HIV, and 11 who had previously abandoned a daily antituberculosis regimen; 53 had more than one of these risk factors. Treatment included isoniazid and rifampicin for six months and pyrazinamide during the first two months. Patients who failed to take their medication on two consecutive occasions were actively sought by telephone or by personal search. After two months of treatment 95 of the 102 patients had taken their medication regularly and 90 of them had negative cultures. Four of the remaining patients had negative cultures after three months. At the end of the six months 87 patients had completed treatment and were considered cured. Only 15 patients abandoned the treatment (13 of whom had more than one risk factor). Only three relapses occurred in the 102 patients at one year follow up and in the 88 patients followed for two years. Two patients required a change of treatment due to major side effects. Although intravenous drug abuse was the only predictor of non-compliance in the multivariate analysis, if the available variables in the second month of treatment were analysed, current poor compliance and abandonment of treatment in the past were found to be significantly associated with non-compliance. This study shows the efficacy of this intermittent regimen and the effectiveness of a directly observed treatment programme.

  10. Anti-mycobacterium tuberculosis activity of polyherbal medicines ...

    African Journals Online (AJOL)

    2017-09-03

    Sep 3, 2017 ... Abstract. Background: The emergence of drug-resistant strains of Mycobacterium tuberculosis has become a global public health problem. Polyherbal medicines offer great hope for developing alternative drugs for the treatment of tuberculosis. Objective: To evaluate the anti-tubercular activity of polyherbal ...

  11. Evaluation of Active Case Finding (ACF of Tuberculosis in Slums Population in North of Iran

    Directory of Open Access Journals (Sweden)

    Reza Hoseinpoor

    2017-05-01

    Full Text Available Background At present of the limitation of the current case finding strategies and the global urgency to improve tuberculosis (TB case finding, a renewed interest in active case finding (ACF has risen. World Health Organization (WHO calls for research on TB screening among low-income countries because of the limitation of the passive case finding strategies. We aimed to evaluated Active Case Finding strategy for TB among the slums population in North of Iran (Gorgan city and comprise this procedure to Passive Case Finding. Materials and Methods We conducted a house-to-house survey from April 2016 to July 2016 by trained health volunteers for TB in ten urban slums of Gorgan. Individuals with TB symptoms were identified through targeted screening using a standardized questionnaire and investigated further for TB. Descriptive analyses were performed using Stata-12. Results During study period, of 22,741 individuals screened for TB, 112 (0.49% were identified as TB suspects; 95 suspects were evaluated for TB. TB was diagnosed in four individuals, representing 4.2% of those evaluated for TB as suspected cases. The incidence rate of tuberculosis was 17.5 in 100.000 people in slums population of Gorgan. Of the four detected cases, three individuals had pulmonary TB that among them two cases had new smear-positive TB. Conclusion ACF could supplement current strategies to yield additional TB cases, lead to early diagnosis and better treatment.

  12. Evaluation of two line probe assays for rapid detection of Mycobacterium tuberculosis, tuberculosis (TB) drug resistance, and non-TB Mycobacteria in HIV-infected individuals with suspected TB.

    Science.gov (United States)

    Luetkemeyer, Anne F; Kendall, Michelle A; Wu, Xingye; Lourenço, Maria Cristina; Jentsch, Ute; Swindells, Susan; Qasba, Sarojini S; Sanchez, Jorge; Havlir, Diane V; Grinsztejn, Beatriz; Sanne, Ian M; Firnhaber, Cynthia

    2014-04-01

    Limited performance data from line probe assays (LPAs), nucleic acid tests used for the rapid diagnosis of tuberculosis (TB), nontuberculosis mycobacteria (NTM), and Mycobacterium tuberculosis drug resistance are available for HIV-infected individuals, in whom paucibacillary TB is common. In this study, the strategy of testing sputum with GenoType MTBDRplus (MTBDR-Plus) and GenoType Direct LPA (Direct LPA) was compared to a gold standard of one mycobacterial growth indicator tube (MGIT) liquid culture. HIV-positive (HIV(+)) individuals with suspected TB from southern Africa and South America with tuberculosis culture positive, of which 276 (72.8%) were acid-fast bacillus (AFB) smear positive. MTBDR-Plus had a sensitivity of 81.0% and a specificity of 100%, with sensitivities of 44.1% in AFB smear-negative versus 94.6% in AFB smear-positive specimens. For specimens that were positive for M. tuberculosis by MTBDR-Plus, the sensitivity and specificity for rifampin resistance were 91.7% and 96.6%, respectively, and for isoniazid (INH) they were 70.6% and 99.1%. The Direct LPA had a sensitivity of 88.4% and a specificity of 94.6% for M. tuberculosis detection, with a sensitivity of 72.5% in smear-negative specimens. Ten of 639 MGIT cultures grew Mycobacterium avium complex or Mycobacterium kansasii, half of which were detected by Direct LPA. Both LPA assays performed well in specimens from HIV-infected individuals, including in AFB smear-negative specimens, with 72.5% sensitivity for M. tuberculosis identification with the Direct LPA and 44.1% sensitivity with MTBDR-Plus. LPAs have a continued role for use in settings where rapid identification of INH resistance and clinically relevant NTM are priorities.

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

    Directory of Open Access Journals (Sweden)

    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. Tuberculosis

    Directory of Open Access Journals (Sweden)

    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.

  15. Different screening strategies (single or dual for the diagnosis of suspected latent tuberculosis: a cost effectiveness analysis

    Directory of Open Access Journals (Sweden)

    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

  16. Activation of the NLRP3 inflammasome by Mycobacterium tuberculosis is uncoupled from susceptibility to active tuberculosis.

    Science.gov (United States)

    Dorhoi, Anca; Nouailles, Geraldine; Jörg, Sabine; Hagens, Kristine; Heinemann, Ellen; Pradl, Lydia; Oberbeck-Müller, Dagmar; Duque-Correa, Maria Adelaida; Reece, Stephen T; Ruland, Jürgen; Brosch, Roland; Tschopp, Jürg; Gross, Olaf; Kaufmann, Stefan H E

    2012-02-01

    As a hallmark of tuberculosis (TB), Mycobacterium tuberculosis (MTB) induces granulomatous lung lesions and systemic inflammatory responses during active disease. Molecular regulation of inflammation is associated with inflammasome assembly. We determined the extent to which MTB triggers inflammasome activation and how this impacts on the severity of TB in a mouse model. MTB stimulated release of mature IL-1β in macrophages while attenuated M. bovis BCG failed to do so. Tubercle bacilli specifically activated the NLRP3 inflammasome and this propensity was strictly controlled by the virulence-associated RD1 locus of MTB. However, Nlrp3-deficient mice controlled pulmonary TB, a feature correlated with NLRP3-independent production of IL-1β in infected lungs. Our studies demonstrate that MTB activates the NLRP3 inflammasome in macrophages in an ESX-1-dependent manner. However, during TB, MTB promotes NLRP3- and caspase-1-independent IL-1β release in myeloid cells recruited to lung parenchyma and thus overcomes NLRP3 deficiency in vivo in experimental models. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Binding and Activation of Human Plasminogen by Mycobacterium tuberculosis

    Science.gov (United States)

    Monroy, Verónica; Amador, Angelica; Ruiz, Blanca; Espinoza-Cueto, Patricia; Xolalpa, Wendy; Mancilla, Raul; Espitia, Clara

    2000-01-01

    The first evidence of the interaction of Mycobacterium tuberculosis with the plasminogen system is herein reported. By FACScan analysis and affinity blotting, lysine-dependent binding of plasminogen to M. tuberculosis was demonstrated. The binding molecules were 30-, 60-, and 66-kDa proteins present in cell wall and soluble protein extracts. The activation of plasminogen, which occurred only in presence of fibrin and was not inhibited by the host serpin, α2-antiplasmin, was also demonstrated. PMID:10858253

  18. Increased risk of active tuberculosis after cancer diagnosis.

    Science.gov (United States)

    Simonsen, Dennis F; Farkas, Dóra K; Horsburgh, Charles R; Thomsen, Reimar W; Sørensen, Henrik T

    2017-06-01

    Cancer may increase risk of active tuberculosis but evidence is sparse. We therefore examined tuberculosis risk in patients with incident cancer using Danish nationwide medical databases. We conducted a matched follow-up study comparing risk of active tuberculosis in cancer-exposed individuals to that in a general population comparison cohort, matched on gender, age, and country of origin, in different follow-up intervals using Cox regression. We identified 290,944 patients with incident cancer and 871,147 matched comparison cohort members during 1 January, 2004-30 November, 2013. After adjusting for comorbidities, the overall adjusted hazard ratio (aHR) for tuberculosis among cancer patients was 2.48 (95% confidence interval [CI]: 1.99-3.10). The highest tuberculosis risks were observed following cancers of the aerodigestive tract (aHR = 8.12; 95% CI: 4.33-15.22), tobacco-related cancers (aHR = 5.01; 95% CI: 3.37-7.44), and hematological cancers (aHR = 4.88; 95% CI: 2.27-10.48). Tuberculosis risk was highly elevated within the first year after cancer diagnosis (aHR = 4.14; 95% CI: 2.88-5.96), with a 6.78-fold increased aHR for cancer patients receiving cytostatics or radiotherapy. Beyond five years of observation, the overall aHR for tuberculosis remained at 2.66 (95% CI: 1.22-5.81). Cancer is a clinical predictor for increased risk of active tuberculosis, probably related to decreased infection barriers, immunosuppression, and shared risk factors. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  19. Prevalence of tuberculosis, HIV, and TB-HIV co-infection among pulmonary tuberculosis suspects in a predominantly pastoralist area, northeast Ethiopia

    Science.gov (United States)

    Belay, Mulugeta; Bjune, Gunnar; Abebe, Fekadu

    2015-01-01

    Background TB-HIV co-infection is one of the biggest public health challenges in sub-Saharan Africa. Although there is a wealth of information on TB-HIV co-infection among settled populations in Africa and elsewhere, to our knowledge, there are no published reports on TB-HIV co-infection from pastoral communities. In this study, we report the prevalence of TB, HIV and TB-HIV co-infection among pulmonary TB suspects in the Afar Regional State of Ethiopia. Design In a cross-sectional study design, 325 pulmonary TB suspects were included from five health facilities. Three sputum samples (spot-morning-spot) were collected from each participant. Sputum samples were examined for the presence of acid fast bacilli using Ziehl–Neelsen staining method, and culture was done on the remaining sputum samples. Participants were interviewed and HIV tested. Results Of the 325 pulmonary TB suspects, 44 (13.5%) were smear positive, and 105 (32.3%) were culture positive. Among smear-positive patients, five were culture negative and, therefore, a total of 110 (33.8%) suspects were bacteriologically confirmed pulmonary TB patients. Out of 287 pulmonary TB suspects who were tested for HIV infection, 82 (28.6%) were HIV positive. A significantly higher proportion of bacteriologically confirmed pulmonary TB patients [40 (40.4%)] were HIV co-infected compared with patients without bacteriological evidence for pulmonary TB [42 (22.3%)]. However, among ethnic Afar pastoralists, HIV infections in smear- and/or culture-negative pulmonary TB suspects [7 (7.6%)] and bacteriologically confirmed pulmonary TB patients [4 (11.8%)] were comparable. On multivariable logistic regression analysis, Afar ethnicity was independently associated with low HIV infection [OR=0.16 (95% CI: 0.07–0.37)], whereas literacy was independently associated with higher HIV infection [OR=2.21 (95% CI: 1.05–4.64)]. Conclusions Although the overall prevalence of TB-HIV co-infection in the current study is high, ethnic

  20. Prevalence of tuberculosis, HIV, and TB-HIV co-infection among pulmonary tuberculosis suspects in a predominantly pastoralist area, northeast Ethiopia

    Directory of Open Access Journals (Sweden)

    Mulugeta Belay

    2015-12-01

    Full Text Available Background: TB-HIV co-infection is one of the biggest public health challenges in sub-Saharan Africa. Although there is a wealth of information on TB-HIV co-infection among settled populations in Africa and elsewhere, to our knowledge, there are no published reports on TB-HIV co-infection from pastoral communities. In this study, we report the prevalence of TB, HIV and TB-HIV co-infection among pulmonary TB suspects in the Afar Regional State of Ethiopia. Design: In a cross-sectional study design, 325 pulmonary TB suspects were included from five health facilities. Three sputum samples (spot-morning-spot were collected from each participant. Sputum samples were examined for the presence of acid fast bacilli using Ziehl–Neelsen staining method, and culture was done on the remaining sputum samples. Participants were interviewed and HIV tested. Results: Of the 325 pulmonary TB suspects, 44 (13.5% were smear positive, and 105 (32.3% were culture positive. Among smear-positive patients, five were culture negative and, therefore, a total of 110 (33.8% suspects were bacteriologically confirmed pulmonary TB patients. Out of 287 pulmonary TB suspects who were tested for HIV infection, 82 (28.6% were HIV positive. A significantly higher proportion of bacteriologically confirmed pulmonary TB patients [40 (40.4%] were HIV co-infected compared with patients without bacteriological evidence for pulmonary TB [42 (22.3%]. However, among ethnic Afar pastoralists, HIV infections in smear- and/or culture-negative pulmonary TB suspects [7 (7.6%] and bacteriologically confirmed pulmonary TB patients [4 (11.8%] were comparable. On multivariable logistic regression analysis, Afar ethnicity was independently associated with low HIV infection [OR=0.16 (95% CI: 0.07–0.37], whereas literacy was independently associated with higher HIV infection [OR=2.21 (95% CI: 1.05–4.64]. Conclusions: Although the overall prevalence of TB-HIV co-infection in the current study is

  1. OPPORTUNITIES TO DIAGNOSE ACTIVE TUBERCULOSIS IN THE PATIENTS WITH CLINICALLY CURED RESPIRATORY TUBERCULOSIS

    Directory of Open Access Journals (Sweden)

    G. S. Balasanyants

    2017-01-01

    Full Text Available Goal of the study: to evaluate the test with tuberculous recombinant allergen (TRA in the patients with effective treatment course due to tuberculosis, to investigate the impact of clinical, epidemiological and social factors on persistence of active tuberculosis.Materials and methods. Patients were divided into 2 groups basing on time period after completion of the main treatment course. Group I – 32 patients (up to 6 months, group II – 63 patients (more than 6 months.Results of the study. Results of TRA tests in Group I remained positive in 34.4% of patients and in Group II - 23.8%. The average size of the induration in Group I made 10 mm(95% CI 6.5-13.3, in Group II – 13 mm (95% CI 8.4-19.7 Patients from Group I had positive results of TRA test more often in case of initial infiltrate form of pulmonary tuberculosis and bacillary excretion. In patients from Group II the positive TRA results correlated with presence of concurrent conditions and exposure to a tuberculosis case in the past. Positive results were confidently more often observed in lonely patients in both groups. TRA test can be a valuable tool to evaluate the risk of tuberculosis relapse after completion of the main treatment course. 

  2. The utility of Xpert MTB/RIF performed on bronchial washings obtained in patients with suspected pulmonary tuberculosis in a high prevalence setting.

    Science.gov (United States)

    Barnard, Dewald A; Irusen, Elvis M; Bruwer, Johannes W; Plekker, Danté; Whitelaw, Andrew C; Deetlefs, Jacobus D; Koegelenberg, Coenraad F N

    2015-09-16

    Xpert MTB/RIF has been shown to have a superior sensitivity to microscopy for acid fast bacilli (AFB) in sputum and has been recommended as a standard first line investigation for pulmonary tuberculosis (PTB). Bronchoscopy is a valuable tool in diagnosing PTB in sputum negative patients. There is limited data on the utility of Xpert MTB/RIF performed on bronchial lavage specimens. Our aim was to evaluate the diagnostic efficiency of Xpert MTB/RIF performed on bronchial washings in sputum scarce/negative patients with suspected PTB. All patients with a clinical and radiological suspicion of PTB who underwent bronchoscopy between January 2013 and April 2014 were included. The diagnostic efficiencies of Xpert MTB/RIF and microscopy for AFB were compared to culture for Mycobacterium tuberculosis. Thirty nine of 112 patients were diagnosed with culture-positive PTB. Xpert MTB/RIF was positive in 36/39 with a sensitivity of 92.3% (95% CI 78-98%) for PTB, which was superior to that of smear microscopy (41%; 95% CI 26.0-57.8%, p = 0.005). The specificities of Xpert MTB/RIF and smear microscopy were 87.7% (95% CI 77.4-93.9%) and 98.6% (95% CI 91.6%-99.9%) respectively. Xpert MTB/RIF had a positive predictive value of 80% (95% CI; 65-89.9%) and negative predictive value of 95.5% (95% CI 86.6-98.8%). 3/9 patients with Xpert MTB/RIF positive culture negative results were treated for PTB based on clinical and radiological findings. Xpert MTB/RIF has a higher sensitivity than smear microscopy and similar specificity for the immediate confirmation of PTB in specimens obtained by bronchial washing, and should be utilised in patients with a high suspicion of pulmonary tuberculosis.

  3. Impact of port of entry referrals on initiation of follow-up evaluations for immigrants with suspected tuberculosis: Illinois.

    Science.gov (United States)

    Bell, Teal R; Molinari, NoelleAngelique M; Blumensaadt, Sena; Selent, Monica U; Arbisi, Michael; Shah, Neha; Christiansen, Demian; Philen, Rossanne; Puesta, Benjamin; Jones, Joshua; Lee, Deborah; Vang, Arnold; Cohen, Nicole J

    2013-08-01

    US-bound immigrants with suspected non-infectious TB are encouraged to be medically re-evaluated after arrival in the United States. We evaluated the Centers for Disease Control and Prevention's immigrant referral process, designed to facilitate timely post-arrival evaluations. Over 1,200 immigrants with suspected TB arriving during October 1, 2008-September 30, 2010 were identified. In 2011, differences in days to evaluation initiation were assessed by referral type using survival analysis and Cox proportional hazard models. Among those receiving any referral, median time to post-arrival evaluation was significantly lower compared with immigrants receiving no referral (16 vs. 69 days, respectively; p immigrants receiving any referral initiated follow-up at 4 times the rate (adjusted hazard ratio = 4.0; p ports of entry will improve timeliness and increase the proportion of immigrants initiating domestic evaluation.

  4. 38 CFR 3.374 - Effect of diagnosis of active tuberculosis.

    Science.gov (United States)

    2010-07-01

    ... active tuberculosis. 3.374 Section 3.374 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS... Considerations Relative to Specific Diseases § 3.374 Effect of diagnosis of active tuberculosis. (a) Service diagnosis. Service department diagnosis of active pulmonary tuberculosis will be accepted unless a board of...

  5. Anti Tuberculosis Activity of Forest Kedondong (Spondias pinnata Stembark Extract Against Multiple Drug Resistance (MDR Strain of Mycobacterium Tuberculosis

    Directory of Open Access Journals (Sweden)

    Ida Bagus Putra Dwija

    2016-04-01

    Full Text Available Background: Forest Kedondong (Spondias pinnata traditionally known as “loloh cemcem” and commonly used as a chronic cough remedy. Previous research showed that methanol extract of Forest Kedondong leaves active against MDR strain of Mycobacterium tuberculosis. The aim of this study were to determine the phytochemical constituent and anti tuberculosis activity of stem bark extract of this plant against MDR strain of M. tuberculosis. Method: Coarsely powder of Forest Kedondong stem bark was extracted successively with n-hexane, chloroform and 80% ethanol. Anti tuberculosis assay of chloroform and ethanol extract was conducted using proportion method with Lowenstein-Jensen medium within 3 different concentration of extract of 1, 10, and 100 mg/mL. Activity was evaluated by inhibition of extract against M. tuberculosis growth, which was calculated by mean reduction in number of colonies on extract containing medium compared to control. Results and Discussion: Phytochemical test showed that chloroform extract contains terpenoid and flavonoids. Ethanol extract contains terpenoid, polyphenols and flavonoids. These extracts were active against MDR strain of M. tuberculosis with 100% inhibition at concentration of 100 mg/mL. Chloroform extract has higher inhibition against M. tuberculosis growth than Ethanol extract. Conclusions: These extracts were potentially developed to an anti tuberculosis constituent from natural product.

  6. Native New Zealand plants with inhibitory activity towards Mycobacterium tuberculosis

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    Swift Simon

    2010-06-01

    Full Text Available Abstract Background Plants have long been investigated as a source of antibiotics and other bioactives for the treatment of human disease. New Zealand contains a diverse and unique flora, however, few of its endemic plants have been used to treat tuberculosis. One plant, Laurelia novae-zelandiae, was reportedly used by indigenous Maori for the treatment of tubercular lesions. Methods Laurelia novae-zelandiae and 44 other native plants were tested for direct anti-bacterial activity. Plants were extracted with different solvents and extracts screened for inhibition of the surrogate species, Mycobacterium smegmatis. Active plant samples were then tested for bacteriostatic activity towards M. tuberculosis and other clinically-important species. Results Extracts of six native plants were active against M. smegmatis. Many of these were also inhibitory towards M. tuberculosis including Laurelia novae-zelandiae (Pukatea. M. excelsa (Pohutukawa was the only plant extract tested that was active against Staphylococcus aureus. Conclusions Our data provide support for the traditional use of Pukatea in treating tuberculosis. In addition, our analyses indicate that other native plant species possess antibiotic activity.

  7. Tuberculosis

    Directory of Open Access Journals (Sweden)

    Elena Morán López

    2001-04-01

    Full Text Available En la actualidad la incidencia de la tuberculosis ha aumentado. El Mycobacterium tuberculosis infecta frecuentemente a las personas con SIDA, debido a que en estos pacientes hay una reducción de la resistencia mediada por células T, lo que propicia que este bacilo pueda desarrollar la enfermedad con una frecuencia superior a la de las personas sanas. La transmisión de la enfermedad puede ser por vía directa, de un individuo afectado a otro, fundamentalmente por las gotitas de saliva que contengan a este microorganismo, o por vía indirecta por la inhalación del bacilo que se puede encontrar por meses en los objetos de uso diario, debido a su gran resistencia. Las micobacterias que producen tuberculosis en el hombre inmunocompetente son la Mycobacterium tuberculosis y la bovis, otros tipos pueden provocar tuberculosis en individuos inmunocomprometidos. La patogenicidad de este bacilo está relacionada con su capacidad para escapar de la destrucción inducida por los macrófagos y para provocar hipersensibilidad de tipo retardado. Esta enfermedad tiene muy pocas manifestaciones bucales, lo que se observa generalmente es una úlcera que toma como asiento fundamental el dorso de la lengua. La tuberculosis amenaza con convertirse en una enfermedad incurable por la deficiente administración de los programas contra ésta, por lo que la OMS plantea para su detección y tratamiento el DOTS (tratamiento observado directamente, de corta duración que comienza a tener resultados satisfactorios, aunque en el último quinquenio, el 88 % de los pacientes que se estimaban como infectados por tuberculosis no recibieron DOTS.At present, the incidence of tuberculosis is on the rise. Mycobacterium tuberculosis often infests AIDS patients due to the fact that these persons´T-cell mediated resistance is reduced, which favors the development of the disease at a higher rate than in healthy people. The disease can be transmitted directly, that is , from an

  8. Spooky Suspects

    Science.gov (United States)

    Pacifici, Lara

    2011-01-01

    This activity presents an option for covering biology content while engaging students in an investigation that highlights the spirit of Halloween. Students are engaged in the story line and have fun trying to solve the mystery kidnapping by using science skills to examine the evidence and eliminate some ghoulish suspects. (Contains 1 figure.)

  9. Delayed culture conversion due to cigarette smoking in active pulmonary tuberculosis patients

    NARCIS (Netherlands)

    Nijenbandring de Boer, Renee; Oliveira e Souza Filho, João Baptista de; Cobelens, Frank; Ramalho, Daniela de Paula; Campino Miranda, Pryscilla Fernandes; Logo, Karina de; Oliveira, Hedi; Mesquita, Eliene; Oliveira, Martha Maria; Kritski, Afrânio

    2014-01-01

    Although many studies have assessed factors affecting culture conversion during tuberculosis treatment, few have looked into the effect of tobacco smoking. This study included 89 active pulmonary tuberculosis patients with positive sputum culture upon presentation and collected information regarding

  10. Detection of Anti-Paracoccidioides brasiliensis antibodies in suspected tuberculosis patients = Detecção de anticorpos anti-Paracoccidioides brasiliensis em pacientes suspeitos de tuberculose

    Directory of Open Access Journals (Sweden)

    Maria Luiza Dias Fraga Peron

    2010-07-01

    Full Text Available Paracoccidioidomycosis (PCM is an important systemic mycosis in LatinAmerica that occurs as active disease in 1-2% of Paracoccidioides brasiliensis infected people. Like PCM, tuberculosis (TB affects mainly the lungs and the clinical and radiological aspects do notalways allow differentiation between them. The aim of this study was to carry out serological investigation for detecting anti-P. brasiliensis antibodies, by three serological methods, in patientswith symptoms suggestive of pulmonary TB. From August 2005 to September 2006, 76 patients with pulmonary symptoms suspected for TB were attended at the Regional Specialties Center Laboratory in the city of Paranavaí, Paraná, Brazil and submitted to microbiological TB research, ELISA, immunodiffusion and immunoblotting for PCM. Of all the individuals, 21 (27.63% were reactive to P. brasiliensis by ELISA and 11 (14.47% showed a laboratory diagnosis of pulmonary TB. Of all the individuals serologically reactive to P. brasiliensis, by ELISA, none had positive results by immunodiffusion and one reacted with antigen 43 kDa when Immunobloting was carried out. Our results lead us to reflect a necessity to obtain a more specific serologic test for diagnosis of PCM disease in patients with respiratory symptoms considering the high number of individuals reactive to P. brasiliensis especially in endemic areas.Paracoccidioidomicose (PCM é importante micose sistêmica na América Latina, que ocorre como doença ativa em 1-2% dos indivíduos infectados com Paracoccidioides brasiliensis. Assim como a PCM, a tuberculose (TB afeta principalmente os pulmões, porém os aspectos clínicos e radiológicos nem sempre permitem a diferenciação entreessas doenças. O objetivo deste estudo foi realizar um inquérito sorológico para a detecção de anticorpos anti-P. brasiliensis, utilizando três métodos sorológicos, em pacientes com sintomassugestivos de tuberculose pulmonar. De agosto de 2005 a setembro de

  11. Cholesterol plays a larger role during Mycobacterium tuberculosis in vitro dormancy and reactivation than previously suspected.

    Science.gov (United States)

    Soto-Ramirez, Maria D; Aguilar-Ayala, Diana A; Garcia-Morales, Lazaro; Rodriguez-Peredo, Sofia M; Badillo-Lopez, Claudia; Rios-Muñiz, Diana E; Meza-Segura, Mario A; Rivera-Morales, Gelen Y; Leon-Solis, Lizbel; Cerna-Cortes, Jorge F; Rivera-Gutierrez, Sandra; Helguera-Repetto, Addy C; Gonzalez-Y-Merchand, Jorge A

    2017-03-01

    It is known that cholesterol plays a key role for Mycobacterium tuberculosis (Mtb) adaptation and survival within the host, thus contributing to the establishment of dormancy. It has been extensively demonstrated that fatty acids are the main energy source of Mtb during infection and dormancy, and it has been proposed that these molecules are implicated in reactivation of bacilli from a dormant state. We used in vitro models to analyze Mtb gene expression during dormancy and reactivation when fatty acids and cholesterol are the unique carbon source in the media. Our results suggest that cholesterol might function as a signal to trigger Mtb expression of some genes required for stress protection earlier than the one induced by fatty acids alone, indicating that cholesterol is very favorable for its development. This process is so conducive that cholesterol-adapted bacilli can reactivate their growth after NRP2 dormancy state even 10 min post ventilation. Thus, we hypothesize that cholesterol is not only involved in Mtb dormancy but that it also plays a critical role for favorable and almost immediate reactivation from an in vitro long-lasting dormant state induced by hypoxia. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    OpenAIRE

    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 ...

  13. Progression to active tuberculosis, but not transmission, varies by Mycobacterium tuberculosis lineage in The Gambia

    NARCIS (Netherlands)

    de Jong, Bouke C.; Hill, Philip C.; Aiken, Alex; Awine, Timothy; Antonio, Martin; Adetifa, Ifedayo M.; Jackson-Sillah, Dolly J.; Fox, Annette; Deriemer, Kathryn; Gagneux, Sebastien; Borgdorff, Martien W.; McAdam, Keith P. W. J.; Corrah, Tumani; Small, Peter M.; Adegbola, Richard A.

    2008-01-01

    BACKGROUND: There is considerable variability in the outcome of Mycobacterium tuberculosis infection. We hypothesized that Mycobacterium africanum was less likely than M. tuberculosis to transmit and progress to tuberculosis disease. METHODS: In a cohort study of patients with tuberculosis and their

  14. Incidence of Active Tuberculosis and Cohort Retention Among Adolescents in Western Kenya

    NARCIS (Netherlands)

    Nduba, Videlis; van't Hoog, Anna H.; Mitchell, Ellen M. H.; Borgdorff, Martien; Laserson, Kayla F.

    2018-01-01

    Setting: Siaya County, with the highest tuberculosis notification rates in Kenya. Objectives: To determine the incidence of active tuberculosis and 1-year cohort retention in 12-18-year-old adolescents, in preparation for phase III tuberculosis vaccine trials. Methods: Adolescents were enrolled and

  15. Active and latent tuberculosis among HIV-positive injecting drug users in Indonesia

    NARCIS (Netherlands)

    Meijerink, H.; Wisaksana, R.; Lestari, M.; Meilana, I.; Chaidir, L.; Ven, A.J. van der; Alisjahbana, B.; Crevel, R. van

    2015-01-01

    INTRODUCTION: Injecting drug use (IDU) is associated with tuberculosis but few data are available from low-income settings. We examined IDU in relation to active and latent tuberculosis (LTBI) among HIV-positive individuals in Indonesia, which has a high burden of tuberculosis and a rapidly growing

  16. Identification ofMycobacterium tuberculosisin Clinical Specimens of Patients Suspected of Having Extrapulmonary Tuberculosis by Application of Nested PCR on Five Different Genes.

    Science.gov (United States)

    Khosravi, Azar D; Alami, Ameneh; Meghdadi, Hossein; Hosseini, Atta A

    2017-01-01

    Definitive and rapid diagnosis of extrapulmonary tuberculosis (EPTB) is challenging since conventional techniques have limitations due to the paucibacillary nature of the disease. To increase the sensitivity of detection of Mycobacterium tuberculosis (MTB) in EPTB specimens, we performed a nested PCR assay targeting several genes of MTB on EPTB specimens. A total of 100 clinical specimens from suspected cases of EPTB were processed. Standard staining for acid fast bacilli (AFB) was performed as the preliminary screening test. Extracted DNAs from specimens were subjected to Nested PCR technique for the detection of five different MTB target genes of IS6110, IS1081, hsp65kd, mbp64 , and mtp40 . On performing AFB staining, only 13% of specimens were positive, of which ascites fluid (33.3%), followed by pleural effusion (30.8%) showed the greatest AFB positivity rate. We demonstrated slight improvement in yields in lymph node which comprised the majority of specimens in this study, by employing PCR targeted to IS6110 - and hsp65-genes in comparison to AFB staining. However, the yields in ascites fluid and pleural effusion were not substantially improved by PCR, but those from bone and wound were, as in nested PCR employing either gene, the same positivity rate were obtained for ascites fluid (33.3%), while for pleural effusion specimens only IS1081 based PCR showed identical positivity rate with AFB stain (30.8%). The results for bone and wound specimens, however, demonstrated an improved yield mainly by employing IS1081 gene. Here, we report higher detection rate of EPTB in clinical specimens using five different targeted MTB genes. This nested PCR approach facilitates the comparison and the selection of the most frequently detected genes. Of course this study demonstrated the priority of IS1081 followed by mtp40 and IS6110 , among the five tested genes and indicates the effectiveness of any of the three genes in the design of an efficient nested-PCR test that

  17. [A cross sectional survey on the prevalence of active pulmonary tuberculosis in three 'key' elderly population].

    Science.gov (United States)

    Li, Shuguang; Zhang, Xiulei; Zhu, Li; Li, Haitao; Guo, Xiaoyan; Wang, Yu; Liang, Mingli; Li, Rong; Chu, Dan

    2014-06-01

    To conduct a survey on the prevalence of active pulmonary tuberculosis among 65 year olds or above. Study subjects would include those with characteristics of TB suspicious symptoms, diabetes and close contacts. Purpose-sampling method was applied to choose 3 counties in Shandong province as the study sites, relying on the local basic public health service, for those elderly under 65 years old or above. The study team would introduce the process and contents of this study to the subjects followed by chest X-ray and sputum smears on those registered tuberculosis suspects, patients with diabetes, TB close contacts in the past 2 years, from January to September, 2013. 82 active pulmonary TB cases were identified among 9 041 cases who received the examination, with a crude prevalence rate as 9.1‰. From patients having both suspicious TB and diabetic symptoms, patients with diabetes or having suspicious symptoms of TB, the prevalence rates of active TB were 115‰, 3.4‰, 0.9‰ respectively. No active pulmonary TB case was found in the TB close contacts, patients with diabetes, or those people with suspicious TB symptoms. TB prevalence rates among all the above mentioned groups were significantly different (χ(2) = 697.478, P = 0.000). Prevalence rate of active pulmonary TB with diabetes was 18 times (RR = 17.951) higher than those non-diabetic patients, and 2 times higher than those with suspicious symptoms (RR = 3.860). Results from single factor analysis showed that diabetes were closely related to the prevalence of pulmonary tuberculosis(χ(2) = 46.637, P = 0.000), the longer duration of diabetes and the higher risk of tuberculosis(RR > 1). Our data showed that active pulmonary TB prevalence was high in elderly diabetes patients which suggesting that 'Key crowd screening program' should be introduced into case-finding strategy on TB, with special focus on TB patients with diabetes or those people having suspicious symptoms of TB.

  18. Phloretin Exerts Anti-Tuberculosis Activity and Suppresses Lung Inflammation

    Directory of Open Access Journals (Sweden)

    Dasom Jeon

    2017-01-01

    Full Text Available An increase in the prevalence of the drug-resistant Mycobacteria tuberculosis necessitates developing new types of anti-tuberculosis drugs. Here, we found that phloretin, a naturally-occurring flavonoid, has anti-mycobacterial effects on H37Rv, multi-drug-, and extensively drug-resistant clinical isolates, with minimum inhibitory concentrations of 182 and 364 μM, respectively. Since Mycobacteria cause lung inflammation that contributes to tuberculosis pathogenesis, anti-inflammatory effects of phloretin in interferon-γ-stimulated MRC-5 human lung fibroblasts and lipopolysaccharide (LPS-stimulated dendritic cells were investigated. The release of interleukin (IL-1β, IL-12, and tumor necrosis factor (TNF-α was inhibited by phloretin. The mRNA levels of IL-1β, IL-6, IL-12, TNF-α, and matrix metalloproteinase-1, as well as p38 mitogen-activated protein kinase and extracellular signal-regulated kinase phosphorylation, were suppressed. A mouse in vivo study of LPS-stimulated lung inflammation showed that phloretin effectively suppressed the levels of TNF-α, IL-1β, and IL-6 in lung tissue with low cytotoxicity. Phloretin was found to bind M. tuberculosis β-ketoacyl acyl carrier protein synthase III (mtKASIII with high affinity (7.221 × 107 M−1; a binding model showed hydrogen bonding of A-ring 2′-hydroxy and B-ring 4-hydroxy groups of phloretin with Asn261 and Cys122 of mtKASIII, implying that mtKASIII can be a potential target protein. Therefore, phloretin can be a useful dietary natural product with anti-tuberculosis benefits.

  19. Multiple cytokine responses in discriminating between active tuberculosis and latent tuberculosis infection.

    Science.gov (United States)

    Wu, Jing; Wang, Sen; Lu, Chanyi; Shao, Lingyun; Gao, Yan; Zhou, Zumo; Huang, Heqing; Zhang, Ying; Zhang, Wenhong

    2017-01-01

    Cytokines play an important role in cell-mediated immune responses against Mycobacterium tuberculosis (Mtb) infection. Cytokine profile specifically associated with active tuberculosis (ATB) patients, subjects with latent tuberculosis infection (LTBI) and non-infected individuals remains to be determined. We enrolled a total of 92 subjects including patients with ATB (n = 25), LTBI (n = 36) and healthy controls (HC, n = 31) to investigate the cytokine production by peripheral blood mononuclear cells after Mtb purified protein derivative (PPD) stimulation which was evaluated by a beads-based multiplex assay system. The production of IL-1β, IL-2, IL-6, IL-10, IL-17, G-CSF, IFN-γ, IP-10, MIP-1α and TNF-α was abundantly induced by PPD in all three groups. The levels of IL-2, IL-10, IFN-γ, IP-10 and TNF-α were significantly higher in LTBI group than in ATB group. The combination of PPD-stimulated IL-2 and IL-10 accurately identified 84.0% of ATB and 88.9% of LTBI. We validated the use of PPD-stimulated IL-2 and IL-10 test combined with T-SPOT.TB test in a cohort of 44 subjects with TB suspicion. The sensitivity and specificity of the combined test were 83.3% and 92.3%, respectively. The PPD-stimulated IL-2/IFN-γ ratio (p < 0.001) in LTBI subjects was significantly higher than in active TB patients. Our study identified cytokine patterns characteristic of ATB and LTBI. Cytokines such as IL-2 and IL-10 may serve as biomarkers for distinguishing ATB from LTBI and healthy control and may contribute to intervention and improvement in TB diagnosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Anti-Mycobacterium tuberculosis activity of fungus Phomopsis stipata

    Directory of Open Access Journals (Sweden)

    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.

  1. Anti-Mycobacterium tuberculosis activity of fungus Phomopsis stipata

    Science.gov (United States)

    de Prince, Karina Andrade; Sordi, Renata; Pavan, Fernando Rogério; Barreto Santos, Adolfo Carlos; Araujo, Angela R.; Leite, Sergio R.A.; Leite, Clarice Q. F.

    2012-01-01

    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. PMID:24031821

  2. Are intestinal helminths risk factors for developing active tuberculosis?

    DEFF Research Database (Denmark)

    Elias, Daniel; Mengistu, Getahun; Akuffo, Hannah

    2006-01-01

    OBJECTIVES: To determine the prevalence of intestinal helminth infections in active tuberculosis patients and their healthy household contacts and to assess its association with active TB in an area endemic for both types of infections. METHODS: Smear-positive pulmonary TB patients and healthy......: Intestinal helminth infection may be one of the risk factors for the development of active pulmonary TB in addition to HIV infection. This finding may have important implications in the control of TB in helminth endemic areas of the world....

  3. Nutritional supplements for people being treated for active tuberculosis.

    Science.gov (United States)

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

    2016-06-29

    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. To assess the effects of oral nutritional supplements in people being treated with antituberculous drug therapy for active tuberculosis. 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. 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. 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. Thirty-five trials, including 8283 participants, met the inclusion criteria of this review. Macronutrient supplementation

  4. Nutritional supplements for people being treated for active tuberculosis

    Science.gov (United States)

    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

  5. Active and passive screening for tuberculosis in Vaud Canton, Switzerland.

    Science.gov (United States)

    Monney, Murielle; Zellweger, Jean-Pierre

    2005-08-06

    This retrospective study compared the bacteriological and clinical presentation of tuberculosis and the outcome of treatment in immigrants notified for TB after active screening by chest X-ray at the border with other patients detected by passive screening. Retrospective study of all patients notified for TB in Vaud Canton in 2001 and 2002. In Vaud Canton 78% of the 179 patients notified for TB were foreign-born. Among 71 asylum seekers actively screened at the border, 49.3% [CI 37.4-61.2] were symptom-free vs 17.6% [CI 10.3-24.9] among 108 passively screened patients. In the passively screened group, the proportion of asymptomatic patients was 15.4% for Swiss patients, 8.6% for foreign workers, and 29.4% for other foreigners. The average duration of symptoms before diagnosis among patients with complaints was 2 months in actively screened foreign-born, compared to 2.5 months in passively screened patients (no significant difference by Wilcoxon-Mann-Whitney test). The proportion of pulmonary TB cases with positive smear or culture was 63.4% in actively screened patients vs 70.4% in passively detected cases. Among actively screened patients with bacteriological confirmation, 42.2% [CI 27.2-57.2] were asymptomatic compared to 13% [CI 5.31-20.7] for passively screened patients. Considering only smear positive patients, the proportion of symptom-free patients was 22.2% [CI 9.6-34.8] in 45 actively screened cases vs 11.7% [4.4-19.0] for 77 passive screening. Cure and treatment completion rate for new cases reached 88% for foreign workers, 83% for asylum seekers, 85% for Swiss patients, and 78% for other foreigners. Actively screened patients were more frequently asymptomatic than passively detected cases, even when considering only patients with bacteriological confirmation. The active screening by chest X-ray of an immigrant population with a high prevalence of tuberculosis allows the early detection and treatment of tuberculosis. This may contribute to the protection

  6. Detection of anti-tuberculosis activity in some folklore plants by radiometric BACTEC assay.

    Science.gov (United States)

    Gupta, V K; Shukla, C; Bisht, G R S; Saikia, D; Kumar, S; Thakur, R L

    2011-01-01

    The anti-tubercular drugs are less effective because of the emergence of multi-drug resistant (MDR) and extensively drug resistant (XDR) strains of M. tuberculosis, so plants being an alternative source of anti-microbial compounds. The aim of this study was to investigate anti-tuberculosis potential of the plants using Mycobacterium smegmatis as a rapid screening model for detection of anti-mycobacterial activity and further to evaluate the active plants for anti-tuberculosis activity against M. tuberculosis using radiometric BACTEC assay. The 15 plants were screened for anti-mycobacterial activity against M. smegmatis by the disk diffusion assay. The ethanolic extracts of Mallotus philippensis, Vitex negundo, Colebrookea oppositifolia, Rumex hastatus, Mimosa pudica, Kalanchoe integra and Flacourtia ramontchii were active against M. smegmatis in primary screening. The anti-tuberculosis potential was identified in the leaves extracts of Mallotus philippensis by radiometric BACTEC assay. The ethanolic extract of M. philippensis showed anti-tuberculosis activity against virulent and avirulent strains of M. tuberculosis H(37) Rv and M. tuberculosis H(37) Ra with minimum inhibitory concentration 0·25 and 0·125 mg ml(-1), respectively. The inhibition in growth index values of M. tuberculosis was observed in the presence of ethyl acetate fraction at a minimum concentration of 0·05 mg ml(-1). We found that BACTEC radiometric assay is a valuable method for detection of anti-tuberculosis activity of the plant extracts. The results indicate that ethanolic extract and ethyl acetate fraction of M. philippensis exhibited significant anti-mycobacterial activity against M. tuberculosis. These findings provide scientific evidence to support the traditional medicinal uses of M. philippensis and indicate a promising potential of this plant for the development of anti-tuberculosis agent. © 2010 The Authors. Letters in Applied Microbiology © 2010 The Society for Applied

  7. Proteomic Analysis of Plasma in Adult Active Pulmonary Tuberculosis Patients with Diabetes Mellitus.

    Science.gov (United States)

    Zhang, Xiulian; Ma, Aiguo; Sun, Shuangling; Sun, Yongye

    2015-01-01

    There is a high burden of both diabetes and tuberculosis in China. Diabetes depresses the immunologic response that facilitates the development of infectious diseases, including infection by Mycobacterium tuberculosis, the agent of tuberculosis. Tuberculosis is the third cause of death among subjects with non-communicable diseases, and among the non-communicable diseases, diabetes is one of the most important. The relationship between diabetes and tuberculosis has already been object of many investigations but the association between these two diseases is not fully understood. The aim of this study was to determine whether relative qualitative and quantitative differences in protein expression of plasma could be related to active pulmonary tuberculosis complicated with diabetes. Biological parameters are useful tools for understanding and monitoring complicated disease processes. Our study employed two-dimensional gel electrophoresis and mass spectrometry to analyze the proteins associated with active pulmonary tuberculosis complicated with diabetes. Under the baseline condition, we found that the levels of α-1 antitrypsin precursor, vitamin D-binding protein precursor, CD5 antigen like precursor, clusterin precursor, apolipoprotein A-I precursor, haptoglobin, and fibrinogen γ-chain differed between patients with active pulmonary tuberculosis and active pulmonary tuberculosis complicated with diabetes subjects. Western blotting results confirmed differential expression of clusterin. We identified active pulmonary tuberculosis complicated with diabetes-associated proteins in plasma. C-terminal haptoglobin is a possible candidate protein of interest, which might be a link between active pulmonary tuberculosis and diabetes. The dynamics of protein expression during disease progression may improve our understanding of the pathogenesis of active pulmonary tuberculosis complicated with diabetes.

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

    Directory of Open Access Journals (Sweden)

    Simon Blankley

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

  9. Evaluation of Xpert® MTB/RIF Assay in Induced Sputum and Gastric Lavage Samples from Young Children with Suspected Tuberculosis from the MVA85A TB Vaccine Trial.

    Science.gov (United States)

    Bunyasi, Erick Wekesa; Tameris, Michele; Geldenhuys, Hennie; Schmidt, Bey-Marrie; Luabeya, Angelique Kany Kany; Mulenga, Humphrey; Scriba, Thomas J; Hanekom, Willem A; Mahomed, Hassan; McShane, Helen; Hatherill, Mark

    2015-01-01

    Diagnosis of childhood tuberculosis is limited by the paucibacillary respiratory samples obtained from young children with pulmonary disease. We aimed to compare accuracy of the Xpert® MTB/RIF assay, an automated nucleic acid amplification test, between induced sputum and gastric lavage samples from young children in a tuberculosis endemic setting. We analyzed standardized diagnostic data from HIV negative children younger than four years of age who were investigated for tuberculosis disease near Cape Town, South Africa [2009-2012]. Two paired, consecutive induced sputa and early morning gastric lavage samples were obtained from children with suspected tuberculosis. Samples underwent Mycobacterial Growth Indicator Tube [MGIT] culture and Xpert MTB/RIF assay. We compared diagnostic yield across samples using the two-sample test of proportions and McNemar's χ2 test; and Wilson's score method to calculate sensitivity and specificity. 1,020 children were evaluated for tuberculosis during 1,214 admission episodes. Not all children had 4 samples collected. 57 of 4,463[1.3%] and 26 of 4,606[0.6%] samples tested positive for Mycobacterium tuberculosis on MGIT culture and Xpert MTB/RIF assay respectively. 27 of 2,198[1.2%] and 40 of 2,183[1.8%] samples tested positive [on either Xpert MTB/RIF assay or MGIT culture] on induced sputum and gastric lavage samples, respectively. 19/1,028[1.8%] and 33/1,017[3.2%] admission episodes yielded a positive MGIT culture or Xpert MTB/RIF assay from induced sputum and gastric lavage, respectively. Sensitivity of Xpert MTB/RIF assay was 8/30[26.7%; 95% CI: 14.2-44.4] for two induced sputum samples and 7/31[22.6%; 11.4-39.8] [p = 0.711] for two gastric lavage samples. Corresponding specificity was 893/893[100%;99.6-100] and 885/890[99.4%;98.7-99.8] respectively [p = 0.025]. Sensitivity of Xpert MTB/RIF assay was low, compared to MGIT culture, but diagnostic performance of Xpert MTB/RIF did not differ sufficiently between induced sputum

  10. Risk Factors of Active Tuberculosis in People Living with HIV/AIDS ...

    African Journals Online (AJOL)

    BACKGROUND: Determinants of active tuberculosis among People Living with HIV/AIDS (PLHA) are not well elucidated in countries with limited resources. The objective of this study was to assess distal and proximate determinants of active tuberculosis among people living with HIV/AIDS in southwest. Ethiopia.

  11. Prevalence, risk factors and social context of active pulmonary tuberculosis among prison inmates in Tajikistan.

    Directory of Open Access Journals (Sweden)

    Daniel E Winetsky

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

  12. Avaliação de um escore clínico para rastreamento de suspeitos de tuberculose pulmonar Evaluación de un escore para rastreo de sospechosos de tuberculosis pulmonar Assessment of a clinical score for screening suspected pulmonary tuberculosis cases

    Directory of Open Access Journals (Sweden)

    Cristiano Bel Alves de Castro

    2011-12-01

    symptoms were collected. The presumptive diagnosis of pulmonary tuberculosis was made by summing up the scores of the data collected. The diagnosis of active tuberculosis was based on bacteriological findings and medical criteria. There were estimated sensitivity, specificity, positive predictive value and negative predictive value for a set prevalence, and 95% confidence intervals for different score cutoffs. The score performance was assessed using the receiver operating characteristic (ROC curve. RESULTS: For the diagnosis of tuberculosis, cough for more than one week and cough for more than three weeks showed a sensitivity of 88.2% (86.2, 90.2 and 61.1% (57.93, 64.3, specificity 19.2% (16.6, 21.8 and 51.3% (48.1, 54.5, respectively. The clinical score of 8 had a sensitivity of 83.13% (77.8, 87.6, specificity of 51.8% (48.5, 55.1, positive predictive value of 91.6% (90.0, 83.2 and negative predictive value of 32.9% (30.1, 35.7. CONCLUSIONS: Cough for more than three weeks showed low sensitivity and specificity. A highly sensitive clinical score can be an alternative tool for screening pulmonary tuberculosis as it allows early care of suspected cases and standard nursing care approach.

  13. Influence on intraocular pressure of the postural change and daily activities in the early morning in suspected glaucoma patients

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    Ting Chen

    2014-05-01

    Full Text Available AIM:To evaluate the influence on intraocular pressure(IOPof the postural change and daily activities in the early morning in suspected glaucoma patients.METHODS:The supine and sitting IOP were measured and analyzed on 51 suspected glaucoma patients(100 eyeswith Icare rebound tonometer before and after getting up and daily activities in the early morning. RESULTS: The mean of sitting IOP of 51 patients was 17.12±4.53mmHg, which was significantly lower than the mean of supine IOP(19.14±5.51mmHg. The mean of IOP before and after daily activity of 51 patients were 17.12±4.53mmHg and 14.44±3.90mmHg respectively, which showed significantly difference. CONCLUSION:Postural change and daily activities can result in significant changes of IOP in suspected glaucoma patients.

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

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    Tenna Ephrem

    2015-02-01

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

  15. Liquid vs Solid Culture Medium to Evaluate Proportion and Time to Change in Management of Suspects of Tuberculosis-A Pragmatic Randomized Trial in Secondary and Tertiary Health Care Units in Brazil.

    Science.gov (United States)

    Moreira, Adriana da Silva Rezende; Huf, Gisele; Vieira, Maria Armanda Monteiro da Silva; Costa, Paulo Albuquerque da; Aguiar, Fábio; Marsico, Anna Grazia; Fonseca, Leila de Souza; Ricks, Mônica; Oliveira, Martha Maria; Detjen, Anne; Fujiwara, Paula Isono; Squire, Stephen Bertel; Kritski, Afranio Lineu

    2015-01-01

    The use of liquid medium (MGIT960) for tuberculosis (TB) diagnosis was recommended by WHO in 2007. However, there has been no evaluation of its effectiveness on clinically important outcomes. A pragmatic trial was carried out in a tertiary hospital and a secondary health care unit in Rio de Janeiro City, Brazil. Participants were 16 years or older, suspected of having TB. They were excluded if only cerebral spinal fluid or blood specimens were available for analysis. MGIT960 technique was compared with the Lowenstein-Jensen (LJ) method for laboratory diagnosis of active TB. Primary outcome was the proportion of patients who had their initial medical management changed within 2 months after randomisation. Secondary outcomes were: mean time for changing the procedure, patient satisfaction with the overall treatment and adverse events. Data were analysed by intention-to-treat. Between April 2008 and September 2011, 693 patients were enrolled (348 to MGIT, 345 to LJ). Smear and culture results were positive for 10% and 15.7% of participants, respectively. Patients in the MGIT arm had their initial medical management changed more frequently than those in the LJ group (10.1% MGIT vs 3.8% LJ, RR 2.67 95% CI 1.44-.96, p = 0.002, NNT 16, 95% CI 10-39). Mean time for changing the initial procedure was greater in LJ group at both sites: 20.0 and 29.6 days in MGIT group and 52.2 and 64.3 in LJ group (MD 33.5, 95% CI 30.6-36.4, p = 0.0001). No other important differences were observed. This study suggests that opting for the MGIT960 system for TB diagnosis provides a promising case management model for improving the quality of care and control of TB. Controlled-Trials.com ISRCTN79888843.

  16. Liquid vs Solid Culture Medium to Evaluate Proportion and Time to Change in Management of Suspects of Tuberculosis-A Pragmatic Randomized Trial in Secondary and Tertiary Health Care Units in Brazil.

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    Adriana da Silva Rezende Moreira

    Full Text Available The use of liquid medium (MGIT960 for tuberculosis (TB diagnosis was recommended by WHO in 2007. However, there has been no evaluation of its effectiveness on clinically important outcomes.A pragmatic trial was carried out in a tertiary hospital and a secondary health care unit in Rio de Janeiro City, Brazil. Participants were 16 years or older, suspected of having TB. They were excluded if only cerebral spinal fluid or blood specimens were available for analysis. MGIT960 technique was compared with the Lowenstein-Jensen (LJ method for laboratory diagnosis of active TB. Primary outcome was the proportion of patients who had their initial medical management changed within 2 months after randomisation. Secondary outcomes were: mean time for changing the procedure, patient satisfaction with the overall treatment and adverse events. Data were analysed by intention-to-treat. Between April 2008 and September 2011, 693 patients were enrolled (348 to MGIT, 345 to LJ. Smear and culture results were positive for 10% and 15.7% of participants, respectively. Patients in the MGIT arm had their initial medical management changed more frequently than those in the LJ group (10.1% MGIT vs 3.8% LJ, RR 2.67 95% CI 1.44-.96, p = 0.002, NNT 16, 95% CI 10-39. Mean time for changing the initial procedure was greater in LJ group at both sites: 20.0 and 29.6 days in MGIT group and 52.2 and 64.3 in LJ group (MD 33.5, 95% CI 30.6-36.4, p = 0.0001. No other important differences were observed.This study suggests that opting for the MGIT960 system for TB diagnosis provides a promising case management model for improving the quality of care and control of TB.Controlled-Trials.com ISRCTN79888843.

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

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    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.

  18. Plasma drug activity assay for treatment optimization in tuberculosis patients.

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    Heysell, Scott K; Mtabho, Charles; Mpagama, Stellah; Mwaigwisya, Solomon; Pholwat, Suporn; Ndusilo, Norah; Gratz, Jean; Aarnoutse, Rob E; Kibiki, Gibson S; Houpt, Eric R

    2011-12-01

    Low antituberculosis (TB) drug levels are common, but their clinical significance remains unclear, and methods of measurement are resource intensive. Subjects initiating treatment for sputum smear-positive pulmonary TB were enrolled from Kibong'oto National TB Hospital, Tanzania, and levels of isoniazid, rifampin, ethambutol, and pyrazinamide were measured at the time of typical peak plasma concentration (C(2 h)). To evaluate the significance of the effect of observed drug levels on Mycobacterium tuberculosis growth, a plasma TB drug activity (TDA) assay was developed using the Bactec MGIT system. Time to detection of plasma-cocultured M. tuberculosis versus time to detection of control growth was defined as a TDA ratio. TDA assays were later performed using the subject's own M. tuberculosis isolate and C(2 h) plasma from the Tanzanian cohort and compared to drug levels and clinical outcomes. Sixteen subjects with a mean age of 37.8 years ± 10.7 were enrolled. Fourteen (88%) had C(2 h) rifampin levels and 11 (69%) had isoniazid levels below 90% of the lower limit of the expected range. Plasma spiked with various concentrations of antituberculosis medications found TDA assay results to be unaffected by ethambutol or pyrazinamide. Yet with a range of isoniazid and rifampin concentrations, TDA exhibited a statistically significant correlation with drug level and drug MIC, and a TDA of ~1.0 indicated the presence of multidrug-resistant TB. In Tanzania, low (≤ 2.0) TDA was significantly associated with both lower isoniazid and rifampin C(2 h) levels, and very low (≤ 1.5) TDA corresponded to a trend toward lack of cure. Study of TDA compared to additional clinical outcomes and as a therapeutic management tool is warranted.

  19. A case of tuberculosis reactivation suspected of cancer progression during oral tyrosine kinase inhibitor treatment in a patient diagnosed as non-small cell lung cancer.

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    Lee, Hwa Young; Kim, Jin Woo; Yeo, Chang Dong

    2017-08-01

    We report a first case of a patient experiencing reactivation of pulmonary tuberculosis (TB) during treatment of oral tyrosine kinase inhibitor (TKI) with non-small cell lung cancer (NSCLC). A 44-year-old male patient visited the hospital with cough. He had been treated with erlotinib (oral TKI) for 8 months after being diagnosed as NSCLC with sensitive epidermal growth factor receptor mutation in our clinic. At initial chest imaging, the patient had fibroatelectatic calcified granuloma in the right upper lobe (RUL) apex as well as 1.9 cm × 2.5 cm sized cancer mass encasing the RUL bronchus. He had not been treated for active pulmonary TB before. He had no known history of contact with active TB patients. During the past treatment period, he had shown overall stable response to erlotinib for 8 months. However, chest computed tomography taken for the fourth response evaluation showed increased number and size of nodules with bronchial luminal narrowing in RUL compared to the last exam, suggesting disease progression. We performed bronchoscopy to re-biopsy the cancer mass. Mucosal biopsy and bronchial washing fluid culture revealed active endobronchial pulmonary TB rather than lung cancer progression. Based on these study results, we started anti-TB medications without changing chemotherapy regimen. After 7 months of treatment for pulmonary TB with erlotinib maintenance, he has been shown successful regression of pulmonary TB with stable chemotherapeutic response. Previously, several reports have described the effect of anti-cancer therapy on the treatment of active TB. However, there has been no case report presenting TB reactivation during oral TKI treatment in NSCLC. Therefore, we suggest that the risk of TB reactivation should be considered in patients with solid organ malignancies even if targeted agents are used. Moreover, misdiagnosis of disease progression must be ruled out.

  20. The risk and timing of tuberculosis diagnosed in smear-negative TB suspects: a 12 month cohort study in Harare, Zimbabwe.

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    Munyaradzi Dimairo

    Full Text Available BACKGROUND: Cases of smear-negative TB have increased dramatically in high prevalence HIV settings and pose considerable diagnostic and management challenges. METHODS AND FINDINGS: Between February 2006 and July 2007, a cohort study nested within a cluster-randomised trial of community-based case finding strategies for TB in Harare, Zimbabwe was undertaken. Participants who had negative sputum smears and remained symptomatic of TB were follow-up for one year with standardised investigations including HIV testing, repeat sputum smears, TB culture and chest radiography. Defaulters were actively traced to the community. The objectives were to investigate the incidence and risk factors for TB. TB was diagnosed in 218 (18.2% participants, of which 39.4% was bacteriologically confirmed. Most cases (84.2% were diagnosed within 3 months, but TB incidence remained high thereafter (111.3 per 1000 person-years, 95% CI: 86.6 to 146.3. HIV prevalence was 63.3%, and HIV-infected individuals had a 3.5-fold higher risk of tuberculosis than HIV-negative individuals. CONCLUSION: We found that diagnosis of TB was insensitive and slow, even with early radiography and culture. Until more sensitive and rapid diagnostic tests become widely available, a much more proactive and integrated approach towards prompt initiation of ART, ideally from within TB clinics and without waiting for TB to be excluded, is needed to minimise the risk and consequences of diagnostic delay.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    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 sympt...

  2. Active pulmonary tuberculosis: Role for amikacin in early treatment.

    Science.gov (United States)

    Méchaï, F; Figoni, J; Leblanc, C; Gousseff, M; Vignier, N; Bouchaud, O

    2016-09-01

    To evaluate the efficacy of amikacin on sputum conversion during initial sputum smear positive tuberculosis treatment. Single-center observational cohort study (2012-2013) evaluating time to sputum smear conversion with standard treatment (ST) versus standard treatment+amikacin (IV 15mg/kg/day) for seven days (STamK). Forty-five patients were included. Median time to smear negative samples was 26.5 days (14-56) for the 30 (66.7%) patients included in the ST group and 48 days (19.5-69.5) for the 15 patients (33.3%) included in the STamK group (P=0.76). Time to negative culture was only known for 27 patients (61.4%): 47.5 days (26-58) for 18 patients in the ST group and 40 days (14-77) for nine patients in the STamK group. Despite our small sample size, the addition of amikacin in active tuberculosis treatment did not seem to impact time to smear conversion or period of contagiousness. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. Mefloquine and Its Enantiomers Are Active against Mycobacterium tuberculosis In Vitro and in Macrophages

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    Luiz E. Bermudez

    2014-01-01

    Full Text Available Objective. Tuberculosis is a serious problem of public health. The increase on the number of clinical cases of tuberculosis infected with multidrug resistant (MDR M. tuberculosis calls for the development of novel therapy. Design. We investigated the effect of mefloquine and two enantiomers, (+erythro-mefloquine and (+threo-mefloquine against M. tuberculosis strains in the environment resembling the aspects of the granuloma environment and in macrophages. Results. The results suggest that mefloquine (racemic mixture and (+erythro-mefloquine have bactericidal activity against M. tuberculosis strains both in acidic, low oxygen tension and in macrophages. The activity, however, was impaired under increased osmolarity. Conclusion. Identification of the target for mefloquine in the pathogen will allow for the development of novel drugs with antituberculosis activity.

  4. Quantification of disease activity in patients undergoing leucocyte scintigraphy for suspected inflammatory bowel disease

    Energy Technology Data Exchange (ETDEWEB)

    Cheow, Heok K.; Voutnis, Demetrius D.; Evans, John W.; Szczepura, Katy R.; Swift, E. Anna; Bird, Nicholas J.; Ruparelia, Prina; Solanki, Chandra K.; Ballinger, James R.; Chilvers, Edwin R.; Peters, A. Michael [Addenbrooke' s Hospital, Department of Nuclear Medicine, Cambridge (United Kingdom); Middleton, Stephen J. [Addenbrooke' s Hospital, Department of Gastroenterology, Cambridge (United Kingdom)

    2005-03-01

    Whole-body gamma camera counting is an alternative to faecal {sup 111}In collection for quantifying disease activity in inflammatory bowel disease (IBD) but requires administration of imaging activities of {sup 111}In. The aim of this study was to explore a dedicated whole-body counter which requires 20-fold less activity than gamma camera counting. Thirty patients with known or suspected IBD received {sup 99m}Tc-granulocytes ({proportional_to}200 MBq) and {sup 111}In-granulocytes ({proportional_to}0.5 MBq). The {sup 99m}Tc-cells were injected 45 min after the {sup 111}In-cells and immediately after a baseline {sup 111}In whole-body count. The decay-corrected count at 120 h was expressed as a fraction of baseline to give whole-body {sup 111}In retention (WBR). One patient was excluded as the injected cells were non-viable. Median 45-min intravascular {sup 111}In recovery was 35% in patients compared with 43% in six normal volunteers (p<0.05). WBR in normals ranged from 91% to 93% and in 11 patients with negative {sup 99m}Tc imaging from 87% to 96%. Only one of 11 patients with negative imaging had WBR <90% while 11/12 patients with WBR <90% had abnormal imaging. Ten of 13 patients with Crohn's disease (CD) had abnormal imaging. The lowest WBR in these ten was 77% and six had values of >90%. There was a significant association between WBR and {sup 99m}Tc image grade (R{sub s}=0.73, p<0.002) in 16 patients without CD, but not in 13 patients with CD (R{sub s}=0.54, p>0.05). Dedicated whole-body counting is able to quantify disease activity in IBD but may give normal values in active CD. (orig.)

  5. Serum levels of interleukin-6 in contacts of active pulmonary tuberculosis

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    Fernando Henrique Azevedo Lopes

    2013-12-01

    Full Text Available INTRODUCTION: It is estimated that over two billion individuals are infected by Mycobacterium tuberculosis worldwide. Interleukin-6 (IL-6 is an important cytokine whose serum levels are commonly high in active pulmonary tuberculosis (TB. IL-6 screening in contacts of patients with TB may be useful to monitor the progress of the infectious process and to infer the risk of progression to active disease. OBJECTIVE: To evaluate the serum levels of interleukin-6 in contacts of patients with active pulmonary tuberculosis and to compare them with two other groups: a patients affected by active pulmonary tuberculosis; b non-contacts of tuberculosis. METHODS: Cross-sectional study with 15 contacts of patients with active pulmonary tuberculosis, selected according to the protocol recommended by the Ministry of Health. The serum levels of interleukin-6 were measured by Enzyme-linked immunosorbent assay (ELISA. The same test was also applied in the two comparison groups: 38 patients with active pulmonary tuberculosis (confirmed by clinical examination, X-rays of the chest and baciloscopy and 63 non-contacts (healthy blood donors. RESULTS: In the contact group, the median IL-6 concentration was 1.7 pg/ml (0.96-4.8 pg/ml. For those affected by active pulmonary tuberculosis and non-contact individuals, these values corresponded to 4.3 pg/ml (0.5-24 pg/ml and 0.5 pg/ml (0-2.8 pg/ml, respectively (p < 0.0001. CONCLUSION: Contacts of patients with active pulmonary tuberculosis had significantly higher IL-6 serum levels (3.4 times higher in relation to non-contact individuals, but on a lower level (2.5 times lower when compared to those affected by active disease.

  6. Mycobacterium tuberculosis 19-kDa lipoprotein promotes neutrophil activation.

    Science.gov (United States)

    Neufert, C; Pai, R K; Noss, E H; Berger, M; Boom, W H; Harding, C V

    2001-08-01

    Certain microbial substances, e.g., LPS, can activate neutrophils or prime them to enhance their response to other activating agents, e.g., fMLP. We investigated the role of the Mycobacterium tuberculosis (MTB) 19-kDa lipoprotein in activation of human neutrophils. MTB 19-kDa lipoprotein initiated phenotypic changes characteristic of neutrophil activation, including down-regulation of CD62 ligand (L-selectin) and up-regulation of CD35 (CR1) and CD11b/CD18 (CR3, Mac-1). In addition, exposure of neutrophils to MTB 19-kDa lipoprotein enhanced the subsequent oxidative burst in response to fMLP as assessed by oxidation of dihydrorhodamine 123 (determined by flow cytometry). LPS also produced these effects with similar kinetics, but an oligodeoxynucleotide containing a CpG motif failed to induce any priming or activation response. Although the effects of LPS required the presence of serum, neutrophil activation by MTB 19-kDa lipoprotein occurred independently of serum factors, suggesting the involvement of different receptors and signaling mechanisms for LPS and MTB 19-kDa lipoprotein. Thus, MTB 19-kDa lipoprotein serves as a pathogen-associated molecular pattern that promotes neutrophil priming and activation.

  7. Home humidity increased risk of tuberculosis in children living with adult active tuberculosis cases

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    Pudji Lestari

    2016-02-01

    Full Text Available Indonesia is one of the countries with the largest number of tuberculosis (TB cases in the world. Environmental factors play significant roles in infection and disease development in children living with adult active TB cases. The aim of this study was to explore the environmental factors affecting TB risk in children, including humidity and number of people living in the same house with the children.  Using a cross-sectional study design, children living with active TB adults for at least 8 weeks were recruited. The subjects underwent clinical examination, tuberculin skin test (TST and radiological investigations. Home visits were conducted three times daily, namely in the morning, at midday, and in the evening, to measure humidity by digital hygrometer and to observe home conditions. Of 56 index cases living with active TB adults in an urban low socio-economic setting, 64 contact TB children were recruited. These children were classified as class I with negative TST and no clinical signs, class II with positive TST and no clinical signs, and class III with both positive TST and clinical signs. There were 32 (50% class I, 10 (15.6% class II and 22 (34.3% class III children. However, a sub-sample of 43 showed positive results for Mtb 16S rRNA, indicating that all children were infected. The humidity cut-off point was set at 75%, p=0.04 and EP 2.09 (CI= 1.32-3.29, signifying that children living in houses with a humidity higher than 75%, were twice more likely to be tuberculin positive. Environmental conditions playing a role in disease development were humidity and number of people living in the house.

  8. Evaluation and Comparison of Body Mass Index and Albumin Level in Patients with Active Tuberculosis and Latent Tuberculosis Infection

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    Fatemeh Heidarnezhad

    2016-06-01

    Full Text Available Introduction: Limited data are available on the relationship between nutritional status and tuberculosis. The aim of this study was to evaluate and compare the body mass index (BMI and serum albumin level in patients with active tuberculosis (ATB and latent tuberculosis (LTB. Materials and Methods: A cross-sectional study was conducted on 17 patients newly diagnosed with pulmonary TB  who were referred in Iran, during September 2011 to March 2012 and 17 latent tuberculosis infection individuals. Standard method was performed to collect an early morning fasting blood sample for albumin (by the bromocresolgreen method. Also (BMI was calculated as body weight divided by height squared (kg/m2. Results: One-sample Kolmogorov-Smirnov test was used to check normal distribution data The mean ± Standard deviation(SD for albumin in the patients and controls were 3.62±0/56 and 4.68±0.25, respectively. BMI in the patients and controls were 19.46±2.79 and  25.4±3.46, respectively. The serum albumin level was significantly lower in the patient group, compared to the control group (P

  9. Active tuberculosis in psoriasis patients treated with TNF antagonists: a French nationwide retrospective study.

    Science.gov (United States)

    Guinard, E; Bulai Livideanu, C; Barthélémy, H; Viguier, M; Reguiai, Z; Richard, M A; Jullien, D; Beneton, N; Bara, C; Vabres, P; Grandvuillemin, A; Marguery, M C; Amelot, F; Konstantinou, M P; Bagheri, H; Paul, C

    2016-08-01

    There is limited information about active tuberculosis (TB) occurring in psoriasis patients treated with Tumor necrosis factor (TNF) antagonists. To describe the clinical characteristics of TB in psoriasis patients treated with TNF antagonists. Nationwide retrospective study of psoriasis patients having experienced TB. Cases of TB were collected via three methods: search in the national pharmacosurveillance database, questionnaire to members of the French psoriasis research group, the college of French dermatology professors. We collected demographic data, TNF antagonist used, screening for latent tuberculosis infection, median time between TNF antagonists introduction and first symptoms, tests used for diagnosing TB infection, clinical features of tuberculosis and outcome. Eight centres reported 12 cases of TB between 2006 and 2014. They were nine men and three women with mean age of 49 years. All patients had adequate screening for latent tuberculosis. Three patients had stayed in endemic areas, three reported contact with a patient with TB. Tuberculosis presentation was extrapulmonary in 10 patients. Seven patients were treated with infliximab, four with adalimumab and one with certolizumab. The median time between TNF antagonist introduction and first symptoms of tuberculosis was 23.4 weeks (2-176). Six of the 12 patients had a positive direct examination and/or positive culture for Mycobacterium tuberculosis. Histological samples of affected organs taken from seven patients showed granulomatous inflammation in six, with caseating necrosis in five. Two of the 12 patients died of disseminated TB. This study shows tuberculosis in patients treated with TNF antagonists still occurs despite adherence to tuberculosis prevention guidelines. Prophylactic measures do not fully prevent the occurrence of tuberculosis. Rapid initiation of effective anti-tuberculosis treatment is important even in patients with negative mycobacteriological examination presenting with

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

    DEFF Research Database (Denmark)

    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...

  11. The Cyclic Peptide Ecumicin Targeting ClpC1 Is Active against Mycobacterium tuberculosis In Vivo

    Science.gov (United States)

    Gao, Wei; Kim, Jin-Yong; Anderson, Jeffrey R.; Akopian, Tatos; Hong, Seungpyo; Jin, Ying-Yu; Kandror, Olga; Kim, Jong-Woo; Lee, In-Ae; Lee, Sun-Young; McAlpine, James B.; Mulugeta, Surafel; Sunoqrot, Suhair; Wang, Yuehong; Yang, Seung-Hwan; Yoon, Tae-Mi; Goldberg, Alfred L.; Pauli, Guido F.; Cho, Sanghyun

    2014-01-01

    Drug-resistant tuberculosis (TB) has lent urgency to finding new drug leads with novel modes of action. A high-throughput screening campaign of >65,000 actinomycete extracts for inhibition of Mycobacterium tuberculosis viability identified ecumicin, a macrocyclic tridecapeptide that exerts potent, selective bactericidal activity against M. tuberculosis in vitro, including nonreplicating cells. Ecumicin retains activity against isolated multiple-drug-resistant (MDR) and extensively drug-resistant (XDR) strains of M. tuberculosis. The subcutaneous administration to mice of ecumicin in a micellar formulation at 20 mg/kg body weight resulted in plasma and lung exposures exceeding the MIC. Complete inhibition of M. tuberculosis growth in the lungs of mice was achieved following 12 doses at 20 or 32 mg/kg. Genome mining of lab-generated, spontaneous ecumicin-resistant M. tuberculosis strains identified the ClpC1 ATPase complex as the putative target, and this was confirmed by a drug affinity response test. ClpC1 functions in protein breakdown with the ClpP1P2 protease complex. Ecumicin markedly enhanced the ATPase activity of wild-type (WT) ClpC1 but prevented activation of proteolysis by ClpC1. Less stimulation was observed with ClpC1 from ecumicin-resistant mutants. Thus, ClpC1 is a valid drug target against M. tuberculosis, and ecumicin may serve as a lead compound for anti-TB drug development. PMID:25421483

  12. Natural killer cell activity in multidrug-resistant pulmonary tuberculosis.

    Science.gov (United States)

    Yildiz, P; Kadakal, F; Tütüncü, Y; Deniz, G; Gürel, N; Adin, S; Yilmaz, V

    2001-01-01

    Multidrug-resistant pulmonary tuberculosis (MDRTB), a major problem in developing countries, may result from either insufficiency of host cellular immune response or mycobacterial mechanisms which has been more intensively investigated so far. The aim of the study was to investigate natural killer cell activity (NKA) and T lymphocyte subsets in HIV- patients with secondary MDRTB. 20 male patients with MDRTB (mean age 38 +/- 8 years), 15 nonresistant tuberculosis male patients (NRTB) (mean age 36 +/- 11 years) and 12 healthy male controls (mean age 35 +/- 8 years) were included. The percentages of CD3+, CD4+, CD8+, CD25+, CD11b+ and CD16+56+ cells were measured by flow-cytometric analysis of peripheral blood lymphocytes (PBL). NKA was evaluated using the anticandidal index method. The mean tuberculin response was higher in MDRTB and NRTB patients compared to controls (15.4 +/- 3.8, 15.1 +/- 3.3 and 10.9 +/- 2.8 mm, respectively; p PBL subsets or NKA. The percentages of both CD3+ and CD3+CD4+ T lymphocytes were significantly lower in MDRTB (62.4 +/- 12.1 and 33.9 +/- 9.0%) compared to NRTB (70.8 +/- 7.5 and 42.9 +/- 8.6%; p < 0.05). Patients with MDRTB had significantly lower NKA compared to NRTB and controls (30.9 +/- 11.3, 49.7 +/- 15.5 and 40.0 +/- 8.5%, respectively; p < 0.01). This reduction in NKA may suggest a role for impaired NK function in the pathogenesis of MDRTB in HIV- patients. Copyright 2001 S. Karger AG, Basel

  13. Prevalence of Mycobacterium avium and Mycobacterium tuberculosis in blood cultures of Brazilian AIDS patients after introduction of highly active retroviral therapy

    Directory of Open Access Journals (Sweden)

    S.M. Nakatani

    Full Text Available The use of highly active antiretroviral therapy (HAART for the treatment of HIV infection has been associated with a marked reduction in the incidence of most opportunistic infections. From April 2001 to February 2002, 80 blood samples from patients who were suspected to have disseminated mycobacterial infection, presenting fever and (preferably a CD4 T cell count < 100.0 cell/mL were investigated. Twelve (15% of the 80 blood cultures were positive for mycobacteria, with Mycobacterium avium being identified in 7 (8.8% samples and M. tuberculosis in 5 (6.2%. The TCD4+ count at the time of M. avium bacteremia ranged from 7cells/µL (average of 48.5 cell/µL, while in M. tuberculosis bacteremia it ranged from 50.0 cells/µL (average of 80.0 cell/µL. The prevalence of M. avium bacteremia in our study follows the expected decline in opportunistic infections observed after the introduction of HAART; however, mycobacteremia by M. tuberculosis still indicates a high prevalence of tuberculosis infection in AIDS patients.

  14. Primary lung cancer coexisting with active pulmonary tuberculosis.

    Science.gov (United States)

    Varol, Y; Varol, U; Unlu, M; Kayaalp, I; Ayranci, A; Dereli, M S; Guclu, S Z

    2014-09-01

    Lung cancer and pulmonary tuberculosis (TB) comorbidity is a clinical problem that presents a challenge for the diagnosis and treatment of both diseases. To clarify the clinical and survival characteristics of cases with both lung cancer and active pulmonary TB. From 2008 to 2013, 3350 TB patients admitted to the TB Department of the Chest Diseases Hospital of Izmir, Turkey, were evaluated. In 38 (1.1%) male patients, lung cancer and TB were found to coexist. Almost all of the patients were diagnosed at Stage III (n = 14, 36.8%) or IV (n = 17, 44.7%) lung cancer, whereas four (10.6%) had Stage II and three (7.9%) had Stage I disease. Squamous cell lung cancer was the predominant histology (n = 23, 60.7%). The median overall survival among patients was 13.4 months (95%CI 8.09-18.8). One-year survival rates for patients with Stages I, II, III and IV were respectively 100%, 75%, 57% and 40%. The present study demonstrates that lung cancer combined with active pulmonary TB most frequently presents as squamous cell carcinoma, with a male predominance. The overall survival of lung cancer patients did not change even with concomitant active TB.

  15. Neurohormonal activation and diagnostic value of cardiac peptides in patients with suspected mild heart failure

    DEFF Research Database (Denmark)

    Mikkelsen, Kirsten V.; Bie, Peter; Møller, Jacob E.

    2006-01-01

    accuracy of cardiac peptides to detect any left ventricular dysfunction (LVD) in patients referred from primary care with suspected HF before institution of medical therapy. METHODS: Of 166 referred patients 150 were consecutively included (14 were excluded and two refused consent). Echocardiography...

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  17. Tuberculosis Screening and Active Tuberculosis among HIV-Infected Persons in a Canadian Tertiary Care Centre

    Directory of Open Access Journals (Sweden)

    Paul Brassard

    2009-01-01

    Full Text Available RATIONALE: HIV infection increases the risk of reactivation of latent tuberculosis (TB. The present study evaluates how latent TB is detected and treated to determine the effectiveness of screening in HIV-infected patients with diverse risk profiles.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. In vitro activities of DA-7157 and DA-7218 against Mycobacterium tuberculosis and Nocardia brasiliensis.

    Science.gov (United States)

    Vera-Cabrera, Lucio; Gonzalez, Eva; Rendon, Adrian; Ocampo-Candiani, Jorge; Welsh, Oliverio; Velazquez-Moreno, Victor M; Choi, Sung Hak; Molina-Torres, Carmen

    2006-09-01

    The in vitro activities of DA-7157, a novel oxazolidinone, against clinical isolates of Nocardia brasiliensis and Mycobacterium tuberculosis were determined. Equal MIC(50)s and MIC(90)s (0.25 and 0.5 microg/ml, respectively) were found for susceptible and multidrug-resistant isolates of M. tuberculosis. The N. brasiliensis isolates showed an MIC(90) of 1 microg/ml and an MIC(50) of 1 microg/ml. The DA-7157 prodrug, DA-7218, exhibited similar MICs for M. tuberculosis but fivefold-higher MICs for N. brasiliensis.

  20. An Early Morning Sputum Sample Is Necessary for the Diagnosis of Pulmonary Tuberculosis, Even with More Sensitive Techniques: A Prospective Cohort Study among Adolescent TB-Suspects in Uganda

    Directory of Open Access Journals (Sweden)

    Willy Ssengooba

    2012-01-01

    Full Text Available The World Health Organization (WHO recommends collection of two sputum samples for tuberculosis (TB diagnosis, with at least one being an early morning (EM using smear microscopy. It remains unclear whether this is necessary even when sputum culture is employed. Here, we determined the diagnostic yield from spot and the incremental yield from the EM sputum sample cultures among TB-suspected adolescents from rural Uganda. Sputum samples (both spot and early-morning from 1862 adolescents were cultured by the Lowenstein-Jensen (LJ and Mycobacterium Growth Indicator Tube (MGIT methods. For spot samples, the diagnostic yields for TB were 19.0% and 57.1% with LJ and MGIT, respectively, whereas the incremental yields (not totals of the early-morning sample were 9.5% and 42.9% (P<0.001 with LJ and MGIT, respectively. Among TB-suspected adolescents in rural Uganda, the EM sputum culture has a high incremental diagnostic yield. Therefore, EM sputum in addition to spot sample culture is necessary for improved TB case detection.

  1. Association between diabetes mellitus and active tuberculosis in Africa and the effect of HIV.

    Science.gov (United States)

    Bailey, S L; Ayles, H

    2017-03-01

    To determine current evidence for the association between diabetes and active tuberculosis in Africa, and how HIV modifies, or not, any association between diabetes and active tuberculosis. We conducted a systematic review by searching the EMBASE, Global Health and MEDLINE databases. Studies were eligible for inclusion if they explored the association between diabetes mellitus prevalence and active tuberculosis incidence or prevalence, used a comparison group, were conducted in an African population and adjusted the analysis for at least age. Study characteristics were compared, and risk of bias was assessed. The range of effect estimates was determined for the primary association and for effect modification by HIV. Three eligible studies were identified: two investigated the primary association and two investigated HIV as a potential effect modifier. All studies were case-control studies, including a combined total of 1958 tuberculosis cases and 2111 non-tuberculosis controls. Diabetes diagnostic methods and analysis strategies varied between studies. Individual study adjusted odds ratios of active tuberculosis for the effect of diabetes mellitus (unstratified) ranged from 0.88 (95% CI 0.17-4.58) to 10.7 (95% CI 4.5-26.0). Individual study P-values for HIV interaction ranged from 0.01 to 0.83. Quantitative synthesis of individual study data was not performed due to heterogeneity between studies. Few data currently exist on the association between diabetes and active tuberculosis in Africa, and on the effect of HIV on this association. Existing data are disparate. More regional research is needed to guide policy and practice on the care and control of tuberculosis and diabetes in Africa. © 2016 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

  2. [Acute intestinal tuberculosis].

    Science.gov (United States)

    Nguyen Duc, C; Pha Hai, B; Pham Van, T; Ton That, B; Huguier, M

    2006-05-01

    To report cases from Vietnam of intestinal tuberculosis disease, which is uncommon but did not disappear in occidental countries. Seventy-six patients were included in this retrospective study. Mean age was 40 years and sex ratio M/F was 6. Diagnosis was established on pathological examination of resected specimen or on presence of Mycobacterium tuberculosis or by polymerase chain reaction. Intestinal obstruction or subobstruction was the most usual symptom (68%), and thereafter peritoneal symptoms with pain and tenderness (17%). Five patients had intractable digestive haemorrhage. Thirty-six patients had no past history or active pulmonary tuberculosis (47%). Lesions of stenosis on barium enema and thickness of intestinal wall on CT-scan were not specific. Sixty-two patients were operated on (82%) and 14 were not. Surgical techniques differed according symptoms, site and type of lesions. Intestinal resections were performed in half of the patients, others undergoing stomies or enterolysis. There were eight postoperative deaths (13% of patients operated on), seven out of these deaths were attributable to cachexy. In the postoperative period, all the patients were medically treated and follow-up in the antituberculosis centre of Hanoi. Symptomatology and operative findings of intestinal tuberculosis are similar to those observed in Crohn's disease, and sometimes in amoeboma or lymphoma. In face of stenosis and intestinal wall thickness, probability of intestinal tuberculosis is high in endemic area, but diagnosis must be suspected in occidental countries, mainly in patients immigrated coming from these areas, patients with immuno-deficiency even if they did not have past or present pulmonary tuberculosis.

  3. Active and latent tuberculosis among HIV-positive injecting drug users in Indonesia.

    Science.gov (United States)

    Meijerink, Hinta; Wisaksana, Rudi; Lestari, Mery; Meilana, Intan; Chaidir, Lydia; van der Ven, Andre J A M; Alisjahbana, Bachti; van Crevel, Reinout

    2015-01-01

    Injecting drug use (IDU) is associated with tuberculosis but few data are available from low-income settings. We examined IDU in relation to active and latent tuberculosis (LTBI) among HIV-positive individuals in Indonesia, which has a high burden of tuberculosis and a rapidly growing HIV epidemic strongly driven by IDU. Active tuberculosis was measured prospectively among 1900 consecutive antiretroviral treatment (ART)-naïve adult patients entering care in a clinic in West Java. Prevalence of LTBI was determined cross-sectionally in a subset of 518 ART-experienced patients using an interferon-gamma release assay. Patients with a history of IDU (53.1%) more often reported a history of tuberculosis treatment (34.8% vs. 21.9%, p history of IDU (29.1 vs. 30.4%, NS). The risk estimates did not change after adjustment for CD4 cell count or ART. HIV-positive individuals with a history of IDU in Indonesia have more active tuberculosis, with similar rates of LTBI. Within the HIV clinic, LTBI screening and isoniazid preventive therapy may be prioritized to patients with a history of IDU.

  4. Pulmonary Immune-Compartment-Specific Interferon Gamma Responses in HIV-Infected Individuals with Active Tuberculosis (TB in an Area of High TB Prevalence

    Directory of Open Access Journals (Sweden)

    S. Buldeo

    2012-01-01

    Full Text Available There is a paucity of data on the pulmonary immune-compartment interferon gamma (IFNγ response to M. tuberculosis, particularly in settings of high tuberculosis (TB prevalence and in HIV-coinfected individuals. This data is necessary to understand the diagnostic potential of commercially available interferon gamma release assays (IGRAs in both the pulmonary immune-compartment and peripheral blood. We used intracellular cytokine staining by flow cytometry to assess the IFNγ response to purified protein derivative (PPD and early secretory antigen 6 (ESAT6 in induced sputa (ISp and blood samples from HIV-infected, smear-negative, TB suspects. We found that individuals with active TB disease produced significantly less IFNγ in response to PPD in their induced sputa samples than individuals with non-active TB (control group. This difference was not reflected in the peripheral blood, even within the CD27− CD4+ memory T lymphocyte population. These findings suggest that progression to active TB disease may be associated with the loss of IFNγ secretion at the site of primary infection. Our findings highlight the importance of studying pulmonary immune-compartment M. tuberculosis specific responses to elucidate IFNγ secretion across the spectrum of TB disease.

  5. Dutch Suspects of Terrorist Activity: A Study of Their Biographical Backgrounds Based on Primary Sources.

    Directory of Open Access Journals (Sweden)

    Maarten van Leyenhorst

    2017-09-01

    Full Text Available With the impending defeat of ISIS in Syria and Iraq, supporters of terrorist groups, among them home-grown supporters and returning foreign fighters, have become a huge security threat to their country of return. Some have committed attacks in western countries, even while under the surveillance of authorities. Counter-terrorism is confronted with enormous challenges. One of the most prominent issues is the absence of evidence based knowledge on early warning signs. Experts on radicalization and terrorism have emphasized that neither typologies of terrorists nor accurate descriptions of generalizable risks can be made. This leads to opportunities for those who are willing to prepare and commit acts of terrorism to do so, without the agencies in charge of monitoring such individuals being able to accurately identify relevant threats. An additional deficiency in counter-terrorism research, is its dependency on historic and secondary source material. One of various actors in the Netherlands tasked to evaluate and mitigate relevant risks of terrorist suspects and offenders, is the Dutch Probation Service (DPS. In response to today’s prevailing terrorist threat, a specialized section of the DPS is set up to identify and supervise potential problem behaviour of those who are suspected or convicted of terrorism. The authors have been involved in this Unit Terrorism, Extremism and Radicalization (TER for years. As professionals of TER, the authors have had unique access to both judicial data, such as police files and prosecutor’s data, as to experts in the Dutch field of counter-terrorism. The authors have analysed the pre-sentencing advices of twenty-six clients of the DPS. These files are comprised of several socio-economic, historical, psychopathological and behavioural indicators. The goals are to learn from the analysis of the biographical backgrounds of the suspects and to stimulate the debate on management and supervision of terrorist

  6. Gamma/delta T cell subsets in patients with active Mycobacterium tuberculosis infection and tuberculin anergy.

    Science.gov (United States)

    Szereday, L; Baliko, Z; Szekeres-Bartho, J

    2003-02-01

    Earlier data suggest that gamma/delta T cells may play an important role in the immune response to Mycobacterium tuberculosis. The aim of this study was to determine the percentage of different gamma/delta subsets in peripheral blood of active tuberculosis patients with a positive or negative tuberculin reaction. Thirty-eight patients infected with M. tuberculosis and 22 healthy controls were included in the study. Venous blood was taken before starting antimycobacterial treatment. Lymphocytes were reacted with monoclonal antibodies specific for different gamma/delta V chains (Vdelta1, Vdelta2, Vgamma9 and Vgamma4). The results were analysed in the context of tuberculin reactivity and X-ray findings. Our results revealed a selective loss of Vgamma9/Vdelta2 T cells in the peripheral blood of tuberculin-negative patients with active tuberculosis compared to healthy controls, while the ratio of Vgamma9/Vdelta2 T cells in the peripheral blood of patients with a positive skin test did not differ from that of healthy controls. These findings demonstrate a relationship between the loss of the major M. tuberculosis-reactive subset of gammadelta T cells and the absence of tuberculin reactivity. The data are consistent with the hypothesis that gammadelta T cells play a role in the protective immune response to M. tuberculosis infection.

  7. γ/δ T cell subsets in patients with active Mycobacterium tuberculosis infection and tuberculin anergy

    Science.gov (United States)

    SZEREDAY, L; BALIKO, Z; SZEKERES-BARTHO, J

    2003-01-01

    Earlier data suggest that γ/δ T cells may play an important role in the immune response to Mycobacterium tuberculosis. The aim of this study was to determine the percentage of different γ/δ subsets in peripheral blood of active tuberculosis patients with a positive or negative tuberculin reaction. Thirty-eight patients infected with M. tuberculosis and 22 healthy controls were included in the study. Venous blood was taken before starting antimycobacterial treatment. Lymphocytes were reacted with monoclonal antibodies specific for different γ/δ V chains (Vδ1, Vδ2, Vγ9 and Vγ4). The results were analysed in the context of tuberculin reactivity and X-ray findings. Our results revealed a selective loss of Vγ9/Vδ2 T cells in the peripheral blood of tuberculin-negative patients with active tuberculosis compared to healthy controls, while the ratio of Vγ9/Vδ2 T cells in the peripheral blood of patients with a positive skin test did not differ from that of healthy controls. These findings demonstrate a relationship between the loss of the major M. tuberculosis-reactive subset of γδ T cells and the absence of tuberculin reactivity. The data are consistent with the hypothesis that γδ T cells play a role in the protective immune response to M. tuberculosis infection. PMID:12562390

  8. Evaluation of the antimycobacterium activity of the constituents from Ocimum basilicum against Mycobacterium tuberculosis.

    Science.gov (United States)

    Siddiqui, Bina S; Bhatti, Huma A; Begum, Sabira; Perwaiz, Sobiya

    2012-10-31

    Ocimum basilicum belongs to the genus Ocimum (Lamiaceae). Many species of this genus including O. basilicum have been traditionally used for the treatment of a variety of diseases including respiratory diseases and symptoms of tuberculosis. The aim of the study was to evaluate the activity of pure constituents of O. basilicum, a plant used in traditional medicine to treat respiratory diseases including symptoms of tuberculosis, against Mycobacterium tuberculosis H37Rv. The crude methanolic extract from the aerial parts (leaves, fruits and flowers) of the plant was separated into EtOAc and water subextracts and the EtOAc subextract was further divided into acidic and neutral fractions. Each of these was subjected to fractionation through column chromatography followed by prep. TLC. Several pure compounds were thus isolated and their activity was determined against M. tuberculosis H37Rv using MABA assay. Nine compounds were assayed for antituberculosis activity which exhibited upto 49% inhibition of M. tuberculosis H37Rv at 6.25 μg/mL. These include one new compound bacilicin, the structure of which was elucidated based on 2D-NMR (HSQC, HMBC, COSY and NOESY) and Ms spectral analysis. The known compounds were identified on the basis of comparison of their spectral data with those reported earlier. Inhibition of M. tuberculosis by pure compounds from O. basilicum supports the use of this plant in ethnomedicine as a remedy for symptoms of tuberculosis. The results also suggest that the activity of the plant may be due to a synergistic effect of active compounds including those investigated in the present studies, and hence this plant is a potential candidate for obtaining further new antituberculosis natural products. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  9. Renal tuberculosis

    Directory of Open Access Journals (Sweden)

    Džamić Zoran

    2016-01-01

    Full Text Available Tuberculosis is still a significant health problem in the world, mostly in developing countries. The special significance lies in immunocompromised patients, particularly those suffering from the HIV. Urogenital tuberculosis is one of the most common forms of extrapulmonary tuberculosis, while the most commonly involved organ is the kidney. Renal tuberculosis occurs by hematogenous dissemination of mycobacterium tuberculosis from a primary tuberculosis foci in the body. Tuberculosis is characterized by the formation of pathognomonic lesions in the tissues - granulomata. These granulomata may heal spontaneously or remain stable for years. In certain circumstances in the body associated with immunosuppression, the disease may be activated. Central caseous necrosis occurs within tuberculoma, leading to formation of cavities that destroy renal parenchyma. The process may gain access to the collecting system, forming the caverns. In this way, infection can be spread distally to renal pelvis, ureter and bladder. Scaring of tissue by tuberculosis process may lead to development of strictures of the urinary tract. The clinical manifestations are presented by nonspecific symptoms and signs, so tuberculosis can often be overlooked. Sterile pyuria is characteristic for urinary tuberculosis. Dysuric complaints, flank pain or hematuria may be presented in patients. Constitutional symptoms of fever, weight loss and night sweats are presented in some severe cases. Diagnosis is made by isolation of mycobacterium tuberculosis in urine samples, by cultures carried out on standard solid media optimized for mycobacterial growth. Different imaging studies are used in diagnostics - IVU, CT and NMR are the most important. Medical therapy is the main modality of tuberculosis treatment. The first line anti-tuberculosis drugs include isoniazid, rifampicin, pyrazinamide and ethambutol. Surgical treatment is required in some cases, to remove severely damaged kidney, if

  10. Viral hepatitis prevalence in patients with active and latent tuberculosis.

    Science.gov (United States)

    Nooredinvand, Hesam Ahmadi; Connell, David W; Asgheddi, Mahmoud; Abdullah, Mohammed; O'Donoghue, Marie; Campbell, Louise; Wickremasinghe, Melissa I; Lalvani, Ajit; Kon, Onn Min; Khan, Shahid A

    2015-08-07

    To assess the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and association with drug induced liver injury (DILI) in patients undergoing anti-tuberculosis (TB) therapy. Four hundred and twenty nine patients with newly diagnosed TB - either active disease or latent infection - who were due to commence anti-TB therapy between September 2008 and May 2011 were included. These patients were prospectively tested for serological markers of HBV, HCV and human immunodeficiency virus (HIV) infections - hepatitis B core antigen (HBcAg), hepatitis B surface antigen (HBsAg), hepatitis B e antigen, IgG and IgM antibody to HBcAg (anti-HBc), HCV IgG antibody and HIV antibody using a combination of enzyme-linked immunosorbent assay, Western blot assay and polymerase chain reaction techniques. Patients were reviewed at least monthly during the TB treatment initiation phase. Liver function tests were measured prior to commencement of anti-TB therapy and 2-4 wk later. Liver function tests were also performed at any time the patient had significant nausea, vomiting, rash, or felt non-specifically unwell. Fisher's exact test was used to measure significance in comparisons of proportions between groups. A P value of less than 0.05 was considered statistically significant. Of the 429 patients, 270 (62.9%) had active TB disease and 159 (37.1%) had latent TB infection. 61 (14.2%) patients had isolated anti-HBc positivity, 11 (2.6%) were also HBsAg positive and 7 (1.6%) were HCV-antibody positive. 16/270 patients with active TB disease compared to 2/159 patients with latent TB infection had markers of chronic viral hepatitis (HBsAg or HCV antibody positive; P = 0.023). Similarly the proportion of HBsAg positive patients were significantly greater in the active vs latent TB infection group (10/43 vs 1/29, P = 0.04). The prevalence of chronic HBV or HCV was significantly higher than the estimated United Kingdom prevalence of 0.3% for each. We found no association

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

    Directory of Open Access Journals (Sweden)

    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

  12. IFNG-mediated immune responses enhance autophagy against Mycobacterium tuberculosis antigens in patients with active tuberculosis

    Science.gov (United States)

    Rovetta, Ana I; Peña, Delfina; Hernández Del Pino, Rodrigo E; Recalde, Gabriela M; Pellegrini, Joaquín; Bigi, Fabiana; Musella, Rosa M; Palmero, Domingo J; Gutierrez, Marisa; Colombo, María I; García, Verónica E

    2015-01-01

    Protective immunity against Mycobacterium tuberculosis (Mtb) requires IFNG. Besides, IFNG-mediated induction of autophagy suppresses survival of virulent Mtb in macrophage cell lines. We investigated the contribution of autophagy to the defense against Mtb antigen (Mtb-Ag) in cells from tuberculosis patients and healthy donors (HD). Patients were classified as high responders (HR) if their T cells produced significant IFNG against Mtb-Ag; and low responders (LR) when patients showed weak or no T cell responses to Mtb-Ag. The highest autophagy levels were detected in HD cells whereas the lowest quantities were observed in LR patients. Interestingly, upon Mtb-Ag stimulation, we detected a positive correlation between IFNG and MAP1LC3B-II/LC3-II levels. Actually, blockage of Mtb-Ag-induced IFNG markedly reduced autophagy in HR patients whereas addition of limited amounts of IFNG significantly increased autophagy in LR patients. Therefore, autophagy collaborates with human immune responses against Mtb in close association with specific IFNG secreted against the pathogen. PMID:25426782

  13. Role of the Health Department in Tuberculosis Prevention and Control-Legal and Public Health Considerations.

    Science.gov (United States)

    Jeffries, Carla; Lobue, Phil; Chorba, Terence; Metchock, Beverly; Kashef, Ijaz

    2017-03-01

    Because tuberculosis is caused by an infectious organism that is spread from person to person through the air, public health measures are essential to control the disease. There are three priority strategies for tuberculosis prevention and control in the United States: (i) identifying and treating persons who have tuberculosis disease; (ii) finding persons exposed to infectious tuberculosis patients, evaluating them for Mycobacterium tuberculosis infection and disease, and providing subsequent treatment, if appropriate; and (iii) testing populations at high risk for latent tuberculosis infection (LTBI) and treating those persons who are infected to prevent progression to disease. These strategies for prevention and control of tuberculosis are discussed in a framework containing the following important topics: historical and epidemiological context of tuberculosis control, organization of public health tuberculosis control programs, legal basis for public health authority, conducting overall planning and development of policy, identifying persons who have clinically active tuberculosis, evaluation of immigrants, managing persons who have or who are suspected of having disease, medical consultation, interjurisdictional referrals, identifying and managing persons infected with Mycobacterium tuberculosis, providing laboratory and diagnostic services, collecting and analyzing data, and providing training and education. This chapter describes the role of the health department in the context of these components. This discussion is primarily applicable to tuberculosis prevention and control programs in the United States.

  14. Anti-tuberculosis activities of the crude methanolic extract and ...

    African Journals Online (AJOL)

    The crude extract was prepared using soxhlet extraction apparatus while the purified fractions were obtained by column chromatography. The two media were inoculated with M. tuberculosis strains, after which the crude and purified extracts were added. After 4-6 weeks incubation, colony forming units were counted and ...

  15. Severe hypovitaminosis D in active tuberculosis patients and its predictors

    NARCIS (Netherlands)

    Wang, Qiuzhen; Liu, Yufeng; Ma, Yan; Han, Lei; Dou, Mei; Zou, Yue; Sun, Limei; Tian, Hong; Li, Tongxia; Jiang, Guofeng; Du, Baoli; Kou, Tingyan; Song, Jiaqi; Kok, Frans J.; Schouten, Evert G.

    2017-01-01

    Background & aims: Tuberculosis (TB) patients have a significant vitamin D deficiency (VDD) endemic, which may be closely related to the onset and progress of the disease. The comorbidity of diabetes (DM) and TB has posed an increasing challenge in recent years. However, the influence of DM

  16. Accurate Diagnosis of Pediatric Active Tuberculosis and Disease ...

    African Journals Online (AJOL)

    Control of Mycobacterium tuberculosis (MTB) infection is often mediated by cellular immune responses. In respect to this, MTB specific CD4 T cells play a central role and their maturation in response to bacterial invasion is characterized by changes in their expression patterns for some surface molecules like CD27.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    infection, because they were absent from M. tuberculosis-noninfected individuals. Control CMV peptide/HLA-A*0201 tetramers stained CD8(+) T cells in M. tuberculosis-infected and noninfected individuals equally, whereas Ebola peptide/HLA-A*0201 tetramers were negative. In conclusion, the M. tuberculosis...

  18. The prodrug activator EtaA from Mycobacterium tuberculosis is a Baeyer-Villiger monooxygenase

    NARCIS (Netherlands)

    Fraaije, M.W.; Heidekamp, A.J; Fortin, R; Janssen, D.B.

    2004-01-01

    EtaA is a newly identified FAD-containing monooxygenase that is responsible for activation of several thioamide prodrugs in Mycobacterium tuberculosis. It was found that purified EtaA displays a remarkably low activity with the antitubercular prodrug ethionamide. Hinted by the presence of a

  19. Prevalence of tuberculosis, HIV and respiratory symptoms in two Zambian communities: implications for tuberculosis control in the era of HIV.

    Directory of Open Access Journals (Sweden)

    Helen Ayles

    Full Text Available The Stop TB Partnership target for tuberculosis is to have reduced the prevalence of tuberculosis by 50% comparing 2015 to 1990. This target is challenging as few prevalence surveys have been conducted, especially in high burden tuberculosis and HIV countries. Current tuberculosis control strategies in high HIV prevalent settings are therefore based on limited epidemiological evidence and more evidence is needed from community-based surveys to inform improved policy formulation.8044 adults were sampled from 2 sub-districts (wards in Lusaka province, Zambia. Questionnaires were used to screen for symptoms, respiratory samples were obtained for culture and oral secretions collected for HIV testing. 79 individuals were found to have Mycobacterium tuberculosis in their sputum, giving an adjusted overall prevalence of tuberculosis of 870/100,000 (95% CI 570-1160/100,000. The adjusted overall prevalence of HIV was 28.61% (95% CI 26.04-31.19. HIV- infection was significantly associated with prevalent tuberculosis (Adj OR 2.3, 95% CI 1.42-3.74 and the population attributable fraction of HIV for prevalent tuberculosis was 36%. Symptoms such as prolonged cough (adj OR 12.72, 95% CI 7.05-22.94 and fever (Adj OR 2.04, 95%CI 1.23-3.39, were associated with prevalent tuberculosis, but 8 (10% individuals with prevalent tuberculosis denied having any symptoms at all and only 34 (43% would have been classified as a TB suspect by current guidelines.Undiagnosed tuberculosis is a challenge for tuberculosis control and new approaches are needed if we are to reach international targets. Epidemiological studies can inform screening algorithms for both detection and prevention of active tuberculosis.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. [Registration of suspected adverse effects by the Bureau Adverse Effects Drugs; research activities in 1993].

    Science.gov (United States)

    Stricker, B H; Ottervanger, J P; van der Klauw, M M

    1994-10-15

    In 1993, the Netherlands Centre for Monitoring of Adverse Reactions to Drugs received 1585 reports of suspected adverse reactions. The most important reports concerned myocardial infarction due to sumatriptan, cholestatic hepatitis due to itraconazole, agranulocytosis due to trazodone and bleeding due to fluoxetine and fluvoxamine. Other published reports concerned cholestatic hepatitis due to amoxicillin/clavulanic acid, hair loss due to beta-blockers, muscle necrosis due to diclofenac, bronchospasm, apnoea and cardiac arrest due to dipyridamole perfusion scintigraphy, interaction of fluvoxamine/fluoxetine and coumarins, liver enzyme elevations due to heparin, skin reactions due to Imedeen, deafness due to neomycin, addiction to nicotine chewing gum, atrial fibrillation and skin reactions due to nicotine patches, interaction between oral contraceptives and terbinafine, neonatal problems caused by psychopharmacological agents, parapemphigus caused by sulfasalazine, taste loss due to terbinafine en intracranial bleeding after use of tranylcypromine and beer. Pharmacoepidemiological studies were performed concerning methods for record linkage, the communication process with respect to the acitretin alert and the adverse events due to sumatriptan.

  2. Activity against drug resistant-tuberculosis strains of plants used in Mexican traditional medicine to treat tuberculosis and other respiratory diseases.

    Science.gov (United States)

    Camacho-Corona, María Del Rayo; Ramírez-Cabrera, Mónica A; Santiago, Omar González-; Garza-González, Elvira; Palacios, Isidoro de Paz; Luna-Herrera, Julieta

    2008-01-01

    Tuberculosis (TB) kills about 3 million people per year worldwide. Furthermore, TB is an infectious disease associated with HIV patients, and there is a rise in multidrug-resistant TB (MDR-TB) cases around the world. There is a need for new anti-TB agents. The study evaluated the antimycobacterial activity of nine plants used in Mexican traditional medicine to treat tuberculosis and other respiratory diseases. Nasturtium officinale showed the best activity (MIC = 100 microg/mL) against the sensitive Mycobacterium tuberculosis. The following plants were active also but at 200 microg/mL: Citrus sinensis, Citrus aurantifolia, Foeniculum vulgare, Larrea tridentata, Musa acuminata and Olea europaea. Contrary to the above data, activity against drug-resistant variants of M. tuberculosis was more evident, e.g. N. officinale was the most potent (MIC < or = 100 microg/mL) against the four mono-resistant variants tested; F. vulgare and O. europaea were active against all the resistant variants (MICs < or = 100 microg/mL). The most susceptible variant was the isoniazid resistant, being inhibited by C. aurantifolia, C. sinensis and O. europaea (MIC = 25 microg/mL). These data point to the importance of biological testing of extracts against drug-resistant M. tuberculosis isolates, and the bioguided assay of these extracts for the identification of lead compounds against MDR-TB isolates. Copyright (c) 2007 John Wiley & Sons, Ltd.

  3. Latent Tuberculosis in Health Care Workers Exposed to Active Tuberculosis in a Tertiary Care Hospital in Oman.

    Science.gov (United States)

    Khamis, Faryal; Al-Lawati, Adil; Al-Zakwani, Ibrahim; Al-Abri, Seif; Al-Naamani, Jaleelah; Al-Harthi, Harith; Al-Jardani, Amina; Al-Harthi, Aliya

    2016-07-01

    Data on the prevalence of tuberculosis (TB) in healthcare workers (HCW) in Oman and the Arabian Gulf is scarce. The aim of this study was to estimate the prevalence of latent tuberculosis (LTB) among HCW exposed to active TB in one of the tertiary care hospitals in Muscat. Exposed HCW were screened for LTB from January to June 2012 using skin tuberculin and serum interferon tests. Candidates were followed-up for a total of nine months. Descriptive statistics were used to summarize the data. A total of 371 exposed HCW were involved in the study. The incidence of LTB in exposed HCW was 33.2% (n = 123). Almost 54% (66/123) of the HCW started treatment and only 42.4% (28/66) completed the full nine-month treatment course. The high prevalence of LTBI in exposed HCW merits further evaluation of the screening and treatment programs in the country. Future countrywide studies are warranted to provide more precise statistics on the prevalence and management of this public health issue.

  4. Intracellular activity of tedizolid phosphate and ACH-702 versus Mycobacterium tuberculosis infected macrophages.

    Science.gov (United States)

    Molina-Torres, Carmen A; Barba-Marines, Alejandra; Valles-Guerra, Orestes; Ocampo-Candiani, Jorge; Cavazos-Rocha, Norma; Pucci, Michael J; Castro-Garza, Jorge; Vera-Cabrera, Lucio

    2014-04-04

    Due to the emergency of multidrug-resistant strains of Mycobacterium tuberculosis, is necessary the evaluation of new compounds. Tedizolid, a novel oxazolidinone, and ACH-702, a new isothiazoloquinolone, were tested against M. tuberculosis infected THP-1 macrophages. These two compounds significantly decreased the number of intracellular mycobacteria at 0.25X, 1X, 4X and 16X the MIC value. The drugs were tested either in nanoparticules or in free solution. Tedizolid and ACH-702 have a good intracellular killing activity comparable to that of rifampin or moxifloxacin.

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

    Directory of Open Access Journals (Sweden)

    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

  6. Re-activation of bovine tuberculosis in a patient treated with infliximab

    DEFF Research Database (Denmark)

    Larsen, Mette Vang; Thomsen, V Ø; Sørensen, Inge Juul

    2008-01-01

    Treatment with tumour necrosis factor-alpha inhibitors increases the risk of tuberculosis (TB). Screening for latent TB infection (LTBI) and prophylactic treatment has become mandatory. A 79-yr-old female with a history of severe erosive sero-positive rheumatoid arthritis was screened for LTBI......-infected cattle. Re-activation of bovine tuberculosis is a risk in people with recent or previous exposure to unpasteurised dairy products. The QuantiFERON-TB test has the potential to detect Mycobacterium bovis infection. Indeterminate test results reflect either anergy, due to poor immunity, or technical...... problems and should be cautiously interpreted and as a minimum be repeated. Studies are ongoing to determine the role of QuantiFERON-TB testing in the screening for latent tuberculosis infection....

  7. Plasminogen activator inhibitor type I may contribute to transient, non-specific changes in immunity in the subacute phase of murine tuberculosis.

    NARCIS (Netherlands)

    Kager, L.M.; Windt, G.J. van der; Wieland, C.W.; Florquin, S.; Veer, C. van't; Poll, T. van der

    2012-01-01

    Tuberculosis, caused by Mycobacterium (M.) tuberculosis, is a devastating infectious disease causing many deaths worldwide. Non-specific host defense mechanisms such as the coagulation and fibrinolytic system may give insight in possible new therapeutic targets. Plasminogen activator inhibitor

  8. 38 CFR 3.378 - Changes from activity in pulmonary tuberculosis pension cases.

    Science.gov (United States)

    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 Compensation...

  9. Stem bromelain-induced macrophage apoptosis and activation curtail Mycobacterium tuberculosis persistence.

    Science.gov (United States)

    Mahajan, Sahil; Chandra, Vemika; Dave, Sandeep; Nanduri, Ravikanth; Gupta, Pawan

    2012-08-01

    Mycobacterium tuberculosis, the causative agent of tuberculosis, has a remarkable ability to usurp its host's innate immune response, killing millions of infected people annually. One approach to manage infection is prevention through the use of natural agents. In this regard, stem bromelain (SBM), a pharmacologically active member of the sulfhydryl proteolytic enzyme family, obtained from Ananas comosus and possessing a remarkable ability to induce the innate and acquired immune systems, is important. We evaluated SBM's ability to induce apoptosis and free-radical generation in macrophages. We also studied antimycobacterial properties of SBM and its effect on foamy macrophages. SBM treatment of peritoneal macrophages resulted in the upregulation of proapoptotic proteins and downregulation of antiapoptotic proteins. Additionally, SBM treatment activated macrophages, curtailed the levels of free glutathione, and augmented the production of hydrogen peroxide, superoxide anion, peroxynitrite, and nitric oxide. SBM cleaves CD36 and reduced the formation of foam cells, the hallmark of M. tuberculosis infection. These conditions created an environment for the increased clearance of M. tuberculosis. Together these data provide a mechanism for antimycobacterial activity of SBM and provide important insights for the use of cysteine proteases as immunomodulatory agents.

  10. Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil

    Directory of Open Access Journals (Sweden)

    Tatiane eCoelho

    2015-04-01

    Full Text Available Drug resistant tuberculosis continues to increase and new approaches for its treatment are necessary. The identification of M. tuberculosis clinical isolates presenting efflux as part of their resistant phenotype has a major impact in tuberculosis treatment. In this work, we used a checkerboard procedure combined with the tetrazolium microplate-based assay (TEMA to study single combinations between antituberculosis drugs and efflux inhibitors (EIs against multidrug resistant M. tuberculosis clinical isolates using the fully susceptible strain H37Rv as reference. Efflux activity was studied on a real-time basis by a fluorometric method that uses ethidium bromide as efflux substrate. Quantification of efflux pump genes mRNA transcriptional levels were performed by RT-qPCR. The fractional inhibitory concentrations (FIC indicated synergistic activity for the interactions between isoniazid, rifampicin, amikacin, ofloxacin, and ethidium bromide plus the EIs verapamil, thioridazine and chlorpromazine. The FICs ranged from 0.25, indicating a four-fold reduction on the MICs, to 0.015, 64-fold reduction. The detection of active efflux by real-time fluorometry showed that all strains presented intrinsic efflux activity that contributes to the overall resistance which can be inhibited in the presence of the EIs. The quantification of the mRNA levels of the most important efflux pump genes on these strains shows that they are intrinsically predisposed to expel toxic compounds as the exposure to subinhibitory concentrations of antibiotics were not necessary to increase the pump mRNA levels when compared with the non-exposed counterpart. The results obtained in this study confirm that the intrinsic efflux activity contributes to the overall resistance in multidrug resistant clinical isolates of M. tuberculosis and that the inhibition of efflux pumps by the EIs can enhance the clinical effect of antibiotics that are their substrates.

  11. Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil

    Science.gov (United States)

    Coelho, Tatiane; Machado, Diana; Couto, Isabel; Maschmann, Raquel; Ramos, Daniela; von Groll, Andrea; Rossetti, Maria L.; Silva, Pedro A.; Viveiros, Miguel

    2015-01-01

    Drug resistant tuberculosis continues to increase and new approaches for its treatment are necessary. The identification of M. tuberculosis clinical isolates presenting efflux as part of their resistant phenotype has a major impact in tuberculosis treatment. In this work, we used a checkerboard procedure combined with the tetrazolium microplate-based assay (TEMA) to study single combinations between antituberculosis drugs and efflux inhibitors (EIs) against multidrug resistant M. tuberculosis clinical isolates using the fully susceptible strain H37Rv as reference. Efflux activity was studied on a real-time basis by a fluorometric method that uses ethidium bromide as efflux substrate. Quantification of efflux pump genes mRNA transcriptional levels were performed by RT-qPCR. The fractional inhibitory concentrations (FIC) indicated synergistic activity for the interactions between isoniazid, rifampicin, amikacin, ofloxacin, and ethidium bromide plus the EIs verapamil, thioridazine and chlorpromazine. The FICs ranged from 0.25, indicating a four-fold reduction on the MICs, to 0.015, 64-fold reduction. The detection of active efflux by real-time fluorometry showed that all strains presented intrinsic efflux activity that contributes to the overall resistance which can be inhibited in the presence of the EIs. The quantification of the mRNA levels of the most important efflux pump genes on these strains shows that they are intrinsically predisposed to expel toxic compounds as the exposure to subinhibitory concentrations of antibiotics were not necessary to increase the pump mRNA levels when compared with the non-exposed counterpart. The results obtained in this study confirm that the intrinsic efflux activity contributes to the overall resistance in multidrug resistant clinical isolates of M. tuberculosis and that the inhibition of efflux pumps by the EIs can enhance the clinical effect of antibiotics that are their substrates. PMID:25972842

  12. Lung Neutrophils Facilitate Activation of Naïve Antigen Specific CD4+ T Cells During Mycobacterium tuberculosis Infection1

    Science.gov (United States)

    Blomgran, Robert; Ernst, Joel D.

    2012-01-01

    Initiation of the adaptive immune response to Mycobacterium tuberculosis occurs in the lung-draining mediastinal lymph node, and requires transport of M. tuberculosis by migratory dendritic cells (DCs) to the local lymph node. The previously-published observations that: 1) neutrophils are a transiently prominent population of M. tuberculosis-infected cells in the lungs early in infection; and 2) that the peak of infected neutrophils immediately precedes the peak of infected DCs in the lungs, prompted us to characterize the role of neutrophils in the initiation of adaptive immune responses to M. tuberculosis. We found that, although depletion of neutrophils in vivo increased the frequency of M. tuberculosis infected DCs in the lungs, it decreased trafficking of DCs to the mediastinal lymph node. This resulted in delayed activation (CD69 expression) and proliferation of naïve M. tuberculosis Ag85B-specific CD4 T cells in the mediastinal lymph node. To further characterize the role for neutrophils in DC-migration we used a Transwell chemotaxis system and found that DCs that were directly infected by M. tuberculosis migrated poorly in response to CCL19, an agonist for the chemokine receptor CCR7. In contrast, DCs that had acquired M. tuberculosis through uptake of infected neutrophils exhibited unimpaired migration. These results reveal a mechanism wherein neutrophils promote adaptive immune responses to M. tuberculosis by delivering M. tuberculosis to DCs in a form that make DCs more effective initiators of naïve CD4 T cell activation. These observations provide insight into a mechanism for neutrophils to facilitate initiation of adaptive immune responses in tuberculosis. PMID:21555529

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Mortality in Severe Human Immunodeficiency Virus-Tuberculosis Associates With Innate Immune Activation and Dysfunction of Monocytes.

    Science.gov (United States)

    Janssen, Saskia; Schutz, Charlotte; Ward, Amy; Nemes, Elisa; Wilkinson, Katalin A; Scriven, James; Huson, Mischa A; Aben, Nanne; Maartens, Gary; Burton, Rosie; Wilkinson, Robert J; Grobusch, Martin P; Van der Poll, Tom; Meintjes, Graeme

    2017-07-01

    Case fatality rates among hospitalized patients diagnosed with human immunodeficiency virus (HIV)-associated tuberculosis remain high, and tuberculosis mycobacteremia is common. Our aim was to define the nature of innate immune responses associated with 12-week mortality in this population. This prospective cohort study was conducted at Khayelitsha Hospital, Cape Town, South Africa. Hospitalized HIV-infected tuberculosis patients with CD4 counts active tuberculosis were recruited as controls. Whole blood was stimulated with Escherichia coli derived lipopolysaccharide, heat-killed Streptococcus pneumoniae, and Mycobacterium tuberculosis. Biomarkers of inflammation and sepsis, intracellular (flow cytometry) and secreted cytokines (Luminex), were assessed for associations with 12-week mortality using Cox proportional hazard models. Second, we investigated associations of these immune markers with tuberculosis mycobacteremia. Sixty patients were included (median CD4 count 53 cells/µL (interquartile range [IQR], 22-132); 16 (27%) died after a median of 12 (IQR, 0-24) days. Thirty-one (52%) grew M. tuberculosis on blood culture. Mortality was associated with higher concentrations of procalcitonin, activation of the innate immune system (% CD16+CD14+ monocytes, interleukin-6, tumour necrosis factor-ɑ and colony-stimulating factor 3), and antiinflammatory markers (increased interleukin-1 receptor antagonist and lower monocyte and neutrophil responses to bacterial stimuli). Tuberculosis mycobacteremia was not associated with mortality, nor with biomarkers of sepsis. Twelve-week mortality was associated with greater pro- and antiinflammatory alterations of the innate immune system, similar to those reported in severe bacterial sepsis.

  15. Autonomic nervous system dysfunction in the course of active pulmonary tuberculosis.

    Science.gov (United States)

    Raimondi, Gianfranco; Contini, Silvia; Maria Legramante, Jacopo; Bocchino, Marialuisa; Sacco, Sergio; Pallante, Marco; Cazzola, Mario; Saltini, Cesare

    2007-08-01

    Functional alterations of the autonomic nervous system have been described in relation to chronic hypoxemia in chronic obstructive pulmonary diseases. Aim of the present study was to investigate the occurrence of neuro-vegetative dysfunction during active tuberculosis in the absence of hypoxemia. Fifteen patients affected by pulmonary tuberculosis under standard therapy and 17 matched controls were enrolled. Activation of the sympathetic system was induced by the tilt-up test. Systolic and diastolic arterial pressures and the R-R interval were monitored for 15 min by Finapres and ECG. The baroreflex sensitivity was evaluated by the spontaneous sequences method. Systolic and diastolic pressures were significantly higher at basal conditions and showed a less increase during the tilt test in tuberculosis patients compared to healthy controls. The basal R-R interval was shorter and its reduction during the tilt test was less evident in patients. The baroreflex sensitivity was decreased in patients at basal conditions and its reduction during the tilt test was less evident than in controls. Our preliminary results suggest the presence in tuberculosis patients of an altered autonomic cardiovascular regulation, which is a reduced function of the baroreflex control of the sinus node.

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

    DEFF Research Database (Denmark)

    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....... The accuracy of the QFT-RD1 test will vary with the prevalence of LTBI. We suggest that the QFT-RD1 test could be a very useful supplementary tool for the diagnosis of TB....

  17. Circadian profiling reveals higher histamine plasma levels and lower diamine oxidase serum activities in 24% of patients with suspected histamine intolerance compared to food allergy and controls.

    Science.gov (United States)

    Pinzer, T C; Tietz, E; Waldmann, E; Schink, M; Neurath, M F; Zopf, Y

    2017-11-20

    Histamine intolerance is thought to trigger manifold clinical symptoms after ingesting histamine-rich food due to reduced activity of diamine oxidase (DAO). No study has hitherto systematically assessed daily fluctuations of histamine levels and DAO activities in symptomatic patients. The aim of the study was to investigate the presence of histamine intolerance, to therefore establish day profiles of histamine levels and DAO activities, and to compare the results between patients with suspected histamine intolerance, food allergy and healthy controls. We determined day profiles of histamine plasma levels and DAO serum activities in 33 patients with suspected histamine intolerance, in 21 patients with proven food allergy and in 10 healthy control patients. Clinical symptoms, food intolerances and further clinical and laboratory chemical parameters were evaluated. Twenty-four percent (8 of 33) suspected histamine-intolerant patients showed elevated histamine levels during the day. That might be caused by constantly and significantly reduced DAO activities in these patients compared to food-allergic and control patients. The remaining 25 patients presented normal histamine levels and DAO activities, but an increased prevalence of multiple food intolerances compared to the other subgroup of suspected histamine-intolerants. There was no correlation between subjective complaints and serological histamine parameters in patients with suspected histamine intolerance. We determined by daily profiling that decreased DAO activities correlated with elevated histamine levels in a subgroup of suspected histamine-intolerants. This finding discriminates these patients from food intolerant individuals with similar clinical symptoms and strongly suggests the presence of histamine intolerance. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  18. Mechanistic and functional insights into fatty acid activation in Mycobacterium tuberculosis

    OpenAIRE

    Arora, Pooja; Goyal, Aneesh; Natarajan, Vivek T.; Rajakumara, Eerappa; Verma, Priyanka; Gupta, Radhika; Yousuf, Malikmohamed; Trivedi, Omita A.; Mohanty, Debasisa; Tyagi, Anil; Sankaranarayanan, Rajan; Rajesh S Gokhale

    2009-01-01

    The recent discovery of fatty acyl-AMP ligases (FAALs) in Mycobacterium tuberculosis (Mtb) provided a new perspective to fatty acid activation dogma. These proteins convert fatty acids to corresponding adenylates, which is an intermediate of acyl-CoA-synthesizing fatty acyl-CoA ligases (FACLs). Presently, it is not evident how obligate pathogens like Mtb have evolved such new themes of functional versatility and whether the activation of fatty acids to acyl-adenylates could indeed be a genera...

  19. Evaluation and Uncertainty of a New Method to Detect Suspected Nuclear and WMD Activity: Project Report

    Energy Technology Data Exchange (ETDEWEB)

    Kurzeja, R. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Werth, D. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Buckley, R. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2017-09-29

    The Atmospheric Technology Group at SRNL developed a new method to detect signals from Weapons of Mass Destruction (WMD) activities in a time series of chemical measurements at a downwind location. This method was tested with radioxenon measured in Russia and Japan after the 2013 underground test in North Korea. This LDRD calculated the uncertainty in the method with the measured data and also for a case with the signal reduced to 1/10 its measured value. The research showed that the uncertainty in the calculated probability of origin from the NK test site was small enough to confirm the test. The method was also wellbehaved for small signal strengths.

  20. Impaired IFN-α-mediated signal in dendritic cells differentiates active from latent tuberculosis.

    Directory of Open Access Journals (Sweden)

    Stefania Parlato

    Full Text Available Individuals exposed to Mycobacterium tuberculosis (Mtb may be infected and remain for the entire life in this condition defined as latent tuberculosis infection (LTBI or develop active tuberculosis (TB. Among the multiple factors governing the outcome of the infection, dendritic cells (DCs play a major role in dictating antibacterial immunity. However, current knowledge on the role of the diverse components of human DCs in shaping specific T-cell response during Mtb infection is limited. In this study, we performed a comparative evaluation of peripheral blood circulating DC subsets as well as of monocyte-derived Interferon-α DCs (IFN-DCs from patients with active TB, subjects with LTBI and healthy donors (HD. The proportion of circulating myeloid BDCA3+ DCs (mDC2 and plasmacytoid CD123+ DCs (pDCs declined significantly in active TB patients compared to HD, whereas the same subsets displayed a remarkable activation in LTBI subjects. Simultaneously, the differentiation of IFN-DCs from active TB patients resulted profoundly impaired compared to those from LTBI and HD individuals. Importantly, the altered developmental trait of IFN-DCs from active TB patients was associated with down-modulation of IFN-linked genes, marked changes in molecular signaling conveying antigen (Ag presentation and full inability to induce Ag-specific T cell response. Thus, these data reveal an important role of IFN-α in determining the induction of Mtb-specific immunity.

  1. Tuberculosis and Diabetes

    Science.gov (United States)

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

  2. Ethiopian plants with proven and suspected molluscicidal activity: a new approach in plant evaluation.

    Science.gov (United States)

    Kloos, H; McCullough, F S

    1985-06-01

    Using available information on the toxicity, phytochemistry, ethnomedical uses and geographic distribution of plants, potentially suitable species are identified for the control of intermediate hosts of schistosomiasis in Ethiopia's lowlands where endod (Phytolacca dodecandra) is not available. Of 46 species with moderate to high snail-killing potency, 35 are indigenous to Ethiopia. They include 12 plant species with molluscicidal levels similar to those of endod, four of which are particularly suitable for snail control because of their low mammalian toxicity. Another 127 species indigenous to Ethiopia belong to genera with proven molluscicidal activity. The model for plant screening used here permits preliminary assessment of the suitability of plant resources in a given region or locality for snail control programs using existing data, without prior testing of local plants, making this approach appropriate for many developing countries.

  3. Over-expression of thymosin β4 in granulomatous lung tissue with active pulmonary tuberculosis.

    Science.gov (United States)

    Kang, Yun-Jeong; Jo, Jin-Ok; Ock, Mee Sun; Yoo, Young-Bin; Chun, Bong-Kwon; Oak, Chul-Ho; Cha, Hee-Jae

    2014-05-01

    Recent studies have shown that thymosin β4 (Tβ4) stimulates angiogenesis by inducing vascular endothelial growth factor (VEGF) expression and stabilizing hypoxia inducible factor-1α (HIF-1α) protein. Pulmonary tuberculosis (TB), a type of granulomatous disease, is accompanied by intense angiogenesis and VEGF levels have been reported to be elevated in serum or tissue inflamed by pulmonary tuberculosis. We investigated the expression of Tβ4 in granulomatous lung tissues at various stages of active pulmonary tuberculosis, and we also examined the expression patterns of VEGF and HIF-1α to compare their Tβ4 expression patterns in patients' tissues and in the tissue microarray of TB patients. Tβ4 was highly expressed in both granulomas and surrounding lymphocytes in nascent granulomatous lung tissue, but was expressed only surrounding tissues of necrotic or caseous necrotic regions. The expression pattern of HIF-1α was similar to that of Tβ4. VEGF was expressed in both granulomas and blood vessels surrounding granulomas. The expression pattern of VEGF co-localized with CD31 (platelet endothelial cell adhesion molecule, PECAM-1), a blood endothelial cell marker, and partially co-localized with Tβ4. However, the expression of Tβ4 did not co-localize with alveolar macrophages. Stained alveolar macrophages were present surrounding regions of granuloma highly expressing Tβ4. We also analyzed mRNA expression in the sputum of 10 normal and 19 pulmonary TB patients. Expression of Tβ4 was significantly higher in patients with pulmonary tuberculosis than in normal controls. These data suggest that Tβ4 is highly expressed in granulomatous lung tissue with active pulmonary TB and is associated with HIF-1α- and VEGF-mediated inflammation and angiogenesis. Furthermore, the expression of Tβ4 in the sputum of pulmonary tuberculosis patients can be used as a potential marker for diagnosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Interferon-gamma response to the treatment of active pulmonary and extra-pulmonary tuberculosis.

    Science.gov (United States)

    Liang, L; Shi, R; Liu, X; Yuan, X; Zheng, S; Zhang, G; Wang, W; Wang, J; England, K; Via, L E; Cai, Y; Goldfeder, L C; Dodd, L E; Barry, C E; Chen, R Y

    2017-10-01

    Interferon-gamma (IFN-γ) release assays (IGRAs) are used to diagnose tuberculosis (TB) but not to measure treatment response. To measure IFN-γ response to active anti-tuberculosis treatment. Patients from the Henan Provincial Chest Hospital, Henan, China, with TB symptoms and/or signs were enrolled into this prospective, observational cohort study and followed for 6 months of treatment, with blood and sputum samples collected at 0, 2, 4, 6, 8, 16 and 24 weeks. The QuantiFERON® TB-Gold assay was run on collected blood samples. Participants received a follow-up telephone call at 24 months to determine relapse status. Of the 152 TB patients enrolled, 135 were eligible for this analysis: 118 pulmonary (PTB) and 17 extra-pulmonary TB (EPTB) patients. IFN-γ levels declined significantly over time among all patients (P = 0.002), with this decline driven by PTB patients (P = 0.001), largely during the initial 8 weeks of treatment (P = 0.019). IFN-γ levels did not change among EPTB patients over time or against baseline culture or drug resistance status. After 6 months of effective anti-tuberculosis treatment, IFN-γ levels decreased significantly in PTB patients, largely over the initial 8 weeks of treatment. IFN-γ concentrations may offer some value for monitoring anti-tuberculosis treatment response among PTB patients.

  5. Diagnostic value of pleural fluid adenosine deaminase activity in tuberculosis pleurisy

    Directory of Open Access Journals (Sweden)

    Abbas ali Niazi

    2009-09-01

    Full Text Available Background: Diagnosis of tuberculosis pleurisies is difficult because of its nonspecific clinical presentation and insufficient traditional diagnostic methods. We investigated the use of adenosine deaminase (ADA activity in tuberculosis pleurisies. Methods: A number of 85 patients were analyzed with exudative pleural effusions. Using the ROC curve, we determined the optimal cutoff for TB pleurisy. Results: A number of 58 exudative samples were nontuberculous (non-TB and 27 were tuberculosis (TB. There was statistically significant difference (p<0.0001 between the means of pleural fluid ADA levels among the TB and non-TB populations. The prevalence of TB pleurisy in the studied population was 31%. Using the cutoff point equal to 35 for diagnosing TB effusions the sensitivity and specificity 70.3% and 91.3%, respectively. The positive predictive value (PPV was 79.1% and the negative predictive value (NPV was 86.8%. A pleural fluid ADA value <19 IU/L suggests that a tuberculosis effusion is highly unlikely. Conclusion: Pleural fluid total ADA assay is a sensitive and specific test suitable for rapid diagnosis of TB pleurisy.

  6. Target prediction for an open access set of compounds active against Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Francisco Martínez-Jiménez

    Full Text Available Mycobacterium tuberculosis, the causative agent of tuberculosis (TB, infects an estimated two billion people worldwide and is the leading cause of mortality due to infectious disease. The development of new anti-TB therapeutics is required, because of the emergence of multi-drug resistance strains as well as co-infection with other pathogens, especially HIV. Recently, the pharmaceutical company GlaxoSmithKline published the results of a high-throughput screen (HTS of their two million compound library for anti-mycobacterial phenotypes. The screen revealed 776 compounds with significant activity against the M. tuberculosis H37Rv strain, including a subset of 177 prioritized compounds with high potency and low in vitro cytotoxicity. The next major challenge is the identification of the target proteins. Here, we use a computational approach that integrates historical bioassay data, chemical properties and structural comparisons of selected compounds to propose their potential targets in M. tuberculosis. We predicted 139 target--compound links, providing a necessary basis for further studies to characterize the mode of action of these compounds. The results from our analysis, including the predicted structural models, are available to the wider scientific community in the open source mode, to encourage further development of novel TB therapeutics.

  7. Latent tuberculosis infection and active tuberculosis in patients with psoriasis: a study on the incidence of tuberculosis and the prevalence of latent tuberculosis disease in patients with moderate-severe psoriasis in Spain. BIOBADADERM registry.

    Science.gov (United States)

    Sánchez-Moya, A I; García-Doval, I; Carretero, G; Sánchez-Carazo, J; Ferrandiz, C; Herrera Ceballos, E; Alsina, M; Ferrán, M; López-Estebaranz, J-L; Gómez-García, F; De la Cueva Dobao, P; Carrascosa, J-M; Vanaclocha, F; Belinchón, I; Peral, F; Dauden, E

    2013-11-01

    The incidence of tuberculosis (TB) or the prevalence of latent tuberculosis infection (LTBI) in psoriasis patients has not been described in the Spanish population. We carried out a study with the objectives: (i) To describe the incidence of TB in patients with psoriasis on systemic treatment in the Spanish population; (ii) To determine the prevalence of LTBI in patients who are candidates for biological treatment; and (iii) To investigate the level of compliance with current recommendations for LTBI and TB screening. Data were obtained from BIOBADADERM (Spanish registry for systemic biological and non-biological treatments in psoriasis). An analysis was performed of the exposed cohort to determine the prevalence of LTBI and to describe compliance with the screening guidelines. A total of 1425 patients were registered in BIOBADADERM. They included 793 (56%) patients exposed to biological treatment and 632 (44%) treated with conventional systemic drug. Overall follow-up was 3720 person-years. Of the 793, 20.5% (163) were diagnosed with LTBI before starting biological treatment. The rate of active TB for the exposed cohort was 145 cases × 100,000 patient-years (95% CI 54-389). No case of TB was found in the control group. Screening for LTBI was performed in 83% of the exposed sample. Patients with psoriasis who are exposed to biological treatment appear to be at greater risk for tuberculosis. In Spain, up to 20% of patients with psoriasis who are candidates for biological therapy have LTBI. There continues to be a significant percentage of errors in compliance with clinical guidelines. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

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

    NARCIS (Netherlands)

    Altena ,van Richard; Duggirala, Sridevi; Gröschel, M. I.; van der Werf, Tjip S.

    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

  9. Integrating active tuberculosis case finding in antenatal services in Zambia.

    Science.gov (United States)

    Kancheya, N; Luhanga, D; Harris, J B; Morse, J; Kapata, N; Bweupe, M; Henostroza, G; Reid, S E

    2014-12-01

    Three out-patient antenatal care (ANC) clinics in Lusaka, Zambia. To estimate tuberculosis (TB) prevalence in human immunodeficiency virus (HIV) infected and symptomatic, non-HIV-infected pregnant women and explore the feasibility of routine TB screening in ANC settings. Peer educators administered TB symptom questionnaires to pregnant women attending their first ANC clinic visit. Presumptive TB patients were defined as all HIV-infected women and symptomatic non-HIV-infected women. Sputum samples were tested using smear microscopy and culture to estimate TB prevalence. All 5033 (100%) women invited to participate in the study agreed, and 17% reported one or more TB symptoms. Among 1152 presumed TB patients, 17 (1.5%) had previously undiagnosed culture-confirmed TB; 2 (12%) were smear-positive. Stratified by HIV status, TB prevalence was 10/664 (1.5%, 95%CI 0. 7-2.8) among HIV-infected women and 7/488 (1.4%, 95%CI 0.6-2.9) among symptomatic non-HIV-infected women. In HIV-infected women, the only symptom significantly associated with TB was productive cough; symptom screening was only 50% sensitive. There is a sizable burden of TB in pregnant women in Zambia, which may lead to adverse maternal and infant outcomes. TB screening in ANC settings in Zambia is acceptable and feasible. More sensitive diagnostics are needed.

  10. [Thoracic manifestation of tuberculosis].

    Science.gov (United States)

    Kienzl-Palma, D; Prosch, H

    2016-10-01

    Tuberculosis (TB) is a granulomatous disease caused by Mycobacterium tuberculosis and transmission is via an airborne route by droplet infection. In the majority of cases patients have thoracic TB, which most frequently presents with hilar lymphadenopathy and pulmonary manifestation. Due to the rise in incidence of TB in central Europe to be expected over the coming years, it is essential to be acquainted with the radiological manifestations of pulmonary TB, particularly to be able to discriminate active from inactive TB. Due to the use of molecular techniques entailing DNA fingerprinting, the traditional classification of TB in primary and postprimary TB is being challenged. These genetic studies have revealed that variations in the clinical and radiographic appearance of TB are mainly affected by the immune status of the patients. Due to the low prevalence of TB in central Europe and the wide variation of radiological presentations, the diagnosis and therapy of TB is often delayed. In this article, the radiographic manifestations of thoracic TB are summarized and discussed. Together with the medical history and bacteriological tests, chest X‑ray imaging and computed tomography (CT) play a major role not only in the detection of TB but also in the follow-up during and after therapy. Chest X‑radiographs should be the primary diagnostic method in patients with suspected TB in screening as well as for diagnosis and therapy monitoring. The use of CT is more sensitive than chest radiographs and is frequently performed after chest radiographs to obtain detailed information about subtle parenchymal changes or lymph node manifestation. When active TB is suspected CT should be performed. Tree in bud, lobular consolidations, centrilobular nodules, cavities and ground-glass opacification are typical changes in active TB.

  11. Co-existence of HIV, active tuberculosis and aspergilloma in a single individual--a case report.

    Science.gov (United States)

    Singh, Urvinder Pal; Aneja, Pooja; Aditi; Patel, Kalpesh

    2013-01-01

    Tuberculosis (TB) is a disease as old as mankind, whereas in India the first case of Human Immunodeficiency Virus (HIV) was reported in 1986. HIV and TB are so closely connected that their relationship is often described as a co-epidemic. Aspergilloma (Fungal Ball, Mycetoma) represents a saprophytic growth of aspergillus that colonizes in the preformed cavities commonly due to pulmonary tuberculosis (PTB). We report a case of HIV, active pulmonary tuberculosis and aspergilloma occurring in the same patient. Despite our best efforts, we could not lay our hands on any similar case in the medical literature.

  12. The anti-tubercular activity of Melia azedarach L. and Lobelia chinensis Lour. and their potential as effective anti-Mycobacterium tuberculosis candidate agents

    Directory of Open Access Journals (Sweden)

    Won Hyung Choi

    2016-10-01

    Conclusions: These results demonstrate that M. azedarach and L. chinensis extracts not only have unique anti-M. tuberculosis activity, but also induce the selective anti-M. tuberculosis effects by consistently inhibiting or blocking the growth of M. tuberculosis through a new pharmacological action. Therefore, this study suggests the potential of them as effective candidate agents of next-generation for developing a new anti-tuberculosis drug, as well as the advantage for utilizing traditional medicinal plants as one of effective strategies against tuberculosis.

  13. Determination of the activity of standard anti-tuberculosis drugs against intramacrophage Mycobacterium tuberculosis, in vitro: MGIT 960 as a viable alternative for BACTEC 460

    Directory of Open Access Journals (Sweden)

    Sarbjit Singh Jhamb

    Full Text Available BACTEC 460 has now been phased out, so the search for an alternative is imperative. We have determined the activity of standard anti-tuberculosis drugs against intramacrophage Mycobacterium tuberculosis, in vitro, by using BACTEC 460 and MGIT 960 methods. The minimum inhibitory concentrations of isoniazid, rifampicin, ethambutol and streptomycin against intracellular M. tuberculosis H37Rv were found to be 0.2, 0.8, 8.0, and 5.0 µg/mL, respectively, by both methods. These results show a significant (p < 0.001 concordance between minimum inhibitory concentrations obtained by these two different methods. MGIT 960 system uses a robust florescence quenching-based oxygen sensor, requires no radioisotope, is safe, and relatively easy to operate. Apparently, this is the first report wherein MGIT 960 has been validated for anti-tubercular susceptibility testing against intracellular M. tuberculosis H37Rv. Our preliminary data thus clearly demonstrate that the MGIT 960 method can be considered as a promising alternative to BACTEC 460 method.

  14. CFP-10 from Mycobacterium tuberculosis Selectively Activates Human Neutrophils through a Pertussis Toxin-Sensitive Chemotactic Receptor

    OpenAIRE

    Welin, Amanda; Björnsdottir, Halla; Winther, Malene; Christenson, Karin; Oprea, Tudor; Karlsson, Anna; Forsman, Huamei; Dahlgren, Claes; Bylund, Johan

    2014-01-01

    Upon infection with Mycobacterium tuberculosis, neutrophils are massively recruited to the lungs, but the role of these cells in combating the infection is poorly understood. Through a type VII secretion system, M. tuberculosis releases a heterodimeric protein complex, containing a 6-kDa early secreted antigenic target (ESAT-6) and a 10-kDa culture filtrate protein (CFP-10), that is essential for virulence. Whereas the ESAT-6 component possesses multiple virulence-related activities, no direc...

  15. The prevalence of pulmonary tuberculosis in Jeonbug Province

    Energy Technology Data Exchange (ETDEWEB)

    Rhee, S. J.; Moon, M. C.; Song, H. Y.; Choi, K. C. [Jeonbug Natinal University College of Medicine, Jeonju (Korea, Republic of)

    1981-12-15

    A photofluorographic mass survey of P-A chest had been done to the 13136 residents (male 6264, female 6872) in Jeonbug province, Korea for about 2 years from May 5, to Dec.19, 1978 and from Mar. 5, to Dec. 22, 1979. The results are as follows: 1. The prevalence rate of all active pulmonary tuberculosis is 5.3%. 2. The prevalence rate of male(8.8%) is 4.2 times higher than that of female (2.1%). 3. The prevalence rates of all old age groups above fifty years are higher than that of remainder under fifty years of age. Of these, 61-70 years old age group is highest in prevalence rate. 4. According to extent of active pulmonary tuberculosis, 77.5% is minimal, 15.4% is moderately advanced, and 7.1% is far advanced. Inactive pulmonary tuberculosis are 39 cases (0.3% to objective population). 5. In the incidence of the involved side, right side is about 2 times higher than the left, and involvement of both sides is increased in moderately and far advance pulmonary tuberculosis. In all pulmonary tuberculosis, one or both upper lung fields are most commonly involved. The incidences of cavity in moderately and far advanced pulmonary tuberculosis show no significant difference. 6. The incidences of other intrathoracic lesions are as follows: suspected hypertensive heart disease 2.4%, dextrocardia with situs inversus 0.04%, pleural calcification 0.4%, pleural thickening 0.2%, pleural effusion 0.1%, pneumonia 0.02%, bronchiectasis 0.1%, lung abscess 0.02%, C.O.P.D. 0.2%, suspected lung tumor 0.06%, pneumothorax 0.0076%, and suspected mediastinal tumor 0.02%.

  16. Mycobacterium tuberculosis lipoproteins directly regulate human memory CD4(+) T cell activation via Toll-like receptors 1 and 2.

    Science.gov (United States)

    Lancioni, Christina L; Li, Qing; Thomas, Jeremy J; Ding, XueDong; Thiel, Bonnie; Drage, Michael G; Pecora, Nicole D; Ziady, Assem G; Shank, Samuel; Harding, Clifford V; Boom, W Henry; Rojas, Roxana E

    2011-02-01

    The success of Mycobacterium tuberculosis as a pathogen relies on its ability to regulate the host immune response. M. tuberculosis can manipulate adaptive T cell responses indirectly by modulating antigen-presenting cell (APC) function or by directly interacting with T cells. Little is known about the role of M. tuberculosis molecules in direct regulation of T cell function. Using a biochemical approach, we identified lipoproteins LprG and LpqH as major molecules in M. tuberculosis lysate responsible for costimulation of primary human CD4(+) T cells. In the absence of APCs, activation of memory CD4(+) T cells with LprG or LpqH in combination with anti-CD3 antibody induces Th1 cytokine secretion and cellular proliferation. Lipoprotein-induced T cell costimulation was inhibited by blocking antibodies to Toll-like receptor 2 (TLR2) and TLR1, indicating that human CD4(+) T cells can use TLR2/TLR1 heterodimers to directly respond to M. tuberculosis products. M. tuberculosis lipoproteins induced NF-κB activation in CD4(+) T cells in the absence of TCR co-engagement. Thus, TLR2/TLR1 engagement alone by M. tuberculosis lipoprotein triggered intracellular signaling, but upregulation of cytokine production and proliferation required co-engagement of the TCR. In conclusion, our results demonstrate that M. tuberculosis lipoproteins LprG and LpqH participate in the regulation of adaptive immunity not only by inducing cytokine secretion and costimulatory molecules in innate immune cells but also through directly regulating the activation of memory T lymphocytes.

  17. Role of Metal Ions on the Activity of Mycobacterium tuberculosis Pyrazinamidase

    Science.gov (United States)

    Sheen, Patricia; Ferrer, Patricia; Gilman, Robert H.; Christiansen, Gina; Moreno-Román, Paola; Gutiérrez, Andrés H.; Sotelo, Jun; Evangelista, Wilfredo; Fuentes, Patricia; Rueda, Daniel; Flores, Myra; Olivera, Paula; Solis, José; Pesaresi, Alessandro; Lamba, Doriano; Zimic, Mirko

    2012-01-01

    Pyrazinamidase of Mycobacterium tuberculosis catalyzes the conversion of pyrazinamide to the active molecule pyrazinoic acid. Reduction of pyrazinamidase activity results in a level of pyrazinamide resistance. Previous studies have suggested that pyrazinamidase has a metal-binding site and that a divalent metal cofactor is required for activity. To determine the effect of divalent metals on the pyrazinamidase, the recombinant wild-type pyrazinamidase corresponding to the H37Rv pyrazinamide-susceptible reference strain was expressed in Escherichia coli with and without a carboxy terminal. His-tagged pyrazinamidase was inactivated by metal depletion and reactivated by titration with divalent metals. Although Co2+, Mn2+, and Zn2+ restored pyrazinamidase activity, only Co2+ enhanced the enzymatic activity to levels higher than the wild-type pyrazinamidase. Cu2+, Fe2+, Fe3+, and Mg2+ did not restore the activity under the conditions tested. Various recombinant mutated pyrazinamidases with appropriate folding but different enzymatic activities showed a differential pattern of recovered activity. X-ray fluorescence and atomic absorbance spectroscopy showed that recombinant wild-type pyrazinamidase expressed in E. coli most likely contained Zn. In conclusion, this study suggests that M. tuberculosis pyrazinamidase is a metalloenzyme that is able to coordinate several ions, but in vivo, it is more likely to coordinate Zn2+. However, in vitro, the metal-depleted enzyme could be reactivated by several divalent metals with higher efficiency than Zn. PMID:22764307

  18. Measurement of phenotype and absolute number of circulating heparin-binding hemagglutinin, ESAT-6 and CFP-10, and purified protein derivative antigen-specific CD4 T cells can discriminate active from latent tuberculosis infection.

    Science.gov (United States)

    Hutchinson, Paul; Barkham, Timothy M S; Tang, Wenying; Kemeny, David M; Chee, Cynthia Bin-Eng; Wang, Yee T

    2015-02-01

    The tuberculin skin test (TST) and interferon gamma (IFN-γ) release assays (IGRAs) are used as adjunctive tests for the evaluation of suspected cases of active tuberculosis (TB). However, a positive test does not differentiate latent from active TB. We investigated whether flow cytometric measurement of novel combinations of intracellular cytokines and surface makers on CD4 T cells could differentiate between active and latent TB after stimulation with Mycobacterium tuberculosis-specific proteins. Blood samples from 60 patients referred to the Singapore Tuberculosis Control Unit for evaluation for active TB or as TB contacts were stimulated with purified protein derivative (PPD), ESAT-6 and CFP-10, or heparin-binding hemagglutinin (HBHA). The CD4 T cell cytokine response (IFN-γ, interleukin-2 [IL-2], interleukin-17A [IL-17A], interleukin-22 [IL-22], granulocyte-macrophage colony-stimulating factor [GM-CSF], and tumor necrosis factor alpha [TNF-α]) and surface marker expression (CD27, CXCR3, and CD154) were then measured. We found that the proportion of PPD-specific CD4 T cells, defined as CD154(+) TNF-α(+) cells that were negative for CD27 and positive for GM-CSF, gave the strongest discrimination between subjects with latent and those with active TB (area under the receiver operator characteristic [ROC] curve of 0.9277; P CFP-10-responding to HBHA-responding CD4 T cells was significantly different between the two study populations. In conclusion, we found novel markers of M. tuberculosis-specific CD4 cells which differentiate between active and latent TB. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  19. Detection and confirmation of alkaloids in leaves of Justicia adhatoda and bioinformatics approach to elicit its anti-tuberculosis activity.

    Science.gov (United States)

    Jha, Deepak Kumar; Panda, Likun; Lavanya, P; Ramaiah, Sudha; Anbarasu, Anand

    2012-11-01

    The extraction and determination of alkaloids was performed and confirmed by phytochemical analysis. Six different quinazoline alkaloids (vasicoline, vasicolinone, vasicinone, vasicine, adhatodine and anisotine) were found in the leaf of Justicia adhatoda (J. adhatoda). The presence of the peaks obtained through HPLC indicated the diverse nature of alkaloid present in the leaf. The enzyme β-ketoacyl-acyl-carrier protein synthase III that catalyses the initial step of fatty acid biosynthesis (FabH) via a type II fatty acid synthase has unique structural features and universal occurrence in Mycobacterium tuberculosis (M. tuberculosis). Thus, it was considered as a target for designing of anti-tuberculosis compounds. Docking simulations were conducted on the above alkaloids derived from J. adhatoda. The combination of docking/scoring provided interesting insights into the binding of different inhibitors and their activity. These results will be useful for designing inhibitors for M. tuberculosis and also will be a good starting point for natural plant-based pharmaceutical chemistry.

  20. Presepsin as a novel diagnostic biomarker for differentiating active pulmonary tuberculosis from bacterial community acquired pneumonia.

    Science.gov (United States)

    Qi, Zhi-Jiang; Yu, Han; Zhang, Jing; Li, Chun-Sheng

    2018-03-01

    The expression of presepsin in active pulmonary tuberculosis (APTB) is unknown. We observed the expression of presepsin in APTB, and to evaluate the value for discriminating between APTB and bacterial community acquired pneumonia (BCAP). Consecutive APTB patients who were accurately diagnosed by sputum culture and BCAP patients were enrolled from August 2013 to July 2015. Clinical data were collected, and plasma presepsin concentrations were tested. Receiver operating characteristic (ROC) curves were performed for diagnostic analysis. In all, 133 healthy individuals, 103 APTB and 202 BCAP patients were enrolled. Presepsin concentrations in APTB group (218.0 [146.0, 368.0] pg/ml) were higher than those in the healthy control group (128.0 [101.5, 176.5] pg/ml, P<0.001), and lower than the concentrations measured in the BCAP group (532.0 [364.0, 852.3] pg/ml, P<0.001). Simple APTB and miliary tuberculosis patients showed no significant differences in presepsin concentrations. Compared with both Gram-positive and negative bacteria, Mycobacterium tuberculosis caused a limited increase of presepsin. With the cut-off value set at 401pg/ml, presepsin demonstrated high positive predictive value, allowing initial discriminating between APTB and BCAP. Presepsin combined with CURB-65 score could significantly improve the discrimination ability. Presepsin concentrations in APTB patients were slightly increased, and may be helpful for initial discrimination between APTB and BCAP. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Prevalence and Impact of Diabetes Mellitus Among Patients with Active Pulmonary Tuberculosis in South Korea.

    Science.gov (United States)

    Lee, Eun Hye; Lee, Jung Mo; Kang, Young Ae; Leem, Ah Young; Kim, Eun Young; Jung, Ji Ye; Park, Moo Suk; Kim, Young Sam; Kim, Se Kyu; Chang, Joon; Kim, Song Yee

    2017-04-01

    South Korea has an increasing prevalence of diabetes and a relatively high burden of tuberculosis. We aimed to determine the prevalence of diabetes in patients with active pulmonary tuberculosis (PTB) and examine the effect of diabetes on tuberculosis treatment outcomes. Data from patients ≥30 years diagnosed with and treated for PTB between January 2010 and December 2012 at Severance Hospital, a 2000-bed tertiary referral hospital in Seoul, South Korea, were analyzed and compared with data from a contemporaneous general population sample extracted from KNHANES V. Diabetes prevalence was 24.2% (252/1044) among patients with PTB and 11.6% (1700/14,655) among controls. Diabetes [odds ratios (OR) 2.56, 95% confidence interval (CI) 1.56-4.21, P Diabetes was the only factor associated with unsuccessful treatment outcomes (OR 1.67, 95% CI 1.03-2.70, P = 0.039). The prevalence of diabetes was markedly higher in patients with PTB than in a sample of the general South Korean population. Diabetes may delay sputum conversion and adversely affect treatment outcomes; detection and management of diabetes in patients with PTB is crucial.

  2. Potential of Zanthoxylum leprieurii as a source of active compounds against drug resistant Mycobacterium tuberculosis.

    Science.gov (United States)

    Bunalema, Lydia; Fotso, Ghislain Wabo; Waako, Paul; Tabuti, John; Yeboah, Samuel O

    2017-02-02

    Tuberculosis (TB) is still a global health problem mainly due to development of resistance and co-infection with the Human immune Virus (HIV). Treatment of multi and extensively drug resistant TB requires use of second line drugs which are less efficacious, expensive and very toxic. This has necessitated a need to search for new treatment regimens especially from medicinal plants. Zanthoxylum leprieurii, a plant species from Rutaceae is used locally in the treatment of tuberculosis in Uganda. The aim of the study was to isolate, identify and characterize bio active compounds from Z. leprieurii stem bark with antimycobacterial activity. Crude extracts, fractions and compounds from air dried stem bark of Z. leprieurii were tested against pan sensitive (H37rv), isoniazid resistant (TMC 301) and rifampicin resistant (TMC 331) strains of M. tuberculosis using micro plate alamar blue assay. Isolation of active compounds was done by using column chromatography and thin layer chromatography. They were analysed using nuclear magnetic resonance spectroscopy and mass spectroscopy. The methanol extract had minimum inhibitory concentrations (MIC) of 47.5, 75.3 and 125.0 μg/ml on the pan sensitive strain, rifampicin resistant and isozianid resistant strains of M. tuberculosis respectively. The chloroform extract had MIC values of 260 μg/ml agnaist the pan sensitive strain and 156 μg/ml on the rifampicin resistant strain. Of the sixteen fractions from the methanol extract, fraction Za 4 (MIC = 6.3 μg/mL, 23.0 μg/mL, 11.7 μg/mL) and Za 6 (MIC = 11.7 μg/mL 31.2 μg/ml, 31.2 μg/ml) were the most active. Three acridone alkaloids; hydroxy-1, 3-dimethoxy-10-methyl-9-acridone (1), 1-hydroxy-3-methoxy-10-methyl-9-acridone (2) and 3-hydroxy-1, 5, 6-trimethoxy-9-acridone (3) were isolated from Za 4 and Za 6 . The MIC of compound 3 was found to be 5.1 μg/ml, 4.5 μg/ml and 3.9 μg/ml on H37rv, TMC 331 and TMC 301 while that of 1 was found to be 1.5 μg/ml, 8.3

  3. Systematic Survey of Serine Hydrolase Activity in Mycobacterium tuberculosis Defines Changes Associated with Persistence

    Energy Technology Data Exchange (ETDEWEB)

    Ortega, Corrie; Anderson, Lindsey N.; Frando, Andrew; Sadler, Natalie C.; Brown, Robert W.; Smith, Richard D.; Wright, Aaron T.; Grundner, Christoph

    2016-02-01

    The transition between replication and non-replication underlies much of Mycobacterium tuberculosis (Mtb) pathogenicity, as non- or slowly replicating Mtb are responsible for persistence and poor treatment outcomes. Therapeutic targeting of non-replicating, persistent populations is a priority for tuberculosis treatment, but only few drug targets in non-replicating Mtb are currently known. Here, we directly measure the activity of the highly diverse and druggable serine hydrolases (SHs) during active replication and non-replication by activity-based proteomics. We predict serine hydrolase activity for 78 proteins, including 27 proteins with previously unknown function, and identify 37 SHs that remain active even in the absence of replication, providing a set of candidate persistence targets. Non-replication was associated with large shifts in the activity of the majority of SHs. These activity changes were largely independent of SH abundance, indicating extensive post-translational regulation. By probing a large cross-section of druggable Mtb enzyme space during replication and non-replication, we identify new SHs and suggest new persistence targets.

  4. A case of suspect “cyanosis”

    Directory of Open Access Journals (Sweden)

    Elisabetta Antonucci

    2013-05-01

    Full Text Available CLINICAL CASE A 70-year old woman was admitted to our hospital because of fever, asthenia and a suspected stroke. Her medical history showed a congenital cardiopathy (Patent Foramen Ovale, PFO. Skin and oral mucosa pigmentation, orthostatic hypotension, hypoglycemia and hyponatriemia arose the suspect of Addison’s disease. The diagnosis was confirmed by the evaluation of basal levels of plasma ACTH and serum cortisol, and serum cortisol levels after ACTH stimulation. Abdominal CT scan showed atrophy and calcification of adrenal glands. CONCLUSIONS In most cases, Addison’s disease is provoked by autoimmune destruction of the adrenal cortex; however, in our reported patient, tuberculosis could be a possible cause.

  5. Diagnosis of Pediatric Pulmonary Tuberculosis by Stool PCR

    OpenAIRE

    Wolf, Hilary; Mendez, Melissa; Gilman, Robert H.; Sheen, Patricia; Soto, Giselle; Velarde, Angie K.; Zimic, Mirko; Escombe, A. Roderick; Montenegro,Sonia; Oberhelman, Richard A.; Evans, Carlton A.

    2008-01-01

    Pediatric pulmonary tuberculosis diagnosis is difficult because young children are unable to expectorate sputum samples. Testing stool for tuberculosis DNA from swallowed sputum may diagnose pulmonary tuberculosis. Hospitalized children with suspected tuberculosis had stool, nasopharyngeal, and gastric aspirates cultured that confirmed pulmonary tuberculosis in 16/236 patients. Twenty-eight stored stools from these 16 children were used to evaluate stool polymerase chain reaction (PCR) for tu...

  6. Tuberculosis (TB)

    Science.gov (United States)

    ... with facebook share with twitter share with linkedin Tuberculosis Go to Information for Researchers ► Tuberculosis (TB) is ... are drug resistant. Why Is the Study of Tuberculosis a Priority for NIAID? Tuberculosis is one of ...

  7. Synthetic calanolides with bactericidal activity against replicating and nonreplicating Mycobacterium tuberculosis.

    Science.gov (United States)

    Zheng, Purong; Somersan-Karakaya, Selin; Lu, Shichao; Roberts, Julia; Pingle, Maneesh; Warrier, Thulasi; Little, David; Guo, Xiaoyong; Brickner, Steven J; Nathan, Carl F; Gold, Ben; Liu, Gang

    2014-05-08

    It is urgent to introduce new drugs for tuberculosis to shorten the prolonged course of treatment and control drug-resistant Mycobacterium tuberculosis (Mtb). One strategy toward this goal is to develop antibiotics that eradicate both replicating (R) and nonreplicating (NR) Mtb. Naturally occurring (+)-calanolide A was active against R-Mtb. The present report details the design, synthesis, antimycobacterial activities, and structure-activity relationships of synthetic calanolides. We identified potent dual-active nitro-containing calanolides with minimal in vitro toxicity that were cidal to axenic Mtb and Mtb in human macrophages, while sparing Gram-positive and -negative bacteria and yeast. Two of the nitrobenzofuran-containing lead compounds were found to be genotoxic to mammalian cells. Although genotoxicity precluded clinical progression, the profound, selective mycobactericidal activity of these calanolides will be useful in identifying pathways for killing both R- and NR-Mtb, as well as in further structure-based design of more effective and drug-like antimycobacterial agents.

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

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    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.

  9. The role of Vdelta2+T-cells in patients with active Mycobacterium tuberculosis infection and tuberculin anergy.

    Science.gov (United States)

    Szereday, L; Baliko, Z; Szekeres-Bartho, J

    2008-03-01

    Tuberculosis (TB) is one of the most common major infectious diseases. In humans, acquired protective immunity to Mycobacterium tuberculosis depends on T-cells and involves multiple T-cell subsets; however, the pathways used by T-cells to restrict the growth of M. tuberculosis are poorly understood. To investigate the possible role of Vdelta2+T-cells and regulatory T-cells in the immune response to M. tuberculosis. As Vdelta2+T-cell function has been shown to be impaired in patients with M. tuberculosis infection, we investigated the percentage of perforin and Fas ligand (FasL) positive Vdelta2+T-cells and the possible role of activating and inhibitory natural killer (NK) cell receptors as well as that of regulatory T-cells in the control of tuberculin responsiveness. Tuberculin-negative patients demonstrated decreased perforin expression and increased FasL expression, which could not be explained by dysregulation of NK cell receptor expression or altered regulatory T-cell function. Altered cytotoxic capacity and apoptotic potential of Vdelta2+T-cells provide a plausible explanation for defective cellular immune functions in M. tuberculosis-infected anergic patients.

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

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    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

  11. Tuberculosis screening in patients with HIV: use of audit and feedback to improve quality of care in Ghana

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    Stephanie Bjerrum

    2016-08-01

    Full Text Available Background: Tuberculosis screening of people living with HIV (PLHIV can contribute to early tuberculosis diagnosis and improved patient outcomes. Evidence-based guidelines for tuberculosis screening are available, but literature assessing their implementation and the quality of clinical practice is scarce. Objectives: To assess tuberculosis screening practices and the effectiveness of audit and performance feedback to improve quality of tuberculosis screening at HIV care clinics in Ghana. Design: Healthcare providers at 10 large HIV care clinics prospectively registered patient consultations during May and October 2014, before and after a performance feedback intervention in August 2014. The outcomes of interest were overall tuberculosis suspicion rate during consultations and provider adherence to the International Standards for Tuberculosis Care and the World Health Organizations’ guidelines for symptom-based tuberculosis screening among PLHIV. Results: Twenty-one healthcare providers registered a total of 2,666 consultations; 1,368 consultations before and 1,298 consultations after the feedback intervention. Tuberculosis suspicion rate during consultation increased from 12.6 to 20.9% after feedback (odds ratio, OR 1.83; 95% confidence interval, CI: 1.09–3.09. Before feedback, sputum smear microscopy was requested for 58.7% of patients with suspected tuberculosis, for 47.2% of patients with cough ≥2 weeks, and for 27.5% of patients with a positive World Health Organization (WHO symptom screen (any of current cough, fever, weight loss or night sweats. After feedback, patients with a positive WHO symptom screen were more likely to be suspected of tuberculosis (OR 2.21; 95% CI: 1.19–4.09 and referred for microscopy (OR 2.71; 95% CI: 1.25–5.86. Conclusions: A simple prospective audit tool identified flaws in clinical practices for tuberculosis screening of PLHIV. There was no systematic identification of people with suspected active

  12. Modifiable factors associated with active pulmonary tuberculosis in a ...

    African Journals Online (AJOL)

    Conclusions: Modifiable factors associated with active PTB in Nakuru G.K prison are: HIV status, BCG vaccination, PTB case contact, poverty and poor personal hygiene. We recommend HIV counselling and testing of all PTB patients, screening for TB upon prison entry and TB contact investigation and improving personal ...

  13. Mycobacterium tuberculosis Rv2882c Protein Induces Activation of Macrophages through TLR4 and Exhibits Vaccine Potential.

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    Han-Gyu Choi

    Full Text Available Macrophages constitute the first line of defense against Mycobacterium tuberculosis and are critical in linking innate and adaptive immunity. Therefore, the identification and characterization of mycobacterial proteins that modulate macrophage function are essential for understanding tuberculosis pathogenesis. In this study, we identified the novel macrophage-activating protein, Rv2882c, from M. tuberculosis culture filtrate proteins. Recombinant Rv2882c protein activated macrophages to secrete pro-inflammatory cytokines and express co-stimulatory and major histocompatibility complex molecules via Toll-like receptor 4, myeloid differentiation primary response protein 88, and Toll/IL-1 receptor-domain-containing adaptor inducing IFN-beta. Mitogen-activated protein kinases and NF-κB signaling pathways were involved in Rv2882c-induced macrophage activation. Further, Rv2882c-treated macrophages induced expansion of the effector/memory T cell population and Th1 immune responses. In addition, boosting Bacillus Calmette-Guerin vaccination with Rv2882c improved protective efficacy against M. tuberculosis in our model system. These results suggest that Rv2882c is an antigen that could be used for tuberculosis vaccine development.

  14. TNF-dependent regulation and activation of innate immune cells are essential for host protection against cerebral tuberculosis.

    Science.gov (United States)

    Francisco, Ngiambudulu M; Hsu, Nai-Jen; Keeton, Roanne; Randall, Philippa; Sebesho, Boipelo; Allie, Nasiema; Govender, Dhirendra; Quesniaux, Valerie; Ryffel, Bernhard; Kellaway, Lauriston; Jacobs, Muazzam

    2015-06-26

    Tuberculosis (TB) affects one third of the global population, and TB of the central nervous system (CNS-TB) is the most severe form of tuberculosis which often associates with high mortality. The pro-inflammatory cytokine tumour necrosis factor (TNF) plays a critical role in the initial and long-term host immune protection against Mycobacterium tuberculosis (M. tuberculosis) which involves the activation of innate immune cells and structure maintenance of granulomas. However, the contribution of TNF, in particular neuron-derived TNF, in the control of cerebral M. tuberculosis infection and its protective immune responses in the CNS were not clear. We generated neuron-specific TNF-deficient (NsTNF(-/-)) mice and compared outcomes of disease against TNF(f/f) control and global TNF(-/-) mice. Mycobacterial burden in brains, lungs and spleens were compared, and cerebral pathology and cellular contributions analysed by microscopy and flow cytometry after M. tuberculosis infection. Activation of innate immune cells was measured by flow cytometry and cell function assessed by cytokine and chemokine quantification using enzyme-linked immunosorbent assay (ELISA). Intracerebral M. tuberculosis infection of TNF(-/-) mice rendered animals highly susceptible, accompanied by uncontrolled bacilli replication and eventual mortality. In contrast, NsTNF(-/-) mice were resistant to infection and presented with a phenotype similar to that in TNF(f/f) control mice. Impaired immunity in TNF(-/-) mice was associated with altered cytokine and chemokine synthesis in the brain and characterised by a reduced number of activated innate immune cells. Brain pathology reflected enhanced inflammation dominated by neutrophil influx. Our data show that neuron-derived TNF has a limited role in immune responses, but overall TNF production is necessary for protective immunity against CNS-TB.

  15. Active and latent tuberculosis in prisoners in the Central-West Region of Brazil

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    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.

  16. Tea Drinking and Its Association with Active Tuberculosis Incidence among Middle-Aged and Elderly Adults: The Singapore Chinese Health Study

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    Avril Zixin Soh

    2017-05-01

    Full Text Available Experimental studies showed that tea polyphenols may inhibit growth of Mycobacterium tuberculosis. However, no prospective epidemiologic study has investigated tea drinking and the risk of active tuberculosis. We investigated this association in the Singapore Chinese Health Study, a prospective population-based cohort of 63,257 Chinese aged 45–74 years recruited between 1993 and 1998 in Singapore. Information on habitual drinking of tea (including black and green tea and coffee was collected via structured questionnaires. Incident cases of active tuberculosis were identified via linkage with the nationwide tuberculosis registry up to 31 December 2014. Cox proportional hazard models were used to estimate the relation of tea and coffee consumption with tuberculosis risk. Over a mean 16.8 years of follow-up, we identified 1249 incident cases of active tuberculosis. Drinking either black or green tea was associated with a dose-dependent reduction in tuberculosis risk. Compared to non-drinkers, the hazard ratio (HR (95% confidence interval (CI was 1.01 (0.85–1.21 in monthly tea drinkers, 0.84 (0.73–0.98 in weekly drinkers, and 0.82 (0.71–0.96 in daily drinkers (p for trend = 0.003. Coffee or caffeine intake was not significantly associated with tuberculosis risk. In conclusion, regular tea drinking was associated with a reduced risk of active tuberculosis.

  17. Humoral immunity in tuberculin skin test anergy and its role in high-risk persons exposed to active tuberculosis

    Science.gov (United States)

    Encinales, Liliana; Zuñiga, Joaquin; Yunis, Maria; Granados-Montiel, Julio; Granados, Julio; Almeciga, Ingrid; Clavijo, Olga; Awad, Carlos; Collazos, Vilma; Vargas-Rojas, María Inés; Bañales-Mendez, José Luis; Vazquez-Castañeda, Lilia; Stern, Joel N.; Romero, Viviana; Frindkis-Hareli, Masha; Terreros, Daniel; Fernandez-Viña, Marcelo; Yunis, Edmond J.

    2009-01-01

    The most common test to identify latent tuberculosis is the Tuberculin skin test that detects T cell responses of delayed type hypersensitivity type IV. Since it produces false negative reactions in active tuberculosis or in high-risk persons exposed to tuberculosis patients as shown in this report, we studied antibody profiles to explain the anergy of such responses in high-risk individuals without active infection. Our results showed that humoral immunity against Tuberculin, regardless of the result of the Tuberculin skin test is important for protection from active tuberculosis and that the presence of high antibody titers is a more reliable indicator of infection latency suggesting that latency can be based on the levels of antibodies together with in vitro proliferation of peripheral blood mononuclear cells in the presence of the purified protein derivative. Importantly, anti-Tuberculin IgG antibody levels mediate the anergy described herein, which could also prevent reactivation of disease in high-risk individuals with high antibody titers. Such IgG Tuberculin antibodies were also found associated with blocking and/or stimulation of in vitro cultures of PBMC with Tuberculin. In this regard, future studies need to establish if immune responses to Mycobacterium tuberculosis can generate a broad spectrum of reactions either toward Th1 responses favoring stimulation by cytokines or by antibodies and those toward diminished responses by Th2 cytokines or blocking by antibodies; possibly involving mechanisms of antibody dependent protection from Mtb by different subclasses of IgG. PMID:20004475

  18. Crystal structures of the kinase domain of the sulfate-activating complex in Mycobacterium tuberculosis.

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    Ömer Poyraz

    Full Text Available In Mycobacterium tuberculosis the sulfate activating complex provides a key branching point in sulfate assimilation. The complex consists of two polypeptide chains, CysD and CysN. CysD is an ATP sulfurylase that, with the energy provided by the GTPase activity of CysN, forms adenosine-5'-phosphosulfate (APS which can then enter the reductive branch of sulfate assimilation leading to the biosynthesis of cysteine. The CysN polypeptide chain also contains an APS kinase domain (CysC that phosphorylates APS leading to 3'-phosphoadenosine-5'-phosphosulfate, the sulfate donor in the synthesis of sulfolipids. We have determined the crystal structures of CysC from M. tuberculosis as a binary complex with ADP, and as ternary complexes with ADP and APS and the ATP mimic AMP-PNP and APS, respectively, to resolutions of 1.5 Å, 2.1 Å and 1.7 Å, respectively. CysC shows the typical APS kinase fold, and the structures provide comprehensive views of the catalytic machinery, conserved in this enzyme family. Comparison to the structure of the human homolog show highly conserved APS and ATP binding sites, questioning the feasibility of the design of specific inhibitors of mycobacterial CysC. Residue Cys556 is part of the flexible lid region that closes off the active site upon substrate binding. Mutational analysis revealed this residue as one of the determinants controlling lid closure and hence binding of the nucleotide substrate.

  19. Respiratory symptoms and active tuberculosis in a prison in Southern Brazil: associated epidemiologic variables

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    Jeane Zanini Rocha

    2013-10-01

    Full Text Available Backgound and Objectives: This study is justified by the high TB prevalence in prisons, which constitutes a public health problem and aims to estimate the prevalence of active tuberculosis (TB and determine the variables associated with respiratory symptoms in a prison in Brazil. Methods: This is a descriptive study of 262 inmates divided into respiratory symptomatic and asymptomatic groups. Samples were evaluated by microscopy following the cultivation of the sputum from symptomatic individuals. Associated epidemiological variables were also evaluated. Results: Among the 262 inmates included, 178 (68% were considered symptomatic, and of these, 25 (14% were diagnosed with active TB. The contribution of culturing in the detection of TB cases was 48%. The prevalence of active TB was 9,542/100.000. Low educational level, use of drugs and alcohol, prison recidivism, and previous TB and HIV-positive status were associated with the presence of respiratory symptoms. Being male, single, black, a prison recidivist, an alcoholic and HIV-seropositive was associated with the development of TB. The rate of TB/HIV co infection was 60%. The outcome was death in 12% of patients. Drug therapy interruption was reported by 96% of patients. Conclusions: The studied population showed a high prevalence of TB and TB/HIV co-infection. In addition, the rates of drug therapy interruption and mortality were alarmingly elevated. KEYWORDS: Epidemiology. Tuberculosis. Coinfections. HIV infection. Prisons.

  20. [Clinical and radiological features of pulmonary tuberculosis manifested as interstitial lung diseases.].

    Science.gov (United States)

    Shi, Ju-Hong; Feng, Rui-E; Tian, Xin-Lun; Xu, Wen-Bing; Xu, Zuo-Jun; Liu, Hong-Rui; Zhu, Yuan-Jue

    2009-12-01

    The purpose of this paper was to investigate the clinical and radiological features of pulmonary tuberculosis presenting as interstitial lung diseases (ILD). We analyzed the data of cases suspected of diffuse parenchyma lung diseases at this hospital between October 2003 and October 2007. The diagnosis of active pulmonary tuberculosis was based on epithelioid granuloma or positive acid-fast bacilli in lung biopsy and changes on serial radiographs obtained during treatment. The data of a series of 230 consecutive patients with suspected ILD were retrospectively analyzed. The diagnosis was confirmed by lung biopsy. Twelve patients were confirmed to have pulmonary tuberculosis. There were 5 males and 7 females with a mean age of 38 +/- 11 years (range, 17 - 68). The median course of disease in these patients was 3 months (range, 0.5 - 18 months). Patients with pulmonary tuberculosis presented with fever (11/12), cough (9/12), weight loss (7/12), dyspnea (7/12), lymphadenopathy (4/12), and splenohepatomegaly (2/12). On chest CT scan, ground-glass attenuation was identified in 4, bilateral patchy infiltration in 5, tree-in-bud appearance 1, and centrilobular lesions in 2 of the 12 patients. During the follow-up period (median, 9 month, range from 3 to 12 month), 11 patients improved, but 1 died of diabetic ketoacidosis. The diagnosis of pulmonary tuberculosis should be considered in suspected ILD patients presenting with fever, splenohepatomegaly and lymphadenopathy.

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

    Science.gov (United States)

    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... connection for pulmonary tuberculosis. When under consideration, all available service department films and...

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

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    Michala V Rose

    Full Text Available AIM: 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. METHODS: Sensitivity and specificity of QFT and TST for diagnosing active TB as well as indeterminate QFT rates and IFN-γ levels were assessed in 211 TB suspect children in a Tanzanian district hospital and contrasted in 90 adults with confirmed pulmonary TB. RESULTS: Sensitivity of QFT and TST in children with confirmed TB was 19% (5/27 and 6% (2/31 respectively. In adults sensitivity of QFT and TST was 84% (73/87 and 85% (63/74. The QFT indeterminate rate in children and adults was 27% and 3%. Median levels of IFN-γ were lower in children than adults, particularly children <2 years and HIV infected. An indeterminate result was associated with age <2 years but not malnutrition or HIV status. Overall childhood mortality was 19% and associated with an indeterminate QFT result at baseline. CONCLUSION: QFT and TST showed poor performance and a surprisingly low sensitivity in children. In contrast the performance in Tanzanian adults was good and comparable to performance in high-income countries. Indeterminate results in children were associated with young age and increased mortality. Neither test can be recommended for diagnosing active TB in children with immature or impaired immunity in a high-burden setting.

  3. Analysis of the Phenotype of Mycobacterium tuberculosis-Specific CD4+ T Cells to Discriminate Latent from Active Tuberculosis in HIV-Uninfected and HIV-Infected Individuals

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    Catherine Riou

    2017-08-01

    Full Text Available Several immune-based assays have been suggested to differentiate latent from active tuberculosis (TB. However, their relative performance as well as their efficacy in HIV-infected persons, a highly at-risk population, remains unclear. In a study of 81 individuals, divided into four groups based on their HIV-1 status and TB disease activity, we compared the differentiation (CD27 and KLRG1, activation (HLA-DR, homing potential (CCR4, CCR6, CXCR3, and CD161 and functional profiles (IFNγ, IL-2, and TNFα of Mycobacterium tuberculosis (Mtb-specific CD4+ T cells using flow cytometry. Active TB disease induced major changes within the Mtb-responding CD4+ T cell population, promoting memory maturation, elevated activation and increased inflammatory potential when compared to individuals with latent TB infection. Moreover, the functional profile of Mtb-specific CD4+ T cells appeared to be inherently related to their degree of differentiation. While these specific cell features were all capable of discriminating latent from active TB, irrespective of HIV status, HLA-DR expression showed the best performance for TB diagnosis [area-under-the-curve (AUC = 0.92, 95% CI: 0.82–1.01, specificity: 82%, sensitivity: 84% for HIV− and AUC = 0.99, 95% CI: 0.98–1.01, specificity: 94%, sensitivity: 93% for HIV+]. In conclusion, these data support the idea that analysis of T cell phenotype can be diagnostically useful in TB.

  4. The two PPX-GppA homologues from Mycobacterium tuberculosis have distinct biochemical activities.

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    Mei Y Choi

    Full Text Available Inorganic polyphosphate (poly-P, guanosine pentaphosphate (pppGpp and guanosine tetraphosphate (ppGpp are ubiquitous in bacteria. These molecules play a variety of important physiological roles associated with stress resistance, persistence, and virulence. In the bacterial pathogen Mycobacterium tuberculosis, the identities of the proteins responsible for the metabolism of polyphosphate and (pppGpp remain to be fully established. M. tuberculosis encodes two PPX-GppA homologues, Rv0496 (MTB-PPX1 and Rv1026, which share significant sequence similarity with bacterial exopolyphosphatase (PPX and guanosine pentaphosphate 5'-phosphohydrolase (GPP proteins. Here we delineate the respective biochemical activities of the Rv0496 and Rv1026 proteins and benchmark these against the activities of the PPX and GPP proteins from Escherichia coli. We demonstrate that Rv0496 functions as an exopolyphosphatase, showing a distinct preference for relatively short-chain poly-P substrates. In contrast, Rv1026 has no detectable exopolyphosphatase activities. Analogous to the E. coli PPX and GPP enzymes, the exopolyphosphatase activities of Rv0496 are inhibited by pppGpp and, to a lesser extent, by ppGpp alarmones, which are produced during the bacterial stringent response. However, neither Rv0496 nor Rv1026 have the ability to hydrolyze pppGpp to ppGpp; a reaction catalyzed by E. coli PPX and GPP. Both the Rv0496 and Rv1026 proteins have modest ATPase and to a lesser extent ADPase activities. pppGpp alarmones inhibit the ATPase activities of Rv1026 and, to a lesser extent, the ATPase activities of Rv0496. We conclude that PPX-GppA family proteins may not possess all the catalytic activities implied by their name and may play distinct biochemical roles involved in polyphosphate and (pppGpp metabolic pathways.

  5. Tuberculosis and nutrition

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    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. Ion Channel Blockers as Antimicrobial Agents, Efflux Inhibitors, and Enhancers of Macrophage Killing Activity against Drug Resistant Mycobacterium tuberculosis.

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    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

  7. High Affinity Inha Inhibitors with Activity Against Drug-Resistant Strains of Mycobacterium Tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. Plasma Drug Activity Assay for Treatment Optimization in Tuberculosis Patients ▿ †

    Science.gov (United States)

    Heysell, Scott K.; Mtabho, Charles; Mpagama, Stellah; Mwaigwisya, Solomon; Pholwat, Suporn; Ndusilo, Norah; Gratz, Jean; Aarnoutse, Rob E.; Kibiki, Gibson S.; Houpt, Eric R.

    2011-01-01

    Low antituberculosis (TB) drug levels are common, but their clinical significance remains unclear, and methods of measurement are resource intensive. Subjects initiating treatment for sputum smear-positive pulmonary TB were enrolled from Kibong'oto National TB Hospital, Tanzania, and levels of isoniazid, rifampin, ethambutol, and pyrazinamide were measured at the time of typical peak plasma concentration (C2 h). To evaluate the significance of the effect of observed drug levels on Mycobacterium tuberculosis growth, a plasma TB drug activity (TDA) assay was developed using the Bactec MGIT system. Time to detection of plasma-cocultured M. tuberculosis versus time to detection of control growth was defined as a TDA ratio. TDA assays were later performed using the subject's own M. tuberculosis isolate and C2 h plasma from the Tanzanian cohort and compared to drug levels and clinical outcomes. Sixteen subjects with a mean age of 37.8 years ± 10.7 were enrolled. Fourteen (88%) had C2 h rifampin levels and 11 (69%) had isoniazid levels below 90% of the lower limit of the expected range. Plasma spiked with various concentrations of antituberculosis medications found TDA assay results to be unaffected by ethambutol or pyrazinamide. Yet with a range of isoniazid and rifampin concentrations, TDA exhibited a statistically significant correlation with drug level and drug MIC, and a TDA of ∼1.0 indicated the presence of multidrug-resistant TB. In Tanzania, low (≤2.0) TDA was significantly associated with both lower isoniazid and rifampin C2 h levels, and very low (≤1.5) TDA corresponded to a trend toward lack of cure. Study of TDA compared to additional clinical outcomes and as a therapeutic management tool is warranted. PMID:21968363

  9. Nutritional supplements for people being treated for active tuberculosis: A technical summary.

    Science.gov (United States)

    Grobler, L; Durao, S; Van der Merwe, S M; Wessels, J; Naude, C E

    2017-12-13

    Tuberculosis and nutrition are intrinsically linked in a complex relationship. Altered metabolism and loss of appetite associated with tuberculosis may result in undernutrition, which in turn may worsen the disease or delay recovery. We highlight an updated Cochrane review assessing the effects of oral nutritional supplements in people with active tuberculosis who are receiving antituberculosis drug therapy. The review authors conducted a comprehensive search (February 2016) for all randomised controlled trials comparing any oral nutritional supplement, given for at least 4 weeks, with no nutritional intervention, placebo or dietary advice only in people receiving antituberculosis treatment. Of the 35 trials (N=8 283 participants) included, seven assessed the provision of free food or high-energy supplements, six assessed multi-micronutrient supplementation, and 21 assessed single- or dual-micronutrient supplementation. There is currently insufficient evidence to indicate whether routinely providing free food or high-energy supplements improves antituberculosis treatment outcomes (i.e. reduced death and increased cure rates at 6 and 12 months), but it probably improves weight gain in some settings. Plasma levels of zinc, vitamin D, vitamin E and selenium probably improve with supplementation, but currently no reliable evidence demonstrates that routine supplementation with multi-, single or dual micronutrients above the recommended daily intake has clinical benefits (i.e. reduced death, increased cure rate at 6 and 12 months, improved nutritional status) in patients receiving antituberculosis treatment. In South Africa, most provinces implement a supplementation protocol based on nutritional assessment and classification of individuals rather than on disease diagnosis or treatment status.

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

    Science.gov (United States)

    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. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Renal tuberculosis

    OpenAIRE

    Džamić Zoran; Dimitrijević Vladan

    2016-01-01

    Tuberculosis is still a significant health problem in the world, mostly in developing countries. The special significance lies in immunocompromised patients, particularly those suffering from the HIV. Urogenital tuberculosis is one of the most common forms of extrapulmonary tuberculosis, while the most commonly involved organ is the kidney. Renal tuberculosis occurs by hematogenous dissemination of mycobacterium tuberculosis from a primary tuberculosis foci in the body. Tuberculosis is charac...

  12. Mechanistic and functional insights into fatty acid activation in Mycobacterium tuberculosis

    Science.gov (United States)

    Arora, Pooja; Goyal, Aneesh; Natarajan, Vivek T; Rajakumara, Eerappa; Verma, Priyanka; Gupta, Radhika; Yousuf, Malikmohamed; Trivedi, Omita A.; Mohanty, Debasisa; Tyagi, Anil; Sankaranarayanan, Rajan; Gokhale, Rajesh S.

    2009-01-01

    The recent discovery of fatty acyl-AMP ligases (FAALs) in Mycobacterium tuberculosis (Mtb) provided a new perspective to fatty acid activation dogma. These proteins convert fatty acids to corresponding adenylates, which is an intermediate of acyl-CoA-synthesizing fatty acyl-CoA ligases (FACLs). Presently, it is not evident how obligate pathogens like Mtb have evolved such new themes of functional versatility and whether the activation of fatty acids to acyl-adenylates could indeed be a general mechanism. Here, based on elucidation of the first structure of a FAAL protein and by generating loss- as well as gain-of-function mutants that interconvert FAAL and FACL activities, we demonstrate that an insertion motif dictates formation of acyl-adenylate. Since FAALs in Mtb are crucial nodes in biosynthetic network of virulent lipids, inhibitors directed against these proteins provide a unique multi-pronged approach of simultaneously disrupting several pathways. PMID:19182784

  13. Mycobacterial excretory secretory-31 protein with serine protease and lipase activities: An immunogen and drug target against tuberculosis infection.

    Science.gov (United States)

    Harinath, Bhaskar C

    2016-12-01

    patients suspected of TB attending Kasturba Hospital-a tertiary health care center. The characterization of ES-31 antigen protein showed that ES-31 is a 31-kDa protein antigen with zinc containing serine protease as well as lipase activities and shown to be a chymotrypsin-like protein which has the catalytic triad responsible for both the activities. Addition of serine protease inhibitors: (1) pefabloc; (2) 3,4 dichloroisocoumarin; (3) phenyl methyl sulfonyl fluoride (53-76%); and metallo-protease inhibitors: (1) EDTA; (2) 1,10 phenanthroline (46-61%), lipase inhibitor, orlistat (61%), or anti-ES-31 serine protease antibody (89%) inhibited the Mycobacterium tuberculosis (MTB) H37Ra growth in axenic culture which is further confirmed by a decreased amount of ES-31 protein secreted in the culture filtrate. The importance of excretory secretory ES-31 protein for the survival of MTB H37Ra and H37Rv bacilli has been shown by 77% and 78% growth inhibition in macrophage culture by protease inhibitor pefabloc and was further confirmed by the enhancement of growth of TB bacilli in the presence of ES-31. Inhibition of ES-31 leads to the growth inhibition of MTB bacilli, suggesting that ES-31 is important for entry and multiplication of bacilli and an important drug target for exploring new drugs for TB based on protease and lipase activities of ES-31 protein. Copyright © 2016.

  14. Pulmonary sarcoidosis shortly after spinal tuberculosis infection: a diagnostic challenge.

    Science.gov (United States)

    Luetkens, Julian A; Zoghi, Shahram; Rockstroh, Jürgen K; Naehle, Claas P

    2014-04-11

    Tuberculosis and sarcoidosis share similar histopathological findings. An aetiological connection between these diseases has been discussed. We report a case of pulmonary sarcoidosis, which occurred shortly after an isoniazid (INH)-resistant spinal tuberculosis was diagnosed which was suspected to be a miliary tuberculosis. This report illustrates the need to sensitise clinicians to two possible important causes of lung parenchyma alterations under tuberculostatic therapy.

  15. Laparoscopy can be used to diagnose peritoneal tuberculosis

    DEFF Research Database (Denmark)

    Ferløv Schwensen, Jakob; Bulut, Mustafa; Nordholm-Carstensen, Andreas

    2014-01-01

    and widespread pale nodules were found throughout the peritoneum. Consequently, the patient was diagnosed with peritoneal tuberculosis. This case demonstrates that atypical manifestations of tuberculosis exist in Denmark and that laparoscopy with biopsy can be performed to obtain the diagnosis when suspecting...... peritoneal tuberculosis....

  16. [Serologic cross-reactions to Leishmania infantum using indirect immunofluorescence in HIV+ and HIV- patients with active tuberculosis].

    Science.gov (United States)

    López-Vélez, R; Turientes, M C; Gómez-Mampaso, E

    1998-03-01

    Clinical presentation of disseminated tuberculosis and visceral leishmaniosis can be very similar, mainly in those infected with HIV, being serology a useful tool in making a differential diagnosis. Cross-reactions of IFAT serodiagnosis of visceral leishmaniosis with other diseases are well known, but few data is available with tuberculosis. Detection of serum antibodies against Leishmania, using a commercial IFAT kit, was attempted in sera of 51 patients with active pulmonar and/or extrapulmonar tuberculosis (25 HIV+ and 26 HIV-). Overall cross-reactions was found in 19.6% patients without significative differences in between 2 groups, but differences in positive serum titres was observed: one at 1/256, three at 1/160, and one at 1/80 dilution, in the HIV+ group, whereas all 5 patients in HIV- group cross-reacted at 1/80 dilution. Recognition of specific leishmanial antigenic bands by serum antibodies of patients with tuberculosis were not clearly defined by Western-blot. IFAT technique for leishmaniosis cross-react in 20% of patients with tuberculosis.

  17. Notch4 Negatively Regulates the Inflammatory Response to Mycobacterium tuberculosis Infection by Inhibiting TAK1 Activation.

    Science.gov (United States)

    Zheng, Ruijuan; Liu, Haipeng; Zhou, Yilong; Yan, Dapeng; Chen, Jianxia; Ma, Dapeng; Feng, Yonghong; Qin, Lianhua; Liu, Feng; Huang, Xiaochen; Wang, Jie; Ge, Baoxue

    2017-12-08

    Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection remains a global threat to human health, but knowledge of the molecular mechanisms underlying the pathogenesis of TB is still limited. Although Notch4, a member of the Notch receptor family, is involved in the initiation of mammary tumors, its function in Mtb infection remains unclear. In this study, we found that Notch4-deficient mice were more resistant to Mtb infection with a much lower bacterial burden and less pathological changes in the lungs. Notch4 inhibited Mtb-induced production of proinflammatory cytokines by interaction with TAK1 and inhibition of its activation. Furthermore, we found the NICD4 prevented TRAF6 autoubiquitination and suppressed TRAF6-mediated TAK1 polyubiquitination. Finally, Notch inhibitors made mice more resistant to Mtb infection. These results suggest that Notch4 is a negative regulator of Mtb-induced inflammatory response, and treatment with a Notch inhibitor could serve as a new therapeutic strategy for TB. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  18. Biofabrication of polyphenols stabilized reduced graphene oxide and its anti-tuberculosis activity.

    Science.gov (United States)

    Han, Wei; Niu, Wen-Yi; Sun, Bing; Shi, Guang-Can; Cui, Xiu-Qin

    2016-12-01

    A facile one step eco-friendly method for the reduction graphene oxide by Cinnamomumverum (C. verum) bark extract is reported in this work. This approach avoids the utilization of hazardous chemical reagents. The characterization results of various spectroscopic and microscopic techniques for the prepared graphene oxide (GO) and reduced graphene oxide (RGO) afford a strong indication of the removal of oxygen functionalities of GO after reduction and following stabilization by the oxidised polyphenols. Fourier transform infrared spectral results showed the capping of oxidised polyphenols onto the surface of reduced graphene oxide which further prevent their aggregation. Additionally, the prepared graphene nanosheets were tested for their antituberculosis activity against standard strain such as M. tuberculosis H37Ra. The obtained results suggested that the synthesized graphene acts as an effective growth inhibitors against M. tuberculosis H37Ra making it applicable for targeted drug delivery by combining with other chemical drugs as a therapeutic index. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Etanercept Exacerbates Inflammation and Pathology in a Rabbit Model of Active Pulmonary Tuberculosis

    Science.gov (United States)

    Tsenova, Liana; O'Brien, Paul; Holloway, Jennifer; Peixoto, Blas; Soteropoulos, Patricia; Fallows, Dorothy; Subbian, Selvakumar

    2014-01-01

    Treatment of chronic inflammatory diseases with tumor necrosis factor alpha (TNF-α) antagonists has been associated with increased risk of tuberculosis (TB). We examined the usefulness of the rabbit model of active pulmonary TB for studying the impact of the human immune modulatory reagent etanercept on the host immune response. Control of Mycobacterium tuberculosis (Mtb) infection, disease pathology, and the global transcriptional response in Mtb-infected lungs of rabbits were studied. Etanercept treatment exacerbated disease pathology and reduced bacillary control in the lungs, compared with infected untreated animals. Reduced collagen and fibrin deposition in the granulomas was associated with significant downregulation of the collagen metabolism and fibrosis network genes and upregulation of genes in the inflammatory response and cell recruitment networks in the lungs of etanercept treated, compared with untreated rabbits. Our results suggest that targeting the TNF-α signaling pathway disrupts the tissue remodeling process, which is required for the formation and maintenance of well-differentiated granulomas and for control of Mtb growth in the lungs. These results validate the use of the rabbit model for investigating the impact of selected human immune modulatory drugs, such as a TNF-α antagonist, on the host immune response and pathogenesis in TB. PMID:24831609

  20. Serological testing versus other strategies for diagnosis of active tuberculosis in India: a cost-effectiveness analysis.

    Directory of Open Access Journals (Sweden)

    David W Dowdy

    2011-08-01

    Full Text Available Undiagnosed and misdiagnosed tuberculosis (TB drives the epidemic in India. Serological (antibody detection TB tests are not recommended by any agency, but widely used in many countries, including the Indian private sector. The cost and impact of using serology compared with other diagnostic techniques is unknown.Taking a patient cohort conservatively equal to the annual number of serological tests done in India (1.5 million adults suspected of having active TB, we used decision analysis to estimate costs and effectiveness of sputum smear microscopy (US$3.62 for two smears, microscopy plus automated liquid culture (mycobacterium growth indicator tube [MGIT], US$20/test, and serological testing (anda-tb ELISA, US$20/test. Data on test accuracy and costs were obtained from published literature. We adopted the perspective of the Indian TB control sector and an analysis frame of 1 year. Our primary outcome was the incremental cost per disability-adjusted life year (DALY averted. We performed one-way sensitivity analysis on all model parameters, with multiway sensitivity analysis on variables to which the model was most sensitive. If used instead of sputum microscopy, serology generated an estimated 14,000 more TB diagnoses, but also 121,000 more false-positive diagnoses, 102,000 fewer DALYs averted, and 32,000 more secondary TB cases than microscopy, at approximately four times the incremental cost (US$47.5 million versus US$11.9 million. When added to high-quality sputum smears, MGIT culture was estimated to avert 130,000 incremental DALYs at an incremental cost of US$213 per DALY averted. Serology was dominated by (i.e., more costly and less effective than MGIT culture and remained less economically favorable than sputum smear or TB culture in one-way and multiway sensitivity analyses.In India, sputum smear microscopy remains the most cost-effective diagnostic test available for active TB; efforts to increase access to quality-assured microscopy

  1. Evaluation of anti-Mycobacterium tuberculosis activity of Campomanesia adamantium (Myrtaceae

    Directory of Open Access Journals (Sweden)

    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.

  2. Evaluation of anti-Mycobacterium tuberculosis activity of Campomanesia adamantium (Myrtaceae)

    Energy Technology Data Exchange (ETDEWEB)

    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)

  3. C4-alkylthiols with activity against Moraxella catarrhalis and Mycobacterium tuberculosis.

    Science.gov (United States)

    Kostova, Maya B; Myers, Carey J; Beck, Tim N; Plotkin, Balbina J; Green, Jacalyn M; Boshoff, Helena I M; Barry, Clifton E; Deschamps, Jeffrey R; Konaklieva, Monika I

    2011-11-15

    Antimicrobial resistance represents a global threat to healthcare. The ability to adequately treat infectious diseases is increasingly under siege due to the emergence of drug-resistant microorganisms. New approaches to drug development are especially needed to target organisms that exhibit broad antibiotic resistance due to expression of β-lactamases which is the most common mechanism by which bacteria become resistant to β-lactam antibiotics. We designed and synthesized 20 novel monocyclic β-lactams with alkyl- and aryl-thio moieties at C4, and subsequently tested these for antibacterial activity. These compounds demonstrated intrinsic activity against serine β-lactamase producing Mycobacterium tuberculosis wild type strain (Mtb) and multiple (n=6) β-lactamase producing Moraxella catarrhalis clinical isolates. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Chlorinated coumarins from the polypore mushroom Fomitopsis officinalis and their activity against Mycobacterium tuberculosis.

    Science.gov (United States)

    Hwang, Chang Hwa; Jaki, Birgit U; Klein, Larry L; Lankin, David C; McAlpine, James B; Napolitano, José G; Fryling, Nicole A; Franzblau, Scott G; Cho, Sang Hyun; Stamets, Paul E; Wang, Yuehong; Pauli, Guido F

    2013-10-25

    An EtOH extract of the polypore mushroom Fomitopsis officinalis afforded two new naturally occurring chlorinated coumarins, which were identified as the previously synthesized compounds 6-chloro-4-phenyl-2H-chromen-2-one (1) and ethyl 6-chloro-2-oxo-4-phenyl-2H-chromen-3-carboxylate (2). The structures of the two isolates were deduced by ab initio spectroscopic methods and confirmed by chemical synthesis. In addition, an analogue of each was synthesized as 7-chloro-4-phenyl-2H-chromen-2-one (3) and ethyl 7-chloro-2-oxo-4-phenyl-2H-chromen-3-carboxylate (4). All four compounds were characterized physicochemically, and their antimicrobial activity profiles revealed a narrow spectrum of activity with lowest MICs against the Mycobacterium tuberculosis complex.

  5. Immune Complexes Isolated from Patients with Pulmonary Tuberculosis Modulate the Activation and Function of Normal Granulocytes

    Science.gov (United States)

    Senbagavalli, P.; Hilda, J. Nancy; Ramanathan, V. D.; Kumaraswami, V.; Nutman, Thomas B.

    2012-01-01

    Circulating immune complexes (ICs) are associated with the pathogenesis of several diseases. Very little is known about the effect of ICs on the host immune response in patients with tuberculosis (TB). The effects of ICs isolated from patients with TB in modulating the release of calcium, cytokines, and granular proteins were studied in normal granulocytes, as were their chemotactic, phagocytic, and oxidative burst processes. ICs from TB patients induced decreased production of cytokines and platelet-activating factor (PAF) from normal granulocytes. ICs from TB patients also induced enhanced chemotaxis and phagocytosis but caused diminished oxidative burst. This was accompanied by an increased release in intracellular calcium. On the other hand, ICs from TB patients induced increased release of the granular proteins human neutrophil peptides 1 to 3 (HNP1–3). Thus, ICs from patients with TB exhibit a profound effect on granulocyte function with activation of certain effector mechanisms and dampening of others. PMID:23100480

  6. CFP-10 from Mycobacterium tuberculosis selectively activates human neutrophils through a pertussis toxin-sensitive chemotactic receptor.

    Science.gov (United States)

    Welin, Amanda; Björnsdottir, Halla; Winther, Malene; Christenson, Karin; Oprea, Tudor; Karlsson, Anna; Forsman, Huamei; Dahlgren, Claes; Bylund, Johan

    2015-01-01

    Upon infection with Mycobacterium tuberculosis, neutrophils are massively recruited to the lungs, but the role of these cells in combating the infection is poorly understood. Through a type VII secretion system, M. tuberculosis releases a heterodimeric protein complex, containing a 6-kDa early secreted antigenic target (ESAT-6) and a 10-kDa culture filtrate protein (CFP-10), that is essential for virulence. Whereas the ESAT-6 component possesses multiple virulence-related activities, no direct biological activity of CFP-10 has been shown, and CFP-10 has been described as a chaperone protein for ESAT-6. We here show that the ESAT-6:CFP-10 complex induces a transient release of Ca(2+) from intracellular stores in human neutrophils. Surprisingly, CFP-10 rather than ESAT-6 was responsible for triggering the Ca(2+) response, in a pertussis toxin-sensitive manner, suggesting the involvement of a G-protein-coupled receptor. In line with this, the response was accompanied by neutrophil chemotaxis and activation of the superoxide-producing NADPH-oxidase. Neutrophils were unique among leukocytes in responding to CFP-10, as monocytes and lymphocytes failed to produce a Ca(2+) signal upon stimulation with the M. tuberculosis protein. Hence, CFP-10 may contribute specifically to neutrophil recruitment and activation during M. tuberculosis infection, representing a novel biological role for CFP-10 in the ESAT-6:CFP-10 complex, beyond the previously described chaperone function. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Uzum, Kazim; Karahan, Okkes I.; Dogan, Sukru; Coskun, Abdulhakim E-mail: coskuna@erciyes.edu.tr; Topcu, Faik

    2003-12-01

    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

  8. The characteristic profiles of PD-1 and PD-L1 expressions and dynamic changes during treatment in active tuberculosis.

    Science.gov (United States)

    Shen, Lei; Shi, Hong; Gao, Yan; Ou, Qinfang; Liu, Qianqian; Liu, Yuanyuan; Wu, Jing; Zhang, Wenhong; Fan, Lin; Shao, Lingyun

    2016-12-01

    PD-1 is a cell surface receptor of activated T and B lymphocytes and it's role in tuberculosis is controversial because of lack of congruence between clinical study and animal model. To investigate the immunological pathogenesis mechanisms of tuberculosis and to develop the immune therapy target essential for controlling tuberculosis, here we explored the expression characteristics and dynamic changes of PD-1/PD-L1 pathway in different CD4+T cell subsets. We enrolled 24 human subjects including 15 active tuberculosis (ATB) patients and 9 healthy donors (HD). The expressions of PD-1 and PD-L1 on CD4+T cells increased significantly in ATB patients than HD. ATB patients had a higher proportion of regulatory T cells (Treg, CD4+CD25 + Foxp3+) than HD. The expressions of PD-1 and PD-L1 increased remarkably on CD4+T cell subsets, including Treg cells, Tresp (CD4+CD25-) cells and Teff (CD4+CD25 + Foxp3-) cells. Finally, clinical improvement following effective anti-TB therapy is correlated with significantly decreased expression of PD-1 in Tresp and Teff cells, but not in Treg cells. Thus, expression profiles of PD-1 in T cell subpopulations may be used as a candidate to predict the clinical efficacy of anti-tuberculosis therapy. Modulation of PD-1/PD-L1 pathway in CD4 subsets may offer an immunotherapy target for the control of tuberculosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. All-trans retinoic acid-triggered antimicrobial activity against Mycobacterium tuberculosis is dependent on NPC2.

    Science.gov (United States)

    Wheelwright, Matthew; Kim, Elliot W; Inkeles, Megan S; De Leon, Avelino; Pellegrini, Matteo; Krutzik, Stephan R; Liu, Philip T

    2014-03-01

    A role for vitamin A in host defense against Mycobacterium tuberculosis has been suggested through epidemiological and in vitro studies; however, the mechanism is unclear. In this study, we demonstrate that vitamin A-triggered antimicrobial activity against M. tuberculosis requires expression of NPC2. Comparison of monocytes stimulated with all-trans retinoic acid (ATRA) or 1,25-dihydroxyvitamin D3 (1,25D3), the biologically active forms of vitamin A and vitamin D, respectively, indicates that ATRA and 1,25D3 induce mechanistically distinct antimicrobial activities. Stimulation of primary human monocytes with ATRA did not result in expression of the antimicrobial peptide cathelicidin, which is required for 1,25D3 antimicrobial activity. In contrast, ATRA triggered a reduction in the total cellular cholesterol concentration, whereas 1,25D3 did not. Blocking ATRA-induced cellular cholesterol reduction inhibits antimicrobial activity as well. Bioinformatic analysis of ATRA- and 1,25D3-induced gene profiles suggests that NPC2 is a key gene in ATRA-induced cholesterol regulation. Knockdown experiments demonstrate that ATRA-mediated decrease in total cellular cholesterol content and increase in lysosomal acidification are both dependent upon expression of NPC2. Expression of NPC2 was lower in caseous tuberculosis granulomas and M. tuberculosis-infected monocytes compared with normal lung and uninfected cells, respectively. Loss of NPC2 expression ablated ATRA-induced antimicrobial activity. Taken together, these results suggest that the vitamin A-mediated antimicrobial mechanism against M. tuberculosis requires NPC2-dependent expression and function, indicating a key role for cellular cholesterol regulation in the innate immune response.

  10. Mycobactericidal activity of sutezolid (PNU-100480 in sputum (EBA and blood (WBA of patients with pulmonary tuberculosis.

    Directory of Open Access Journals (Sweden)

    Robert S Wallis

    Full Text Available Sutezolid (PNU-100480 is a linezolid analog with superior bactericidal activity against Mycobacterium tuberculosis in the hollow fiber, whole blood and mouse models. Like linezolid, it is unaffected by mutations conferring resistance to standard TB drugs. This study of sutezolid is its first in tuberculosis patients.Sputum smear positive tuberculosis patients were randomly assigned to sutezolid 600 mg BID (N = 25 or 1200 mg QD (N = 25, or standard 4-drug therapy (N = 9 for the first 14 days of treatment. Effects on mycobacterial burden in sputum (early bactericidal activity or EBA were monitored as colony counts on agar and time to positivity in automated liquid culture. Bactericidal activity was also measured in ex vivo whole blood cultures (whole blood bactericidal activity or WBA inoculated with M. tuberculosis H37Rv.All patients completed assigned treatments and began subsequent standard TB treatment according to protocol. The 90% confidence intervals (CI for bactericidal activity in sputum over the 14 day interval excluded zero for all treatments and both monitoring methods, as did those for cumulative WBA. There were no treatment-related serious adverse events, premature discontinuations, or dose reductions due to laboratory abnormalities. There was no effect on the QT interval. Seven sutezolid-treated patients (14% had transient, asymptomatic ALT elevations to 173±34 U/L on day 14 that subsequently normalized promptly; none met Hy's criteria for serious liver injury.The mycobactericidal activity of sutezolid 600 mg BID or 1200 mg QD was readily detected in sputum and blood. Both schedules were generally safe and well tolerated. Further studies of sutezolid in tuberculosis treatment are warranted.ClinicalTrials.gov NCT01225640.

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

    National Research Council Canada - National Science Library

    Lorent, Natalie; Choun, Kimcheng; Malhotra, Shelly; Koeut, Pichenda; Thai, Sopheak; Khun, Kim Eam; Colebunders, Robert; Lynen, Lut

    2015-01-01

    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...

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

    Science.gov (United States)

    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; Croda, Julio

    2015-01-22

    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. We administered a questionnaire and tuberculin skin test (TST) to a population-based sample of inmates from 12 prisons in Central-West Brazil and collected sera for HIV testing and two sputum samples for smear microscopy and culture from participants reporting a cough of any duration. Hierarchical Poisson regression models were used to evaluate factors associated with latent tuberculosis infection (LTBI). We recruited 3,380 inmates, of which 2,861 (84.6%) were males from 8 prisons, and 519 (15.4%) were females from 4 prisons. Among the 1,020 (30%) subjects who reported a cough, we obtained sputum from 691 (68%) and identified 31 cases of active TB for a point prevalence of 917 (95% CI, 623-1302) per 100,000 prisoners. Evaluation of the two sputum smear samples failed to identify 74% of the TB cases, and 29% of the cases reported less than 2 weeks of symptoms. Obtaining a second culture identified an additional 7 (24%) cases. The prevalences of LTBI were 22.5% and 11.7% for male and female prisoners, respectively and duration of incarceration (in years) was associated with LTBI in male and female in the multivariable model (1.04, 95% CI, 1.01-1.07 and 1.34, 95% CI, 1.06-1.70, respectively). The prevalence of LTBI is 8.6% among newly incarcerated inmates, among whom LTBI prevalence significantly increased by 5% with each year of incarceration. Although the overall LTBI prevalence among inmates in Central-West Brazil is low, tuberculosis incidence is high (>1,800/100,00), likely due to the high force of infection among a largely susceptible inmate population. Efforts to reduce transmission in prisons may require mass

  13. The presence of a booster phenomenon among contacts of active pulmonary tuberculosis cases: a retrospective cohort

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    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

  14. In Vivo Molecular Dissection of the Effects of HIV-1 in Active Tuberculosis.

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    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

  15. Characterization of Antibacterial and Hemolytic Activity of Synthetic Pandinin 2 Variants and Their Inhibition against Mycobacterium tuberculosis

    Science.gov (United States)

    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

  16. Pulmonary tuberculosis

    Science.gov (United States)

    TB; Tuberculosis - pulmonary; Mycobacterium - pulmonary ... Pulmonary TB is caused by the bacterium Mycobacterium tuberculosis (M tuberculosis) . TB is contagious. This means the bacteria is easily spread from an infected person ...

  17. Digital platform for improving non-radiologists' and radiologists' interpretation of chest radiographs for suspected tuberculosis - a method for supporting task-shifting in developing countries

    Energy Technology Data Exchange (ETDEWEB)

    Semakula-Katende, Namakula S.; Lucas, Susan [University of the Witwatersrand, Department of Radiology, Faculty of Health Sciences, Witwatersrand (South Africa); Andronikou, Savvas [University of Bristol, Department of Radiology/CRIC Bristol, Bristol (United Kingdom); Bristol Royal Hospital for Children, Department of Radiology, Bristol (United Kingdom)

    2016-09-15

    Shifting X-ray interpretation to non-radiologists can help to address radiologist shortages in developing countries. To determine the change in accuracy of non-radiologists and radiologists for the radiographic diagnosis of paediatric tuberculosis after a short skill-development course. Participants interpreted 15 paediatric chest radiographs before and after a 30-minute course using three possible responses: (1) diagnostic for tuberculosis, (2) abnormal but inconclusive for diagnosis of tuberculosis and (3) normal. We compared proportions of correct diagnoses, sensitivity, and specificity, before and after the course. We included 256 participants comprising 229 non-radiologists (134 radiographers, 32 paediatricians, 39 Medecins Sans Frontieres clinicians and 24 physicians including paediatricians) and 27 radiologists. Mean change proportions of correct diagnosis ranged from -27% to 53% for individuals and 9% to 20% for groups. All groups showed a statistically significant improvement. Mean change in diagnostic sensitivity ranged from -38% to 100% for individuals and from 16% to 41% for groups. All groups showed a statistically significant improvement. Mean change in specificity ranged from -57% to 57% for individuals and from -15% to -4% for groups. The decrease was statistically significant for physicians, paediatricians and radiographers. The course resulted in increased correct diagnoses and improved sensitivity at the expense of specificity. (orig.)

  18. Chronic destructive pulmonary tuberculosis: assessment of disease activity by computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Nam, Kyung Jin; Jeong, Yeon Joo [Dept. of Radiology, Pusan National Univ. Hospital, Pusan National Univ. School of Medicine and Medical Research Inst., Pusan (Korea, Republic of)], E-mail: jeongyj@pusan.ac.kr; Kim, Yeong Dae; I, Hoseok [Thoracic and Cardiovascular Surgery, Pusan National Univ. Hospital, Pusan National Univ. School of Medicine and Medical Research Inst., Pusan (Korea, Republic of); Kim, Kun-Il; Lee, Jun Woo [Dept. of Radiology, Pusan National Univ. Yangsan Hospital, Pusan National Univ. School of Medicine, Pusan (Korea, Republic of); Park, Hye Kyung [Internal Medicine, and Pusan National Univ. Hospital, Pusan National Univ. School of Medicine and Medical Research Inst., Pusan (Korea, Republic of)

    2012-11-15

    Background Determination of disease activity of chronic destructive pulmonary tuberculosis (TB) on imaging studies can be difficult because several imaging findings due to disease chronicity such as a residual cavity can be misinterpreted as an active disease. Purpose To evaluate computed tomography (CT) findings to predict active disease in patients with chronic destructive pulmonary TB. Material and Methods CT findings of 36 patients with chronic active destructive pulmonary TB and 78 patients with chronic inactive destructive pulmonary TB were reviewed and their patterns of lung lesions were compared. Statistical comparisons were performed using chi-square and Student's T tests for univariate analyses, and a stepwise logistic regression method was used for multivariate analysis. Results Based on univariate analyses, cavitary destruction (P = 0.015), non-branching centrilobular nodules (P < 0.001), tree-in-bud pattern (P < 0.001), airspace nodules (P < 0.001), and cavities in other lobes (P = 0.001) were more frequently seen in chronic active destructive pulmonary TB. A stepwise logistic regression analysis demonstrated that tree-in-bud pattern (odds ratio, 52.3; 95% confidence interval, 6.2-437.2; P < 0.001) were significant CT findings associated with active disease. Conclusion Tree-in-bud pattern were the most characteristic CT findings to predict active disease in patients with chronic destructive pulmonary TB.

  19. Th2 biased immune response in cases with active Mycobacterium tuberculosis infection and tuberculin anergy.

    Science.gov (United States)

    Balikó, Z; Szereday, L; Szekeres-Bartho, J

    1998-11-01

    This study was aimed at investigating the immunologic relationship between cytokine production pattern and tuberculin negativity in patients with active Mycobacterium tuberculosis infection. After classifying patients by the extent of pulmonary involvement and the size of the tuberculin reaction, we evaluated the rate of cytokine positivity in peripheral blood to determine whether there is a characteristic cellular immune reaction pattern which could partly explain the tuberculin negativity in some of these cases. The significance of tuberculin anergy occurring in some cases with M. tuberculosis infection is still not clear. We investigated the ratio of IL- 4, IL-10, IL-12, CD-4, CD-8 expressing lymphocytes in the peripheral blood of patients with active M. tuberculosis infection and correlated the percentage of the reactive cells with the positivity or negativity of tuberculin skin reactions. Twenty-eight patients were included in the study, with 11 healthy volunteers serving as controls. 10 ml of venous blood was drawn before starting anti-mycobacterial treatment. A tuberculin skin test was performed, introducing intracutaneously 5 TU PPD on the forearm with results evaluated after 72 h. Consistent with the reactivity or non-reactivity of the tuberculin skin test, we found a significantly higher ratio of IL-4 and IL-10 positive lymphocytes and a significantly lower ratio of IL-12 in the peripheral blood of patients with tuberculin anergy than in that of tuberculin positive patients or healthy donors. There was no difference in the ratio of the CD-4 CD-8 positive lymphocytes among the three groups. To evaluate whether the differences could be explained by the degree of pulmonary tubercular involvement, we classified the patients into three groups according to the extent and type of X-ray findings. Seven out of eight tuberculin negative patients were classified as grade III, whereas in the tuberculin positive group only seven out of 20 fell in this category. There

  20. Frequency of Mycobacterium Tuberculosis Infection among Iranian Patients with HIV/AIDS by PPD Test

    Directory of Open Access Journals (Sweden)

    Fatemeh Fattahi

    2010-02-01

    Full Text Available Persons infected with the Human Immunodeficiency Virus (HIV are particularly susceptible to tuberculosis, either by latent infection reactivation or by a primary infection with rapid progression to active disease. This study was done to determine the frequency of tuberculosis infection among Iranian patients with HIV/AIDS. A total of 262 HIV/AIDS patients attending all three HIV/AIDS health care centers of Tehran, Iran were enrolled in this study. A detailed history and physical examination were obtained from all HIV patients suspected of having pulmonary M. tuberculosis. A positive PPD skin test was used as a diagnostic parameter for probability of TB infection. Out of 262 HIV/AIDS patients, a total of 63 (24% were shown to have the tuberculosis infection based on a positive PPD skin test. Of the patients with positive PPD skin test, 22 (35% had pulmonary Tuberculosis, 2 (3.2% had extrapulmonary tuberculosis, and 39 (53% had no evidence of M. tuberculosis infection (latent infection. Also 8 (12.7% had history of long term residence in a foreign country, 32 (50.8% were exposed to an index case, and 9 (14.3% had past history of pulmonary tuberculosis, while only 33.3% had clinical manifestations of TB (active disease. There was no resistant case of tuberculosis. Our study showed that near 24% of Iranian patients with HIV/AIDS were infected with M. tuberculosis. This finding denotes the need to improve the diagnostic and preventive measures, and also prompt treatment of this type of infection in the HIV infected individuals.

  1. Reaching the underserved: Active tuberculosis case finding in urban slums in southeastern Nigeria.

    Science.gov (United States)

    Ogbudebe, Chidubem L; Chukwu, Joseph N; Nwafor, Charles C; Meka, Anthony O; Ekeke, Ngozi; Madichie, Nelson O; Anyim, Moses C; Osakwe, Chijioke; Onyeonoro, Ugochukwu; Ukwaja, Kingsley N; Oshi, Daniel C

    2015-03-01

    Nigeria ranks 10th among 22 high TB burden countries with low TB case detection that relies on passive case finding. Although there is increasing body of evidence that active case finding (ACF) has improved TB case finding in urban slums in some parts of the world, this strategy had not been implemented in Nigeria despite the pervasiveness of urban slums in the country. To assess the yield and profile of TB in urban slums in Nigeria through ACF. A prospective, implementation study was conducted in three urban slums of southeastern Nigeria. Individuals with TB symptoms were identified through targeted screening using a standardized questionnaire and investigated further for TB. Descriptive and bivariate analyses were performed using SPSS. Among 16,743 individuals screened for TB, 6361 (38.0%) were identified as TB suspects; 5894 suspects were evaluated for TB. TB was diagnosed in 1079 individuals, representing 6.4% of the screened population and 18.3% of those evaluated for TB. Of the 1079 cases found, 97.1% (n=1084) had pulmonary TB (PTB), and majority (65%) had new smear-positive TB. Children (slum population. Targeted screening of out-patients, TB contacts, and HIV-infected patients should be optimized for active TB case finding in Nigeria. Copyright © 2015 Asian African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.

  2. Re-activation of bovine tuberculosis in a patient treated with infliximab

    DEFF Research Database (Denmark)

    Larsen, Mette Vang; Thomsen, V Ø; Sørensen, Inge Juul

    2008-01-01

    before initiation of treatment with infliximab. The tuberculin skin test (TST) was negative, chest radiography was normal and she had no known risk factors for TB. After 4 months of treatment with infliximab, the patient developed ascites caused by Mycobacterium bovis. The TST was repeatedly negative......-infected cattle. Re-activation of bovine tuberculosis is a risk in people with recent or previous exposure to unpasteurised dairy products. The QuantiFERON-TB test has the potential to detect Mycobacterium bovis infection. Indeterminate test results reflect either anergy, due to poor immunity, or technical....... QuantiFERON-TB (QFT) testing performed during screening and immunosuppressive treatment was indeterminate, whereas the QFT test performed at the time of ascites puncture was positive. The patient history revealed previous work at a dairy, with probable exposure to unpasteurised milk from M. bovis...

  3. Two enzymes with redundant fructose bisphosphatase activity sustain gluconeogenesis and virulence in Mycobacterium tuberculosis.

    Science.gov (United States)

    Ganapathy, Uday; Marrero, Joeli; Calhoun, Susannah; Eoh, Hyungjin; de Carvalho, Luiz Pedro Sorio; Rhee, Kyu; Ehrt, Sabine

    2015-08-10

    The human pathogen Mycobacterium tuberculosis (Mtb) likely utilizes host fatty acids as a carbon source during infection. Gluconeogenesis is essential for the conversion of fatty acids into biomass. A rate-limiting step in gluconeogenesis is the conversion of fructose 1,6-bisphosphate to fructose 6-phosphate by a fructose bisphosphatase (FBPase). The Mtb genome contains only one annotated FBPase gene, glpX. Here we show that, unexpectedly, an Mtb mutant lacking GLPX grows on gluconeogenic carbon sources and has detectable FBPase activity. We demonstrate that the Mtb genome encodes an alternative FBPase (GPM2, Rv3214) that can maintain gluconeogenesis in the absence of GLPX. Consequently, deletion of both GLPX and GPM2 is required for disruption of gluconeogenesis and attenuation of Mtb in a mouse model of infection. Our work affirms a role for gluconeogenesis in Mtb virulence and reveals previously unidentified metabolic redundancy at the FBPase-catalysed reaction step of the pathway.

  4. Nitric Oxide Modulates Macrophage Responses toMycobacterium tuberculosisInfection through Activation of HIF-1α and Repression of NF-κB.

    Science.gov (United States)

    Braverman, Jonathan; Stanley, Sarah A

    2017-09-01

    IFN-γ is essential for control of Mycobacterium tuberculosis infection in vitro and in vivo. However, the mechanisms by which IFN-γ controls infection remain only partially understood. One of the crucial IFN-γ target genes required for control of M. tuberculosis is inducible NO synthase (iNOS). Although NO produced by iNOS is thought to have direct bactericidal activity against M. tuberculosis , the role of NO as a signaling molecule has been poorly characterized in the context M. tuberculosis infection. In this study, we found that iNOS broadly regulates the macrophage transcriptome during M. tuberculosis infection, activating antimicrobial pathways while also limiting inflammatory cytokine production. The transcription factor hypoxia inducible factor-1α (HIF-1α) was recently shown to be critical for IFN-γ-mediated control of M. tuberculosis infection. We found that HIF-1α function requires NO production, and that HIF-1α and iNOS are linked by a positive feedback loop that amplifies macrophage activation. Furthermore, we found that NO inhibits NF-κB activity to prevent hyperinflammatory responses. Thus, NO activates robust microbicidal programs while also limiting damaging inflammation. IFN-γ signaling must carefully calibrate an effective immune response that does not cause excessive tissue damage, and this study identifies NO as a key player in establishing this balance during M. tuberculosis infection. Copyright © 2017 by The American Association of Immunologists, Inc.

  5. Synthesis and evaluation of M. tuberculosis salicylate synthase (MbtI) inhibitors designed to probe plasticity in the active site.

    Science.gov (United States)

    Manos-Turvey, Alexandra; Cergol, Katie M; Salam, Noeris K; Bulloch, Esther M M; Chi, Gamma; Pang, Angel; Britton, Warwick J; West, Nicholas P; Baker, Edward N; Lott, J Shaun; Payne, Richard J

    2012-12-14

    Mycobacterium tuberculosis salicylate synthase (MbtI) catalyses the first committed step in the biosynthesis of mycobactin T, an iron-chelating siderophore essential for the virulence and survival of M. tuberculosis. Co-crystal structures of MbtI with members of a first generation inhibitor library revealed large inhibitor-induced rearrangements within the active site of the enzyme. This plasticity of the MbtI active site was probed via the preparation of a library of inhibitors based on a 2,3-dihydroxybenzoate scaffold with a range of substituted phenylacrylate side chains appended to the C3 position. Most compounds exhibited moderate inhibitory activity against the enzyme, with inhibition constants in the micromolar range, while several dimethyl ester variants possessed promising anti-tubercular activity in vitro.

  6. Symptom screening rules to identify active pulmonary tuberculosis: Findings from the Zambian South African Tuberculosis and HIV/AIDS Reduction (ZAMSTAR trial prevalence surveys.

    Directory of Open Access Journals (Sweden)

    M M Claassens

    Full Text Available High tuberculosis (TB burden countries should consider systematic screening among adults in the general population. We identified symptom screening rules to be used in addition to cough ≥2 weeks, in a context where X-ray screening is not feasible, aiming to increase the sensitivity of screening while achieving a specificity of ≥85%.We used 2010 Zambia South Africa Tuberculosis and HIV/AIDS Reduction (ZAMSTAR survey data: a South African (SA training dataset, a SA testing dataset for internal validation and a Zambian dataset for external validation. Regression analyses investigated relationships between symptoms or combinations of symptoms and active disease. Sensitivity and specificity were calculated for candidate rules.Among all participants, the sensitivity of using only cough ≥2 weeks as a screening rule was less than 25% in both SA and Zambia. The addition of any three of six TB symptoms (cough <2 weeks, night sweats, weight loss, fever, chest pain, shortness of breath, or 2 or more of cough <2 weeks, night sweats, and weight loss, increased the sensitivity to ~38%, while reducing specificity from ~95% to ~85% in SA and ~97% to ~92% in Zambia. Among HIV-negative adults, findings were similar in SA, whereas in Zambia the increase in sensitivity was relatively small (15% to 22%.High TB burden countries should investigate cost-effective strategies for systematic screening: one such strategy could be to use our rule in addition to cough ≥2 weeks.

  7. Global Chemical Composition and Antioxidant and Anti-Tuberculosis Activities of Various Extracts of Globularia alypum L. (Globulariaceae Leaves

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    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·+.

  8. Activity of Medicinal Plant Extracts on Multiplication of Mycobacterium tuberculosis under Reduced Oxygen Conditions Using Intracellular and Axenic Assays.

    Science.gov (United States)

    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.

  9. Activity of Medicinal Plant Extracts on Multiplication of Mycobacterium tuberculosis under Reduced Oxygen Conditions Using Intracellular and Axenic Assays

    Directory of Open Access Journals (Sweden)

    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.

  10. Mycobacteria-specific cytokine responses as correlates of treatment response in active and latent tuberculosis.

    Science.gov (United States)

    Clifford, Vanessa; Tebruegge, Marc; Zufferey, Christel; Germano, Susie; Forbes, Ben; Cosentino, Lucy; McBryde, Emma; Eisen, Damon; Robins-Browne, Roy; Street, Alan; Denholm, Justin; Curtis, Nigel

    2017-08-01

    A biomarker indicating successful tuberculosis (TB) therapy would assist in determining appropriate length of treatment. This study aimed to determine changes in mycobacteria-specific antigen-induced cytokine biomarkers in patients receiving therapy for latent or active TB, to identify biomarkers potentially correlating with treatment success. A total of 33 adults with active TB and 36 with latent TB were followed longitudinally over therapy. Whole blood stimulation assays using mycobacteria-specific antigens (CFP-10, ESAT-6, PPD) were done on samples obtained at 0, 1, 3, 6 and 9 months. Cytokine responses (IFN-γ, IL-1ra, IL-2, IL-10, IL-13, IP-10, MIP-1β, and TNF-α) in supernatants were measured by Luminex xMAP immunoassay. In active TB cases, median IL-1ra (with CFP-10 and with PPD stimulation), IP-10 (CFP-10, ESAT-6), MIP-1β (ESAT-6, PPD), and TNF-α (ESAT-6) responses declined significantly over the course of therapy. In latent TB cases, median IL-1ra (CFP-10, ESAT-6, PPD), IL-2 (CFP-10, ESAT-6), and IP-10 (CFP-10, ESAT-6) responses declined significantly. Mycobacteria-specific cytokine responses change significantly over the course of therapy, and their kinetics in active TB differ from those observed in latent TB. In particular, mycobacteria-specific IL-1ra responses are potential correlates of successful therapy in both active and latent TB. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  11. Use of Activity Space in a Tuberculosis Outbreak: Bringing Homeless Persons Into Spatial Analyses.

    Science.gov (United States)

    Worrell, Mary Claire; Kramer, Michael; Yamin, Aliya; Ray, Susan M; Goswami, Neela D

    2017-01-01

    Tuberculosis (TB) causes significant morbidity and mortality in US cities, particularly in poor, transient populations. During a TB outbreak in Fulton County, Atlanta, GA, we aimed to determine whether local maps created from multiple locations of personal activity per case would differ significantly from traditional maps created from single residential address. Data were abstracted for patients with TB disease diagnosed in 2008-2014 and receiving care at the Fulton County Health Department. Clinical and activity location data were abstracted from charts. Kernel density methods, activity space analysis, and overlay with homeless shelter locations were used to characterize case spatial distribution when using single versus multiple addresses. Data were collected for 198 TB cases, with over 30% homeless US-born cases included. Greater spatial dispersion of cases was found when utilizing multiple versus single addresses per case. Activity spaces of homeless and isoniazid (INH)-resistant cases were more spatially congruent with one another than non-homeless and INH-susceptible cases (P homeless persons, who made up a large portion of the Fulton County outbreak. We demonstrate how activity space analysis, prominent in exposure science and chronic disease, supports that routine capture of multiple location TB data may facilitate spatially different public health interventions than traditional surveillance maps.

  12. Altered protein and iron levels of patients with active tuberculosis in ...

    African Journals Online (AJOL)

    Backgound: Tuberculosis as a state of chronic inflammation impacts on haematologic functions of the body. Objectives: This study aimed at assessing iron parameters and serum protein levels of ninety tuberculosis patients aged fifteen to sixty years, enrolled from Dr Lawrence Henshaw Memorial Hospital, Calabar, Nigeria.

  13. Sutherlandia frutescens (Fabaceae extracts used for treating tuberculosis do not have high activity against Mycobacterium smegmatis

    Directory of Open Access Journals (Sweden)

    Itumeleng H. Mabusa

    2017-12-01

    Full Text Available Sutherlandia frutescens (L R. Br. contains several essential, bioactive compounds with clinically proven pharmacological activities. Sutherlandia is prescribed for people with tuberculosis but it is still not known what compounds in this plant act against Mycobacterium tuberculosis and its mode of action. This study is aimed at determining if S. frutescens extracts contain antimycobacterial compounds. Aerial parts of S. frutescens were dried, ground and extracted with ethanol, dichloromethane: methanol 1:1 (v/v and water. The chemical profiling was done using high-performance liquid chromatography-mass spectroscopy (HPLC-MS and thin layer chromatography (TLC. TLC plates were developed in butanol:acetic acid:water (BAW to the ratio of 21:6:3; chloroform:methanol:water:formic acid (CMWF1 [60:15:2:1] and (CMWF2 [21:9:1:0.3]. Qualitative antioxidant activity was done, using 2.2-diphenylpacryl-1-hydrazyl (DPPH. Antimycobacterial activity of the plant extracts was evaluated, using micro-dilution and bioautographic methods against Mycobacterium smegmatis. Low antimycobacterial activity against M. smegmatis was observed on the bioautograms. The ethanol extracts contained more compounds compared to water extracts on HPLC-MS chromatographic profiles. The average Minimum Inhibitory Concentration (MIC values for all the extracts were 0.61 mg/mL units and the DCM:MeOH (1:1 extract had the lowest MIC value of 0.28 mg/mL. The results showed that the plant could be further explored for possible antimycobacterial agents. Low activity was observed, possibly due to low replication of bacilli and non-replicating organisms. The study provides preliminary scientific validation of the traditional medicinal use of this plant. Further studies are required to identify the bioactive compounds in the DCM:MeOH 1:1 extract which showed significant antimycobacterial activities.   Research correlation: This article is the original version, of which an Afrikaans

  14. Bactericidal activity of an imidazo[1, 2-a]pyridine using a mouse M. tuberculosis infection model.

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    Yong Cheng

    Full Text Available Tuberculosis remains a global threat due in part to the long treatment regimen and the increased prevalence of drug resistant M. tuberculosis strains. Therefore, new drug regimens are urgently required to combat this deadly disease. We previously synthesized and evaluated a series of new anti-tuberculosis compounds which belong to the family of imidazo[1,2-a]pyridines. This family of compounds showed low nM MIC (minimal inhibitory concentration values against M. tuberculosis in vitro. In this study, a derivative of imidazo[1,2-a]pyridines, (N-(4-(4-chlorophenoxybenzyl-2,7-dimethylimidazo[1,2-a]pyridine-3-carboxamide (ND-09759, was selected as a promising lead compound to determine its protective efficacy using a mouse infection model. Pharmacokinetic analysis of ND-09759 determined that at a dosage of 30 mg/kg mouse body weight (PO gave a maximum serum drug concentration (Cmax of 2.9 µg/ml and a half-life of 20.1 h. M. tuberculosis burden in the lungs and spleens was significantly decreased in mice treated once daily 6 days per week for 4-weeks with ND-09759 compared to untreated mice and this antibiotic activity was equivalent to isoniazid (INH and rifampicin (RMP, two first-line anti-TB drugs. We observed slightly higher efficacy when using a combination of ND-09759 with either INH or RMP. Finally, the histopathological analysis revealed that infected mice treated with ND-09759 had significantly reduced inflammation relative to untreated mice. In conclusion, our findings indicate ND-09759 might be a potent candidate for the treatment of active TB in combination with current standard anti-TB drugs.

  15. Activity against Mycobacterium tuberculosis with concomitant induction of cellular immune responses by a tetraaza-macrocycle with acetate pendant arms.

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

    Sester, M; Sotgiu, G; Lange, C

    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......-SPOT.TB®, respectively. Although the diagnostic sensitivities of both IGRAs were higher than that of tuberculin skin tests, it was still not high enough to use as a rule out test for TB. Positive evidence for the use of IGRAs in compartments other than blood will require more independent and carefully designed...

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

    Science.gov (United States)

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

    2015-01-01

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

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

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    Solomon Ali

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

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

    Science.gov (United States)

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

    2015-01-01

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

  20. 2-aminoimidazoles potentiate ß-lactam antimicrobial activity against Mycobacterium tuberculosis by reducing ß-lactamase secretion and increasing cell envelope permeability.

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    Albert B Jeon

    Full Text Available There is an urgent need to develop new drug treatment strategies to control the global spread of drug-sensitive and multidrug-resistant Mycobacterium tuberculosis (M. tuberculosis. The ß-lactam class of antibiotics is among the safest and most widely prescribed antibiotics, but they are not effective against M. tuberculosis due to intrinsic resistance. This study shows that 2-aminoimidazole (2-AI-based small molecules potentiate ß-lactam antibiotics against M. tuberculosis. Active 2-AI compounds significantly reduced the minimal inhibitory and bactericidal concentrations of ß-lactams by increasing M. tuberculosis cell envelope permeability and decreasing protein secretion including ß-lactamase. Metabolic labeling and transcriptional profiling experiments revealed that 2-AI compounds impair mycolic acid biosynthesis, export and linkage to the mycobacterial envelope, counteracting an important defense mechanism reducing permeability to external agents. Additionally, other important constituents of the M. tuberculosis outer membrane including sulfolipid-1 and polyacyltrehalose were also less abundant in 2-AI treated bacilli. As a consequence of 2-AI treatment, M. tuberculosis displayed increased sensitivity to SDS, increased permeability to nucleic acid staining dyes, and rapid binding of cell wall targeting antibiotics. Transcriptional profiling analysis further confirmed that 2-AI induces transcriptional regulators associated with cell envelope stress. 2-AI based small molecules potentiate the antimicrobial activity of ß-lactams by a mechanism that is distinct from specific inhibitors of ß-lactamase activity and therefore may have value as an adjunctive anti-TB treatment.

  1. How Long Does Antimycobacterial Antibiotic-loaded Bone Cement Have In Vitro Activity for Musculoskeletal Tuberculosis?

    Science.gov (United States)

    Lee, Jae Hoo; Han, Chang Dong; Cho, Sang-Nae; Yang, Ick Hwan; Lee, Woo Suk; Baek, Seung-Hun; Shin, Jae Won; Husein, Khalid Elfadil Ibrahim; Park, Kwan Kyu

    2017-11-01

    Antibiotic-loaded bone cement is accepted as an effective treatment modality for musculoskeletal tuberculosis. However, comparative information regarding combinations and concentrations of second-line antimycobacterial drugs, such as streptomycin and amoxicillin and clavulanic acid, are lacking. (1) In antibiotic-loaded cement, is there effective elution of streptomycin and Augmentin(®) (amoxicillin and clavulanic acid) individually and in combination? (2) What is the antibacterial activity duration for streptomycin- and amoxicillin and clavulanic acid -loaded cement? Six different types of bone cement discs were created by mixing 40 g bone cement with 1 or 2 g streptomycin only, 0.6 g or 1.2 g Augmentin(®) (amoxicillin and clavulanic acid) only, and a combination of 1 g streptomycin plus 0.6 g amoxicillin and clavulanic acid and 2 g streptomycin plus 1.2 g amoxicillin and clavulanic acid. Five bone discs of each type were incubated in phosphate buffered saline for 30 days with renewal of the phosphate buffered saline every day. The quantity of streptomycin and/or amoxicillin and clavulanic acid in eluates were measured by a liquid chromatography-mass spectrometry system, and the antimycobacterial activity of eluates against Mycobacterium tuberculosis H37Rv, were calculated by comparing the minimal inhibitory concentration of each eluate with that of tested drugs using broth dilution assay on microplate. Streptomycin was detected in eluates for 30 days (in 1 g and 2 g discs), whereas 1.2 g amoxicillin and clavulanate eluted until Day 7 and 0.6 g amoxicillin and clavulanate until Day 3. All eluates in streptomycin-containing discs (streptomycin only, and in combination with amoxicillin and clavulanic acid) had effective antimycobacterial activity for 30 days, while amoxicillin and clavulanate-only preparations were only active until Day 14. The antimycobacterial activity of eluates of 2 g streptomycin plus 1.2 g amoxicillin and clavulanate were higher than those

  2. Diabetes mellitus increases the risk of active tuberculosis: a systematic review of 13 observational studies.

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    Christie Y Jeon

    2008-07-01

    Full Text Available BACKGROUND: Several studies have suggested that diabetes mellitus (DM increases the risk of active tuberculosis (TB. The rising prevalence of DM in TB-endemic areas may adversely affect TB control. We conducted a systematic review and a meta-analysis of observational studies assessing the association of DM and TB in order to summarize the existing evidence and to assess methodological quality of the studies. METHODS AND FINDINGS: We searched the PubMed and EMBASE databases to identify observational studies that had reported an age-adjusted quantitative estimate of the association between DM and active TB disease. The search yielded 13 observational studies (n = 1,786,212 participants with 17,698 TB cases. Random effects meta-analysis of cohort studies showed that DM was associated with an increased risk of TB (relative risk = 3.11, 95% CI 2.27-4.26. Case-control studies were heterogeneous and odds ratios ranged from 1.16 to 7.83. Subgroup analyses showed that effect estimates were higher in non-North American studies. CONCLUSION: DM was associated with an increased risk of TB regardless of study design and population. People with DM may be important targets for interventions such as active case finding and treatment of latent TB and efforts to diagnose, detect, and treat DM may have a beneficial impact on TB control.

  3. Success of active tuberculosis case detection among high-risk groups in urban slums in Pakistan.

    Science.gov (United States)

    Fatima, R; Qadeer, E; Enarson, D A; Creswell, J; Stevens, R H; Stevens, R; Hinderaker, S G; Anwar, K; ul Haq, M

    2014-09-01

    In Pakistan, patients with symptoms suggestive of tuberculosis (TB) seek care from a wide array of health care providers, many of whom do not notify cases to the National TB Programme (NTP). We evaluated an active case detection intervention in five randomly selected districts in urban slums of Sindh Province, Pakistan. To evaluate the increase in case notification of smear-positive TB by active case finding at community-based chest camps by engaging the private providers. A cross-sectional study of TB case detection associated with a project using integrated intervention and chest camps. From April 2011 to September 2012, the total number of clients seen in the camps was 165 280. Of all the attendees, 13 481 (12.7%) were examined by sputum smear microscopy. The proportion of smear-positive results was significantly higher among those from engaged private providers than among those referred from camps (OR 1.54, 95%CI 1.42-1.66). During the project, the total number of smear-positive TB notifications increased over the intervention period from 5158 to 8275. Active case detection by engaging private providers and chest camps can significantly increase the number of smear-positive TB case notifications.

  4. 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

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    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

  5. Antigen induced production of υ-interferon ex vivo, in the peripheral blood of patients with active pulmonary tuberculosis

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    Z. M. Zagdyn

    2013-01-01

    Full Text Available Tuberculosis (TB is one of the most significant problems in the Russian Health Care. Russia remains on the list of the 22 countries with a high TB incidence and on the third place in the world with a high prevalence of Drug Resistant TB [1]. It is urgently needed to develop new TB diagnostic methods as well as effective measures of the specific TB prevention, including a development of the novel vaccines, so we have to know better about the most immunogenic antigens of Mycobacterium Tuberculosis. We studied the Interferon-Q production in the whole blood after stimulating immune response with different proteins of Mycobacterium Tuberculosis in patients with active TB. The study results permitted us to evaluate the immunogenicity of the previously known proteins (Ag85a и ESAT-6 in comparison to the recently identified ones (Rv2957, Rv2958c и Rv0447, analyzing simultaneously their relation to tuberculin, as well as to antigens of the different viruses (Human Immunodeficiency Virus, Cytomegalovirus, Epstein-Barr Virus, Influenza Virus. Protein Rv2958c, unlike protein ESAT-6, showed the high immunogenicity in comparison to tuberculin. The expressed immunogenicity of protein Rv2958c might be indicated a possible greatest specificity of immune response to this antigen in TB patients. Meanwhile, bacillary tuberculosis was strongly associated with low immune response to this protein. Also we were found statistical differences in immune responses of patients to the different Mycobacterium Tuberculosis antigens depending on the drug sensitivity. In addition it was interesting to know about a significantly low immune response of patients with Drug Resistant TB to protein pp65 CMV.

  6. [Clinical analysis of 44 cases of leukemia complicated with active tuberculosis-a single-center report].

    Science.gov (United States)

    Li, Jun; Jiang, Meng; Yang, Yi-ming; Liu, Ting; Niu, Ting

    2013-07-01

    To analyze the prevalence, clinical features, diagnosis, potential risk factors, anti-tuberculosis treatment efficacy and prognosis of the patients with leukemia complicated with active tuberculosis (TB). A retrospective study was performed to analyze the clinical characteristics, relevant examination data, diagnosis methods and follow-up data about 44 leukemia cases complicated with active TB from January 2006 to December 2011 in our single center. The prevalence of leukemia complicated with active TB was 1.70% (pulmonary TB 1.35%, extra-pulmonary TB 0.35%) and no statistically significant difference was found between each subgroup of acute and chronic leukemia groups (P>0.05). Most of the patients were men, with a male to female ratio of 2.14:1, the median age of 40 years old (range 16 to 78), presenting as atypical clinical manifestations, such as high fever, cough, and so on. Eighteen patients (40.9%) were diagnosed with definitely etiological evidence while the other 26 patients (59.1%) were diagnosed clinically. The extra-pulmonary TB group had a higher purified protein derivative (PPD) test positive rate than that of the pulmonary TB group (88.9% vs 42.9%, P=0.020). The chest CT and T-cell spot of tuberculosis test (T-SPOT.TB) were helpful tools for diagnosis. The potential risk factors included age, sex, nutritional status, neutropenia, decreased cellular immunity, type and course of leukemia, etc. The significant differences in age, gender, administration route of immunosuppressive drugs were found between neutropenic and non-neutropenic groups (Pleukemia complicated with active TB is higher than the general population in our single center. The main characteristics including various potential risk factors, atypical clinical features, diagnoses mainly made by clinical features were found in our patients with leukemia complicated with active TB. However, it showed that these patients demonstrated good responses to the first-line anti-tuberculosis therapy and

  7. Accuracy of immunodiagnostic tests for active tuberculosis using single and combined results: a multicenter TBNET-Study.

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    Delia Goletti

    Full Text Available BACKGROUND: The clinical application of IFN-gamma release assays (IGRAs has recently improved the diagnosis of latent tuberculosis infection. In a multicenter study of the Tuberculosis Network European Trialsgroup (TBNET we aimed to ascertain in routine clinical practice the accuracy of a novel assay using selected peptides encoded in the mycobacterial genomic region of difference (RD 1 for the diagnosis of active tuberculosis in comparison with tuberculin skin test (TST, QuantiFERON-TB GOLD In-Tube (Cellestis Ltd., Carnegie, Australia and T-SPOT.TB (Oxfordimmunotec, Abingdon, UK. PRINCIPAL FINDINGS: 425 individuals from 6 different European centres were prospectively enrolled. We found that sensitivity of the novel test, TST, QuantiFERON-TB GOLD In-Tube and T-SPOT.TB was respectively 73.1%, 85.3%, 78.1%, and 85.2%; specificity was respectively 70.6%, 48.0%, 61.9% and 44.3%; positive likelihood ratios were respectively 2.48, 1.64, 2.05, and 1.53; negative likelihood ratios were respectively 0.38, 0.31, 0.35, 0.33. Sensitivity of TST combined with the novel test, QuantiFERON-TB GOLD In-Tube and T-SPOT.TB increased up to 92.4%, 97.7% and 97.1%, respectively. The likelihood ratios of combined negative results of TST with, respectively, the novel test, QuantiFERON-TB GOLD In-Tube and T-SPOT.TB were 0.19, 0.07 and 0.10. CONCLUSIONS: The assay based on RD1 selected peptides has similar accuracy for active tuberculosis compared with TST and commercial IGRAs. Then, independently of the spectrum of antigens used in the assays to elicit mycobacterial specific immune responses, the novel test, IGRAs, and the TST do not allow an accurate identification of active tuberculosis in clinical practice. However, the combined use of the novel assay or commercial IGRAs with TST may allow exclusion of tuberculosis.

  8. Active tuberculosis case finding interventions among immigrants, refugees and asylum seekers in Italy

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    Monica Sañé Schepisi

    2016-06-01

    Full Text Available In Italy tuberculosis (TB is largely concentrated in vulnerable groups such as migrants and in urban settings. We analyzed three TB case finding interventions conducted at primary centers and mobile clinics for regular/ irregular immigrants and refugees/asylum seekers performed over a four-year period (November 2009-March 2014 at five different sites in Rome and one site in Milan, Italy. TB history and presence of symptoms suggestive of active TB were investigated by verbal screening through a structured questionnaire in migrants presenting for any medical condition to out-patient and mobile clinics. Individuals reporting TB history or symptoms were referred to a TB clinic for diagnostic workup. Among 6347 migrants enrolled, 891 (14.0% reported TB history or symptoms suggestive of active TB and 546 (61.3% were referred to the TB clinic. Of them, 254 (46.5% did not present for diagnostic evaluation. TB was diagnosed in 11 individuals representing 0.17% of those screened and 3.76% of those evaluated. The overall yield of this intervention was in the range reported for other TB screening programs for migrants, although we recorded an unsatisfactory adherence to diagnostic workup. Possible advantages of this intervention include low cost and reduced burden of medical procedures for the screened population.

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

    DEFF Research Database (Denmark)

    Doherty, T Mark; Demissie, Abebech; Olobo, Joseph

    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....

  10. Interferon-gamma inducible protein 10 as a biomarker for active tuberculosis and latent tuberculosis infection in children: A case-control study

    DEFF Research Database (Denmark)

    Alsleben, Neele; Ruhwald, Morten; Rüssmann, Holger

    2012-01-01

    Background: Interferon-gamma (IFN-γ) release assays (IGRAs) are suboptimally sensitive to diagnose tuberculosis (TB) and latent TB infection (LTBI) in young children. In this study we compared Mycobacterium tuberculosis antigen-stimulated IFN-γ inducible protein 10 (IP-10) responses in children...

  11. Potential role of M. tuberculosis specific IFN-γ and IL-2 ELISPOT assays in discriminating children with active or latent tuberculosis.

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    Elena Chiappini

    Full Text Available BACKGROUND: Although currently available IGRA have been reported to be promising markers for TB infection, they cannot distinguish active tuberculosis (TB from latent infection (LTBI. OBJECTIVE: Children with LTBI, active TB disease or uninfected were prospectively evaluated by an in-house ELISPOT assay in order to investigate possible immunological markers for a differential diagnosis between LTBI and active TB. METHODS: Children at risk for TB infection prospectively enrolled in our infectious disease unit were evaluated by in-house IFN-γ and IL-2 based ELISPOT assays using a panel of Mycobacterium tuberculosis antigens. RESULTS: Twenty-nine children were classified as uninfected, 21 as LTBI and 25 as active TB cases (including 5 definite and 20 probable cases. Significantly higher IFN-γ ELISPOT responses were observed in infected vs. uninfected children for ESAT-6 (p<0.0001, CFP-10 (p<0.0001, TB 10.3 (p = 0.003, and AlaDH (p = 0.001, while differences were not significant considering Ag85B (p = 0.063, PstS1 (p = 0.512, and HspX (16 kDa (p = 0.139. IL-2 ELISPOT assay responses were different for ESAT-6 (p<0.0001, CFP-10 (p<0.0001, TB 10.3 (p<0.0001, HspX (16 kDa (p<0.0001, PstS1 (p<0.0001 and AlaDH (p = 0.001; but not for Ag85B (p = 0.063. Comparing results between children with LTBI and those with TB disease differences were significant for IFN-γ ELISPOT only for AlaDH antigen (p = 0.021 and for IL-2 ELISPOT assay for AlaDH (p<0.0001 and TB 10.3 antigen (p = 0.043. ROC analyses demonstrated sensitivity of 100% and specificity of 81% of AlaDH-IL-2 ELISPOT assay in discriminating between latent and active TB using a cut off of 12.5 SCF per million PBMCs. CONCLUSION: Our data suggest that IL-2 based ELISPOT with AlaDH antigen may be of help in discriminating children with active from those with latent TB.

  12. Peer-led active tuberculosis case-finding among people living with HIV: lessons from Nepal.

    Science.gov (United States)

    Joshi, Dipu; Sthapit, Raisha; Brouwer, Miranda

    2017-02-01

    People living with a human immunodeficiency virus (HIV) infection have a high risk of tuberculosis and should undergo regular screening. However, they can be difficult to reach because they are stigmatized and discriminated against. In Nepal, the nongovernmental organization Naya Goreto implemented a peer-led tuberculosis screening project in which people living with HIV volunteered to contact others in this high-risk population. Volunteers took part in a short training course, after which they attempted to contact people living with HIV through existing networks and self-help groups. Tuberculosis screening and testing were carried out in accordance with national guidelines. In Nepal, the prevalence of HIV infection is 0.3% in the general population but is much higher, at 6%, in people in Kathmandu who inject drugs. To date, the health system has not been able to implement systematic tuberculosis screening in people living with HIV. Between May 2014 and mid-September 2015, 30 volunteers screened 6642 people in 10 districts, 5430 (82%) of whom were living with HIV. Of the 6642, 6046 (91%) were tested for tuberculosis and 287 (4.3%) were diagnosed with the disease, 240 of whom were HIV-positive. Of those with tuberculosis, 270 (94%) initiated treatment. Using peers to contact people living with HIV for tuberculosis screening resulted in a high participation rate and the identification of a considerable number of HIV-positive tuberculosis patients. Follow-up during treatment was difficult in this highly mobile group and needs more attention in future interventions.

  13. [Head and neck tuberculosis: a still urgent problem].

    Science.gov (United States)

    Bruzgielewicz, A; Wysocki, J; Osuch-Wójcikiewicz, E

    1995-01-01

    The upper respiratory tract is an unusual site for tuberculous infection. Most of the cases are secondary to active pulmonary tuberculosis. We present thirty five cases of tuberculosis localize in the head and neck region. There were twelve patients with lymphonodular tuberculosis, eleven patients with laryngeal tuberculosis, six patients with oral and pharyngeal tuberculosis, three patients with partoid gland tuberculosis, two patients with nose and paranasal sinuses tuberculosis and one patient with middle ear tuberculosis. This cases exemplifies the difficulty in diagnosis of tuberculosis in such an unusual sites.

  14. Yield of undetected tuberculosis and human immunodeficiency virus coinfection from active case finding in urban Uganda.

    Science.gov (United States)

    Sekandi, J N; List, J; Luzze, H; Yin, X-P; Dobbin, K; Corso, P S; Oloya, J; Okwera, A; Whalen, C C

    2014-01-01

    To determine the yield of undetected active tuberculosis (TB), TB and human immunodeficiency virus (HIV) coinfection and the number needed to screen (NNS) to detect a case using active case finding (ACF) in an urban community in Kampala, Uganda. In a door-to-door survey conducted in Rubaga community from January 2008 to June 2009, residents aged ≥15 years were screened for chronic cough (≥2 weeks) and tested for TB disease using smear microscopy and/or culture. Rapid testing was used to screen for HIV infection. The NNS to detect one case was calculated based on population screened and undetected cases found. Of 5102 participants, 3868 (75.8%) were females; the median age was 24 years (IQR 20-30). Of 199 (4%) with chronic cough, 160 (80.4%) submitted sputum, of whom 39 (24.4%, 95%CI 17.4-31.5) had undetected active TB and 13 (8.1%, 95%CI 6.7-22.9) were TB-HIV co-infected. The NNS to detect one TB case was 131 in the whole study population, but only five among the subgroup with chronic cough. ACF obtained a high yield of previously undetected active TB and TB-HIV cases. The NNS in the general population was 131, but the number needed to test in persons with chronic cough was five. These findings suggest that boosting the identification of persons with chronic cough may increase the overall efficiency of TB case detection at a community level.

  15. Activity of trifluoperazine against replicating, non-replicating and drug resistant M. tuberculosis.

    Directory of Open Access Journals (Sweden)

    Meeta J Advani

    Full Text Available Trifluoperazine, a known calmodulin antagonist, belongs to a class of phenothiazine compounds that have multiple sites of action in mycobacteria including lipid synthesis, DNA processes, protein synthesis and respiration. The objective of this study is to evaluate the potential of TFP to be used as a lead molecule for development of novel TB drugs by showing its efficacy on multiple drug resistant (MDR Mycobacterium tuberculosis (M.tb and non-replicating dormant M.tb. Wild type and MDR M.tb were treated with TFP under different growth conditions of stress like low pH, starvation, presence of nitric oxide and in THP-1 infection model. Perturbation in growth kinetics of bacilli at different concentrations of TFP was checked to determine the MIC of TFP for active as well as dormant bacilli. Results show that TFP is able to significantly reduce the actively replicating as well as non-replicating bacillary load. It has also shown inhibitory effect on the growth of MDR M.tb. TFP has shown enhanced activity against intracellular bacilli, presumably because phenothiazines are known to get accumulated in macrophages. This concentration was, otherwise, found to be non-toxic to macrophage in vitro. Our results show that TFP has the potential to be an effective killer of both actively growing and non-replicating bacilli including MDR TB. Further evaluation and in vivo studies with Trifluoperazine can finally help us know the feasibility of this compound to be used as either a lead compound for development of new TB drugs or as an adjunct in the current TB chemotherapy.

  16. Seasonality of tuberculosis

    Directory of Open Access Journals (Sweden)

    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.

  17. Meropenem-clavulanate has high in vitro activity against multidrug-resistant Mycobacterium tuberculosis.

    Science.gov (United States)

    Davies Forsman, L; Giske, C G; Bruchfeld, J; Schön, T; Juréen, P; Ängeby, K

    2015-03-01

    With the relentless increase in multidrug- and extensively-drug resistant tuberculosis (MDR/XDR-TB), new treatment strategies are necessary. Favorable results have been reported by combining a β-lactam antibiotic and a β-lactamase inhibitor. The β-lactamase encoded by the blaC gene of Mycobacterium tuberculosis (MTB) is the major mechanism of resistance to β-lactam antibiotics (e.g., penicillin). Meropenem, a β-lactam antibiotic of the carbapenem group, is a relatively weak substrate for the β-lactamase of MTB. The β-lactamase inhibitor clavulanate irreversibly inactivates the β-lactamase encoded by the blaC gene, thus making the combination of meropenem and clavulanate an interesting treatment alternative for MTB. However, very few isolates of MTB have been tested for this drug combination and few clinical reports exist. Thus, the present study investigates the in vitro activity of meropenem-clavulanate for drug-resistant MTB isolates, including MDR/XDR-TB. The minimum inhibitory concentration (MIC) distribution of meropenem-clavulanate was determined using Middlebrook 7H10, including MDR and XDR strains of MTB (n=68). Meropenem was prepared in a stock solution with a final concentration range of 0.002-512mg/L. Clavulanate was added at a fixed concentration of 64mg/L, to avoid a decline of the β-lactamase to insufficient levels during the experiment. All isolates were evaluated after three weeks of growth. The pan-susceptible strain H37Rv was used as a control. There was a Gaussian MIC-distribution between 0.125 and 2mg/L of meropenem-clavulanate (expressed as the concentration of meropenem), but four isolates had very high MIC levels (16 and 32mg/L), which is likely to be out of reach in clinical doses (Fig. 1). The susceptibility of the isolates to meropenem-clavulanate was not correlated to the level of resistance to first- or second-line anti-tuberculous drugs. The MIC of the pan-susceptible control strain H37Rv was 1mg/L of meropenem, when combined

  18. Variation in C - reactive protein response according to host and mycobacterial characteristics in active tuberculosis.

    Science.gov (United States)

    Brown, James; Clark, Kristina; Smith, Colette; Hopwood, Jennifer; Lynard, Oliver; Toolan, Michael; Creer, Dean; Barker, Jack; Breen, Ronan; Brown, Tim; Cropley, Ian; Lipman, Marc

    2016-06-10

    The C - reactive protein (CRP) response is often measured in patients with active tuberculosis (TB) yet little is known about its relationship to clinical features in TB, or whether responses differ between ethnic groups or with different Mycobacterium tuberculosis (M.tb) strain types. We report the relationship between baseline serum CRP prior to treatment and disease characteristics in a metropolitan population with TB resident in a low TB incidence region. People treated for TB at four London, UK sites between 2003 and 2014 were assessed and data collected on the following characteristics: baseline CRP level; demographics (ethnicity, gender and age); HIV status; site of TB disease; sputum smear (in pulmonary cases) and culture results. The effect of TB strain-type was also assessed in culture-positive pulmonary cases using VNTR typing data. Three thousands two hundred twenty-two patients were included in the analysis of which 72 % had a baseline CRP at or within 4 weeks prior to starting TB treatment. CRP results were significantly higher in culture positive cases compared to culture negative cases: median 49 mg/L (16-103 mg/L) vs 19 mg/L (IQR 5-72 mg/L), p = <0.001. In those with pulmonary disease, smear positive cases had a higher CRP than smear negative cases: 67 mg/L (31-122 mg/L) vs 24 mg/L (7-72 mg/L), p < 0.001. HIV positive cases had higher baseline CRPs than HIV negative cases: 75 mg/L (26-136 mg/L) vs 37 mg/L (10-88 mg/L), p <0.001. Differing sites of disease were associated with differences in baseline CRP: locations that might be expected to have a high mycobacterial load (e.g. pulmonary disease and disseminated disease) had a significantly higher CRP than those such as skin, lymph node or CNS disease, where the mycobacterial load is typically low in HIV negative subjects. In a multivariable log-scale linear regression model adjusting for host characteristics and M.tb strain type, infection with the East African Indian strain

  19. Tuberculosis in newly arrived asylum seekers: A prospective 12 month surveillance study at Friedland, Germany.

    Science.gov (United States)

    Meier, Volker; Artelt, Tanja; Cierpiol, Stefanie; Gossner, Johannes; Scheithauer, Simone

    2016-11-01

    In the European Union tuberculosis prevalence-rates are among the lowest in the world. The prevalence of active tuberculosis in migrant populations has to be analyzed to get valid data on the risk of tuberculosis and for the decision of screening activities. Therefore, we prospectively quantified the risk of active tuberculosis among asylum seekers at time of arrival. Investigation was performed as regular part of the admission screenings for people arriving at Friedland, Germany, a primary major receiving center during one year. In 11.773 newly arrived asylum seekers 16 X-ray investigations gave the suspicion of active tuberculosis, thereof 11 cases could be verified by culture, thereof 9 cases were classified as microscopically positive. These data translate into rates of 136 per 100.000 suspected cases, 93 per 100.000 verified cases, and finally 76 per 100.000 infectious cases, respectively. Prevalence was higher in asylum seekers coming from Eritrea and Russia compared to the main origins of current migration Syria, Afghanistan, Iraq, Iran, and Lebanon. One case of MDR-tuberculosis could be detected in a migrant from Russia. Prevalence rates of tuberculosis in newly arrived asylum seekers are higher than in native European populations. Rates seem to reflect the prevalence in the home countries. X-ray investigation during first examination may help identifying people needing further tests for detecting infectious tuberculosis and therefore may prevent transmission. However due to the low prevalence rates screening procedures have to be reviewed. Copyright © 2016 Elsevier GmbH. All rights reserved.

  20. Kinetics of T cell-activation molecules in response to Mycobacterium tuberculosis antigens

    Directory of Open Access Journals (Sweden)

    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.

  1. Enhancing the role of private practitioners in tuberculosis prevention and care activities in India.

    Science.gov (United States)

    Anand, Tanu; Babu, Ranjith; Jacob, Anil G; Sagili, Karuna; Chadha, Sarabjit S

    2017-01-01

    India accounts for the highest number of incident tuberculosis (TB) cases globally. Hence, to impact the TB incidence world over, there is an urgent need to address and accelerate TB control activities in the country. Nearly, half of the TB patients first seek TB care in private sector. However, the participation of private practitioners (PPs) has been patchy in TB prevention and care and distrust exists between public and private sector. PPs usually have varied diagnostic and treatment practices that are inadequate and amplify the risk of drug resistance. Hence, their regulation and involvement as key stakeholders are important in TB prevention and care in India if we are to achieve TB control at global level. However, there remain certain barriers and gaps, which are preventing their upscaling. The current paper aims to discuss the status of private sector involvement in TB prevention and care in India. The paper also discusses the strategies and initiatives taken by the government in this regard as evidence shows that the involvement of private sector in co-opting directly observed treatment short-course (DOTS) helps to enhance case finding and treatment outcomes; it improves the accessibility of quality TB care with greater geographic coverage. Besides public-private mix, DOTS has been found more cost-effective and reduces financial burden of patients. The paper also offers to present some more solutions both at policy and program level for upscaling the engagement of PPs in the national TB control program.

  2. Enhancing the role of private practitioners in tuberculosis prevention and care activities in India

    Directory of Open Access Journals (Sweden)

    Tanu Anand

    2017-01-01

    Full Text Available India accounts for the highest number of incident tuberculosis (TB cases globally. Hence, to impact the TB incidence world over, there is an urgent need to address and accelerate TB control activities in the country. Nearly, half of the TB patients first seek TB care in private sector. However, the participation of private practitioners (PPs has been patchy in TB prevention and care and distrust exists between public and private sector. PPs usually have varied diagnostic and treatment practices that are inadequate and amplify the risk of drug resistance. Hence, their regulation and involvement as key stakeholders are important in TB prevention and care in India if we are to achieve TB control at global level. However, there remain certain barriers and gaps, which are preventing their upscaling. The current paper aims to discuss the status of private sector involvement in TB prevention and care in India. The paper also discusses the strategies and initiatives taken by the government in this regard as evidence shows that the involvement of private sector in co-opting directly observed treatment short-course (DOTS helps to enhance case finding and treatment outcomes; it improves the accessibility of quality TB care with greater geographic coverage. Besides public-private mix, DOTS has been found more cost-effective and reduces financial burden of patients. The paper also offers to present some more solutions both at policy and program level for upscaling the engagement of PPs in the national TB control program.

  3. Nanoparticles as Antituberculosis Drugs Carriers: Effect on Activity Against Mycobacterium tuberculosis in Human Monocyte-Derived Macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Anisimova, Y.V.; Gelperina, S.I.; Peloquin, C.A.; Heifets, L.B. [National Jewish Medical and Research Center (United States)

    2000-06-15

    This is the first report evaluating the nanoparticle delivery system for three antituberculosis drugs: isoniazid, rifampin, and streptomycin. The typical particle size is 250 nm. We studied accumulation of these drugs in human monocytes as well as their antimicrobial activity against Mycobacterium tuberculosis residing in human monocyte-derived macrophages. Nanoparticle encapsulation increased the intracellular accumulation (cell-association) of all three tested drugs, but it enhanced the antimicrobial activity of isoniazid and streptomycin only. On the other hand, the activity of encapsulated rifampin against intracellular bacteria was not higher than that of the free drug.

  4. Antimicrobial activity of pomegranate fruit constituents against drug-resistant Mycobacterium tuberculosis and β-lactamase producing Klebsiella pneumoniae.

    Science.gov (United States)

    Dey, Diganta; Ray, Ratnamala; Hazra, Banasri

    2015-01-01

    The global surge in multi-drug resistant bacteria and the imminence of tuberculosis pandemic necessitate alternative therapeutic approaches to augment the existing medications. Pomegranate, the fruit of Punica granatum Linn. (Punicaceae), widely recognized for potency against a broad spectrum of bacterial pathogens, deserves further investigation in this respect. This study determines the therapeutic potential of pomegranate juice, extracts of non-edible peel prepared with methanol/water, and its four polyphenolic constituents, namely caffeic acid, ellagic acid, epigallocatechin-3-gallate (EGCG) and quercetin, against drug-resistant clinical isolates. Phenotypic characterisation of Mycobacterium tuberculosis, extended-spectrum β-lactamase (ESBL) and KPC-type carbapenemase producing Klebsiella pneumoniae was performed by biochemical and molecular methods. Resistance profiles of M. tuberculosis and K. pneumoniae were determined using LJ proportion and Kirby-Bauer methods, respectively. Pomegranate fruit extracts, and the compounds, were evaluated at a dose range of 1024-0.5 µg/mL, and 512-0.25 µg/mL, respectively, to determine minimum inhibitory (MIC) and bactericidal concentrations (MBC) against the drug-resistant isolates by the broth micro-dilution method. The peel extracts exhibited greater antimycobacterial activity (MIC 64-1024 μg/mL) than the potable juice (MIC 256 - > 1024 μg/mL). EGCG and quercetin exhibited higher antitubercular (MIC 32-256 μg/mL) and antibacterial (MIC 64-56 μg/mL) potencies than caffeic acid and ellagic acid (MIC 64-512 μg/mL). The pomegranate fruit peel and pure constituents were active against a broad panel of M. tuberculosis and β-lactamase producing K. pneumoniae isolates. EGCG and quercetin need further investigation for prospective application against respiratory infections.

  5. Oral Vaccination with Heat Inactivated Mycobacterium bovis Activates the Complement System to Protect against Tuberculosis

    Science.gov (United States)

    Garrido, Joseba M.; Aranaz, Alicia; Sevilla, Iker; Villar, Margarita; Boadella, Mariana; Galindo, Ruth C.; Pérez de la Lastra, José M.; Moreno-Cid, Juan A.; Fernández de Mera, Isabel G.; Alberdi, Pilar; Santos, Gracia; Ballesteros, Cristina; Lyashchenko, Konstantin P.; Minguijón, Esmeralda; Romero, Beatriz; de Juan, Lucía; Domínguez, Lucas; Juste, Ramón; Gortazar, Christian

    2014-01-01

    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. PMID:24842853

  6. Spatial-temporal distribution of genotyped tuberculosis cases in a county with active transmission.

    Science.gov (United States)

    Agarwal, Saroochi; Nguyen, Duc T; Teeter, Larry D; Graviss, Edward A

    2017-05-31

    Harris County, Texas is the third most populous county in the United States and consistently has tuberculosis rates above the national average. Understanding jurisdictional epidemiologic characteristics for the most common Mycobacterium tuberculosis genotyped clusters is needed for tuberculosis prevention programs. Our objective is to describe the demographic, laboratory, clinical, temporal and geospatial characteristics for the most common Mycobacterium tuberculosis GENType clusters in Harris County from 2009 to 2015. We analyzed data from the Centers for Disease Control and Prevention (CDC) Tuberculosis Genotyping Information Management System (TB GIMS). Chi-square analyses were used to determine associations between selected clusters and specific characteristics of interest. Geographical Information System (GIS) point density and hot spot maps were generated and analyzed with ArcGIS 10.4. In Harris County from 2009 to 2015, 1655 of 1705 (97.1%) culture positive tuberculosis cases were genotyped and assigned a GENType, and 1058 different GENTypes were identified. The analyzed genotype clusters represent 14.1% (233/1655) of all genotyped cases: G00010 (n = 118), G00014 (n = 38), G00769 (n = 33), G01521 (n = 26), and G08964 (n = 18). Male gender (p = 0.002), ethnicity (p tuberculosis GENType clusters seen from 2009 to 2015. The common genotypes were observed primarily in U.S.-born populations despite the large foreign-born population residing in Harris County. GENType was significant distributed spatially and temporally in Harris County in the analyzed time period indicating that there may be outbreaks caused by transmission.

  7. Tuberculosis Fluoroscopy

    Science.gov (United States)

    Follow-up though Dec 31, 2002 has been completed for a study of site-specific cancer mortality among tuberculosis patients treated with artificial lung collapse therapy in Massachusetts tuberculosis sanatoria (1930-1950).

  8. Chemical composition of hexane extract of Citrus aurantifolia and anti-Mycobacterium tuberculosis activity of some of its constituents.

    Science.gov (United States)

    Sandoval-Montemayor, Nallely E; García, Abraham; Elizondo-Treviño, Elizabeth; Garza-González, Elvira; Alvarez, Laura; del Rayo Camacho-Corona, María

    2012-09-19

    The main aim of this study was to isolate and characterize the active compounds from the hexane extract of the fruit peels of Citrus aurantiifolia, which showed activity against one sensitive and three monoresistant (isoniazid, streptomycin or ethambutol) strains of Mycobacterium tuberculosis H37Rv. The active extract was fractionated by column chromatography, yielding the following major compounds: 5-geranyloxypsoralen (1); 5-geranyloxy-7-methoxycoumarin (2); 5,7-dimethoxycoumarin (3); 5-methoxypsoralen (4); and 5,8-dimethoxypsoralen (5). The structures of these compounds were elucidated by 1D and 2D NMR spectroscopy. In addition, GC-MS analysis of the hexane extract allowed the identification of 44 volatile compounds, being 5,7-dimethoxycoumarin (15.79%), 3-methyl-1,2-cyclopentanedione (8.27%), 1-methoxy-ciclohexene (8.0%), corylone (6.93%), palmitic acid (6.89%), 5,8-dimethoxypsoralen (6.08%), a-terpineol (5.97%), and umbelliferone (4.36%), the major constituents. Four isolated coumarins and 16 commercial compounds identified by GC-MS were tested against M. tuberculosis H37Rv and three multidrug-resistant M. tuberculosis strains using the Microplate Alamar Blue Assay. The constituents that showed activity against all strains were 5 (MICs = 25-50 mg/mL), 1 (MICs = 50-100 mg/mL), palmitic acid (MICs = 25-50 mg/mL), linoleic acid (MICs = 50-100 mg/mL), oleic acid (MICs = 100 mg/mL), 4-hexen-3-one (MICs = 50-100 mg/mL), and citral (MICs = 50-100 mg/mL). Compound 5 and palmitic acid were the most active ones. The antimycobacterial activity of the hexane extract of C. aurantifolia could be attributed to these compounds.

  9. IL-10 dependent suppression of type 1, type 2 and type 17 cytokines in active pulmonary tuberculosis.

    Directory of Open Access Journals (Sweden)

    Nathella Pavan Kumar

    Full Text Available 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.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.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.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.

  10. The risk factor of false-negative and false-positive for T-SPOT.TB in active tuberculosis.

    Science.gov (United States)

    Di, Li; Li, Yan

    2018-02-01

    T-SPOT.TB is a promising diagnosis tool to identify both pulmonary tuberculosis and extrapulmonary tuberculosis, as well as latent tuberculosis; however, the factors that affect the results of T-SPOT.TB remains unclear. In this study, we aim to figure out the risk factor of T-SPOT.TB for active TB. A total of 349 patients were recruited between January 1st, 2016 and January 22st, 2017 at Renmin Hospital of Wuhan University, including 98 subjects with TB and 251 subjects with non-TB disease, and received T-SPOT.TB (Oxford Immunotec Ltd). Statistics were analyzed by SPSS 19.0 using logistic regression. The overall specificity and sensitivity of the T-SPOT.TB was 92.83% (233/251; 95%CI 0.8872-0.9557) and 83.67% (82/98; 95%CI 0.7454-0.9010), respectively. Patients with tuberculous meningitis were more likely to have false-negative results (OR 17.4, 95%CI 3.068-98.671; P.05). Tuberculous meningitis was a risk factor of false-negative for T-SPOT.TB, while cured TB was a risk factor of false-positive. © 2017 Wiley Periodicals, Inc.

  11. [Tuberculosis within the laryngologic organs].

    Science.gov (United States)

    Polok, Aleksandra; Namysłowski, Grzegorz; Scierski, Wojciech; Czecior, Eugeniusz; Mrówka-Kata, Katarzyna; Gac, Bogusław

    2005-09-01

    Tuberculosis, considering entry of infection, most frequent concerns the lungs. Rarely we observed extrapulmonary cases of tuberculosis within the bones, joints, urogenital organs and lymph nodes as well as within the head and neck region--larynx, nose and paranasal sinuses, middle ear, pharynx, tonsils, tongue, parotid glands and central nervous system. The diagnosis of head and neck tuberculosis is based on patient's examination as well as on the bacteriologic and histologic study of the biopsy specimen. The aim of the study was to show our own, very rare cases of head and neck tuberculosis. We showed our own experience in the diagnosis and treatment of patients suffer from head and neck tuberculosis. 7 cases of head and neck tuberculosis (4 laryngeal, 2 sinonasal and 1 middle ear) were treated from 1986 to 2004 in the II ENT Department Silesian Medical University in Zabrze. In all the cases the diagnosis was based on the histological examination of the tissue specimen. All of the patients were suspected of the neoplastic disease. We assessed good long-term results after the conservative treatment (sometimes completed by surgery). Tuberculosis of the head and neck region should be taken into consideration during the differential diagnosis of neoplastic diseases.

  12. Antimycobacterial activity of methanolic plant extract of Artemisia capillaris containing ursolic acid and hydroquinone against Mycobacterium tuberculosis.

    Science.gov (United States)

    Jyoti, Md Anirban; Nam, Kung-Woo; Jang, Woong Sik; Kim, Young-Hee; Kim, Su-Kyung; Lee, Byung-Eui; Song, Ho-Yeon

    2016-04-01

    In order to protect against Mycobacterium tuberculosis (MTB) infection, novel drugs and new targets should be screened from the vast source of plants. We investigated the potentiality of the herbal plant of Artemisia capillaris extract (AC) against Mycobacterium tuberculosis. In this study, we isolated ursolic acid and hydroquinone by bio-activity guided fractionation from the methanol extracts of AC, and tested the inhibitory effects against several strains of MTB. Anti-mycobacterial evaluation of these compounds was carried out using the MGIT™ 960 and resazurin assay. Mycobacterial morphological changes due to the treatment of these compounds were further evaluated by Transmission electron microscopy (TEM). Ursolic acid (UA) and hydroquinone (HQ) inhibited the growth of both susceptible and resistant strains of M. tuberculosis. The MIC (minimum inhibitory concentration) values of both UA and HQ were 12.5 μg/ml against the susceptible strains of M. tuberculosis. Also both UA and HQ showed 12.5-25 μg/ml of MIC values against MDR/XDR MTB strains. However, against clinical strains of MTB, UA was found sensitive against those strains that are sensitive against both INH and RFP but resistant against those strains that are resistant to INH. On the other hand HQ was sensitive against all clinical strains. TEM image-analysis of the strain H37Ra after treatment with UA revealed cell wall lysis, whereas HQ-treated cells showed deformed cytoplasmic morphology. All these results indicate that AC extracts containing UA and HQ possess promising chemotherapeutic potency against MTB for future use. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  13. Abdominal tuberculosis mimicking intra-abdominal malignancy: A ...

    African Journals Online (AJOL)

    abdominal masses usually arising from lymphadenopathy which may mimic lymphomas and other malignancies. We present the report of a patient with suspected abdominal malignancy diagnosed with abdominal tuberculosis. Methods: The case ...

  14. The added value of a European Union tuberculosis reference laboratory network--analysis of the national reference laboratory activities.

    Science.gov (United States)

    Drobniewski, F A; Nikolayevskyy, V; Hoffner, S; Pogoryelova, O; Manissero, D; Ozin, A J

    2008-03-18

    National reference laboratories (NRL) and other laboratories are the cornerstones of well-functioning tuberculosis programmes and surveillance activities. However, the scope and activity of NRL services for mycobacterial identification and drug susceptibility testing (DST) has not been examined in detail across the European Union (EU), nor has the added value of cooperation and networking at the European level been explored with regard to strengthening laboratory services. Therefore, the European Centre for Disease Prevention and Control (ECDC) has commissioned a survey to explore these issues and to identify areas of work that could bring added value by supporting networking activities of tuberculosis (TB) reference laboratories in the EU. Structured questionnaires were sent to TB reference laboratory experts in the EU and European Economic Area (EEA) countries, and in three additional countries selected on the basis of their networking activities with EU projects and other initiatives (Switzerland, Croatia and Israel). The compiled results describe the activities and structure of 32 NRLs (29 countries replied, a response rate of 91%). The analysis of the survey led to the following recommendations for strengthening TB laboratory services: (1) implementing of the published European standards for TB laboratory services with respect to infrastructure, national reference functions, biosafety, human resources, quality assurance, operational research (including evaluation of new medical diagnostics), accuracy and speed, appropriately trained staff; (2) ensuring that laboratories only perform activities for which they have demonstrated proficiency; (3) implement validated and standardised second-line drug susceptibility testing (DST), including drugs used to define extensively drug-resistant tuberculosis (XDR TB); (4) aiming to identify Mycobacterium tuberculosis complex (MTBC) and rifampicin (RIF) resistance in over 90% of cultures and cases from smear-positive sputum

  15. Bovine tuberculosis

    Science.gov (United States)

    Tuberculosis (TB) in animals and humans may result from exposure to bacilli within the Mycobacterium tuberculosis complex (i.e., M. tuberculosis, M. bovis, M. africanum, M. pinnipedii, M. microti, M. caprae, or M. canetti) . Mycobacterium bovis is the species most often isolated from tuberculous cat...

  16. Meropenem-clavulanate has high in vitro activity against multidrug-resistant Mycobacterium tuberculosis

    OpenAIRE

    Davies Forsman, L.; Giske, C. G.; Bruchfeld, J.; Schön, T; Juréen, P.; K Ängeby

    2015-01-01

    Aims and objectives: With the relentless increase in multidrug- and extensively-drug resistant tuberculosis (MDR/XDR-TB), new treatment strategies are necessary. Favorable results have been reported by combining a β-lactam antibiotic and a β-lactamase inhibitor. The β-lactamase encoded by the blaC gene of Mycobacterium tuberculosis (MTB) is the major mechanism of resistance to β-lactam antibiotics (e.g., penicillin). Meropenem, a β-lactam antibiotic of the carbapenem group, is a relatively we...

  17. On Combining Multiple-Instance Learning and Active Learning for Computer-Aided Detection of Tuberculosis.

    Science.gov (United States)

    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.

  18. Active use of coyotes (Canis latrans) to detect Bovine Tuberculosis in northeastern Michigan, USA.

    Science.gov (United States)

    Berentsen, A R; Dunbar, M R; Johnson, S R; Robbe-Austerman, S; Martinez, L; Jones, R L

    2011-07-05

    Bovine tuberculosis (bTB) is endemic in white-tailed deer (Odocoileus virginianus) in northeastern Michigan, USA, and research suggests transmission to cattle. Prevalence of the disease in deer is estimated at 1.8%, but as prevalence decreases the difficulty of detection increases. Research suggests coyotes (Canis latrans) have a higher prevalence of bTB in Michigan than deer and sampling coyotes may be a more efficient surveillance tool to detect presence or spread of the disease. Coyotes possess suitable ecological characteristics to serve as a sentinel species, assuming transmission between coyotes is not significant. The question of whether free-ranging coyotes shed Mycobacterium bovis, the causative agent of bTB, has not been previously addressed. We actively used coyotes as a sentinel to detect bTB in infected and uninfected counties in Michigan's Northeastern Lower Peninsula. We determined whether bTB infection was present through bacteriologic culture of lymph nodes and tissues containing lesions and cultured oral/nasal swabs and feces to establish shedding. Seventeen of 171 coyotes were M. bovis culture positive, one of which was from a previously uninfected county. All oral, nasal secretions and feces were culture negative suggesting minimal, if any, shedding of M. bovis. Thus, infection of coyotes is likely to occur through ingestion of infected deer carcasses and not from interaction with conspecifics. These findings support previous research suggesting that coyotes are useful sentinels for bTB. The use of coyotes as a sentinel, may allow wildlife managers to detect the spread of bTB into naïve counties. With earlier detection managers may be able to take proactive surveillance measures to detect the disease in deer and reduce the potential risk to domestic livestock and captive deer herds. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Multidrug-resistant tuberculosis.

    Science.gov (United States)

    Zager, Ellen M; McNerney, Ruth

    2008-01-25

    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. 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 that inclusion of population based statistics in

  20. Multidrug-resistant tuberculosis

    Directory of Open Access Journals (Sweden)

    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

  1. Listeria-vectored vaccine expressing the Mycobacterium tuberculosis 30 kDa major secretory protein via the constitutively active prfA* regulon boosts BCG efficacy against tuberculosis.

    Science.gov (United States)

    Jia, Qingmei; Dillon, Barbara Jane; Masleša-Galić, Saša; Horwitz, Marcus A

    2017-06-19

    A potent vaccine against tuberculosis, one of the world's deadliest diseases, is needed to enhance the immunity of people worldwide, most of whom have been vaccinated with the partially effective BCG vaccine. Here we investigate novel live attenuated recombinant Listeria monocytogenes (rLm) vaccines expressing the Mycobacterium tuberculosis (Mtb) 30 kDa major secretory protein (r30/Ag85B) (rLm30) as heterologous booster vaccines in animals primed with BCG. Using three attenuated Lm vectors, rLm ΔactA (LmI), rLm ΔactA ΔinlB (LmII), and rLm ΔactA ΔinlBprfA* (LmIII), we constructed five rLm30 vaccine candidates expressing the r30 linked in-frame to the Lm Listeriolycin O signal sequence and driven by the hly promoter (h30) or linked in-frame to the ActA N-terminus and driven by the actA promoter (a30). All five rLm30 vaccines secreted r30 in broth and macrophages; while rLm expressing r30 via a constitutively active prfA* regulon (rLmIII/a30) expressed the greatest amount of r30 in broth culture, all five rLm vaccines expressed equivalent amounts of r30 in infected macrophages. In comparative studies, boosting BCG-immunized mice with rLmIII/a30 induced the strongest antigen-specific T-cell responses, including splenic and lung polyfunctional CD4+ T-cells expressing the three cytokines of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-2 (IL-2) (P vaccines were generally more potent booster vaccines than r30 in adjuvant and a recombinant adenovirus vaccine expressing r30. In a setting in which BCG alone was highly immunoprotective, boosting mice with rLmIII/a30, the most potent of the vaccines, significantly enhanced protection against aerosolized Mtb (P <0.01). Copyright © 2017 American Society for Microbiology.

  2. Flourensia cernua: Hexane Extracts a Very Active Mycobactericidal Fraction from an Inactive Leaf Decoction against Pansensitive and Panresistant Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Gloria María Molina-Salinas

    2011-01-01

    Full Text Available The efficacy of decoction in extracting mycobactericidal compounds from Flourensia cernua (Hojasé leaves and fractionation with solvents having ascending polarity was compared with that of (i ethanol extraction by still maceration, extraction with a Soxhlet device, shake-assisted maceration, or ultrasound-assisted maceration, followed by fractionation with n-hexane, ethyl acetate, and n-butanol; (ii sequential extraction with n-hexane, ethyl acetate, and n-butanol, by still maceration, using a Soxhlet device, shake-assisted maceration, or ultrasound-assisted maceration. The in vitro mycobactericidal activity of each preparation was measured against drug-sensitive (SMtb and drug-resistant (RMtb Mycobacterium tuberculosis strains. The results of which were expressed as absolute mycobactericidal activity (AMA. These data were normalized to the ΣAMA of the decoction fraction set. Although decoction was inactive, the anti-RMtb normalized ΣAMA (NAMA of its fractions was comparable with the anti-RMtb NAMA of the still maceration extracts and significantly higher than the anti-SMtb and anti-RMtb NAMAs of every other ethanol extract and serial extract and fraction. Hexane extracted, from decoction, material having 55.17% and 92.62% of antituberculosis activity against SMtb and RMtb, respectively. Although the mycobactericidal activity of decoction is undetectable; its efficacy in extracting F. cernua active metabolites against M. tuberculosis is substantially greater than almost all pharmacognostic methods.

  3. Flourensia cernua: Hexane Extracts a Very Active Mycobactericidal Fraction from an Inactive Leaf Decoction against Pansensitive and Panresistant Mycobacterium tuberculosis

    Science.gov (United States)

    Molina-Salinas, Gloria María; Peña-Rodríguez, Luis Manuel; Mata-Cárdenas, Benito David; Escalante-Erosa, Fabiola; González-Hernández, Silvia; Torres de la Cruz, Víctor Manuel; Martínez-Rodríguez, Herminia Guadalupe; Said-Fernández, Salvador

    2011-01-01

    The efficacy of decoction in extracting mycobactericidal compounds from Flourensia cernua (Hojasé) leaves and fractionation with solvents having ascending polarity was compared with that of (i) ethanol extraction by still maceration, extraction with a Soxhlet device, shake-assisted maceration, or ultrasound-assisted maceration, followed by fractionation with n-hexane, ethyl acetate, and n-butanol; (ii) sequential extraction with n-hexane, ethyl acetate, and n-butanol, by still maceration, using a Soxhlet device, shake-assisted maceration, or ultrasound-assisted maceration. The in vitro mycobactericidal activity of each preparation was measured against drug-sensitive (SMtb) and drug-resistant (RMtb) Mycobacterium tuberculosis strains. The results of which were expressed as absolute mycobactericidal activity (AMA). These data were normalized to the ΣAMA of the decoction fraction set. Although decoction was inactive, the anti-RMtb normalized ΣAMA (NAMA) of its fractions was comparable with the anti-RMtb NAMA of the still maceration extracts and significantly higher than the anti-SMtb and anti-RMtb NAMAs of every other ethanol extract and serial extract and fraction. Hexane extracted, from decoction, material having 55.17% and 92.62% of antituberculosis activity against SMtb and RMtb, respectively. Although the mycobactericidal activity of decoction is undetectable; its efficacy in extracting F. cernua active metabolites against M. tuberculosis is substantially greater than almost all pharmacognostic methods. PMID:21584254

  4. The curative activity of thioridazine on mice infected with Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Martins, Marta; Viveiros, Miguel; Kristiansen, Jette E

    2007-01-01

    BACKGROUND: The aim of the study was to evaluate the effectiveness of thioridazine (TZ) at different dose levels on mice that had been infected intraperitoneally (i.p.) with a high dose of the Mycobacterium tuberculosis ATCC H37Rv strain. SUBJECTS AND METHODS: Groups of five female BALB/C mice were...

  5. miRNA signatures in sera of patients with active pulmonary tuberculosis.

    Directory of Open Access Journals (Sweden)

    Paolo Miotto

    Full Text Available Several studies showed that assessing levels of specific circulating microRNAs (miRNAs is a non-invasive, rapid, and accurate method for diagnosing diseases or detecting alterations in physiological conditions. We aimed to identify a serum miRNA signature to be used for the diagnosis of tuberculosis (TB. To account for variations due to the genetic makeup, we enrolled adults from two study settings in Europe and Africa. The following categories of subjects were considered: healthy (H, active pulmonary TB (PTB, active pulmonary TB, HIV co-infected (PTB/HIV, latent TB infection (LTBI, other pulmonary infections (OPI, and active extra-pulmonary TB (EPTB. Sera from 10 subjects of the same category were pooled and, after total RNA extraction, screened for miRNA levels by TaqMan low-density arrays. After identification of "relevant miRNAs", we refined the serum miRNA signature discriminating between H and PTB on individual subjects. Signatures were analyzed for their diagnostic performances using a multivariate logistic model and a Relevance Vector Machine (RVM model. A leave-one-out-cross-validation (LOOCV approach was adopted for assessing how both models could perform in practice. The analysis on pooled specimens identified selected miRNAs as discriminatory for the categories analyzed. On individual serum samples, we showed that 15 miRNAs serve as signature for H and PTB categories with a diagnostic accuracy of 82% (CI 70.2-90.0, and 77% (CI 64.2-85.9 in a RVM and a logistic classification model, respectively. Considering the different ethnicity, by selecting the specific signature for the European group (10 miRNAs the diagnostic accuracy increased up to 83% (CI 68.1-92.1, and 81% (65.0-90.3, respectively. The African-specific signature (12 miRNAs increased the diagnostic accuracy up to 95% (CI 76.4-99.1, and 100% (83.9-100.0, respectively. Serum miRNA signatures represent an interesting source of biomarkers for TB disease with the potential to

  6. Tuberculosis active case finding in Cambodia: a pragmatic, cost-effectiveness comparison of three implementation models.

    Science.gov (United States)

    James, Richard; Khim, Keovathanak; Boudarene, Lydia; Yoong, Joanne; Phalla, Chea; Saint, Saly; Koeut, Pichenda; Mao, Tan Eang; Coker, Richard; Khan, Mishal Sameer

    2017-08-22

    Globally, almost 40% of tuberculosis (TB) patients remain undiagnosed, and those that are diagnosed often experience prolonged delays before initiating correct treatment, leading to ongoing transmission. While there is a push for active case finding (ACF) to improve early detection and treatment of TB, there is extremely limited evidence about the relative cost-effectiveness of different ACF implementation models. Cambodia presents a unique opportunity for addressing this gap in evidence as ACF has been implemented using different models, but no comparisons have been conducted. The objective of our study is to contribute to knowledge and methodology on comparing cost-effectiveness of alternative ACF implementation models from the health service perspective, using programmatic data, in order to inform national policy and practice. We retrospectively compared three distinct ACF implementation models - door to door symptom screening in urban slums, checking contacts of TB patients, and door to door symptom screening focusing on rural populations aged above 55 - in terms of the number of new bacteriologically-positive pulmonary TB cases diagnosed and the cost of implementation assuming activities are conducted by the national TB program of Cambodia. We calculated the cost per additional case detected using the alternative ACF models. Our analysis, which is the first of its kind for TB, revealed that the ACF model based on door to door screening in poor urban areas of Phnom Penh was the most cost-effective (249 USD per case detected, 737 cases diagnosed), followed by the model based on testing contacts of TB patients (308 USD per case detected, 807 cases diagnosed), and symptomatic screening of older rural populations (316 USD per case detected, 397 cases diagnosed). Our study provides new evidence on the relative effectiveness and economics of three implementation models for enhanced TB case finding, in line with calls for data from 'routine conditions' to be included

  7. Association between diabetes mellitus and active tuberculosis: A systematic review and meta-analysis.

    Science.gov (United States)

    Al-Rifai, Rami H; Pearson, Fiona; Critchley, Julia A; Abu-Raddad, Laith J

    2017-01-01

    The burgeoning epidemic of diabetes mellitus (DM) is one of the major global health challenges. We systematically reviewed the published literature to provide a summary estimate of the association between DM and active tuberculosis (TB). We searched Medline and EMBASE databases for studies reporting adjusted estimates on the TB-DM association published before December 22, 2015, with no restrictions on region and language. In the meta-analysis, adjusted estimates were pooled using a DerSimonian-Laird random-effects model, according to study design. Risk of bias assessment and sensitivity analyses were conducted. 44 eligible studies were included, which consisted of 58,468,404 subjects from 16 countries. Compared with non-DM patients, DM patients had 3.59-fold (95% confidence interval (CI) 2.25-5.73), 1.55-fold (95% CI 1.39-1.72), and 2.09-fold (95% CI 1.71-2.55) increased risk of active TB in four prospective, 16 retrospective, and 17 case-control studies, respectively. Country income level (3.16-fold in low/middle-vs. 1.73-fold in high-income countries), background TB incidence (2.05-fold in countries with >50 vs. 1.89-fold in countries with ≤50 TB cases per 100,000 person-year), and geographical region (2.44-fold in Asia vs. 1.71-fold in Europe and 1.73-fold in USA/Canada) affected appreciably the estimated association, but potential risk of bias, type of population (general versus clinical), and potential for duplicate data, did not. Microbiological ascertainment for TB (3.03-fold) and/or blood testing for DM (3.10-fold), as well as uncontrolled DM (3.30-fold), resulted in stronger estimated association. DM is associated with a two- to four-fold increased risk of active TB. The association was stronger when ascertainment was based on biological testing rather than medical records or self-report. The burgeoning DM epidemic could impact upon the achievements of the WHO "End TB Strategy" for reducing TB incidence.

  8. Peritoneal tuberculosis: A persistent diagnostic dilemma, use complete diagnostic methods

    Directory of Open Access Journals (Sweden)

    L. Salgado Flores

    2015-04-01

    Conclusions: The bacterial and RT-PCR methods had low performance, probably due to the low bacillary load of lesions. The histopathological study with characteristic tuberculosis lesions turned out to be the most useful, and it must be jointly performed with bacteriological and molecular studies in suspected cases of tuberculosis with unknown cause ascites.

  9. Pediatric glaucoma suspects

    Directory of Open Access Journals (Sweden)

    Kooner K

    2014-06-01

    Full Text Available Karanjit Kooner,1 Matthew Harrison,1 Zohra Prasla,1 Mohannad Albdour,1 Beverley Adams-Huet21Department of Ophthalmology, 2Department of Clinical Sciences, Division of Biostatistics, University of Texas Southwestern Medical Center, Dallas, TX, USAPurpose: To report demographic and ocular features of pediatric glaucoma suspects in an ethnically diverse population of North Central Texas.Design: Retrospective cross-sectional chart review.Participants: Subjects included 75 (136 eyes pediatric glaucoma suspects. Patients with one or more of the following risk factors were included: cup-to disc (C/D ratio of ≥0.6; intraocular pressure (IOP ≥21 mmHg; family history of glaucoma; congenital glaucoma in the opposite eye; history of blunt trauma to either eye; and presence of either Sturge–Weber or Axenfeld–Rieger syndrome, or oculodermal melanocytosis.Methods: Data were extracted from electronic patient medical records. Patient records with incomplete data were excluded. The main outcome measures were race, sex, age, IOP, C/D, family history of glaucoma; and glaucoma treatment.Results: Subjects included 28 (37.3% Hispanics, 20 (26.6% African Americans, 20 (26.6% Caucasians, and seven (9.3% Asians. Forty (53.3% of the patients were male. Suspicious optic disc was seen in 57 (76%; elevated IOP in 25 (33.3%; presence of family history in 13 (17.3%, and Sturge–Weber syndrome in nine (12% patients. The average C/D ratio was 0.58±0.2. The C/D ratios of African American (0.65±0.2, Hispanic (0.63±0.2, and Asian (0.62±0.15 patients were significantly greater than those of Caucasians (0.43±0.18; P=0.0004, 0.0003, and 0.0139, respectively. Caucasian patients were the youngest (7.9±4.8 years. Eleven cases (14.7% required medication.Conclusion: Thirty-three point seven percent of patients seen in the glaucoma clinic were glaucoma suspects. The most common risk factors for suspected glaucoma were suspicious optic discs, elevated IOP, and family history

  10. Mineral nutrient uptake from prey and glandular phosphatase activity as a dual test of carnivory in semi-desert plants with glandular leaves suspected of carnivory.

    Science.gov (United States)

    Płachno, Bartosz Jan; Adamec, Lubomír; Huet, Hervé

    2009-09-01

    Ibicella lutea and Proboscidea parviflora are two American semi-desert species of glandular sticky plants that are suspected of carnivory as they can catch small insects. The same characteristics might also hold for two semi-desert plants with glandular sticky leaves from Israel, namely Cleome droserifolia and Hyoscyamus desertorum. The presence of proteases on foliar hairs, either secreted by the plant or commensals, detected using a simple test, has long been considered proof of carnivory. However, this test does not prove whether nutrients are really absorbed from insects by the plant. To determine the extent to which these four species are potentially carnivorous, hair secretion of phosphatases and uptake of N, P, K and Mg from fruit flies as model prey were studied in these species and in Roridula gorgonias and Drosophyllum lusitanicum for comparison. All species examined possess morphological and anatomical adaptations (hairs or emergences secreting sticky substances) to catch and kill small insects. The presence of phosphatases on foliar hairs was tested using the enzyme-labelled fluorescence method. Dead fruit flies were applied to glandular sticky leaves of experimental plants and, after 10-15 d, mineral nutrient content in their spent carcasses was compared with initial values in intact flies after mineralization. Phosphatase activity was totally absent on Hyoscyamus foliar hairs, a certain level of activity was usually found in Ibicella, Proboscidea and Cleome, and a strong response was found in Drosophyllum. Roridula exhibited only epidermal activity. However, only Roridula and Drosophyllum took up nutrients (N, P, K and Mg) from applied fruit flies. Digestion of prey and absorption of their nutrients are the major features of carnivory in plants. Accordingly, Roridula and Drosophyllum appeared to be fully carnivorous; by contrast, all other species examined are non-carnivorous as they did not meet the above criteria.

  11. Tuberculosis (TB): Treatment

    Science.gov (United States)

    ... Education & Training Home Conditions Tuberculosis (TB) Tuberculosis: Treatment Tuberculosis: Treatment Make an Appointment Refer a Patient Ask ... or bones is treated longer. NEXT: Preventive Treatment Tuberculosis: Diagnosis Tuberculosis: History Clinical Trials For more than ...

  12. Strong In Vitro Activities of Two New Rifabutin Analogs against Multidrug-Resistant Mycobacterium tuberculosis ▿ †

    Science.gov (United States)

    García, Ana-Belén; Palacios, Juan J.; Ruiz, María-Jesús; Barluenga, José; Aznar, Fernando; Cabal, María-Paz; García, José María; Díaz, Natalia

    2010-01-01

    Two new rifabutin analogs, RFA-1 and RFA-2, show high in vitro antimycobacterial activities against Mycobacterium tuberculosis. MIC values of RFA-1 and RFA-2 were ≤0.02 μg/ml against rifamycin-susceptible strains and 0.5 μg/ml against a wide selection of multidrug-resistant strains, compared to ≥50 μg/ml for rifampin and 10 μg/ml for rifabutin. Molecular dynamic studies indicate that the compounds may exert tighter binding to mutants of RNA polymerase that have adapted to the rifamycins. PMID:20855731

  13. Seasonal variations in notification of active tuberculosis cases in China, 2005-2012.

    Directory of Open Access Journals (Sweden)

    Xin-Xu Li

    Full Text Available BACKGROUND: Although seasonal variation in tuberculosis (TB incidence has been described in many countries, it remains unknown in China. METHODS: A time series decomposition analysis (X-12-ARIMA was performed to examine the seasonal variation in active TB cases nationwide from 2005 through 2012 in China. Seasonal amplitude was calculated for the evaluation of TB seasonal variation. RESULTS: A total of 7.78 million active TB cases were reported over a period of 8 years. A spring peak (April was observed with seasonal amplitude of 46.3%, compared with the winter trough (February. Most cases in provinces with subtropical and tropical monsoon climate showed lower amplitudes than those in temperate continental, plateau and mountain climate regions. The magnitude of seasonality varied inversely with annual average temperature, r (95% CI = -0.71 (-0.79, -0.61. The seasonal amplitudes were 56.7, 60.5, 40.6, 46.4 and 50.9% for patients aged ≤14, 15-24, 25-44, 45-64, and ≥65 years, respectively. Students demonstrated greater seasonal amplitude than peasants, migrant workers and workers (115.3% vs. 43.5, 41.6 and 48.1%. Patients with pulmonary TB had lower amplitude compared to patients with pleural and other extra-pulmonary TB (EPTB (45.9% vs. 52.0 and 56.3%. Relapse cases with sputum smear positive TB (SS+ TB had significantly higher seasonal amplitude compared to new cases with sputum smear positive TB (52.2% vs. 41.6%. CONCLUSIONS: TB is a seasonal disease in China. The peak and trough of TB transmission actually are in winter and in autumn respectively after factors of delay are removed. Higher amplitudes of TB seasonality are more likely to happen in temperate continental, plateau and mountain climate regions and regions with lower annual average temperature, and young person, students, patients with EPTB and relapse cases with SS+ TB are more likely to be affected by TB seasonality.

  14. Modeling of novel diagnostic strategies for active tuberculosis - a systematic review: current practices and recommendations.

    Directory of Open Access Journals (Sweden)

    Alice Zwerling

    Full Text Available The field of diagnostics for active tuberculosis (TB is rapidly developing. TB diagnostic modeling can help to inform policy makers and support complicated decisions on diagnostic strategy, with important budgetary implications. Demand for TB diagnostic modeling is likely to increase, and an evaluation of current practice is important. We aimed to systematically review all studies employing mathematical modeling to evaluate cost-effectiveness or epidemiological impact of novel diagnostic strategies for active TB.Pubmed, personal libraries and reference lists were searched to identify eligible papers. We extracted data on a wide variety of model structure, parameter choices, sensitivity analyses and study conclusions, which were discussed during a meeting of content experts.From 5619 records a total of 36 papers were included in the analysis. Sixteen papers included population impact/transmission modeling, 5 were health systems models, and 24 included estimates of cost-effectiveness. Transmission and health systems models included specific structure to explore the importance of the diagnostic pathway (n = 4, key determinants of diagnostic delay (n = 5, operational context (n = 5, and the pre-diagnostic infectious period (n = 1. The majority of models implemented sensitivity analysis, although only 18 studies described multi-way sensitivity analysis of more than 2 parameters simultaneously. Among the models used to make cost-effectiveness estimates, most frequent diagnostic assays studied included Xpert MTB/RIF (n = 7, and alternative nucleic acid amplification tests (NAATs (n = 4. Most (n = 16 of the cost-effectiveness models compared new assays to an existing baseline and generated an incremental cost-effectiveness ratio (ICER.Although models have addressed a small number of important issues, many decisions regarding implementation of TB diagnostics are being made without the full benefits of insight from mathematical

  15. Fiberoptic bronchoscopy for the rapid diagnosis of smear-negative pulmonary tuberculosis

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    Shin Jung

    2012-06-01

    Full Text Available Abstract Background This study was aimed to investigate the diagnostic value of fiberoptic bronchoscopy (FOB with chest high-resolution computed tomography (HRCT for the rapid diagnosis of active pulmonary tuberculosis (PTB in patients suspected of PTB but found to have a negative sputum acid-fast bacilli (AFB smear. Methods We evaluated the diagnostic accuracy of results from FOB and HRCT in 126 patients at Gangnam Severance Hospital (Seoul, Korea who were suspected of having PTB. Results Of 126 patients who had negative sputum AFB smears but were suspected of having PTB, 54 patients were confirmed as having active PTB. Hemoptysis was negatively correlated with active PTB. Tree-in-bud appearance on HRCT was significantly associated with active PTB. The sensitivity, specificity, positive predictive value (PPV, and negative predictive value (NPV of FOB alone was 75.9%, 97.2%, 95.3%, and 84.3%, respectively, for the rapid diagnosis of active PTB. The combination of FOB and HRCT improved the sensitivity to 96.3% and the NPV to 96.2%. Conclusions FOB is a useful tool in the rapid diagnosis of active PTB with a high sensitivity, specificity, PPV and NPV in sputum smear-negative PTB-suspected patients. HRCT improves the sensitivity of FOB when used in combination with FOB in sputum smear-negative patients suspected of having PTB.

  16. Multidrug-Resistant Mycobacterium tuberculosis of the Latin American Mediterranean Lineage, Wrongly Identified as Mycobacterium pinnipedii (Spoligotype International Type 863 [SIT863]), Causing Active Tuberculosis in South Brazil

    KAUST Repository

    Dalla Costa, Elis R.

    2015-09-23

    We recently detected the spoligotype patterns of strains of Mycobacterium pinnipedii, a species of the Mycobacterium tuberculosis complex, in sputum samples from nine cases with pulmonary tuberculosis residing in Porto Alegre, South Brazil. Because this species is rarely encountered in humans, we further characterized these nine isolates by additional genotyping techniques, including 24-locus mycobacterial interspersed repetitive-unit–variable-number tandem-repeat (MIRU-VNTR) typing, verification of the loci TbD1, RD9, pks15/1, RDRio, and fbpC, the insertion of IS6110 at a site specific to the M. tuberculosis Latin American Mediterranean (LAM) lineage, and whole-genome sequencing. The combined analysis of these markers revealed that the isolates are in fact M. tuberculosis and more specifically belong to the LAM genotype. Most of these isolates (n = 8) were shown to be multidrug resistant (MDR), which prompted us to perform partial sequencing of the rpoA, rpoB, rpoC, katG, and inhA genes. Seven isolates (77.8%) carried the S315T mutation in katG, and one of these (11%) also presented the C(−17)T single-nucleotide polymorphism (SNP) in inhA. Interestingly, six of the MDR isolates also presented an undescribed insertion of 12 nucleotides (CCA GAA CAA CCC) in codon 516 of rpoB. No putative compensatory mutation was found in either rpoA or rpoC. This is the first report of an M. tuberculosis LAM family strain with a convergent M. pinnipedii spoligotype. These spoligotypes are observed in genotype databases at a modest frequency, highlighting that care must be taken when identifying isolates in the M. tuberculosis complex on the basis of single genetic markers.

  17. Tuberculosis screening in patients with HIV

    DEFF Research Database (Denmark)

    Bjerrrum, Stephanie; Bonsu, Frank; Hanson-Nortey, Nii Nortey

    2016-01-01

    is scarce. OBJECTIVES: To assess tuberculosis screening practices and the effectiveness of audit and performance feedback to improve quality of tuberculosis screening at HIV care clinics in Ghana. DESIGN: Healthcare providers at 10 large HIV care clinics prospectively registered patient consultations during...... May and October 2014, before and after a performance feedback intervention in August 2014. The outcomes of interest were overall tuberculosis suspicion rate during consultations and provider adherence to the International Standards for Tuberculosis Care and the World Health Organizations' guidelines...... screen (any of current cough, fever, weight loss or night sweats). After feedback, patients with a positive WHO symptom screen were more likely to be suspected of tuberculosis (OR 2.21; 95% CI: 1.19-4.09) and referred for microscopy (OR 2.71; 95% CI: 1.25-5.86). CONCLUSIONS: A simple prospective audit...

  18. Safety of Resuming Tumor Necrosis Factor Inhibitors in Ankylosing Spondylitis Patients Concomitant with the Treatment of Active Tuberculosis: A Retrospective Nationwide Registry of the Korean Society of Spondyloarthritis Research.

    Directory of Open Access Journals (Sweden)

    Hye Won Kim

    Full Text Available Patients who develop an active tuberculosis infection during tumor necrosis factor (TNF inhibitor treatment typically discontinue TNF inhibitor and receive standard anti-tuberculosis treatment. However, there is currently insufficient information on patient outcomes following resumption of TNF inhibitor treatment during ongoing anti- tuberculosis treatment. Our study was designed to investigate the safety of resuming TNF inhibitors in ankylosing spondylitis (AS patients who developed tuberculosis as a complication of the use of TNF inhibitors.Through the nationwide registry of the Korean Society of Spondyloarthritis Research, 3929 AS patients who were prescribed TNF inhibitors were recruited between June 2003 and June 2014 at fourteen referral hospitals. Clinical information was analyzed about the patients who experienced tuberculosis after exposure to TNF inhibitors. The clinical features of resumers and non-resumers of TNF inhibitors were compared and the outcomes of tuberculosis were surveyed individually.Fifty-six AS patients were treated for tuberculosis associated with TNF inhibitors. Among them, 23 patients resumed TNF inhibitors, and these patients were found to be exposed to TNF inhibitors for a longer period of time and experienced more frequent disease flare-up after discontinuation of TNF inhibitors compared with those who did not resume. Fifteen patients resumed TNF inhibitors during anti-tuberculosis treatment (early resumers and 8 after completion of anti-tuberculosis treatment (late resumers. Median time to resuming TNF inhibitor from tuberculosis was 3.3 and 9.0 months in the early and late resumers, respectively. Tuberculosis was treated successfully in all resumers and did not relapse in any of them during follow-up (median 33.8 [IQR; 20.8-66.7] months.Instances of tuberculosis were treated successfully in our AS patients, even when given concomitantly with TNF inhibitors. We suggest that early resumption of TNF inhibitors in

  19. A predictive signature gene set for discriminating active from latent tuberculosis in Warao Amerindian children.

    Science.gov (United States)

    Verhagen, Lilly M; Zomer, Aldert; Maes, Mailis; Villalba, Julian A; Del Nogal, Berenice; Eleveld, Marc; van Hijum, Sacha Aft; de Waard, Jacobus H; Hermans, Peter Wm

    2013-02-01

    Tuberculosis (TB) continues to cause a high toll of disease and death among children worldwide. The diagnosis of childhood TB is challenged by the paucibacillary nature of the disease and the difficulties in obtaining specimens. Whereas scientific and clinical research efforts to develop novel diagnostic tools have focused on TB in adults, childhood TB has been relatively neglected. Blood transcriptional profiling has improved our understanding of disease pathogenesis of adult TB and may offer future leads for diagnosis and treatment. No studies applying gene expression profiling of children with TB have been published so far. We identified a 116-gene signature set that showed an average prediction error of 11% for TB vs. latent TB infection (LTBI) and for TB vs. LTBI vs. healthy controls (HC) in our dataset. A minimal gene set of only 9 genes showed the same prediction error of 11% for TB vs. LTBI in our dataset. Furthermore, this minimal set showed a significant discriminatory value for TB vs. LTBI for all previously published adult studies using whole blood gene expression, with average prediction errors between 17% and 23%. In order to identify a robust representative gene set that would perform well in populations of different genetic backgrounds, we selected ten genes that were highly discriminative between TB, LTBI and HC in all literature datasets as well as in our dataset. Functional annotation of these genes highlights a possible role for genes involved in calcium signaling and calcium metabolism as biomarkers for active TB. These ten genes were validated by quantitative real-time polymerase chain reaction in an additional cohort of 54 Warao Amerindian children with LTBI, HC and non-TB pneumonia. Decision tree analysis indicated that five of the ten genes were sufficient to classify 78% of the TB cases correctly with no LTBI subjects wrongly classified as TB (100% specificity). Our data justify the further exploration of our signature set as biomarkers

  20. Antibacterial Activity of Aristolochia brevipes against Multidrug-Resistant Mycobacterium tuberculosis

    OpenAIRE

    María Yolanda Ríos; Patricia Álvarez-Fitz; Ma. Gabriela Rojas-Bribiesca; Julieta Luna-Herrera; Víctor Manuel Navarro-García

    2011-01-01

    The increased incidence of Multidrug-Resistant Mycobacterium tuberculosis (MDR-MT) requires the search for alternative antimycobacterial drugs. The main aim of this study was to evaluate the dichloromethane extract from Aristolochia brevipes (Rhizoma) and the compounds isolated from this extract against several mycobacterial strains, sensitive, resistant (monoresistant), and clinical isolates (multidrug-resistant), using the alamarBlue™ microassay. The extract was fractionated by column chrom...

  1. Identification of 2-aminothiazole-4-carboxylate derivatives active against Mycobacterium tuberculosis H37Rv and the beta-ketoacyl-ACP synthase mtFabH.

    Directory of Open Access Journals (Sweden)

    Qosay Al-Balas

    Full Text Available BACKGROUND: Tuberculosis (TB is a disease which kills two million people every year and infects approximately over one-third of the world's population. The difficulty in managing tuberculosis is the prolonged treatment duration, the emergence of drug resistance and co-infection with HIV/AIDS. Tuberculosis control requires new drugs that act at novel drug targets to help combat resistant forms of Mycobacterium tuberculosis and reduce treatment duration. METHODOLOGY/PRINCIPAL FINDINGS: Our approach was to modify the naturally occurring and synthetically challenging antibiotic thiolactomycin (TLM to the more tractable 2-aminothiazole-4-carboxylate scaffold to generate compounds that mimic TLM's novel mode of action. We report here the identification of a series of compounds possessing excellent activity against M. tuberculosis H(37R(v and, dissociatively, against the beta-ketoacyl synthase enzyme mtFabH which is targeted by TLM. Specifically, methyl 2-amino-5-benzylthiazole-4-carboxylate was found to inhibit M. tuberculosis H(37R(v with an MIC of 0.06 microg/ml (240 nM, but showed no activity against mtFabH, whereas methyl 2-(2-bromoacetamido-5-(3-chlorophenylthiazole-4-carboxylate inhibited mtFabH with an IC(50 of 0.95+/-0.05 microg/ml (2.43+/-0.13 microM but was not active against the whole cell organism. CONCLUSIONS/SIGNIFICANCE: These findings clearly identify the 2-aminothiazole-4-carboxylate scaffold as a promising new template towards the discovery of a new class of anti-tubercular agents.

  2. HIV and tuberculosis in India

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    well as those facing political turmoil, migration, poverty and unemployment and where intravenous drug abuse is rampant. HIV is the most important known risk factor that promotes progression to active TB in people with Mycobacterium tuberculosis infection (TB/HIV A Clinical Manual 2004). The lifetime risk of tuberculosis ...

  3. Clinical correlates of tuberculosis co-infection in HIV-infected children hospitalized in Peru.

    Science.gov (United States)

    Ramírez-Cardich, María E; Kawai, Vivian; Oberhelman, Richard A; Bautista, Christian T; Castillo, María E; Gilman, Robert H

    2006-07-01

    In developing countries, tuberculosis (TB) is responsible for almost 250,000 deaths among children yearly. Active TB in children with human immunodeficiency virus (HIV) infection is difficult to diagnose and progresses rapidly to death. The aim of this preliminary study was to investigate the prevalence and clinical correlates of TB-related illness among HIV-infected children admitted to an infectious diseases ward in Peru, a country where TB is highly endemic. Forty-seven HIV-infected children admitted for a suspected infectious process in a Peruvian hospital were investigated for evidence of clinical tuberculosis by auramine stain, culture, and polymerase chain reaction (PCR) of clinical specimens. Eight children (17%) had evidence of tuberculosis, including five with positive cultures and three with positive PCR tests only. Weight loss was the only feature associated with a positive test for tuberculosis. Radiological changes were very common in both TB-positive and TB-negative groups and these changes were not useful to identify TB-positive cases. Weight loss may be used to identify high-risk HIV positive children who require more aggressive evaluation for tuberculosis. Radiological changes were common in both TB-positive and TB-negative groups.

  4. Esters of pyrazinoic acid are active against pyrazinamide-resistant strains of Mycobacterium tuberculosis and other naturally resistant mycobacteria in vitro and ex vivo within macrophages.

    KAUST Repository

    Pires, David

    2015-10-05

    Pyrazinamide (PZA) is active against major Mycobacterium tuberculosis species (M. tuberculosis, M. africanum, and M. microti), but not against M. bovis and M. avium. The latter two are mycobacteria species involved in human and cattle tuberculosis and in HIV co-infections, respectively. PZA is a first-line agent for the treatment of human tuberculosis and requires activation by a mycobacterial pyrazinamidase to form the active metabolite pyrazinoic acid (POA). As a result of this mechanism, resistance to PZA as often found in tuberculosis patients is caused by point mutations in pyrazinamidase. In previous work, we have shown that POA esters and amides synthesized in our laboratory were stable in plasma. Although the amides did not present significant activity, the esters were active against sensitive mycobacteria at concentrations 5-to-10 fold lower than those of PZA. Here, we report that these POA derivatives possess antibacterial efficacy in vitro and ex vivo against several species and strains of Mycobacterium with natural or acquired resistance to PZA, including M. bovis and M. avium. Our results indicate that the resistance was probably overcome by cleavage of the prodrugs into POA and a long-chain alcohol. Although it is not possible to rule out that the esters may have intrinsic activity per se, we bring evidence here that long-chain fatty alcohols possess a significant anti-mycobacterial effect against PZA-resistant species and strains and are not mere inactive promoieties. These findings may lead to candidate dual-drugs having enhanced activity against both PZA-susceptible and PZA-resistant isolates and being suitable for clinical development.

  5. [Endobronchial tuberculosis].

    Science.gov (United States)

    Manal, E; Nahid, Z; Hanane, B; Najiba, Y

    2017-04-01

    The endobronchial tuberculosis (EBTB) is an uncommon type of tuberculosis. The respiratory symptoms in EBTB are usually nonspecific and misleading. The aim of the study is to determine the clinical features and diagnostic aspects of EBTB. Twenty-eight cases of endobronchial tuberculosis collected from January 2009 to October 2015. EBTB was found in 16 females and 12 males. The mean age was 48 years. The history of tuberculosis and tuberculosis contagion were not found in any case. The respiratory symptoms were dominated by cough and dyspnea. Hemoptysis was found in 7 cases. The chest X-ray showed associated pulmonary lesions in 26 cases. Bronchoscopy finded an endobronchial granular lesion in 15 cases, a tumorous pattern in 7 cases; a thickening spurs in 4 cases and ganglio-bronchial fistula in two cases. Bronchial biopsies had found a caseo-follicular tuberculosis in 27 cases. Pleural biopsy confirmed associated pleural tuberculosis in one case. The research of Koch bacillus in the sputum was positive in 13 cases and culture in 6 cases. The antituberculosis treatment was started in all patients and an oral corticosteroids treatment was associated in 5 cases. The evolution was good in 26 cases. This study showed clinical, radiological and endoscopic bronchial tuberculosis polymorphism making its diagnosis difficult and the importance of a bacteriological and/or histological confirmation. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. Asymptomatic Helminth Infection in Active Tuberculosis Is Associated with Increased Regulatory and Th-2 Responses and a Lower Sputum Smear Positivity

    DEFF Research Database (Denmark)

    Abate, E; Belayneh, M; Idh, J

    2015-01-01

    BACKGROUND: The impact of intestinal helminth infection on the clinical presentation and immune response during active tuberculosis (TB) infection is not well characterized. Our aim was to investigate whether asymptomatic intestinal helminth infection alters the clinical signs and symptoms as wel...

  7. Fumarate reductase activity maintains an energized membrane in anaerobic Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Shinya Watanabe

    2011-10-01

    Full Text Available Oxygen depletion of Mycobacterium tuberculosis engages the DosR regulon that coordinates an overall down-regulation of metabolism while up-regulating specific genes involved in respiration and central metabolism. We have developed a chemostat model of M. tuberculosis where growth rate was a function of dissolved oxygen concentration to analyze metabolic adaptation to hypoxia. A drop in dissolved oxygen concentration from 50 mmHg to 0.42 mmHg led to a 2.3 fold decrease in intracellular ATP levels with an almost 70-fold increase in the ratio of NADH/NAD(+. This suggests that re-oxidation of this co-factor becomes limiting in the absence of a terminal electron acceptor. Upon oxygen limitation genes involved in the reverse TCA cycle were upregulated and this upregulation was associated with a significant accumulation of succinate in the extracellular milieu. We confirmed that this succinate was produced by a reversal of the TCA cycle towards the non-oxidative direction with net CO(2 incorporation by analysis of the isotopomers of secreted succinate after feeding stable isotope ((13C labeled precursors. This showed that the resulting succinate retained both carbons lost during oxidative operation of the TCA cycle. Metabolomic analyses of all glycolytic and TCA cycle intermediates from (13C-glucose fed cells under aerobic and anaerobic conditions showed a clear reversal of isotope labeling patterns accompanying the switch from normoxic to anoxic conditions. M. tuberculosis encodes three potential succinate-producing enzymes including a canonical fumarate reductase which was highly upregulated under hypoxia. Knockout of frd, however, failed to reduce succinate accumulation and gene expression studies revealed a compensatory upregulation of two homologous enzymes. These major realignments of central metabolism are consistent with a model of oxygen-induced stasis in which an energized membrane is maintained by coupling the reductive branch of the TCA

  8. Prevalence of smear positive tuberculosis among outpatient ...

    African Journals Online (AJOL)

    There is paucity of data on the prevalence of pulmonary tuberculosis (PTB) among out-patient attendees from individual Institutions and Health Care Facilities performing sputum smear microscopy in Ghana. This retrospective study analyzed sputum smear microscopy results among pulmonary TB suspected patients ...

  9. Tonsillar tuberculosis : A case report

    Directory of Open Access Journals (Sweden)

    S Karki

    2016-09-01

    Full Text Available Tuberculosis of the oral cavity which is an uncommon occurrence can be primary or secondary. In the absence of active pulmonary tuberculosis, isolated tonsillar tuberculosis is rare. Herein, we report two cases of bilateral tonsillar tuberculosis who presented as recurrent sore throat for which tonsillectomy was done. No active primary pulmonary lesion was found in these cases. Histopathological examination revealed caseating epithelioid granulomas with Langhans giant cells. Ziehl Neelson stain for acid fast bacilli was positive in one case. Tonsillar tuberculosis, though a rare entity, should be considered in the clinical differential diagnosis of tonsillar lesions. Histopathological examination with Ziehl Neelson stain should be performed for definite diagnosis.

  10. Standardized radiographic interpretation of thoracic tuberculosis in children

    Energy Technology Data Exchange (ETDEWEB)

    Concepcion, Nathan David P.; Laya, Bernard F. [St. Luke' s Medical Center, Section of Pediatric Radiology, Institute of Radiology, Taguig City (Philippines); St. Luke' s Medical Center, Section of Pediatric Radiology, Institute of Radiology, Quezon City (Philippines); Andronikou, Savvas [Bristol Royal Hospital for Children and the University of Bristol, Department of Paediatric Radiology, Bristol (United Kingdom); Daltro, Pedro A.N. [Clinica de Diagnostico por Imagem, Section of Pediatric Radiology, Rio de Janeiro (Brazil); Sanchez, Marion O. [St. Luke' s Medical Center, Section of Pediatric Pulmonology, Institute of Pulmonary Medicine, Quezon City (Philippines); Uy, Jacqueline Austine U. [St. Luke' s Medical Center, Section of Pediatric Radiology, Institute of Radiology, Taguig City (Philippines); Lim, Timothy Reynold U. [St. Luke' s Medical Center, Section of Pediatric Radiology, Institute of Radiology, Quezon City (Philippines)

    2017-09-15

    There is a lack of standardized approach and terminology to classify the diverse spectrum of manifestations in tuberculosis. It is important to recognize the different clinical and radiographic patterns to guide treatment. As a result of changing epidemiology, there is considerable overlap in the radiologic presentations of primary tuberculosis and post-primary tuberculosis. In this article we promote a standardized approach in clinical and radiographic classification for children suspected of having or diagnosed with childhood tuberculosis. We propose standardized terms to diminish confusion and miscommunication, which can affect management. In addition, we present pitfalls and limitations of imaging. (orig.)

  11. Antigen smuggling in tuberculosis.

    Science.gov (United States)

    Hudrisier, Denis; Neyrolles, Olivier

    2014-06-11

    The importance of CD4 T lymphocytes in immunity to M. tuberculosis is well established; however, how dendritic cells activate T cells in vivo remains obscure. In this issue of Cell Host & Microbe, Srivastava and Ernst (2014) report a mechanism of antigen transfer for efficient activation of antimycobacterial T cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Local inflammation, dissemination and coalescence of lesions are key for the progression towards active tuberculosis: the bubble model

    Directory of Open Access Journals (Sweden)

    Clara ePrats

    2016-02-01

    Full Text Available The evolution of a tuberculosis (TB infection towards active disease is driven by a combination of factors mostly related to the host response. The equilibrium between control of the bacillary load and the pathology generated is crucial as regards preventing the growth and proliferation of TB lesions. In addition, some experimental evidence suggests an important role of both local endogenous reinfection and the coalescence of neighboring lesions.Herein we propose a mathematical model that captures the essence of these factors by defining three hypotheses: (i lesions grow logistically due to the inflammatory reaction; (ii new lesions can appear as a result of extracellular bacilli or infected macrophages that escape from older lesions; and (iii lesions can merge when they are close enough. This model was implemented in Matlab to simulate the dynamics of several lesions in a 3D space. It was also fitted to available microscopy data from infected C3HeB/FeJ mice, an animal model of active TB that reacts against Mycobacterium tuberculosis with an exaggerated inflammatory response.The results of the simulations show the dynamics observed experimentally, namely an initial increase in the number of lesions followed by oscillations, and an exponential increase in the mean area of the lesions. In addition, further analysis of experimental and simulation results show a strong coincidence of the area distributions of lesions at day 21, thereby highlighting the consistency of the model. Three simulation series removing each one of the hypothesis corroborate their essential role in the dynamics observed.These results demonstrate that three local factors, namely an exaggerated inflammatory response, an endogenous reinfection and a coalescence of lesions, are needed in order to progress towards active TB. The failure of one of these factors stops induction of the disease. This mathematical model may be used as a basis for developing strategies to stop the

  13. Technology and the Glaucoma Suspect

    National Research Council Canada - National Science Library

    Blumberg, Dana M; De Moraes, Carlos Gustavo; Liebmann, Jeffrey M; Garg, Reena; Chen, Cynthia; Theventhiran, Alex; Hood, Donald C

    2016-01-01

    ...), stereoscopic disc photographs, and automated perimetry as assessed by a group of glaucoma specialists in differentiating individuals with early glaucoma from suspects. Forty-six eyes (46 patients...

  14. Evaluation of the Antibody in Lymphocyte Supernatant Assay to Detect Active Tuberculosis.

    Directory of Open Access Journals (Sweden)

    Margaretha Sariko

    Full Text Available We aimed to evaluate the antibody in lymphocyte supernatant (ALS assay as a biomarker to diagnose tuberculosis among adults from Tanzania with and without HIV.Adults admitted with suspicion for tuberculosis had sputa obtained for GeneXpert MTB/RIF, acid-fast bacilli smear and mycobacterial culture; blood was obtained prior to treatment initiation and after 4 weeks. Adults hospitalized with non-infectious conditions served as controls. Peripheral blood mononuclear cells were cultured unstimulated for 72 hours. Anti-mycobacterial antibodies were measured from culture supernatants by ELISA, using BCG vaccine as the coating antigen. Median ALS responses were compared between cases and controls at baseline and between cases over time.Of 97 TB cases, 85 were microbiologically confirmed and 12 were clinically diagnosed. Median ALS responses from TB cases (0.366 OD from confirmed cases and 0.285 from clinical cases were higher compared to controls (0.085, p<0.001. ALS responses did not differ based on HIV status, CD4 count or sputum smear status. Over time, the median ALS values declined significantly (0.357 at baseline; 0.198 after 4-weeks, p<0.001.Robust ALS responses were mounted by patients with TB regardless of HIV status, CD4 count, or low sputum bacillary burden, potentially conferring a unique niche for this immunologic biomarker for TB.

  15. Evaluation of a modified BACTEC method to study the activity of disinfectants against Mycobacterium tuberculosis.

    Science.gov (United States)

    Cutler, R R; Wilson, P; Clarke, F V

    1995-06-01

    BACTEC radiometry could provide a useful tool for evaluating the effect of disinfectants on mycobacteria. The aim of this study was to improve the recovery of mycobacteria in the BACTEC system and thereby develop a new method for disinfectant testing with Mycobacterium tuberculosis. Protein was added to BACTEC 7H12B media. Growth and the recovery of M. tuberculosis after exposure to disinfectants was measured using viable counts and BACTEC radiometry. Protein additives enhanced growth in 7H12B media. After serial dilution of inoculum, 7H12B plus 10% egg yolk recovered mycobacteria from a 10(-2) higher dilution than viable counts. After 5 min disinfection with 3% peroxygen compound (Virkon), 3% Virkon plus saline or 2% gluteraldehyde (Cidex) no mycobacteria were recovered using standard 7H12B. However, using 7H12B plus protein, growth was detected in all of these within 30 days. In contrast, viable counts detected growth with Cidex and Virkon after 5 min disinfection but not from Virkon in saline. Viable counts took 3-8 weeks to determine. Using this modified BACTEC system for the evaluation of disinfectant action on mycobacteria provides advantages in speed, sensitivity and ease of use when compared with viable counts.

  16. Assessment of risk factors for development of active pulmonary tuberculosis in northern part of Ethiopia: a matched case control study.

    Science.gov (United States)

    Berhe, Gebretsadik; Enquselassie, Fikre; Aseffa, Abraham

    2013-10-01

    Understanding the role of various determinants of tuberculosis (TB) is particularly important in countries like Ethiopia where TB is endemic and the resources available to public health intervention are limited However, little information is available on risk factors of TB to be able to effectively and efficiently control TB. To identify and determine the potential host and environmental-related risk factors for development of active pulmonary tuberculosis (PTB) in the Tigray region of Ethiopia. A matched case-control study was conducted from April-August 2011. Cases were defined as all newly diagnosed of PTB patients aged 15 years and above, who were registered by directly observed treatment short-course (DOTS) program health centers found in the randomly selected 16 districts in the region. Controls were age matched with no previous history of TB and chronic cough. For each case, two controls were recruited. Trained nurses collected data using structured and pre-tested questionnaire. Predictors of caseness were identified using conditional logistic regression method. Odds ratio were calculated with 95% confidence intervals to assess the strength of association. Data was collected from 463 cases and 860 controls. The mean age of the cases and controls were 37 +/- 14.9 and 39 +/- 14.5 years, respectively. In the multivariable analysis significant risk factors for active PTB were illiteracy (OR = 1.90, 95% CI: 1.24, 2.93), household food shortage (OR = 2.38, 95% CI: 1.52, 3.73), HIV seropositivity (OR = 2.7, 95% CI: 1.42, 5.13), and past alcohol consumption (OR = 2.44, 95% CI: 1.08, 5.50). Marriage (OR = 95% CI: 0.37, 0.89) was identified as protective factor. Consumption of raw milk, history of imprisonment, having a separate kitchen, history of asthma and history of TB contact were significant risk factors on crude analysis but their significance was not maintained in multivariable analysis. Our study results indicated that household food shortage, HIV sero

  17. [Treatment of tuberculosis].

    Science.gov (United States)

    Ben Amar, J; Dhahri, B; Aouina, H; Azzabi, S; Baccar, M A; El Gharbi, L; Bouacha, H

    2015-01-01

    The aim of this article is to give practicing physicians a practical approach to the treatment of latent and active tuberculosis. Most patients follow TB standard treatment recommended by WHO that depend on category of patient. It is a combination of four essential tuberculosis drugs of the first group: isoniazid, rifampicin, pyrazinamid and ethambutol; in some cases streptomycin can replace ethambutol. This initial phase of intensive treatment is followed by a consolidation phase. Drugs should be administered in the morning on an empty stomach one hour before meals. Treatment of latent tuberculosis (TB) infection is an important component of TB control programs. Preventive treatment can reduce the risk of developing active TB. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  18. Descriptive review of tuberculosis surveillance systems across the circumpolar regions

    DEFF Research Database (Denmark)

    Bourgeois, Annie-Claude; Zulz, Tammy; Soborg, Bolette

    2016-01-01

    BACKGROUND: Tuberculosis is highly prevalent in many Arctic areas. Members of the International Circumpolar Surveillance Tuberculosis (ICS-TB) Working Group collaborate to increase knowledge about tuberculosis in Arctic regions. OBJECTIVE: To establish baseline knowledge of tuberculosis surveilla...... for description of the epidemiology of TB based on surveillance data in circumpolar regions, further study of tuberculosis trends across regions, and recommendation of best practices to improve surveillance activities....

  19. Synthesis of acyl-hydrazone from usnic acid and isoniazid and its anti-Mycobacterium tuberculosis activity

    Directory of Open Access Journals (Sweden)

    Melissa Barrera Tomas

    2017-09-01

    Full Text Available Compound usnic acid (1, isolated from lichen Evernia prunastri (Cajamarca-Peru and the synthesis and characterization of its acyl-hydrazone (2, from the condensation reaction between usnic acid and isoniazid in an ethanol solution under reflux, giving an overall yield of 95%, were evaluated. Both compounds were evaluated and compared with isoniazid according to its anti-Mycobacterium tuberculosis activity based on the tetrazolium microplate assay (TEMA. Compound 1 had MIC (minimal inhibitory concentration value of 16.0 μg/mL in each test of H37Rv (susceptible type, TB DM 97 (resistant wild type and MDR DM 1098 (multi drug resistances type strains. In similar tests, compound 2 MIC values were 2.0, 64.0 and 64.0 μg/mL respectively.

  20. Targeting phenotypically tolerant Mycobacterium tuberculosis

    Science.gov (United States)

    Gold, Ben; Nathan, Carl

    2016-01-01

    While the immune system is credited with averting tuberculosis in billions of individuals exposed to Mycobacterium tuberculosis, the immune system is also culpable for tempering the ability of antibiotics to deliver swift and durable cure of disease. In individuals afflicted with tuberculosis, host immunity produces diverse microenvironmental niches that support suboptimal growth, or complete growth arrest, of M. tuberculosis. The physiological state of nonreplication in bacteria is associated with phenotypic drug tolerance. Many of these host microenvironments, when modeled in vitro by carbon starvation, complete nutrient starvation, stationary phase, acidic pH, reactive nitrogen intermediates, hypoxia, biofilms, and withholding streptomycin from the streptomycin-addicted strain SS18b, render M. tuberculosis profoundly tolerant to many of the antibiotics that are given to tuberculosis patients in a clinical setting. Targeting nonreplicating persisters is anticipated to reduce the duration of antibiotic treatment and rate of post-treatment relapse. Some promising drugs to treat tuberculosis, such as rifampicin and bedaquiline, only kill nonreplicating M. tuberculosis in vitro at concentrations far greater than their minimal inhibitory concentrations against replicating bacilli. There is an urgent demand to identify which of the currently used antibiotics, and which of the molecules in academic and corporate screening collections, have potent bactericidal action on nonreplicating M. tuberculosis. With this goal, we review methods of high throughput screening to target nonreplicating M. tuberculosis and methods to progress candidate molecules. A classification based on structures and putative targets of molecules that have been reported to kill nonreplicating M. tuberculosis revealed a rich diversity in pharmacophores. However, few of these compounds were tested under conditions that would exclude the impact of adsorbed compound acting during the recovery phase of

  1. Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries

    NARCIS (Netherlands)

    Getahun, Haileyesus; Matteelli, Alberto; Abubakar, Ibrahim; Aziz, Mohamed Abdel; Baddeley, Annabel; Barreira, Draurio; den Boon, Saskia; Borroto Gutierrez, Susana Marta; Bruchfeld, Judith; Burhan, Erlina; Cavalcante, Solange; Cedillos, Rolando; Chaisson, Richard; Chee, Cynthia Bin-Eng; Chesire, Lucy; Corbett, Elizabeth; Dara, Masoud; Denholm, Justin; de Vries, Gerard; Falzon, Dennis; Ford, Nathan; Gale-Rowe, Margaret; Gilpin, Chris; Girardi, Enrico; Go, Un-Yeong; Govindasamy, Darshini; D Grant, Alison; Grzemska, Malgorzata; Harris, Ross; Horsburgh, C. Robert; Ismayilov, Asker; Jaramillo, Ernesto; Kik, Sandra; Kranzer, Katharina; Lienhardt, Christian; LoBue, Philip; Lönnroth, Knut; Marks, Guy; Menzies, Dick; Migliori, Giovanni Battista; Mosca, Davide; Mukadi, Ya Diul; Mwinga, Alwyn; Nelson, Lisa; Nishikiori, Nobuyuki; Oordt-Speets, Anouk; Rangaka, Molebogeng Xheedha; Reis, Andreas; Rotz, Lisa; Sandgren, Andreas; Sañé Schepisi, Monica; Schünemann, Holger J.; Sharma, Surender Kumar; Sotgiu, Giovanni; Stagg, Helen R.; Sterling, Timothy R.; Tayeb, Tamara; Uplekar, Mukund; van der Werf, Marieke J.; Vandevelde, Wim; van Kessel, Femke; van't Hoog, Anna; Varma, Jay K.; Vezhnina, Natalia; Voniatis, Constantia; Vonk Noordegraaf-Schouten, Marije; Weil, Diana; Weyer, Karin; Wilkinson, Robert John; Yoshiyama, Takashi; Zellweger, Jean Pierre; Raviglione, Mario

    2015-01-01

    Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health

  2. Drug Resistance Mechanisms in Mycobacterium tuberculosis.

    Science.gov (United States)

    Palomino, Juan Carlos; Martin, Anandi

    2014-07-02

    Tuberculosis (TB) is a serious public health problem worldwide. Its situation is worsened by the presence of multidrug resistant (MDR) strains of Mycobacterium tuberculosis, the causative agent of the disease. In recent years, even more serious forms of drug resistance have been reported. A better knowledge of the mechanisms of drug resistance of M. tuberculosis and the relevant molecular mechanisms involved will improve the available techniques for rapid drug resistance detection and will help to explore new targets for drug activity and development. This review article discusses the mechanisms of action of anti-tuberculosis drugs and the molecular basis of drug resistance in M. tuberculosis.

  3. Colonic tuberculosis mimicking Crohn's disease: case report

    Directory of Open Access Journals (Sweden)

    Roussomoustakaki Maria

    2002-05-01

    Full Text Available Abstract Background Intestinal tuberculosis is a rare disease in western countries, affecting mainly immigrants and immunocompromised patients. Intestinal tuberculosis is a diagnostic challenge, especially when active pulmonary infection is absent. It may mimic many other abdominal diseases. Case presentation Here, we report a case of isolated colonic tuberculosis where the initial diagnostic workup was suggestive of Crohn's disease. Computed tomography findings however, raised the possibility of colonic tuberculosis and the detection of acid-fast bacilli in biopsy specimens confirmed the diagnosis. Conclusions In conclusion, this case highlights the need for awareness of intestinal tuberculosis in the differential diagnosis of chronic intestinal disease

  4. Diagnosis of pediatric pulmonary tuberculosis by stool PCR.

    Science.gov (United States)

    Wolf, Hilary; Mendez, Melissa; Gilman, Robert H; Sheen, Patricia; Soto, Giselle; Velarde, Angie K; Zimic, Mirko; Escombe, A Roderick; Montenegro, Sonia; Oberhelman, Richard A; Evans, Carlton A

    2008-12-01

    Pediatric pulmonary tuberculosis diagnosis is difficult because young children are unable to expectorate sputum samples. Testing stool for tuberculosis DNA from swallowed sputum may diagnose pulmonary tuberculosis. Hospitalized children with suspected tuberculosis had stool, nasopharyngeal, and gastric aspirates cultured that confirmed pulmonary tuberculosis in 16/236 patients. Twenty-eight stored stools from these 16 children were used to evaluate stool polymerase chain reaction (PCR) for tuberculosis diagnosis compared with 28 stool samples from 23 healthy control children. Two DNA extraction techniques were used: fast-DNA mechanical homogenization and Chelex-resin chemical extraction. DNA was tested for tuberculosis DNA with a hemi-nested IS6110 PCR. PCR after Fast-DNA processing was positive for 6/16 culture-proven tuberculosis patients versus 5/16 after Chelex extraction (sensitivity 38% and 31%, respectively). All controls were negative (specificity 100%). If sensitivity can be increased, stool PCR would be a rapid, non-invasive, and relatively bio-secure initial test for children with suspected pulmonary tuberculosis.

  5. Increased Interleukin-4 production by CD8 and gammadelta T cells in health-care workers is associated with the subsequent development of active tuberculosis.

    Science.gov (United States)

    Ordway, Diane J; Costa, Leonor; Martins, Marta; Silveira, Henrique; Amaral, Leonard; Arroz, Maria J; Ventura, Fernando A; Dockrell, Hazel M

    2004-08-15

    We evaluated immune responses to Mycobacterium tuberculosis in 10 health-care workers (HCWs) and 10 non-HCWs and correlated their immune status with the development of active tuberculosis (TB). Twenty individuals were randomly recruited, tested, and monitored longitudinally for TB presentation. Peripheral blood mononuclear cells (PBMCs) from donors were stimulated with M. tuberculosis and tested for cell proliferation and the production of interferon (IFN)- gamma, interleukin (IL)-5, and IL-4, by use of enzyme-linked immunosorbent or flow-cytometric assays. HCWs had higher levels of cell proliferation (24,258 cpm) and IFN- gamma (6373 pg/mL) to M. tuberculosis than did non-HCWs (cell proliferation, 11,462 cpm; IFN- gamma, 3228 pg/mL). Six of 10 HCWs showed increased median percentages of CD8+IL-4+ (4.7%) and gammadelta +IL-4+ (2.3%) T cells and progressed to active TB. HCWs who remained healthy showed increased median percentages of CD8+IFN- gamma+ (25.0%) and gammadelta +IFN- gamma+ (8.0%) and lower percentages of CD8+IL-4+ (0.05%) and gammadelta +IL-4+ (0.03%) T cells.

  6. Factors associated with late presentation of suspected tuberculosis ...

    African Journals Online (AJOL)

    After multivariate logistic regression, gender (P=0,019, OR=1.6), level of education (p=0.029, OR=1.26) and place of first medical care (P= 0.01 OR=1.27), were found to be significantly associated with late presentation. Conclusion: This study shows that age, level of education and place of first medical care are the factors ...

  7. Factors associated with late presentation of suspected tuberculosis ...

    African Journals Online (AJOL)

    abp

    2012-07-31

    Jul 31, 2012 ... In Kenya, there are few studies which have been done to establish the factors that cause patients to delay in seeking medical care. Published data about factors causing late presentation of patients to TB management facilities in Nairobi is scanty. A study similar to this was done in a rural setting in the ...

  8. Macrophages play a dual role during pulmonary tuberculosis in mice

    NARCIS (Netherlands)

    Leemans, Jaklien C.; Thepen, Theo; Weijer, Sebastiaan; Florquin, Sandrine; van Rooijen, Nico; van de Winkel, Jan G.; van der Poll, Tom

    2005-01-01

    Pulmonary macrophages provide the preferred hiding and replication site of Mycobacterium tuberculosis but display antimicrobial functions. This raises questions regarding the role of macrophages during tuberculosis. We depleted lungs of activated macrophages (activated macrophage(-) mice) and

  9. DIFFERENTIAL DIAGNOSTICS OF PROSTATE TUBERCULOSIS

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    E. V. Brizhatyuk

    2017-01-01

    Full Text Available Prostate tuberculosis is difficult to be diagnosed, especially if lesions are limited only by this organ. The article analyses the experience of differential diagnostics of prostate tuberculosis based on the data of examination of 84 patients. 45 of them were diagnosed with prostate tuberculosis, and 39 patients were diagnosed with chronic bacterial prostatitis. Pathognomonic diagnostics criteria of prostate tuberculosis were the following: detection of tuberculous mycobacteria in the prostatic fluid or ejaculate, signs of granulomatous prostatitis with areas of cavernous necrosis in prostate biopsy samples, and prostate cavities visualized by X-ray or ultrasound examinations. Should the above criteria be absent, the disease can be diagnosed based on the combination of indirect signs: symptoms of prostate inflammation with active tuberculosis of the other localization; large prostate calcification, extensive hyperechoic area of the prostate, spermatocystic lesions, leucospermia and hemospermia, failure of the adequate non-specific anti-bacterial therapy.

  10. Reynosin and santamarine: two sesquiterpene lactones from Ambrosia confertiflora with bactericidal activity against clinical strains of Mycobacterium tuberculosis.

    Science.gov (United States)

    Coronado-Aceves, Enrique Wenceslao; Velázquez, Carlos; Robles-Zepeda, Ramón Enrique; Jiménez-Estrada, Manuel; Hernández-Martínez, Javier; Gálvez-Ruiz, Juan Carlos; Garibay-Escobar, Adriana

    2016-11-01

    Tuberculosis is primarily caused by Mycobacterium tuberculosis (Mtb). Previous studies have shown that the dichloromethanic extract of Ambrosia confertiflora DC (Asteraceae) inhibited Mtb. To isolate the compounds responsible for the mycobactericidal activity against clinical Mtb strains. The dichloromethanic extract of aerial parts of A. confertiflora was separated using chromatography columns. Mycobactericidal activity of the isolated compounds was evaluated using the Alamar Blue bioassay (128-16 μg/mL, 7 days). Cytotoxicity was tested against normal cell line L929 using the MTT ([3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium]) assay (100-3.125 μg/mL, 48 h). Compound structures were elucidated by 1H and 13C uni- and bidimensional NMR. Two sesquiterpene lactones (SQLs) with mycobactericidal activity were identified: santamarine and reynosin. Reynosin was the most active compound, with a minimal bactericidal concentration (MBC) of 128 μg/mL against the H37Rv, 366-2009 and 104-2010 Mtb strains and a minimal inhibitory concentration (MIC) of 64, 64, 128, 128 and 128 μg/mL against the H37Rv, 104-2010, 63-2009, 366-2009 and 430-2010 Mtb strains, respectively. Santamarine had MBCs of 128 μg/mL against the H3Rv and 104-2010 Mtb strains and MICs of 128 μg/mL against the H37Rv, 366-2009 and 104-2010 Mtb strains. We also isolated 1,10-epoxyparthenolide but only showed mycobacteriostatic activity (MIC 128 μg/mL) against the Mtb strain. Compounds were tested against the L929 cell line and the calculated selectivity index was <1. This is the first report of the mycobactericidal activity of these compounds against clinical Mtb strains. It is also the first report of the isolation of 1,10-epoxyparthenolide from A. confertiflora. The anti-mycobacterial activity of A. confertiflora was attributed to the SQLs identified.

  11. The anti-mycobacterial activity of Lantana camara a plant traditionally used to treat symptoms of tuberculosis in South-western Uganda.

    Science.gov (United States)

    Kirimuhuzya, Claude; Waako, Paul; Joloba, Moses; Odyek, Olwa

    2009-03-01

    Tuberculosis continues to be a devastating public health problem. Many communities in Uganda use medicinal plants to treat various infections, including respiratory tract infections. There are claims that some can treat tuberculosis. Verifying some of these claims could lead to discovery of lead compounds for development of a TB drug. Chloroform and methanol extracts of L. camara collected from South-western Uganda were screened against three strains of Mycobacterium tuberculosis using the agar-well diffusion method. H37Rv, the rifampicin-resistant TMC-331 and a non-resistant wild strain (28-25271). The MIC and MBC were determined using the Agar dilution method on Middle brook 7H11. The methanol extract showed the highest activity against all the three strains used, with zones of inhibition of 18.0-22.5 mm and MIC values of 20 µg/ml for H37Rv and 15 µg/ml for both TMC-331 and wild stain. The values for rifampicin were 1.0 µg/ml for both H37Rv and wild strain but rifampicin hardly showed any activity on TMC-331. The MBC value for the methanol extract of L. camara was 30µg/ml for the H37Rv, and 20µg/ml for both the TMC-331 and wild strains of M. tuberculosis. The MBC for rifampicin was 2.0µg/ml for both H37Rv and the wild strain. We conclude that L. camara contains principles active against M. tuberculosis, which merit further research.

  12. [Tuberculosis in compromised hosts].

    Science.gov (United States)

    2003-11-01

    Recent development of tuberculosis in Japan tends to converge on a specific high risk group. The proportion of tuberculosis developing particularly from the compromised hosts in the high risk group is especially high. At this symposium, therefore, we took up diabetes mellitus, gastrectomy, dialysis, AIDS and the elderly for discussion. Many new findings and useful reports for practical medical treatment are submitted; why these compromised hosts are predisposed to tuberculosis, tuberculosis diagnostic and remedial notes of those compromised hosts etc. It is an important question for the future to study how to prevent tuberculosis from these compromised hosts. 1. Tuberculosis in diabetes mellitus: aggravation and its immunological mechanism: Kazuyoshi KAWAKAMI (Department of Internal Medicine, Division of Infectious Diseases, Graduate School and Faculty of Medicine, University of the Ryukyus). It has been well documented that diabetes mellitus (DM) is a major aggravating factor in tuberculosis. The onset of this disease is more frequent in DM patients than in individuals with any underlying diseases. However, the precise mechanism of this finding remains to be fully understood. Earlier studies reported that the migration, phagocytosis and bactericidal activity of neutrophils are all impaired in DM patients, which is related to their reduced host defense to infection with extracellular bacteria, such as S. aureus and E. colli. Host defense to mycobacterial infection is largely mediated by cellular immunity, and Th1-related cytokines, such as IFN-gamma and IL-12, play a central role in this response. It is reported that serum level of these cytokines and their production by peripheral blood mononuclear cells (PBMC) are reduced in tuberculosis patients with DM, and this is supposed to be involved in the high incidence of tuberculosis in DM. Our study observed similar findings and furthermore indicated that IFN-gamma and IL-12 production by BCG-stimulated PBMC was lower

  13. Controlling the Seedbeds of Tuberculosis: Diagnosis and Treatment of Tuberculosis Infection

    Science.gov (United States)

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

    2015-01-01

    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 critical opportunity to interrupt tuberculosis transmission and reduce the global burden of tuberculosis disease. Programs focusing on single strategies rather than comprehensive programs that deliver an integrated arsenal for tuberculosis control may continue to struggle. Tuberculosis preventive therapy is a poorly utilized tool that is essential for controlling the reservoirs of disease that drive the current 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. This paper outlines challenges to implementation of preventive therapy and provides pragmatic suggestions for overcoming them. It further advocates for tuberculosis preventive therapy as the core of a renewed global 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, community engagement, and enhance sustainable large scale implementation of preventive therapy programs. PMID:26515679

  14. Alternative Quantiferon cytokines for diagnosis of children with active tuberculosis and HIV co-infection in Ghana.

    Science.gov (United States)

    Lundtoft, Christian; Awuah, Anthony Afum-Adjei; Nausch, Norman; Enimil, Anthony; Mayatepek, Ertan; Owusu-Dabo, Ellis; Jacobsen, Marc

    2017-06-01

    IFN-γ release assays (IGRAs) often present false-negative or indeterminate results in children with tuberculosis. HIV co-infection may contribute to decreased sensitivity of IGRAs by impairing T-cell IFN-γ expression. Measurement of alternative cytokines in QuantiFERON® (QFT) supernatants can circumvent the IFN-γ-dependency and may improve QFT sensitivity. We aimed to identify additional cytokines from QFT supernatants for detection of Mycobacterium tuberculosis infection in children with tuberculosis and HIV co-infection from Ghana. Concentrations of 18 cytokines in QFT supernatants from children (0-16 years) with tuberculosis concomitantly infected with HIV (n = 25) or without HIV (n = 24) from Ghana were measured using cytometric bead array (CBA). 29% of the children showed positive IFN-γ test results, and five cytokines, i.e., IL-6, IL-21, TNF-α, IL-1α and IP-10, detected M. tuberculosis infection with comparable or, for IL-6, with significantly higher sensitivity (59%). Increased age and HIV co-infection were associated with decreased cytokine induction, and especially IL-21 and IP-10 were less prevalent in HIV co-infected children with tuberculosis. Combined cytokine analyses increased proportions of positive tests, and a four-cytokine subset (i.e., IL-6, IL-21, IFN-γ, IL-1α) predicted 78% of the children with tuberculosis correctly. Combined evaluation of IFN-γ and alternative cytokines improved IGRA-sensitivity in children with tuberculosis.

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

    Directory of Open Access Journals (Sweden)

    Karen R Steingart

    2007-06-01

    Full Text Available BACKGROUND: The global tuberculosis epidemic results in nearly 2 million deaths and 9 million new cases of the disease a year. The vast majority of tuberculosis patients live in developing countries, where the diagnosis of tuberculosis relies on the identification of acid-fast bacilli on unprocessed sputum smears using conventional light microscopy. Microscopy has high specificity in tuberculosis-endemic countries, but modest sensitivity which varies among laboratories (range 20% to 80%. Moreover, the sensitivity is poor for paucibacillary disease (e.g., pediatric and HIV-associated tuberculosis. Thus, the development of rapid and accurate new diagnostic tools is imperative. Immune-based tests are potentially suitable for use in low-income countries as some test formats can be performed at the point of care without laboratory equipment. Currently, dozens of distinct commercial antibody detection tests are sold in developing countries. The question is "do they work?" METHODS AND FINDINGS: We conducted a systematic review to assess the accuracy of commercial antibody detection tests for the diagnosis of pulmonary tuberculosis. Studies from all countries using culture and/or microscopy smear for confirmation of pulmonary tuberculosis were eligible. Studies with fewer than 50 participants (25 patients and 25 control participants were excluded. In a comprehensive search, we identified 68 studies. The results demonstrate that (1 overall, commercial tests vary widely in performance; (2 sensitivity is higher in smear-positive than smear-negative samples; (3 in studies of smear-positive patients, Anda-TB IgG by enzyme-linked immunosorbent assay shows limited sensitivity (range 63% to 85% and inconsistent specificity (range 73% to 100%; (4 specificity is higher in healthy volunteers than in patients in whom tuberculosis disease is initially suspected and subsequently ruled out; and (5 there are insufficient data to determine the accuracy of most

  16. Ferritin structure from Mycobacterium tuberculosis: comparative study with homologues identifies extended C-terminus involved in ferroxidase activity.

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    Garima Khare

    Full Text Available Ferritins are recognized as key players in the iron storage and detoxification processes. Iron acquisition in the case of pathogenic bacteria has long been established as an important virulence mechanism. Here, we report a 3.0 Å crystal structure of a ferritin, annotated as Bacterioferritin B (BfrB, from Mycobacterium tuberculosis (Mtb, the causative agent of tuberculosis that continues to be one of the world's deadliest diseases. Similar to the other members of ferritin family, the Mtb BfrB subunit exhibits the characteristic fold of a four-helical bundle that possesses the ferroxidase catalytic centre. We compare the structure of Mtb BfrB with representatives of the ferritin family belonging to the archaea, eubacteria and eukarya. Unlike most other ferritins, Mtb BfrB has an extended C-terminus. To dissect the role of this extended C-terminus, truncated Mtb BfrB was purified and biochemical studies implicate this region in ferroxidase activity and iron release in addition to providing stability to the protein. Functionally important regions in a protein of known 3D-structure can be determined by estimating the degree of conservation of the amino-acid sites with its close homologues. Based on the comparative studies, we identify the slowly evolving conserved sites as well as the rapidly evolving variable sites and analyze their role in relation to structure and function of Mtb BfrB. Further, electrostatic computations demonstrate that although the electrostatic environment of catalytic residues is preserved within the family, extensive variability is exhibited by residues defining the channels and pores, in all likelihood keeping up with the diverse functions executed by these ferritins in varied environments.

  17. The use of mycobacterial interspersed repetitive unit typing and whole genome sequencing to inform tuberculosis prevention and control activities.

    Science.gov (United States)

    Gilbert, Gwendolyn L; Sintchenko, Vitali

    2013-07-01

    Molecular strain typing of Mycobacterium tuberculosis has been possible for only about 20 years; it has significantly improved our understanding of the evolution and epidemiology of Mycobacterium tuberculosis and tuberculosis disease. Mycobacterial interspersed repetitive unit typing, based on 24 variable number tandem repeat unit loci, is highly discriminatory, relatively easy to perform and interpret and is currently the most widely used molecular typing system for tuberculosis surveillance. Nevertheless, clusters identified by mycobacterial interspersed repetitive unit typing sometimes cannot be confirmed or adequately defined by contact tracing and additional methods are needed. Recently, whole genome sequencing has been used to identify single nucleotide polymorphisms and other mutations, between genotypically indistinguishable isolates from the same cluster, to more accurately trace transmission pathways. Rapidly increasing speed and quality and reduced costs will soon make large scale whole genome sequencing feasible, combined with the use of sophisticated bioinformatics tools, for epidemiological surveillance of tuberculosis.

  18. Tuberculose ativa entre profissionais de saúde em Portugal Active tuberculosis among health care workers in Portugal

    Directory of Open Access Journals (Sweden)

    José Castela Torres da Costa

    2011-10-01

    Full Text Available OBJETIVO: Determinar a incidência de tuberculose (TB ativa em uma coorte de profissionais de saúde (PS. MÉTODOS: Estudo descritivo dos casos de TB ativa identificados entre 2005 e 2010 no rastreio de medicina do trabalho efetuado em 6.112 PS. Casos de TB ativa foram definidos como aqueles com identificação de Mycobacterium tuberculosis por microscopia direta ou cultura; aqueles com sintomas ou sinais clínicos de TB e granuloma necrotizante, detectado por histologia; e aqueles com achados radiológicos consistentes com TB ativa. RESULTADOS: Dos 6.112 PS avaliados, houve 62 casos de TB ativa (TB pulmonar, em 43; TB pleural, em 15; TB ganglionar, em 2; TB do pericárdio, em 1; TB cutânea, em 1. Sete PS estavam assintomáticos no momento do diagnóstico. Dos 62 casos de TB ativa, a doença ocorreu nos primeiros 10 anos de exposição ocupacional em 48 e nos primeiros 5 anos em 36. A maioria dos casos verificou-se em médicos e enfermeiros (22 e 21, respectivamente. CONCLUSÕES: O impacto da TB em PS em Portugal é elevado. Os médicos e enfermeiros são os PS com o maior risco de desenvolver TB ativa. Tal como relatado em estudos prévios, parece haver um risco mais elevado de desenvolver essa doença nos primeiros anos de exposição. Em países de elevada incidência, o rastreio de TB nos PS é importante no controle da transmissão dessa doença.OBJECTIVE: To determine the incidence of active tuberculosis (TB in a cohort of health care workers (HCWs. METHODS: Descriptive study of active TB cases identified in an occupational health screening of 6,112 HCWs between 2005 and 2010. Cases of active TB were defined as those in which Mycobacterium tuberculosis was identified by direct microscopy or culture; those in which there were symptoms or clinical signs of TB and necrotizing granuloma, as detected by histology; and those in which the radiological findings were consistent with active TB. RESULTS: Among the 6,112 HCWs evaluated, we identified

  19. Serodiagnostic efficacy of Mycobacterium tuberculosis 30/32-kDa mycolyl transferase complex, ESAT-6, and CFP-10 in patients with active tuberculosis.

    Science.gov (United States)

    Kumar, Gavish; Dagur, Pradeep Kumar; Singh, Prashant Kumar; Shankar, Hari; Yadav, Virendra S; Katoch, Vishwa M; Bajaj, Bharat; Gupta, Rajesh; Sengupta, Utpal; Joshi, Beenu

    2010-02-01

    Elimination of tuberculosis (TB) largely depends upon definitive rapid diagnosis and treatment. Widely used diagnostic tests do not qualify for use in a developing country due to lack of either desired accuracy or their cost. In the present study an enzyme-linked immunosorbent assay was used to evaluate the diagnostic potential of an immuno-dominant 30/32-kDa mycolyl transferase complex (Ag85 complex) and Mycobacterium tuberculosis-specific proteins (ESAT-6 and CFP-10) of the RD1 region. Higher sensitivity (84.1%) with Ag85 complex was observed compared with ESAT-6 (64.9%) and CFP-10 (66%), with almost similar specificity (Ag85: 85.2%, ESAT-6: 88.9%, CFP-10: 85.2%), whereas the individual components of Ag85 complex, i.e. Ag85A, Ag85B, and Ag85C, showed sensitivities of 44.6, 34, and 80.9% and specificities of 55.6, 74.1, and 40.7% respectively. A cocktail of Ag85 complex, ESAT-6, CFP-10, Ag85A, Ag85B, and Ag85C antigens also could not help in increasing either sensitivity (51.1%) or specificity (85.2%). Furthermore, immunoblot analysis using clinical isolates as well as a standard strain (H37Rv) of M. tuberculosis also showed strong reactivity of sera from TB patients to Ag85 complex and, to a lesser extent, also to ESAT-6. To conclude, use of Ag85 complex along with ESAT-6 and CFP-10 seems to be promising in minimizing the heterogeneous sero-responses of adult TB cases.

  20. Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in HIV-positive adults.

    Science.gov (United States)

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

    2016-05-10

    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. 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). 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). 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 evaluated for TB, and a lower quality reference

  1. Synthesis and evaluation of (S,S)-N,N'-bis-[3-(2,2',6,6'-tetramethylbenzhydryloxy)-2-hydroxy-propyl]-ethylenediamine (S2824) analogs with anti-tuberculosis activity.

    Science.gov (United States)

    Zhang, Xuelian; Hu, Yanwei; Chen, Shudan; Luo, Rusong; Yue, Jun; Zhang, Ying; Duan, Wenhu; Wang, Honghai

    2009-11-01

    In order to identify new and potent candidate drugs to treat tuberculosis, a library of compounds was screened, and (S,S)-N,N'-bis-[3-(2,2',6,6'-tetramethylbenzhydryloxy)-2-hydroxy-propyl]-ethylenediamine (S2824) was identified as a hit in the screen. This research discusses our efforts to synthesize and test 30 analogs of this hit for activity against Mycobacterium tuberculosis. Two compounds with homopiperazine ring possess high in vitro activity against drug sensitive and resistant M. tuberculosis with MICs 0.78-3.13 microg/mL (or 1.22-4.88 microM).

  2. Continuous treatment with recombinant Mycobacterium tuberculosis CFP-10-ESAT-6 protein activated human monocyte while deactivated LPS-stimulated macrophage.

    Science.gov (United States)

    Feng, Yonghong; Yang, Xin; Liu, Zhonghua; Liu, Yaoting; Su, Bo; Ding, Yuansheng; Qin, Lianhua; Yang, Hua; Zheng, Ruijuan; Hu, Zhongyi

    2008-01-18

    Influence of the recombinant culture filtered protein 10 (CFP-10) and early-secreted antigenic target 6kDa protein (ESAT-6) (r-CFP-10-ESAT-6, rCE) of Mycobacterium tuberculosis (Mtb) on human monocyte and macrophage activation was investigated using human monocyte, monocyte like THP-1 cell line and monocyte derived macrophage (MDM). rCE solely enhanced TNF-alpha release from human monocytes and THP-1 cells in a dose- and time-dependent manner. rCE enhanced expression of CD80 and CD40, it also synergized with IFN-gamma in induction of TNF-alpha production and HLA-DR expression. Pharmacological agents that selectively inhibit mitogen activated protein kinase activation markedly suppressed rCE-induced TNF- alpha release. However, continuous presence of rCE (>72h) during monocyte to macrophage differentiation inhibited macrophage response to LPS stimulation. Collectively, these data suggest that rCE might have differential influence on monocyte and macrophage activation, which might be correlated with Mtb immune evasion.

  3. Three new phenylpropanoids from the roots of Piper taiwanense and their inhibitory activities on platelet aggregation and Mycobacterium tuberculosis.

    Science.gov (United States)

    Chen, Si; Cheng, Ming-Jen; Wu, Chin-Chung; Peng, Chien-Fang; Huang, Hung-Yi; Chang, Hsun-Shuo; Wang, Chyi-Jia; Chen, Ih-Sheng

    2014-05-01

    Bioassay-guided fractionation of the active AcOEt-soluble fraction from the roots of Piper taiwanense has led to the isolation of two new phenylpropanoids, taiwanensols A and B (1 and 2, resp.), a new natural product, taiwanensol C (3), and 3-acetoxy-4-hydroxy-1-allylbenzene (4). The compounds were obtained as two isomer mixtures (1/2 and 3/4, resp.). Their structures were elucidated by spectroscopic analyses, including 1D- and 2D-NMR spectroscopy and mass spectrometry, and by the comparison of their NMR data with those of related compounds. Compounds 1-4 were evaluated for their antiplatelet and antitubercular activities. The mixtures 1/2 and 3/4 showed potent inhibitory activities against platelet aggregation induced by collagen, with IC50 values of 35.2 and 8.8 μM, respectively. In addition, 1/2 and 3/4 showed antitubercular activities against Mycobacterium tuberculosis H37Rv, with MIC values of 30.0 and 48.0 μg/ml, respectively. Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.

  4. Análise de restrição enzimática do gene hsp65 de isolados clínicos de pacientes com suspeita de tuberculose pulmonar em Teresina, Piauí Restriction enzyme analysis of the hsp65 gene in clinical isolates from patients suspected of having pulmonary tuberculosis in Teresina, Brazil

    Directory of Open Access Journals (Sweden)

    Maria das Graças Motta e Bona

    2011-10-01

    suspected of having pulmonary tuberculosis and to determine the impact that the acquisition of this knowledge has on the therapeutic approach. METHODS: We evaluated 106 patients suspected of having pulmonary tuberculosis and referred to the pulmonology department of a public hospital in the city of Teresina, Brazil. Morning sputum specimens were evaluated for the presence of mycobacteria by sputum smear microscopy and culture. We used PCR and restriction enzyme analysis of the hsp65 gene (PRA-hsp65 to identify the strains of mycobacteria isolated in culture. RESULTS: A total of 206 sputum samples were analyzed. Patient ages ranged from 15 to 87 years, and 67% were male. There was cough in 100% of the cases. The predominant radiographic pattern was moderate disease, observed in 70%. Smear positivity was 76%, and isolation in culture occurred in 91% of the cultures. Traditional tests identified nontuberculous mycobacteria (NTM in 9% of the isolates. The PRA-hsp65 method confirmed these data, showing seven band patterns that were able to identify the isolated species of NTM: Mycobacterium kansasii; M. abscessus 1; M. abscessus 2; M. smegmatis; M. flavescens 1; M. gordonae 5; and M. gordonae 7. All of the patients with NTM were over 60 years of age, and bronchiectasis was seen in 88% of the X-rays. There were two cases of reinfection, initially attributed to M. abscessus and M. kansasii. CONCLUSIONS: In immunocompetent patients, NTM can infect the lungs. It is important to identify the specific NTM in order to establish the correct diagnosis and choose the most appropriate therapeutic regimen. The PRA-hsp65 method is useful in identifying NTM species and can be implemented in molecular biology laboratories that do not specialize in the identification of mycobacteria.

  5. [Smoking and adherence to anti-tuberculosis treatment].

    Science.gov (United States)

    Underner, M; Perriot, J; Peiffer, G; Meurice, J-C; Dautzenberg, B

    2016-02-01

    Smoking and tuberculosis are two major public health issues. Tobacco smoke increases the risk of Mycobacterium tuberculosis infection and the severity of pulmonary tuberculosis. Active smoking increases the risk of relapse of pulmonary and extra-pulmonary tuberculosis after treatment; smokers are less adherent to anti-tuberculosis treatment. Smoking cessation represent a means of controlling the tuberculosis epidemic in developing countries. This general review identified 17 studies in the international literature on the link between active smoking and the adherence to anti-tuberculosis treatment. It highlights a positive association between smoking and a lack of adherence to anti-tuberculosis treatment. This justifies the systematic application of aid to stopping smoking in smokers with tuberculosis. Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  6. Modern lineages of Mycobacterium tuberculosis in Addis Ababa, Ethiopia: implications for the tuberculosis control programe.

    Science.gov (United States)

    Mihret, A; Bekele, Y; Aytenew, M; Assefa, Y; Abebe, M; Wassie, L; Loxton, G A; Yamuah, L; Aseffa, A; Walzl, G; Howe, R

    2012-09-01

    The genotyping of Mycobacterium tuberculosis strains is important to have unique insights into the dissemination dynamics and evolutionary genetics of this pathogen and for TB control as it allows the detection of suspected outbreaks and the tracing of transmission chains. To characterize M. tuberculois isolates collected from newly diagnosed pulmonary TB patients in Addis Ababa One hundred and ninety two sputum samples were cultured on Löwenstein-Jensen (LJ) slants and isolates were heat killed for molecular genotyping. The isolates were characterized using spoligotyping and were compared with the International SpoIDB4 database. T genotype constitutes the most predominant in our study (95, 49.5%) followed by the CAS genotype (42, 21.9%). Other genotypes found were Haarlem (H) (24, 12.5%), the LAM (3, 1.5%), the Beijing genotype (1, 0.5%); four (2.1%) isolates were designated as Unknown. All the isolates belong to the modern lineage and there is high clustering in the genotype of isolates which indicated the presence of recent TB transmission. Therefore, the Tuberculosis Control Programme needs to do more in advocating and strengthening the health system for early detection and treatment of active TB cases as delay in treatment is the key factor in disease transmission.

  7. GeneXpert MTB/RIF Testing in the Management of Patients with Active Tuberculosis; A Real Life Experience from Saudi Arabia.

    Science.gov (United States)

    Omrani, Ali S; Al-Otaibi, Mohammed F; Al-Ateah, Souad M; Al-Onazi, Fahad M; Baig, Kamran; El-Khizzi, Noura A; Albarrak, Ali M

    2014-03-01

    GeneXpert MTB/RIF is a real-time PCR assay with established diagnostic performance in pulmonary and extra-pulmonary forms of tuberculosis. The aim of this study was to assess the contribution of GeneXpert MTB/RIF assay to the management of patients with any form of active tuberculosis in a single large tertiary center in Saudi Arabia, with a special focus on the impact on time to start of antituberculous therapy compared with Ziehl-Neelsen (ZN) smears and mycobacterial cultures. Clinical, radiological and laboratory records for all patients who were commenced on antituberculous therapy between March 2011 and February 2013 were retrospectively reviewed. A total of 140 patients were included, 38.6% of which had pulmonary tuberculosis. GeneXpert MTB/RIF was requested for only 39.2% of patients and was the only reason for starting antituberculous therapy for only 12.1%. The median time to a positive GeneXpert MTB/RIF result was 0 days (IQR 3) compared with 0 day (IQR 1) for smear microscopy (P > 0.999) and 22 days (IQR 21) for mycobacterial cultures (P MTB/RIF result. In a setting wherein physicians are highly experienced in the diagnosis and treatment of tuberculosis, GeneXpert MTB/RIF was remarkably under-utilized and had only a limited impact on decisions related to starting or stopping antituberculous therapy. Cost-effectiveness and clinical utility of routine testing of all smear-negative clinical samples submitted for tuberculosis investigations by GeneXpert MTB/RIF warrant further study.

  8. Characterization of phosphofructokinase activity in Mycobacterium tuberculosis reveals that a functional glycolytic carbon flow is necessary to limit the accumulation of toxic metabolic intermediates under hypoxia.

    Directory of Open Access Journals (Sweden)

    Wai Yee Phong

    Full Text Available Metabolic versatility has been increasingly recognized as a major virulence mechanism that enables Mycobacterium tuberculosis to persist in many microenvironments encountered in its host. Glucose is one of the most abundant carbon sources that is exploited by many pathogenic bacteria in the human host. M. tuberculosis has an intact glycolytic pathway that is highly conserved in all clinical isolates sequenced to date suggesting that glucose may represent a non-negligible source of carbon and energy for this pathogen in vivo. Fructose-6-phosphate phosphorylation represents the key-committing step in glycolysis and is catalyzed by a phosphofructokinase (PFK activity. Two genes, pfkA and pfkB have been annotated to encode putative PFK in M. tuberculosis. Here, we show that PFKA is the sole PFK enzyme in M. tuberculosis with no functional redundancy with PFKB. PFKA is required for growth on glucose as sole carbon source. In co-metabolism experiments, we report that disruption of the glycolytic pathway at the PFK step results in intracellular accumulation of sugar-phosphates that correlated with significant impairment of the cell viability. Concomitantly, we found that the presence of glucose is highly toxic for the long-term survival of hypoxic non-replicating mycobacteria, suggesting that accumulation of glucose-derived toxic metabolites does occur in the absence of sustained aerobic respiration. The culture medium traditionally used to study the physiology of hypoxic mycobacteria is supplemented with glucose. In this medium, M. tuberculosis can survive for only 7-10 days in a true non-replicating state before death is observed. By omitting glucose in the medium this period could be extended for up to at least 40 days without significant viability loss. Therefore, our study suggests that glycolysis leads to accumulation of glucose-derived toxic metabolites that limits long-term survival of hypoxic mycobacteria. Such toxic effect is exacerbated when

  9. Tuberculosis control activities before and after Hurricane Sandy--northeast and mid-Atlantic states, 2012.

    Science.gov (United States)

    2013-03-22

    On October 29, 2012, Hurricane Sandy struck the U.S. northeast and mid-Atlantic seaboard; the effects of the storm extended to southeastern and midwestern states and to eastern Canada. At the time, 1,899 residents in the most affected areas were undergoing treatment for tuberculosis (TB) disease or infection. To ascertain the operational abilities of state and local TB programs during and after the storm and to determine whether lessons learned from a previous hurricane were effective in ensuring continuity of TB patient care, CDC interviewed staff members at all of the affected state and city TB control programs, including those in areas with power outages and flooded streets, tunnels, and subway lines. The interviews determined that continuity of care for TB patients in programs affected by Hurricane Sandy was better preserved than it had been during and after Hurricane Katrina in August 2005. This improvement might be attributed to 1) preparedness measures learned from Hurricane Katrina (e.g., preparing line lists of patients, providing patients with as-needed medications, and making back-up copies of patient records in advance of the storm) and 2) less widespread displacement of persons after Hurricane Sandy than occurred after Hurricane Katrina. Maintaining readiness among clinicians and TB control programs to respond to natural disasters remains essential to protecting public health and preserving TB patients' continuity of care.

  10. Differential expression of antimicrobial peptides in active and latent tuberculosis and its relationship with diabetes mellitus.

    Science.gov (United States)

    Gonzalez-Curiel, Irma; Castañeda-Delgado, Julio; Lopez-Lopez, Nallely; Araujo, Zaida; Hernandez-Pando, Rogelio; Gandara-Jasso, Benjamin; Macias-Segura, Noe; Enciso-Moreno, Antonio; Rivas-Santiago, Bruno

    2011-08-01

    Tuberculosis (TB) is one of the most important infectious diseases, causing 1.8 million deaths annually worldwide. This problem has increased because of the association with human immmunodeficiency virus and diabetes mellitus type 2, mainly in developing countries. In the past few years it has been highlighted the significance of antimicrobial peptides in the immunopathogenesis of TB ex vivo and in experimental models studies. In this study we analyzed the expression of CAMP, DEFA1, DEFB4, and DEFB103A in patients with latent TB and progressive TB with and without comorbidity with diabetes mellitus type 2. Antimicrobial peptide gene expression increased during progressive TB, which could be used as a biomarker for reactivation. By contrast, patients with diabetes mellitus type 2 have lower antimicrobial peptides gene expression, suggesting that the lack of its proper production in these patients contribute to enhance the risk for TB reactivation. Copyright © 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  11. Characterization of suspected illegal skin whitening cosmetics.

    Science.gov (United States)

    Desmedt, B; Van Hoeck, E; Rogiers, V; Courselle, P; De Beer, J O; De Paepe, K; Deconinck, E

    2014-03-01

    An important group of suspected illegal cosmetics consists of skin bleaching products, which are usually applied to the skin of the face, hands and décolleté for local depigmentation of hyper pigmented regions or more importantly, for a generalized reduction of the skin tone. These cosmetic products are suspected to contain illegal active substances that may provoke as well local as systemic toxic effects, being the reason for their banning from the EU market. In that respect, illegal and restricted substances in cosmetics, known to have bleaching properties, are in particular hydroquinone, tretinoin and corticosteroids. From a legislative point of view, all cosmetic products containing a prohibited whitening agent are illegal and must be taken off the EU market. A newly developed screening method using ultra high performance liquid chromatography-time off flight-mass spectrometry allows routine analysis of suspected products. 163 suspected skin whitening cosmetics, collected by Belgian inspectors at high risk sites such as airports and so-called ethnic cosmetic shops, were analyzed and 59% were classified as illegal. The whitening agents mostly detected were clobetasol propionate and hydroquinone, which represent a serious health risk when repeatedly and abundantly applied to the skin. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. [CLINICAL INVESTIGATION OF TUBERCULOSIS PATIENTS IN A GENERAL HOSPITAL LACKING A TUBERCULOSIS WARD IN WESTERN AICHI PREFECTURE.

    Science.gov (United States)

    Nakao, Makoto; Muramatsu, Hideki; Sone, Kazuki; Suzuki, Yuto; Kagawa, Yusuke; Kurokawa, Ryota; Aoki, Sachiko; Okawa, Hironaga; Sato, Hidefumi

    2016-05-01

    With the recent decrease in the number of tuberculosis wards and increase in elderly tuber- culosis patients with comorbidities, the role of regional refer- ral hospitals has become more important in tuberculosis management. [Objective]. This study aimed to assess the current state of tuberculosis management and related issues in a general hospital lacking a tuberculosis ward. [Methods] We retrospectively evaluated the clinical char- acteristics and course of patients diagnosed with tuberculosis by culture testing from April 2008 to March 2015 at Kainan Hospital. [Results] A total of 146 patients (83 males and 63 females; mean age 76, range 18-94 years) were diagnosed with active tuberculosis. Of these, 129 were diagnosed with pulmonary tuberculosis (23 had pulmonary tuberculosis with pleurisy), and 17 patients were diagnosed with extrapulmonary tuber- culosis. The chief complains were cough/sputum in 40 cases, fever in 24, and no symptoms in 36. Associated major comorbidities included diabetes mellitus, chronic kidney disease, and malignancy. In 33 patients, over 30 days were required to diagnose tuberculosis after initial evaluation. Drug-resistant strains were detected in 14 patients. 57 were diagnosed with smear-positive pulmonary tuberculosis, and 66 were transferred to a tuberculosis hospital. Modify in anti- tuberculosis therapy due to adverse reactions were reported in 27 patients. [Conclusion] This study evaluated the current state of tuberculosis management in our hospital. Further educational guidance regarding tuberculosis is needed for the hospital staff, and is important for improvement of tuberculosis management in our hospital.

  13. Diagnosis of pediatric tuberculosis using The Indonesian National Concencus for Pediatric Tuberculosis

    Directory of Open Access Journals (Sweden)

    Heda Melinda D. Nataprawira

    2001-08-01

    Full Text Available Diagnosing tuberculosis (TB in children correctly is critical to appropriate treatment. However, diagnosing TB in children may be difficult and can be imprecise. As our national TB control program has not adequately covered TB in children and adult TB cases still in high rank, our national consensus for pediatric population may facilitate TB diagnosed especially in the field. This cross sectional study as part of longitudinal cohort study of epidemiology of Respiratory Syncitial Virus (RSV in Indonesia (still ongoing was conducted to know whether criteria used in the algorithm in the consensus compatible to suspected TB diagnosis. The study covered 1000 children under five randomly selected in two districts (Cikutra and Ujung Berung Indah located in West Java. By using algorithm of The Indonesian National Consensus For Pediatric Tuberculosis (INCPT with history of known or suspected adult source of TB or early reaction of BCG vaccination and certain general clinical symptoms associated TB as entry criteria for a higher index of suspicion, we diagnosed suspected TB in 57 children. We found that, history of known or suspected adult source of TB and certain general clinical symptoms are two main criteria for suspected TB diagnosis. It appeared that Mantoux test gave a smallest contribution to the diagnosis of suspected TB in the field. No other criterium except known or suspected adult source of TB fulfilled for other five children and prophylactic treatment for TB were given. Those children with suspected TB were given oral anti-tuberculosis (OAT by Directly Observed Treatment Short course (DOTS done by local trained persons.

  14. Use of amplified Mycobacterium tuberculosis direct test (Gen-probe Inc., San Diego, CA, USA in the diagnosis of tubercular synovitis and early arthritis of knee joint

    Directory of Open Access Journals (Sweden)

    Vinay Kumar Aggarwal

    2012-01-01

    Conclusion: AMTDT or Genprobe is a rapid diagnostic test for early diagnosis of tubercular arthritis, but has low sensitivity in knee joint tuberculosis. Nuclear amplification tests are still far from being a single promising alternative to conventional tests in cases of joint tuberculosis. Routine use of arthroscopic biopsies in all suspected cases is helpful in the early diagnosis of knee joint tuberculosis.

  15. Diagnostic yield of active case finding for tuberculosis and HIV at the household level in slums in Haiti.

    Science.gov (United States)

    Rivera, V R; Jean-Juste, M-A; Gluck, S C; Reeder, H T; Sainristil, J; Julma, P; Peck, M; Joseph, P; Ocheretina, O; Perodin, C; Secours, R; Duran-Mendicuti, M; Hashiguchi, L; Cremieux, P Y; Koenig, S P; Pape, J W

    2017-11-01

    Haiti has the highest burden of tuberculosis (TB) in the Americas, with an estimated prevalence of 254 per 100 000 population. The Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic Infections (Groupe Haïtien d'Etude du Sarcome de Kaposi et des Infections Opportunistes, GHESKIO) conducted active case finding (ACF) for TB at the household level in nine slums in Port-au-Prince. We report on the prevalence of undiagnosed TB detected through GHESKIO's ACF campaign. From 1 August 2014 to 31 July 2015, we conducted a retrospective cohort analysis using GHESKIO's ACF campaign data. All individuals who reported chronic cough (cough 2 weeks) were tested for TB at GHESKIO, and those aged 10 years were included in the analyses. Of 104 097 individuals screened in the community, 5598 (5%) reported chronic cough and satisfied the study inclusion criteria. A total of 1110 (20%) were diagnosed with active TB disease (prevalence of 1066/100 000). Of the 5472 (98%) patients tested for human immunodeficiency virus (HIV), 528 (10%) were HIV-positive; 143 (3%) patients were diagnosed with both diseases. Household-level screening for cough with TB and HIV testing for symptomatic patients was a high-yield strategy, leading to the detection of a prevalence of undiagnosed disease exceeding national estimates by more than four-fold for TB, and by five-fold for HIV.

  16. Risk of Active Tuberculosis among Index Case of Householders-A Long-Term Assessment after the Conventional Contacts Study.

    Science.gov (United States)

    Puma, Daniela V; Pérez-Quílez, Olga; Roure, Sílvia; Martínez-Cuevas, Octavio; Bocanegra, Cristina; Feijoo-Cid, Maria; Valerio, Lluís

    2017-03-01

    The aim of this study was to determine the incidence of active tuberculosis (TB) among household contacts of TB-index cases diagnosed during a 7-year period in a public Primary Care Center located in a high-incidence area. A retrospective cohort study was performed. Data collection was based on the capture-recapture method; the two main sources crossed information from TB-index and contact cases from the El Fondo Primary Care Center (Santa Coloma de Gramenet, Spain) and their reports to the National Epidemiologic Surveillance Service. Variables were divided into demographic and health data (result of the Mantoux test, chest X-ray, presence of risk factors, and indication for chemoprophylaxis). Community nurses identified 103 household contacts that underwent the conventional contact study. Overall, 60.19% were male; the mean age was 29.08 years. Only one case of secondary active TB was found, representing an incidence of 0.56% per TB-index case and year. The incidence of new secondary TB among household contacts with TB-index cases was of a case. Nevertheless, a long-term follow-up of these householders beyond the conventional contacts study should be considered in areas with higher incidences of TB or among specific high-risk populations. © 2016 Wiley Periodicals, Inc.

  17. Indoor air pollution from secondhand tobacco smoke, solid fuels, and kerosene in homes with active tuberculosis disease in South Africa.

    Science.gov (United States)

    Elf, Jessica L; Eke, Onyinyechi; Rakgokong, Modiehi; Variava, Ebrahim; Baliram, Yudesh; Motlhaoleng, Katlego; Lebina, Limakatso; Shapiro, Adrienne E; Breysse, Patrick N; Golub, Jonathan E; Martinson, Neil

    2017-11-13

    Secondhand tobacco smoke (SHS), use of solid fuels, and kerosene may play an important role in perpetuating the tuberculosis (TB) epidemic. The purpose of this study was to explore the prevalence of household air pollution (HAP) from these sources in homes of someone with TB in a high HIV-prevalence setting. A convenience sample of homes and household members participating in an ongoing active case-finding study in Matlosana district townships surrounding Klerksdorp, South Africa were included. We found a high prevalence of air pollution from SHS, solid fuels, and kerosene among individuals in homes with a case of prevalent active TB disease in Klerksdorp, South Africa. Adults in 40% of homes reported a daily smoker in the home, and 70% of homes had detectable air nicotine. In homes with a history of previous TB (prior to but not including the index case) as compared to those without previous TB, both SHS (83% vs. 65%, respectively) and solid/kerosene fuel use for more than 1 h/day (27% vs. 21%, respectively) were more prevalent. Larger studies are needed to estimate the risk of TB from these types of air pollution in HIV infected individuals and settings with high HIV prevalence.

  18. Implications of binding mode and active site flexibility for inhibitor potency against the salicylate synthase from Mycobacterium tuberculosis.

    Science.gov (United States)

    Chi, Gamma; Manos-Turvey, Alexandra; O'Connor, Patrick D; Johnston, Jodie M; Evans, Genevieve L; Baker, Edward N; Payne, Richard J; Lott, J Shaun; Bulloch, Esther M M

    2012-06-19

    MbtI is the salicylate synthase that catalyzes the first committed step in the synthesis of the iron chelating compound mycobactin in Mycobacterium tuberculosis. We previously developed a series of aromatic inhibitors against MbtI based on the reaction intermediate for this enzyme, isochorismate. The most potent of these inhibitors had hydrophobic substituents, ranging in size from a methyl to a phenyl group, appended to the terminal alkene of the enolpyruvyl group. These compounds exhibited low micromolar inhibition constants against MbtI and were at least an order of magnitude more potent than the parental compound for the series, which carries a native enolpyruvyl group. In this study, we sought to understand how the substituted enolpyruvyl group confers greater potency, by determining cocrystal structures of MbtI with six inhibitors from the series. A switch in binding mode at the MbtI active site is observed for inhibitors carrying a substituted enolpyruvyl group, relative to the parental compound. Computational studies suggest that the change in binding mode, and higher potency, is due to the effect of the substituents on the conformational landscape of the core inhibitor structure. The crystal structures and fluorescence-based thermal shift assays indicate that substituents larger than a methyl group are accommodated in the MbtI active site through significant but localized flexibility in the peptide backbone. These findings have implications for the design of improved inhibitors of MbtI, as well as other chorismate-utilizing enzymes from this family.

  19. Field assessment of a model tuberculosis outbreak response plan for low-incidence areas

    Directory of Open Access Journals (Sweden)

    Pascopella Lisa

    2007-10-01

    Full Text Available Abstract Background For a regional project in four low-incidence states, we designed a customizable tuberculosis outbreak response plan. Prior to dissemination of the plan, a tuberculosis outbreak occurred, presenting an opportunity to perform a field assessment of the plan. The purpose of the assessment was to ensure that the plan included essential elements to help public health professionals recognize and respond to outbreaks. Methods We designed a semi-structured questionnaire and interviewed all key stakeholders involved in the response. We used common themes to assess validity of and identify gaps in the plan. A subset of participants provided structured feedback on the plan. Results We interviewed 11 public health and six community stakeholders. The assessment demonstrated that (1 almost all of the main response activities were reflected in the plan; (2 the plan added value by providing a definition of a tuberculosis outbreak and guidelines for communication and evaluation. These were areas that lacked written protocols during the actual outbreak response; and (3 basic education about tuberculosis and the interpretation and use of genotyping data were important needs. Stakeholders also suggested adding to the plan questions for evaluation and a section for specific steps to take when an outbreak is suspected. Conclusion An interactive field assessment of a programmatic tool revealed the value of a systematic outbreak response plan with a standard definition of a tuberculosis outbreak, guidelines for communication and evaluation, and response steps. The assessment highlighted the importance of education and training for tuberculosis in low-incidence areas.

  20. In Vitro Activity of Copper(II) Complexes, Loaded or Unloaded into a Nanostructured Lipid System, against Mycobacterium tuberculosis

    Science.gov (United States)

    da Silva, Patricia B.; de Souza, Paula C.; Calixto, Giovana Maria Fioramonti; Lopes, Erica de O.; Frem, Regina C. G.; Netto, Adelino V. G.; Mauro, Antonio E.; Pavan, Fernando R.; Chorilli, Marlus

    2016-01-01

    Tuberculosis (TB) is an infectious disease caused mainly by the bacillus Mycobacterium tuberculosis (Mtb), presenting 9.5 million new cases and 1.5 million deaths in 2014. The aim of this study was to evaluate a nanostructured lipid system (NLS) composed of 10% phase oil (cholesterol), 10% surfactant (soy phosphatidylcholine, sodium oleate), and Eumulgin® HRE 40 ([castor oil polyoxyl-40-hydrogenated] in a proportion of 3:6:8), and an 80% aqueous phase (phosphate buffer pH = 7.4) as a tactic to enhance the in vitro anti-Mtb activity of the copper(II) complexes [CuCl2(INH)2]·H2O (1), [Cu(NCS)2(INH)2]·5H2O (2) and [Cu(NCO)2(INH)2]·4H2O (3). The Cu(II) complex-loaded NLS displayed sizes ranging from 169.5 ± 0.7095 to 211.1 ± 0.8963 nm, polydispersity index (PDI) varying from 0.135 ± 0.0130 to 0.236 ± 0.00100, and zeta potential ranging from −0.00690 ± 0.0896 to −8.43 ± 1.63 mV. Rheological analysis showed that the formulations behave as non-Newtonian fluids of the pseudoplastic and viscoelastic type. Antimycobacterial activities of the free complexes and NLS-loaded complexes against Mtb H37Rv ATCC 27294 were evaluated by the REMA methodology, and the selectivity index (SI) was calculated using the cytotoxicity index (IC50) against Vero (ATCC® CCL-81), J774A.1 (ATCC® TIB-67), and MRC-5 (ATCC® CCL-171) cell lines. The data suggest that the incorporation of the complexes into NLS improved the inhibitory action against Mtb by 52-, 27-, and 4.7-fold and the SI values by 173-, 43-, and 7-fold for the compounds 1, 2 and 3, respectively. The incorporation of the complexes 1, 2 and 3 into the NLS also resulted in a significant decrease of toxicity towards an alternative model (Artemia salina L.). These findings suggest that the NLS may be considered as a platform for incorporation of metallic complexes aimed at the treatment of TB. PMID:27196901

  1. In Vitro Activity of Copper(II Complexes, Loaded or Unloaded into a Nanostructured Lipid System, against Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Patricia B. da Silva

    2016-05-01

    Full Text Available Tuberculosis (TB is an infectious disease caused mainly by the bacillus Mycobacterium tuberculosis (Mtb, presenting 9.5 million new cases and 1.5 million deaths in 2014. The aim of this study was to evaluate a nanostructured lipid system (NLS composed of 10% phase oil (cholesterol, 10% surfactant (soy phosphatidylcholine, sodium oleate, and Eumulgin® HRE 40 ([castor oil polyoxyl-40-hydrogenated] in a proportion of 3:6:8, and an 80% aqueous phase (phosphate buffer pH = 7.4 as a tactic to enhance the in vitro anti-Mtb activity of the copper(II complexes [CuCl2(INH2]·H2O (1, [Cu(NCS2(INH2]·5H2O (2 and [Cu(NCO2(INH2]·4H2O (3. The Cu(II complex-loaded NLS displayed sizes ranging from 169.5 ± 0.7095 to 211.1 ± 0.8963 nm, polydispersity index (PDI varying from 0.135 ± 0.0130 to 0.236 ± 0.00100, and zeta potential ranging from −0.00690 ± 0.0896 to −8.43 ± 1.63 mV. Rheological analysis showed that the formulations behave as non-Newtonian fluids of the pseudoplastic and viscoelastic type. Antimycobacterial activities of the free complexes and NLS-loaded complexes against Mtb H37Rv ATCC 27294 were evaluated by the REMA methodology, and the selectivity index (SI was calculated using the cytotoxicity index (IC50 against Vero (ATCC® CCL-81, J774A.1 (ATCC® TIB-67, and MRC-5 (ATCC® CCL-171 cell lines. The data suggest that the incorporation of the complexes into NLS improved the inhibitory action against Mtb by 52-, 27-, and 4.7-fold and the SI values by 173-, 43-, and 7-fold for the compounds 1, 2 and 3, respectively. The incorporation of the complexes 1, 2 and 3 into the NLS also resulted in a significant decrease of toxicity towards an alternative model (Artemia salina L.. These findings suggest that the NLS may be considered as a platform for incorporation of metallic complexes aimed at the treatment of TB.

  2. Exploring the iron metabolism in multidrug resistant tuberculosis ...

    African Journals Online (AJOL)

    The iron metabolism plays a key role in the progression of active Tuberculosis. Several studies have shown a link between iron metabolism disorders an active tuberculosis. The aim of this study was to explore the iron metabolism of 100 patients with multidrug-resistant tuberculosis (MDR-TB) treated with second generation ...

  3. Exploring the iron metabolism in multidrug resistant tuberculosis ...

    African Journals Online (AJOL)

    The iron metabolism plays a key role in the progression of active Tuberculosis. Several studies have shown a link between iron metabolism disorders an active tuberculosis. The aim of this study was to explore the iron metabolism of 100 patients with multidrug-resistant tuberculosis. (MDR-TB) treated with second ...

  4. Population-level impact of active tuberculosis case finding in an Asian megacity.

    Directory of Open Access Journals (Sweden)

    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.

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

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    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

  6. Evaluating Fluoroquinolone Use in Patients Admitted to the Tuberculosis Outpatient Clinic

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    Sinem İliaz

    2016-08-01

    Full Text Available Objective: Inelaborate use of new quinolones with strong anti-tuberculosis (TB activity leads to difficulty in diagnosis and more importantly, quinolone-resistant Mycobacterium tuberculosis. We aimed to determine the frequency of quinolone use in patients who were referred to our hospital for suspected TB and to evaluate the association between quinolone use and different clinical laboratory parameters. Methods: Between November 15 and December 15, 2013, all patients who were admitted to the TB outpatient clinic with no previous diagnosis of TB were included in this study. Demographic and clinical laboratory findings and history of antibiotic use were recorded. Patients’ quinolone use were questioned by showing fluoroquinolone antibiotic boxes’ photographs available on the market. The departments of the doctors who prescribed quinolones were recorded. Results: The mean age of 179 patients included in the study was 37±16 (15–89 years. Among these, 113 patients (63.1% were male. Seventy five patients (41.9% were diagnosed as tuberculosis according to the clinical-radiological and/or bacteriological findings. Of 179 patients, 58.1% (n=104 had been prescribed antibiotics for current complaints before referral to our clinic. Sixteen patients (15% had been recommended fluoroquinolones. Fluoroquinolones were prescribed by seven internal medicine specialists, five pulmonologists, three emergency medicine specialists, and one family medicine practitioner. Among 16 fluoroquinolones prescribed, nine were moxifloxacin, four were levofloxacin, and three were gemifloxacin. Quinolone use revealed a significant inverse relationship only with the presence of hemoptysis (p=0.04. Conclusion: Besides increased educational activities regarding the rational use of antibiotics in recent years, the quinolone group of antibiotics is still prescribed for suspected TB cases. To avoid quinolone-resistant M. tuberculosis strains, further education is required.

  7. Tuberculosis Multidrogoresistente

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    German A Acevedo

    2013-12-01

    Full Text Available La tuberculosis es una enfermedad infecciosa causada por el Mycobacterium tuberculosis. En el año 2010 se registraron 8.8 millones de casos incidentes en el mundo y en los últimos años han aparecido poblaciones bacterianas de micobacterias con resistencia a los fármacos de primera línea. Se ha definido la presencia de resistencia a rifampicina e isoniacida como multidrogoresistencia, estimándose una incidencia mundial aproximada de 3.6%. Esta revisión de tema se centrará en la situación de la tuberculosis multidrogoresistente en el mundo, incluyendo un análisis regional de la casuística Colombiana. Se comentarán los principales mecanismos de resistencia del microorganismo, los genes implicados en la misma y los factores de riesgo asociados a la generación de resistencia en algunas comunidades.

  8. Visceral leishmaniasis masquerading as tuberculosis in a patient with AIDS

    Science.gov (United States)

    Yaduvanshi, A.; Jain, M.; Jain, S; Jain, S.; Arora, S.

    1999-01-01

    We report a case of visceral leishmaniasis presenting as significant lymphadenopathy in a patient with acquired immune deficiency syndrome. The lymphadenopathy was initially suspected to be tubercular in nature on pathological examination. This report highlights the increasing incidence of acquired immune deficiency syndrome and Leishmania co-infection in India, and the importance of demonstrating tubercle bacilli on culture before suggesting a diagnosis of tuberculosis.


Keywords: leishmaniasis; AIDS; tuberculosis PMID:10567601

  9. Diarylethenes Display In Vitro Anti-TB Activity and Are Efficient Hits Targeting the Mycobacterium tuberculosis HU Protein

    Directory of Open Access Journals (Sweden)

    María Angélica Suarez

    2017-07-01

    Full Text Available Tuberculosis continues to be a great source of concern in global health because of the large reservoir of humans infected with the bacilli and the appearance of clinical isolates resistant to a wide array of anti-tuberculosis drugs. New drugs with novel mechanisms of action on new targets are urgently required to reduce global tuberculosis burden. Mycobacterium tuberculosis nucleoid associated protein (NAP HU has been shown to be druggable and essential for the organism’s survival. In this study, four diarylethenes were synthesized using a one-pot decarboxylated Heck-coupling of coumaric acids with iodoanisoles. The prepared compounds 1–4 were tested for their in vitro growth inhibition of M. tuberculosis H37Rv using the spot culture growth inhibition assay, displaying minimum inhibitory concentrations between 9 and 22 µM. Their cytotoxicity against BHK-21 cell line showed half inhibition at concentrations between 98 and 729 µM. The most selective hit (SI = 81, demonstrated inhibition of M. tuberculosis HU protein involved in maintaining bacterial genome architecture.

  10. [Evaluation of the efficiency of a hospital stage of treatment in delivering antituberculous care to mental patients with active pulmonary tuberculosis].

    Science.gov (United States)

    Borzenko, A S; Zubova, E Iu; Iaitskiĭ, Iu A

    2007-01-01

    The analysis of the results of treatment of two groups of patients from psychotuberculosis units of a mental hospital has shown the advantages of long-term continuous hospital treatment in these patients. In the patients receiving continuous hospital treatment for 3 years, positive changes in the course of pulmonary tuberculosis were observed in 83.5 +/- 2.8% of cases, which is 8 times more frequently than a progressive process (17 (10 +/- 2.3%) patients), p mental state, improvement was achieved in 57.4 +/- 6.3% and the chronic undulating course of the process was observed in 32.8 +/- 6%. It is stated that it is necessary to develop new statutory acts regulating the discharge of patients with active pulmonary tuberculosis and mental disorders (including chronic alcoholism) depending not only their mental state, but also the epidemic hazard they pose.

  11. Detection of lipoarabinomannan as a diagnostic test for tuberculosis.

    Science.gov (United States)

    Sada, E; Aguilar, D; Torres, M; Herrera, T

    1992-09-01

    A coagglutination technique was established for the detection of lipoarabinomannan of Mycobacterium tuberculosis in human serum samples and evaluated for its utility in the diagnosis of tuberculosis at the Instituto Nacional de Enfermedades Respiratorias in Mexico City. The test had a sensitivity of 88% in patients with sputum-smear-positive active pulmonary tuberculosis. The sensitivity in patients with active pulmonary tuberculosis negative for acid-fast bacilli in sputum was 67%. Less favorable results were obtained for patients with AIDS and tuberculosis, with a sensitivity of 57%. The specificity in control patients with lung diseases different from tuberculosis and in healthy subjects was 100%. The positive predictive value was 100%, and the negative predictive value for patients with sputum-positive active pulmonary tuberculosis was 97%. The results of this study suggest that the detection of lipoarabinomannan is an accurate test for the diagnosis of pulmonary tuberculosis.

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

    OpenAIRE

    Mahmood Moosazadeh; Narges Khanjani; Mohammadreza Parsaee

    2015-01-01

    One of the recommended strategies for preventing tuberculosis is to screen high-risk populations with respect to Mycobacterium tuberculosis (TB) infection. The aim of the present study was to investigate latent infection and active tuberculosis in people with close household contact. It was a cross-sectional descriptive, analytical study with the sample size of 668 people from homes with one infected resident. In order to diagnose tuberculosis latent infection, the PPD test was done. To deter...

  13. Periodontitis in patients with focal tuberculosis

    Directory of Open Access Journals (Sweden)

    Alexandrova Е.А.

    2010-12-01

    Full Text Available The research goal is to investigate the mechanisms of formation and peculiarities of periodontitis in patients with focal tuberculosis. Patients with periodontitis and focal tuberculosis are proved to develop local inflammatory reaction with increased infection and activation of proinflammatory cytokines in parodontal pockets fluid. The main risk factor of frequent and durable recurrence of parodontal pathology in case of focal tuberculosis was the development of pathologic process as a cause of disbalance of lipid peroxidation and antioxidant system, endotoxicosis syndrome

  14. Design of Selective Substrates and Activity-Based Probes for Hydrolase Important for Pathogenesis 1 (HIP1) from Mycobacterium tuberculosis.

    Science.gov (United States)

    Lentz, Christian S; Ordonez, Alvaro A; Kasperkiewicz, Paulina; La Greca, Florencia; O'Donoghue, Anthony J; Schulze, Christopher J; Powers, James C; Craik, Charles S; Drag, Marcin; Jain, Sanjay K; Bogyo, Matthew

    2016-11-11

    Although serine proteases are important mediators of Mycobacterium tuberculosis (Mtb) virulence, there are currently no tools to selectively block or visualize members of this family of enzymes. Selective reporter substrates or activity-based probes (ABPs) could provide a means to monitor infection and response to therapy using imaging methods. Here, we use a combination of substrate selectivity profiling and focused screening to identify optimized reporter substrates and ABPs for the Mtb "Hydrolase important for pathogenesis 1" (Hip1) serine protease. Hip1 is a cell-envelope-associated enzyme with minimal homology to host proteases, making it an ideal target for probe development. We identified substituted 7-amino-4-chloro-3-(2-bromoethoxy)isocoumarins as irreversible inhibitor scaffolds. Furthermore, we used specificity data to generate selective reporter substrates and to further optimize a selective chloroisocoumarin inhibitor. These new reagents are potentially useful in delineating the roles of Hip1 during pathogenesis or as diagnostic imaging tools for specifically monitoring Mtb infections.

  15. [Change in the survival of Cuban AIDS patients with tuberculosis in the Highly Active Antiretroviral Therapy (HAART) era].

    Science.gov (United States)

    Reyes-Corcho, Andrés; Capo de Paz, Virginia; Díaz-Jidy, Manuel; Pérez-Avila, Jorge; Bouza-Jiménez, Yadira

    2008-09-01

    HIV infection affected 0.06% of the Cuban population and AIDS associated tuberculosis (TB) represented 4.4% of cases in 2004. The objective of this study was to determine the survival of AIDS patients with TB. 167 individuals of both sexes and ages between 15 and 60 years old were studied; all of them were diagnosed in the Havana's Tropical Medicine Institute "Pedro Kourí", Cuba, between January 1st 1997 and May 31st 2005. The Kaplan-Meier's method and the Long-rank test were used for the survival, and the Cox's multivariate method to identify the variables associated with mortality by means of SPSS 9.0. 78 individuals of the total died at the end of study, 71.8% belonged to the pre highly active antiretroviral therapy (HAART) era and 28.2% to the later period. From all deceased cases due to TB, 82.1% were diagnosed in the pre HAART era. The median survival was 41 months (CI=20-62). TB diagnosis in the pre HAART period, TB not being the first disease indicator of AIDS, suffering from candidiasis of esophagus before TB and a LTCD4+ count < 200 at the diagnosis of TB, were all independently associated with mortality. This study demonstrated the positive impact of HAART in the survival of Cuban AIDS patients with TB and also identified advanced immunodepression and opportunistic infections as predictors of mortality.

  16. Qualitative evaluation of a text messaging intervention to support patients with active tuberculosis: implementation considerations.

    Science.gov (United States)

    Iribarren, Sarah J; Sward, Katherine A; Beck, Susan L; Pearce, Patricia F; Thurston, Diana; Chirico, Cristina

    2015-02-27

    Tuberculosis (TB) remains a major global public health problem and mobile health (mHealth) interventions have been identified as a modality to improve TB outcomes. TextTB, an interactive text-based intervention to promote adherence with TB medication, was pilot-tested in Argentina with results supporting the implementation of trials at a larger scale. The objective of this research was to understand issues encountered during pilot-testing in order to inform future implementation in a larger-scale trial. A descriptive, observational qualitative design guided by a sociotechnical framework was used. The setting was a clinic within a public pulmonary-specialized hospital in Argentina. Data were collected through workflow observation over 115 days, text messages (n=2286), review of the study log, and stakeholder input. Emerging issues were categorized as organizational, human, technical, or sociotechnical considerations. Issues related to the intervention included workflow issues (eg, human, training, security), technical challenges (eg, data errors, platform shortcomings), and message delivery issues (eg, unintentional sending of multiple messages, auto-confirmation problems). System/contextual issues included variable mobile network coverage, electrical and Internet outages, and medication shortages. Intervention challenges were largely manageable during pilot-testing, but need to be addressed systematically before proceeding with a larger-scale trial. Potential solutions are outlined. Findings may help others considering implementing an mHealth intervention to anticipate and mitigate certain challenges. Although some of the issues may be context dependent, other issues such as electrical/Internet outages and limited resources are not unique issues to our setting. Release of new software versions did not result in solutions for certain issues, as specific features used were removed. Therefore, other software options will need to be considered before expanding into a

  17. Surgical aspects of pulmonary tuberculosis: an update.

    Science.gov (United States)

    Dewan, Ravindra Kumar; Pezzella, A Thomas

    2016-10-01

    Tuberculosis remains a major global medical challenge and concern. In the world's population of over 7.4 billion people, 8.6 million are estimated to be infected with Mycobacterium tuberculosis; another 2.2 billion have latent tuberculosis. There is an annual incidence of 16,000 new cases in the USA and 7-8 million new cases worldwide, of which 440,000 are multidrug-resistant or extensively multidrug-resistant, mainly in developing countries or emerging economies. According to the World Health Organization, the incidence of tuberculosis is 133 cases per 100,000 of the population; 3.3% new cases are drug resistant and 20% are already treated cases. Of the drug-resistant cases, 9.7% are extensively drug-resistant. The annual global mortality attributable to tuberculosis is over 1.3 million people. The association with HIV/AIDS in 430,000 people has compounded the global concern and challenge. This review presents the historical indications for surgical treatment of tuberculosis, reviews the current literature and clinical experience, and collates this into increased awareness and contemporary understanding of the indications and need for surgery in primary active tuberculosis, adjuvant surgical therapy for multidrug-resistant tuberculosis, and the complications of chronic tuberculosis sequelae or previous tuberculosis surgery. © The Author(s) 2016.

  18. Functional analysis in mouse embryonic stem cells reveals wild-type activity for three MSH6 variants found in suspected Lynch syndrome patients.

    Directory of Open Access Journals (Sweden)

    Eva A L Wielders

    Full Text Available Lynch syndrome confers an increased risk to various types of cancer, in particular early onset colorectal and endometrial cancer. Mutations in mismatch repair (MMR genes underlie Lynch syndrome, with the majority of mutations found in MLH1 and MSH2. Mutations in MSH6 have also been found but these do not always cause a clear cancer predisposition phenotype and MSH6-defective tumors often do not show the standard characteristics of MMR deficiency, such as microsatellite instability. In particular, the consequences of MSH6 missense mutations are challenging to predict, which further complicates genetic counseling. We have previously developed a method for functional characterization of MSH2 missense mutations of unknown significance. This method is based on endogenous gene modification in mouse embryonic stem cells using oligonucleotide-directed gene targeting, followed by a series of functional assays addressing the MMR functions. Here we have adapted this method for the characterization of MSH6 missense mutations. We recreated three MSH6 variants found in suspected Lynch syndrome families, MSH6-P1087R, MSH6-R1095H and MSH6-L1354Q, and found all three to behave like wild type MSH6. Thus, despite suspicion for pathogenicity from clinical observations, our approach indicates these variants are not disease causing. This has important implications for counseling of mutation carriers.

  19. Smith–Petersen osteotomy combined with anterior debridement and allografting for active thoracic and lumbar spinal tuberculosis with kyphotic deformity in young children

    Science.gov (United States)

    Abulizi, Yakefu; Liang, Wei-Dong; Maimaiti, Maierdan; Sheng, Wei-Bin

    2017-01-01

    Abstract The purpose of this study is to determine the efficacy and safety of Smith–Petersen osteotomy combined with anterior debridement and allogenic strut bone grafting for the treatment of active thoracic and lumbar spinal tuberculosis with kyphotic deformity in young children. Spinal tuberculosis is more destructive in young children and often causes severe kyphosis and paraplegia. Despite much progress has been made, surgical treatment is still controversial and technically challenging. From October 2010 to August 2014, 25 children (11 males, 14 females; aged under 6 years) with active thoracic and lumbar spinal tuberculosis treated by Smith–Petersen osteotomy combined with anterior debridement and allogenic strut bone grafting were enrolled in this study. The pre- and postoperative data, follow-up medical records, imaging studies, and laboratory data were collected prospectively. Clinical outcomes were evaluated on the basis of kyphotic angle and the Frankel motor score system. The changes in C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), clinical symptoms, and complications were investigated. Graft fusion was evaluated using the Bridwell grading criteria. The mean age was 3.5 ± 1.76 years (range, 1–6 years). All patients were followed up for 25 to 45 months (average, 34.3 ± 5.86 months). The average kyphotic angle was changed significantly from a preoperative value of 44.1 ± 10.8° to a postoperative value of 11.4 ± 3.9°, with an average correction rate of 74% (P spinal tuberculosis, Smith–Petersen osteotomy combined with anterior debridement and allogenic strut bone grafting is a safe and simple procedure to achieve sufficient kyphosis correction, good neurological recovery, and reliable anterior column reconstruction. PMID:28796043

  20. Undiagnosed Active Pulmonary Tuberculosis among Pilgrims during the 2015 Hajj Mass Gathering: A Prospective Cross-sectional Study.

    Science.gov (United States)

    Yezli, Saber; Zumla, Alimuddin; Yassin, Yara; Al-Shangiti, Ali M; Mohamed, Gamal; Turkistani, Abdulhafiz M; Alotaibi, Badriah

    2017-11-01

    Mass gatherings pose a risk for tuberculosis (TB) transmission and reactivation of latent TB infection. The annual Hajj pilgrimage attracts 2 million pilgrims many from high TB-endemic countries. We evaluated the burden of undiagnosed active pulmonary TB in pilgrims attending the 2015 Hajj mass gathering. We conducted a prospective cross-sectional study in Mecca, Kingdom of Saudi Arabia, for nonhospitalized adult pilgrims from five high TB-endemic countries. Enrollment criteria were the presence of a cough and the ability to produce a sputum sample. Sputum samples were processed using the Xpert MTB-RIF assay. Data were analyzed for drug-resistant TB, risk factors, and comorbidities by the country of origin. Of 1,164 consenting pilgrims enrolled from five countries: Afghanistan (316), Bangladesh (222), Nigeria (176), Pakistan (302), and South Africa (148), laboratory results were available for 1,063 (91.3%). The mean age of pilgrims was 54.5 (range = 18-94 years) with a male to female ratio of 2.6:1; 27.7% had an underlying comorbidity, with hypertension and diabetes being the most common, 20% were smokers, and 2.8% gave a history of previous TB treatment. Fifteen pilgrims (1.4%) had active previously undiagnosed drug-sensitive pulmonary TB (Afghanistan [12; 80%], Pakistan [2; 13.3%], and Nigeria [1; 6.7%]). No multidrug-resistant TB cases were detected. Pilgrims from high TB-endemic Asian and African countries with undiagnosed active pulmonary TB pose a risk to other pilgrims from over 180 countries. Further studies are required to define the scale of the TB problem during the Hajj mass gathering and the development of proactive screening, treatment and prevention guidelines.

  1. Tuberculosis unit: study of 10 years of activity (1999–2009

    Directory of Open Access Journals (Sweden)

    T. Lopes

    2011-11-01

    Full Text Available Setting: The Pulmonology Service of a Central Hospital in Lisbon created a Unit dedicated to the treatment of tuberculosis (TB. Objectives: Casuistic analysis and assessment of the predictive factors for in-hospital mortality, over a 10-year period. Design: Retrospective study, from April 1999 to September 2009, through the Statistical Package for the Social Sciences application for binary logistic regression. Results: In a total of 1917 patients, most were male (n = 1450; 76%, Caucasian (76.6%, with an average age of 43 ± 15.2 years, and 19.8% were immigrants. The retreatments were responsible for 26% of the hospitalizations. The presence of comorbidities was detected in 85.7%, particularly HIV infection (34.7%. The multidrug-resistant (MDR and the extensively drug resistant (XDR TB occurred in 6.6% and 6.8%, respectively. The average delay was 28.5 ± 54.8 days, with the mortality rate at 8.6%. The mortality risk was more significant amongst men (OR 1.8; 95% CI 1.16–2.90; p < 0.01, in patients with HIV infection (OR 3.7; 95% CI 2.47–5.49; p < 0.001, and amongst those who presented MDR TB (OR 2.5; 95% CI 1.24–5.15; p < 0.01 and XDR TB (OR 5.5; 95% CI 3.14–9.58; p < 0.001. Conclusion: A high percentage of patients presented comorbidities, namely HIV infection. The main factors associated with mortality were HIV infection, XDR TB and MDR TB. Resumo: Introdução: O Serviço de Pneumologia de um Hospital Central de Lisboa criou uma Unidade dedicada exclusivamente ao internamento de casos de tuberculose (TB. Objectivos: Análise casuística e avaliação dos factores preditivos de mortalidade intra-hospitalar, num período de 10 anos. Material/Métodos: Estudo retrospectivo, entre Abril de 1999 e Setembro de 2009, através da aplicação SPSS (Statistical Package for the Social Sciences para a regressão logística binária. Resultados: : Do total de

  2. Learn About Tuberculosis

    Science.gov (United States)

    ... Health and Diseases > Lung Disease Lookup > Tuberculosis (TB) Learn About Tuberculosis Tuberculosis (TB) is an airborne bacterial ... against the resistant TB germs in the body. Learn more about the types of drug resistant TB . ...

  3. Tuberculosis: General Information

    Science.gov (United States)

    TB Elimination Tuberculosis: General Information What is TB? Tuberculosis (TB) is a disease caused by germs that are spread from person ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination CS227840_A What Does a Positive Test ...

  4. Tuberculosis; Eye

    African Journals Online (AJOL)

    muscle could present as a painful swelling over the corresponding part of the eye with associated restriction of ocular motility involving the muscle. TUBERCULOSIS OF THE EYE. CORNEA: Primary infection of the cornea is very rare. Corneal involvement is usually due to a hypersentitivity or cross-reaction whereby the.

  5. Tuberculosis perinatal

    Directory of Open Access Journals (Sweden)

    Jessica Sáenz-Gómez

    2015-01-01

    Conclusiones: La infección perinatal debe sospecharse en niños con sepsis o neumonía sin respuesta a antibióticos. En este caso, el antecedente de la madre con tuberculosis orientó al diagnóstico.

  6. Amino-terminal extension present in the methionine aminopeptidase type 1c of Mycobacterium tuberculosis is indispensible for its activity

    Directory of Open Access Journals (Sweden)

    Kumaran Sangaralingam

    2011-07-01

    Full Text Available Abstract Background Methionine aminopeptidase (MetAP is a ubiquitous enzyme in both prokaryotes and eukaryotes, which catalyzes co-translational removal of N-terminal methionine from elongating polypeptide chains during protein synthesis. It specifically removes the terminal methionine in all organisms, if the penultimate residue is non-bulky and uncharged. The MetAP action for exclusion of N-terminal methionine is mandatory in 50-70% of nascent proteins. Such an activity is required for proper sub cellular localization, additional processing and eventually for the degradation of proteins. Results We cloned genes encoding two such metalloproteases (MtMetAP1a and MtMetAP1c present in Mycobacterium tuberculosis and expressed them as histidine-tagged proteins in Escherichia coli. Although they have different substrate preferences, for Met-Ala-Ser, we found, MtMetAP1c had significantly high enzyme turnover rate as opposed to MtMetAP1a. Circular dichroism spectroscopic studies as well as monitoring of enzyme activity indicated high temperature stability (up to 50°C of MtMetAP1a compared to that of the MtMetAP1c. Modelling of MtMetAP1a based on MtMetAP1c crystal structure revealed the distinct spatial arrangements of identical active site amino acid residues and their mutations affected the enzymatic activities of both the proteins. Strikingly, we observed that 40 amino acid long N-terminal extension of MtMetAP1c, compared to its other family members, contributes towards the activity and stability of this enzyme, which has never been reported for any methionine aminopeptidase. Furthermore, mutational analysis revealed that Val-18 and Pro-19 of MtMetAP1c are crucial for its enzymatic activity. Consistent with this observation, molecular dynamic simulation studies of wild-type and these variants strongly suggest their involvement in maintaining active site conformation of MtMetAP1c. Conclusion Our findings unequivocally emphasized that N

  7. Tuberculosis treatment and drug regimens.

    Science.gov (United States)

    Sotgiu, Giovanni; Centis, Rosella; D'ambrosio, Lia; Migliori, Giovanni Battista

    2015-01-08

    Tuberculosis is an airborne infectious disease treated with combination therapeutic regimens. Adherence to long-term antituberculosis therapy is crucial for maintaining adequate blood drug level. The emergence and spread of drug-resistant Mycobacterium tuberculosis strains are mainly favored by the inadequate medical management of the patients. The therapeutic approach for drug-resistant tuberculosis is cumbersome, because of the poor, expensive, less-effective, and toxic alternatives to the first-line drugs. New antituberculosis drugs (bedaquiline and delamanid) have been recently approved by the health authorities, but they cannot represent the definitive solution to the clinical management of drug-resistant tuberculosis forms, particularly in intermediate economy settings where the prevalence of drug resistance is high (China, India, and former Soviet Union countries). New research and development activities are urgently needed. Public health policies are required to preserve the new and old therapeutic options. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  8. Tuberculosis in healthcare workers, Scotland.

    Science.gov (United States)

    Pollock, Kevin G; McDonald, Eisin; Smith-Palmer, Alison; Johnston, Fiona; Ahmed, Syed

    2017-08-01

    In an attempt to explore healthcare worker acquisition of tuberculosis infection, we conducted population-based surveillance of all cases recorded as healthcare workers reported to Enhanced Surveillance of Mycobacterial Infection from 2000 to 2015. Over the study period, the mean incidence rate of tuberculosis among all healthcare workers was 15.4 per 100,000 healthcare workers. However, the incidence rate of tuberculosis amongst those healthcare workers born outside the UK was 164.8 per 100,000 compared with 5.0 per 100,000 UK-born healthcare workers. Fifty-seven per cent of all non-UK-born healthcare workers were diagnosed within five years of their arrival in the UK and would have been new entrants to the NHS. An effective new entrant occupational health screening programme for latent tuberculosis infection may have prevented some of these active cases of infection.

  9. Tocolytics for suspected intrapartum fetal distress.

    Science.gov (United States)

    Kulier, R; Hofmeyr, G J

    2000-01-01

    Prophylactic tocolysis with betamimetics and other agents has become widespread as a treatment for fetal distress. Uterine relaxation may improve placental blood flow and therefore fetal oxygenation. However there may also be adverse maternal cardiovascular effects. The objective of this review was to assess the effects of tocolytic therapy for suspected fetal distress on fetal, maternal and perinatal outcomes. We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register. Date of last search: February 1999. Randomised trials comparing tocolytic therapy with no treatment or treatment with another tocolytic agent for suspected fetal distress. Two reviewers assessed trial quality and extracted data. Three studies were included. Compared with no treatment, there were fewer failed improvements in fetal heart rate abnormalities with tocolytic therapy (relative risk 0.26, 95% 0.13 to 0.53). Betamimetic therapy compared with magnesium sulphate showed a non-significant trend towards reduced uterine activity (relative risk 0.07, 95% confidence interval 0.00 to 1.10). Betamimetic therapy appears to be able to reduce the number of fetal heart rate abnormalities and perhaps reduce uterine activity. However there is not enough evidence based on clinically important outcomes to evaluate the use of betamimetics for suspected fetal distress.

  10. Resurgence of tuberculosis: a rare case of primary orbitomaxillary tuberculoma.

    Science.gov (United States)

    Kar, Indu Bhusan; Panda, Sachchida Nanda; Mishra, Niranjan; Kar, Rosalin; Singh, Akhilesh Kumar

    2013-07-01

    Extrapulmonary sites of tuberculosis, which represent 15% of all sites, most commonly involve lymph nodes and bones. Facial bones and paranasal sinuses are rarely involved in the process. Tuberculosis of maxilla is an extremely rare condition, which usually presents with involvement of anterior wall of the maxillary sinus. Symptoms may include nasal discharge with partial nasal obstruction and mild pain. It still remains an underdiagnosed entity. We report a case of tuberculoma of the whole left maxilla extending into the orbit, with no previous history of pulmonary tuberculosis. Tuberculosis of paranasal sinus is a rare entity and is nearly always secondary to pulmonary or extrapulmonary tuberculosis, but this report describes the incidence of primary infection of extrapulmonary site. Any chronic granulomatous lesion present over the maxillofacial region which does not respond to initial antibiotic therapy may be suspected as tubercular infection and should be ruled out with priority. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Primary health care staff's perception of childhood tuberculosis

    DEFF Research Database (Denmark)

    Bjerrum, Stephanie; Rose, Michala Vaaben; Bygbjerg, Ib Christian

    2012-01-01

    Background: Diagnosing tuberculosis in children remains a great challenge in developing countries. Health staff working in the front line of the health service delivery system has a major responsibility for timely identification and referral of suspected cases of childhood tuberculosis. This study...... explored primary health care staff’s perception, challenges and needs pertaining to the identification of children with tuberculosis in Muheza district in Tanzania. Methods: We conducted a qualitative study that included 13 semi-structured interviews and 3 focus group discussions with a total of 29 health...... staff purposively sampled from primary health care facilities. Analysis was performed in accordance with the principles of a phenomenological analysis. Results: Primary health care staff perceived childhood tuberculosis to be uncommon in the society and tuberculosis was rarely considered as a likely...

  12. [Tuberculosis in Iceland. 1976].

    Science.gov (United States)

    Sigurdsson, Sigurdur

    2005-01-01

    Because of signs of tuberculous lesions in old skeletons it can be stated with certainty that tuberculosis has occurred in the country shortly after the settlement. From that time and up to the seventeenth century, little or nothing is known about the occurrence of the disease. A few preserved descriptions of diseases and deaths indicate that tuberculosis has existed in the country before the advent of qualified physicians in 1760. On the basis of papers and reports from the first physicians and the first tuberculosis registers the opinions is set forth that the disease has been rare up to the latter part of the nineteenth century. During the two last decades of that century the disease began to spread more rapidly and increased steadily up to the turn of the century. Although reporting of the disease was started in the last decade of the nineteenth century the reporting was first ordered by law with the passage of the first tuberculosis Act in the year 1903. With this legislation official measures for tuberculosis control work really started in the country. The first sanatorium was built in 1910. In 1921 the tuberculosis Act was revised and since then practically all the expenses for the hospitalization and treatment of tuberculous cases has been defrayed by the state. In the year 1935 organized tuberculosis control work was begun and a special physician appointed to direct it. From then on systematic surveys were made, partly in health centers i.e. tuberculosis clinics, which were established in the main towns, and partly by means of transportable X ray units in outlying rural areas of the country. In 1939 the tuberculosis Act was again revised with special reference to the surveys and the activities of the tuberculosis clinics. This act is still in force. Some items of it are described. The procedure of the surveys and the methods of examination are described. The great majority of subjects were tuberculin tested and all positive reactors X rayed. Furthermore, X

  13. Dimerization of inositol monophosphatase Mycobacterium tuberculosis SuhB is not constitutive, but induced by binding of the activator Mg2+

    Directory of Open Access Journals (Sweden)

    Nigou Jérôme

    2007-08-01

    Full Text Available Abstract Background The cell wall of Mycobacterium tuberculosis contains a wide range of phosphatidyl inositol-based glycolipids that play critical structural roles and, in part, govern pathogen-host interactions. Synthesis of phosphatidyl inositol is dependent on free myo-inositol, generated through dephosphorylation of myo-inositol-1-phosphate by inositol monophosphatase (IMPase. Human IMPase, the putative target of lithium therapy, has been studied extensively, but the function of four IMPase-like genes in M. tuberculosis is unclear. Results We determined the crystal structure, to 2.6 Å resolution, of the IMPase M. tuberculosis SuhB in the apo form, and analysed self-assembly by analytical ultracentrifugation. Contrary to the paradigm of constitutive dimerization of IMPases, SuhB is predominantly monomeric in the absence of the physiological activator Mg2+, in spite of a conserved fold and apparent dimerization in the crystal. However, Mg2+ concentrations that result in enzymatic activation of SuhB decisively promote dimerization, with the inhibitor Li+ amplifying the effect of Mg2+, but failing to induce dimerization on its own. Conclusion The correlation of Mg2+-driven enzymatic activity with dimerization suggests that catalytic activity is linked to the dimer form. Current models of lithium inhibition of IMPases posit that Li+ competes for one of three catalytic Mg2+ sites in the active site, stabilized by a mobile loop at the dimer interface. Our data suggest that Mg2+/Li+-induced ordering of this loop may promote dimerization by expanding the dimer interface of SuhB. The dynamic nature of the monomer-dimer equilibrium may also explain the extended concentration range over which Mg2+ maintains SuhB activity.

  14. MDCT abnormalities of small- and medium-sized bronchus in active tuberculosis: a new angle on an old disease

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Jin Kyoung; Ahn, Myeong Im; Jung, Jung Im; Han, Dae Hee (Dept. of Radiology, Seoul St Mary' s Hospital, The Catholic Univ. of Korea, Seoul (Korea, Republic of)), email: lepolder@gmail.com; Kim, Young Kyoon (Dept. of Internal Medicine, Seoul St Mary' s Hospital, The Catholic Univ. of Korea, Seoul (Korea, Republic of)); Oh, Eun-Jee; Park, Yeon-Joon (Dept. of Laboratory Medicine, Seoul St Mary' s Hospital, The Catholic Univ. of Korea, Seoul (Korea, Republic of))

    2011-02-15

    Background: The incidence and findings of tuberculous invasion of the peripheral bronchus have not been fully investigated with MDCT. Purpose: To evaluate the prevalence and findings of MDCT abnormalities of small- and medium-sized bronchus (SMB) in active pulmonary tuberculosis (TB). Material and Methods: Using multiplanar reformation, 35 consecutive MDCT scans (follow-up exams available in 14 patients with a mean interval of 8.1 months) were assessed for following abnormalities of SMB: bronchial impaction (BI), wall thickening, dilatation, peribronchial cuff of soft tissue, and bronchocavitary fistula. It was also assessed whether tree-in-buds (TIB) have a tendency to distribute in the territories of diseased SMB, and whether SMB abnormalities are present in patients with relatively mild disease. Results: SMB abnormalities were observed in 23 (65.7%) patients with active TB. The most frequent finding was wall thickening (n=18, 51.4%), followed by BI (n=13, 37.1%; zigzag-shaped in four), dilatation (n =11, 31.4%), amputated appearance of air column (n=11, 31.4%), peribronchial cuff of soft tissue (n=10, 28.6%), and bronchocavitary fistula (n=8, 22.9%). TIB (n=29; absent in two patients with SMB) was mainly within (n=14) or close to (n=4) the territory of diseased SMB. Follow-up CT frequently showed improvement of wall thickening (11/12) and persistence of bronchial dilatation (11/13). SMB abnormality was present in all of six patients with mild disease. Conclusion: MDCT shows that tuberculous invasion of the peripheral bronchus may be more frequent than previously thought, of which findings include wall thickening, BI, dilatation, amputated appearance of air column, peribronchial cuff of soft tissue and bronchocavitary fistula

  15. Yield of active screening for tuberculosis among asylum seekers in Germany: a systematic review and meta-analysis.

    Science.gov (United States)

    Bozorgmehr, Kayvan; Razum, Oliver; Saure, Daniel; Joggerst, Brigitte; Szecsenyi, Joachim; Stock, Christian

    2017-03-23

    All asylum seekers in Germany undergo upon-entry screening for tuberculosis TB, but comprehensive evidence on the yield is lacking. We compared the national estimates with the international literature in a systematic review and meta-analysis of studies reporting the yield of TB, defined as the fraction of active TB cases detected among asylum seekers screened in Germany upon entry. We searched 11 national and international databases for empirical studies and the internet for grey literature published in English or German without restrictions on publication time. Among 1,253 screened articles, we identified six articles reporting the yield of active TB based on German data, ranging from 0.72 (95% confidence interval (CI): 0.45-1.10) to 6.41 (95% CI: 4.19-9.37) per 1,000 asylum seekers. The pooled estimate across all studies was 3.47 (95% CI: 1.78-5.73; I(2) = 94.9%; p < 0.0001) per 1,000 asylum seekers. This estimate was in line with international evidence (I(2) = 0%; p for heterogeneity 0.55). The meta-analysis of available international estimates resulted in a pooled yield of 3.04 (95% CI: 2.24-3.96) per 1,000. This study provides an estimate across several German federal states for the yield of TB screening in asylum seekers. Further research is needed to develop more targeted screening programmes. This article is copyright of The Authors, 2017.

  16. Comparative study of enzymatic activities of new KatG mutants from low- and high-level isoniazid-resistant clinical isolates of Mycobacterium tuberculosis.

    Science.gov (United States)

    Brossier, Florence; Boudinet, Marlène; Jarlier, Vincent; Petrella, Stéphanie; Sougakoff, Wladimir

    2016-09-01

    Resistance to isoniazid (INH-R) in Mycobacterium tuberculosis is mainly due to mutations at position 315 (S315T) of the catalase-peroxidase KatG. We identified 16 mutations (including 13 biochemically uncharacterized mutations) in KatG from INH-R clinical isolates of M. tuberculosis showing mutations other than S315T. The KatG enzymatic activities (catalase, peroxidase, free radical production and isonicotinoyl-NAD formation) of wild-type KatG and the 16 mutants were determined and correlated to their spatial location in a KatG model structure. Of all mutations studied, H270R, which conferred a high level of INH-R and results in the disruption of a coordination bond with the heme, caused complete loss of all enzymatic KatG activities. The mutants generally associated with a very high level of INH-R were all characterized by a drastic reduction in catalase activity and a marked decrease in INH activation activities. One mutant, A162E, displayed a behavior similar to S315T, i.e. a moderate decrease in catalase activity and a drastic decrease in the formation of the radical form of INH. Finally, the mutants associated with a low level of INH-R showed a moderate reduction in the four catalytic activities, likely stemming from an overall alteration of the folding and/or stability of the KatG protein. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. PET/CT imaging of Mycobacterium tuberculosis infection.

    NARCIS (Netherlands)

    Ankrah, Alfred; Werf, van der Tjip; de Vries, Erik; Dierckx, Rudi; Sathekge, M. M.; Glaudemans, Andor W.J.M.

    Tuberculosis has a high morbidity and mortality worldwide. Mycobacterium tuberculosis (Mtb) has a complex pathophysiology; it is an aerobic bacillus capable of surviving in anaerobic conditions in a latent state for a very long time before reactivation to active disease. In the latent tuberculosis

  18. DETECTION OF MYCOBACTERIUM TUBERCULOSIS IN BLOOD FOR DIAGNOSIS OF GENERALISED TUBERCULOSIS IN HIV-POSITIVE PATIENTS

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    V. N. Zimina

    2017-01-01

    Full Text Available Objective: To study the informative value of the detection of mycobacteria in blood with the cultural method in patients with suspected tuberculous sepsis and to determine the most significant clinical and laboratory criteria for testing. Materials and methods: The investigation to detect M.tuberculosis was fulfilled in 159 HIV-positive patients with suspected tuberculosis sepsis. Blood culture was completed with culture medium Myco/F Lytic Culture Vials and analyzer BACTEC 9050. Results: Mycobacteria were detected in blood of 19 patients (11,9% of all patients: in 18 patients the growth of М. tuberculosis complex was detected (25,3% of all patients with diagnosed tuberculosis and in 1 patient it was Mycobacterium avium complex (0,6% of all patients. It was shown, that the probability of M.tuberculosis detection was especially associated with the severity of the disease, immunosupression (less than 100 cells/mkl, hemoglobin quantity less than 90 g/l (levels were determined through the seeking for the most significant cutoffs. It was not proofed, that meningoencephalitis develops more often in patients with proven bacteremia. There were no evident differences in detection frequency of mycobacteria in sputum between patients with tuberculous sepsis and without it.

  19. Balancing Trained Immunity with Persistent Immune Activation and the Risk of Simian Immunodeficiency Virus Infection in Infant Macaques Vaccinated with Attenuated Mycobacterium tuberculosis or Mycobacterium bovis BCG Vaccine

    Science.gov (United States)

    Jensen, Kara; dela Pena-Ponce, Myra Grace; Piatak, Michael; Shoemaker, Rebecca; Oswald, Kelli; Jacobs, William R.; Fennelly, Glenn; Lucero, Carissa; Mollan, Katie R.; Hudgens, Michael G.; Amedee, Angela; Kozlowski, Pamela A.; Estes, Jacob D.; Lifson, Jeffrey D.; Van Rompay, Koen K. A.; Larsen, Michelle

    2016-01-01

    ABSTRACT Our goal is to develop a pediatric combination vaccine to protect the vulnerable infant population against human immunodeficiency virus type 1 (HIV-1) and tuberculosis (TB) infections. The vaccine consists of an auxotroph Mycobacterium tuberculosis strain that coexpresses HIV antigens. Utilizing an infant rhesus macaque model, we have previously shown that this attenuated M. tuberculosis (AMtb)-simian immunodeficiency virus (SIV) vaccine is immunogenic, and although the vaccine did not prevent oral SIV infection, a subset of vaccinated animals was able to partially control virus replication. However, unexpectedly, vaccinated infants required fewer SIV exposures to become infected compared to naive controls. Considering that the current TB vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), can induce potent innate immune responses and confer pathogen-unspecific trained immunity, we hypothesized that an imbalance between enhanced myeloid cell function and immune activation might have influenced the outcome of oral SIV challenge in AMtb-SIV-vaccinated infants. To address this question, we used archived samples from unchallenged animals from our previous AMtb-SIV vaccine studies and vaccinated additional infant macaques with BCG or AMtb only. Our results show that vaccinated infants, regardless of vaccine strain or regimen, had enhanced myeloid cell responses. However, CD4+ T cells were concurrently activated, and the persistence of these activated target cells in oral and/or gastrointestinal tissues may have facilitated oral SIV infection. Immune activation was more pronounced in BCG-vaccinated infant macaques than in AMtb-vaccinated infant macaques, indicating a role for vaccine attenuation. These findings underline the importance of understanding the interplay of vaccine-induced immunity and immune activation and its effect on HIV acquisition risk and outcome in infants. PMID:27655885

  20. Balancing Trained Immunity with Persistent Immune Activation and the Risk of Simian Immunodeficiency Virus Infection in Infant Macaques Vaccinated with Attenuated Mycobacterium tuberculosis or Mycobacterium bovis BCG Vaccine.

    Science.gov (United States)

    Jensen, Kara; Dela Pena-Ponce, Myra Grace; Piatak, Michael; Shoemaker, Rebecca; Oswald, Kelli; Jacobs, William R; Fennelly, Glenn; Lucero, Carissa; Mollan, Katie R; Hudgens, Michael G; Amedee, Angela; Kozlowski, Pamela A; Estes, Jacob D; Lifson, Jeffrey D; Van Rompay, Koen K A; Larsen, Michelle; De Paris, Kristina

    2017-01-01

    Our goal is to develop a pediatric combination vaccine to protect the vulnerable infant population against human immunodeficiency virus type 1 (HIV-1) and tuberculosis (TB) infections. The vaccine consists of an auxotroph Mycobacterium tuberculosis strain that coexpresses HIV antigens. Utilizing an infant rhesus macaque model, we have previously shown that this attenuated M. tuberculosis (AMtb)-simian immunodeficiency virus (SIV) vaccine is immunogenic, and although the vaccine did not prevent oral SIV infection, a subset of vaccinated animals was able to partially control virus replication. However, unexpectedly, vaccinated infants required fewer SIV exposures to become infected compared to naive controls. Considering that the current TB vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), can induce potent innate immune responses and confer pathogen-unspecific trained immunity, we hypothesized that an imbalance between enhanced myeloid cell function and immune activation might have influenced the outcome of oral SIV challenge in AMtb-SIV-vaccinated infants. To address this question, we used archived samples from unchallenged animals from our previous AMtb-SIV vaccine studies and vaccinated additional infant macaques with BCG or AMtb only. Our results show that vaccinated infants, regardless of vaccine strain or regimen, had enhanced myeloid cell responses. However, CD4+ T cells were concurrently activated, and the persistence of these activated target cells in oral and/or gastrointestinal tissues may have facilitated oral SIV infection. Immune activation was more pronounced in BCG-vaccinated infant macaques than in AMtb-vaccinated infant macaques, indicating a role for vaccine attenuation. These findings underline the importance of understanding the interplay of vaccine-induced immunity and immune activation and its effect on HIV acquisition risk and outcome in infants. Copyright © 2017 American Society for Microbiology.

  1. Discriminating active from latent tuberculosis in patients presenting to community clinics.

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    Gurjinder Sandhu

    Full Text Available BACKGROUND: Because of the high global prevalence of latent TB infection (LTBI, a key challenge in endemic settings is distinguishing patients with active TB from patients with overlapping clinical symptoms without active TB but with co-existing LTBI. Current methods are insufficiently accurate. Plasma proteomic fingerprinting can resolve this difficulty by providing a molecular snapshot defining disease state that can be used to develop point-of-care diagnostics. METHODS: Plasma and clinical data were obtained prospectively from patients attending community TB clinics in Peru and from household contacts. Plasma was subjected to high-throughput proteomic profiling by mass spectrometry. Statistical pattern recognition methods were used to define mass spectral patterns that distinguished patients with active TB from symptomatic controls with or without LTBI. RESULTS: 156 patients with active TB and 110 symptomatic controls (patients with respiratory symptoms without active TB were investigated. Active TB patients were distinguishable from undifferentiated symptomatic controls with accuracy of 87% (sensitivity 84%, specificity 90%, from symptomatic controls with LTBI (accuracy of 87%, sensitivity 89%, specificity 82% and from symptomatic controls without LTBI (accuracy 90%, sensitivity 90%, specificity 92%. CONCLUSIONS: We show that active TB can be distinguished accurately from LTBI in symptomatic clinic attenders using a plasma proteomic fingerprint. Translation of biomarkers derived from this study into a robust and affordable point-of-care format will have significant implications for recognition and control of active TB in high prevalence settings.

  2. A Clinical Algorithm to Identify HIV Patients at High Risk for Incident Active Tuberculosis: A Prospective 5-Year Cohort Study.

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    Susan Shin-Jung Lee

    Full Text Available Predicting the risk of tuberculosis (TB in people living with HIV (PLHIV using a single test is currently not possible. We aimed to develop and validate a clinical algorithm, using baseline CD4 cell counts, HIV viral load (pVL, and interferon-gamma release assay (IGRA, to identify PLHIV who are at high risk for incident active TB in low-to-moderate TB burden settings where highly active antiretroviral therapy (HAART is routinely provided.A prospective, 5-year, cohort study of adult PLHIV was conducted from 2006 to 2012 in two hospitals in Taiwan. HAART was initiated based on contemporary guidelines (CD4 count < = 350/μL. Cox regression was used to identify the predictors of active TB and to construct the algorithm. The validation cohorts included 1455 HIV-infected individuals from previous published studies. Area under the receiver operating characteristic (ROC curve was calculated.Seventeen of 772 participants developed active TB during a median follow-up period of 5.21 years. Baseline CD4 < 350/μL or pVL ≥ 100,000/mL was a predictor of active TB (adjusted HR 4.87, 95% CI 1.49-15.90, P = 0.009. A positive baseline IGRA predicted TB in patients with baseline CD4 ≥ 350/μL and pVL < 100,000/mL (adjusted HR 6.09, 95% CI 1.52-24.40, P = 0.01. Compared with an IGRA-alone strategy, the algorithm improved the sensitivity from 37.5% to 76.5%, the negative predictive value from 98.5% to 99.2%. Compared with an untargeted strategy, the algorithm spared 468 (60.6% from unnecessary TB preventive treatment. Area under the ROC curve was 0.692 (95% CI: 0.587-0.798 for the study cohort and 0.792 (95% CI: 0.776-0.808 and 0.766 in the 2 validation cohorts.A validated algorithm incorporating the baseline CD4 cell count, HIV viral load, and IGRA status can be used to guide targeted TB preventive treatment in PLHIV in low-to-moderate TB burden settings where HAART is routinely provided to all PLHIV. The implementation of this algorithm will avoid unnecessary

  3. Impact of β-Lactamase Inhibition on the Activity of Ceftaroline against Mycobacterium tuberculosis and Mycobacterium abscessus

    Science.gov (United States)

    Dubée, Vincent; Soroka, Daria; Cortes, Mélanie; Lefebvre, Anne-Laure; Gutmann, Laurent; Hugonnet, Jean-Emmanuel; Arthur, Michel

    2015-01-01

    The production of β-lactamases BlaMab and BlaC contributes to β-lactam resistance in Mycobacterium abscessus and Mycobacterium tuberculosis, respectively. Ceftaroline was efficiently hydrolyzed by these enzymes. Inhibition of M. tuberculosis BlaC by clavulanate decreased the ceftaroline MIC from ≥256 to 16 to 64 μg/ml, but these values are clinically irrelevant. In contrast, the ceftaroline-avibactam combination should be evaluated against M. abscessus since it inhibited growth at lower and potentially achievable drug concentrations. PMID:25733512

  4. Performance of a lateral flow immunochromatography test for the rapid diagnosis of active tuberculosis in a large multicentre study in areas with different clinical settings and tuberculosis exposure levels.

    Science.gov (United States)

    Manga, Selene; Perales, Rocio; Reaño, Maria; D'Ambrosio, Lia; Migliori, Giovanni Battista; Amicosante, Massimo

    2016-11-01

    Tuberculosis (TB) continues to cause an outsized burden of morbidity and mortality worldwide, still missing efficient and largely accessible diagnostic tools determining an appropriate control of the disease. Serological tests have the potentially to impact TB diagnosis, in particular in extreme clinical settings. The diagnostic performances of the TB-XT HEMA EXPRESS (HEMA-EXPRESS) immunochromatographic rapid test for active TB diagnosis, based on use of multiple Mycobacterium tuberculosis (MTB) specific antigens, have been evaluated in a large study multicentre TB case-finding study, in populations with different exposure level to TB. A total of 1,386 subjects were enrolled in the six participating centres in Peru: 290 active-TB and 1,096 unaffected subjects. The TB prevalence (overall 20.5%) varied between 4.0% and 41.1% in the different study groups. Overall, the HEMA-EXPRESS test had 30.6% sensitivity (range 3.9-77.9%) and 84.6% specificity (range 51.6-97.3%). A significant inverse correlation between test accuracy (overall 73.5%, range 40.4-96.4%) and TB prevalence in the various study populations was observed (Pearson's r=-0.7985; P=0.05). HEMA-EXPRESS, is rapid and relatively inexpensive test suitable for routine use in TB diagnosis. In low TB prevalence conditions, test performance appears in line with WHO Target Product Profile for TB diagnostics. Performances appear suboptimal in high TB prevalence settings. Appropriate set-up in operative clinical settings has to be considered for novel serological tests for TB diagnosis, particularly for formats suitable for point-of-care use.

  5. Tobacco smoking, alcohol drinking, diabetes, low body mass index and the risk of self-reported symptoms of active tuberculosis: individual participant data (IPD) meta-analyses of 72,684 individuals in 14 high tuberculosis burden countries.

    Science.gov (United States)

    Patra, Jayadeep; Jha, Prabhat; Rehm, Jürgen; Suraweera, Wilson

    2014-01-01

    The effects of multiple exposures on active tuberculosis (TB) are largely undetermined. We sought to establish a dose-response relationship for smoking, drinking, and body mass index (BMI) and to investigate the independent and joint effects of these and diabetes on the risk of self-reported symptoms of active TB disease. We analyzed 14 national studies in 14 high TB-burden countries using self-reports of blood in cough/phlegm and cough lasting > = 3 weeks in the last year as the measures of symptoms of active TB. The random effect estimates of the relative risks (RR) between active TB and smoking, drinking, diabetes, and BMIeducation, the risks of active TB were significantly associated with diabetes and BMIdiabetics with BMIdiabetics who smoked (RR = 3.8), and diabetics who drank alcohol (RR = 3.2). The risks from joint risk factors were generally larger in women than in men, with statistically significant risks for diabetics with BMIdiabetics who smoked (RR = 5.4) and women with BMIalcohol, diabetes, and low BMI are significant individual risk factors but in combination are associated with triple or quadruple the risk of development of recent active TB. These risk factors might help to explain the wide variation in TB across countries.

  6. Distribution of Insertion- and Deletion-Associated Genetic Polymorphisms among Four Mycobacterium tuberculosis Phospholipase C Genes and Associations with Extrathoracic Tuberculosis: a Population-Based Study

    OpenAIRE

    Kong, Y.; Cave, M. D.; Yang, D.; Zhang, L.; Marrs, C. F.; Foxman, B.; Bates, J. H.; Wilson, F.; Mukasa, L. N.; Yang, Z. H.

    2005-01-01

    The Mycobacterium tuberculosis genome contains four phospholipase C (PLC)-encoding genes, designated plcA, plcB, plcC, and plcD, respectively. Each of the four genes contributes to the overall PLC activity of M. tuberculosis. PLC is hypothesized to contribute to M. tuberculosis virulence. Infection of M. tuberculosis strains carrying a truncated plcD gene is associated with the occurrence of extrathoracic tuberculosis. However, whether the other three plc genes are also associated with extrat...

  7. Tuberculosis: looking beyond BCG vaccines.

    Directory of Open Access Journals (Sweden)

    Mustafa Abu S

    2003-01-01

    Full Text Available Tuberculosis (TB is an infectious disease of international importance and ranks among the top 10 causes of death in the World. About one-third of the world′s population is infected with Mycobacterium tuberculosis. Every year, approximately eight million people develop active disease and two million die of TB. The currently used BCG vaccines have shown variable protective efficacies against TB in different parts of the world. Moreover, being a live vaccine, BCG can be pathogenic in immunocompromised recipients. Therefore, there is an urgent need to develop new vaccines against TB. The comparative genome analysis has revealed the existence of several M. tuberculosis-specific regions that are deleted in BCG. The work carried out to determine the immunological reactivity of proteins encoded by genes located in these regions revealed several major antigens of M. tuberculosis, including the 6 kDa early secreted antigen target (ESAT6. Immunization with ESAT6 and its peptide (aa51-70 protects mice challenged with M. tuberculosis. The protective efficacy of immunization further improves when ESAT6 is recombinantly fused with M. tuberculosis antigen 85B. In addition, ESAT6 delivered as a DNA vaccine is also protective in mice. Whether these vaccines would be safe or not cannot be speculated. The answer regarding the safety and efficacy of these vaccines has to await human trials in different parts of the world.

  8. Smear positive extra pulmonary tuberculosis disease at University of Gondar Hospital, Northwest Ethiopia

    Science.gov (United States)

    2013-01-01

    Background While pulmonary tuberculosis is the most common presentation, extra pulmonary tuberculosis is also an important clinical problem. However, no adequate information had been made available on the prevalence of smear positive extra pulmonary tuberculosis in Gondar. The aim of this study was to assess the prevalence and possible risk factors of smear positive extra pulmonary tuberculosis among suspected patients at University of Gondar Hospital. Methods A cross-sectional study on extra pulmonary tuberculosis suspected patients was conducted at University of Gondar Hospital from January 2012 to April, 2012. Specimens of patients suspected of extra pulmonary tuberculosis were obtained from fine needle aspiration and body fluid samples collected by pathologist. Demographic characteristics and other variables were collected using a pretested semi-structured questionnaire. Smears were prepared from each sample and stained by Ziehel Neelson and Wright stain. The result of the study was analyzed with bivariate and multivariate logistic regression. Result A total of 344 extra pulmonary tuberculosis suspected clients were included in the study and specimens were taken from lymph node aspirates and body fluids. The overall prevalence of smear positive extra pulmonary tuberculosis was 34 (9.9%). Of these cases of extra pulmonary tuberculosis, lymph node tuberculosis constituted the largest proportion (82.4%). Among the 34 extra pulmonary tuberculosis patients, over half of them (52.9%) were positive for human immunodeficiency virus. The largest proportion of tuberculosis and human immunodeficiency virus cases occurred among persons with in the age group of 31–40 years. Previous history of tuberculosis (OR = 4.77, 95% CI 1.86-12.24), contact to a known tuberculosis cases (OR = 6.67 95% CI 2.78-16.90), history of underlying diseases (OR = 2.79 95% CI 1.15-6.78) and income (OR = 12.9 95% CI 2.25-68.02) were significantly associated with extra pulmonary

  9. Smear positive extra pulmonary tuberculosis disease at University of Gondar Hospital, Northwest Ethiopia

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    Zenebe Yohannes

    2013-01-01

    Full Text Available Abstract Background While pulmonary tuberculosis is the most common presentation, extra pulmonary tuberculosis is also an important clinical problem. However, no adequate information had been made available on the prevalence of smear positive extra pulmonary tuberculosis in Gondar. The aim of this study was to assess the prevalence and possible risk factors of smear positive extra pulmonary tuberculosis among suspected patients at University of Gondar Hospital. Methods A cross-sectional study on extra pulmonary tuberculosis suspected patients was conducted at University of Gondar Hospital from January 2012 to April, 2012. Specimens of patients suspected of extra pulmonary tuberculosis were obtained from fine needle aspiration and body fluid samples collected by pathologist. Demographic characteristics and other variables were collected using a pretested semi-structured questionnaire. Smears were prepared from each sample and stained by Ziehel Neelson and Wright stain. The result of the study was analyzed with bivariate and multivariate logistic regression. Result A total of 344 extra pulmonary tuberculosis suspected clients were included in the study and specimens were taken from lymph node aspirates and body fluids. The overall prevalence of smear positive extra pulmonary tuberculosis was 34 (9.9%. Of these cases of extra pulmonary tuberculosis, lymph node tuberculosis constituted the largest proportion (82.4%. Among the 34 extra pulmonary tuberculosis patients, over half of them (52.9% were positive for human immunodeficiency virus. The largest proportion of tuberculosis and human immunodeficiency virus cases occurred among persons with in the age group of 31–40 years. Previous history of tuberculosis (OR = 4.77, 95% CI 1.86-12.24, contact to a known tuberculosis cases (OR = 6.67 95% CI 2.78-16.90, history of underlying diseases (OR = 2.79 95% CI 1.15-6.78 and income (OR = 12.9 95% CI 2.25-68.02 were significantly associated

  10. Smear positive extra pulmonary tuberculosis disease at University of Gondar Hospital, Northwest Ethiopia.

    Science.gov (United States)

    Zenebe, Yohannes; Anagaw, Belay; Tesfay, Wogahta; Debebe, Tewodros; Gelaw, Baye

    2013-01-18

    While pulmonary tuberculosis is the most common presentation, extra pulmonary tuberculosis is also an important clinical problem. However, no adequate information had been made available on the prevalence of smear positive extra pulmonary tuberculosis in Gondar. The aim of this study was to assess the prevalence and possible risk factors of smear positive extra pulmonary tuberculosis among suspected patients at University of Gondar Hospital. A cross-sectional study on extra pulmonary tuberculosis suspected patients was conducted at University of Gondar Hospital from January 2012 to April, 2012. Specimens of patients suspected of extra pulmonary tuberculosis were obtained from fine needle aspiration and body fluid samples collected by pathologist. Demographic characteristics and other variables were collected using a pretested semi-structured questionnaire. Smears were prepared from each sample and stained by Ziehel Neelson and Wright stain. The result of the study was analyzed with bivariate and multivariate logistic regression. A total of 344 extra pulmonary tuberculosis suspected clients were included in the study and specimens were taken from lymph node aspirates and body fluids. The overall prevalence of smear positive extra pulmonary tuberculosis was 34 (9.9%). Of these cases of extra pulmonary tuberculosis, lymph node tuberculosis constituted the largest proportion (82.4%). Among the 34 extra pulmonary tuberculosis patients, over half of them (52.9%) were positive for human immunodeficiency virus. The largest proportion of tuberculosis and human immunodeficiency virus cases occurred among persons with in the age group of 31-40 years. Previous history of tuberculosis (OR = 4.77, 95% CI 1.86-12.24), contact to a known tuberculosis cases (OR = 6.67 95% CI 2.78-16.90), history of underlying diseases (OR = 2.79 95% CI 1.15-6.78) and income (OR = 12.9 95% CI 2.25-68.02) were significantly associated with extra pulmonary tuberculosis infection. The prevalence of

  11. Reaching the underserved: Active tuberculosis case finding in urban slums in southeastern Nigeria

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    Chidubem L Ogbudebe

    2015-01-01

    Conclusions: There is high prevalence of TB in Nigeria slum population. Targeted screening of out-patients, TB contacts, and HIV-infected patients should be optimized for active TB case finding in Nigeria.

  12. Tuberculosis in the aftermath of the 2010 earthquake in Haiti.

    Science.gov (United States)

    Koenig, Serena P; Rouzier, Vanessa; Vilbrun, Stalz Charles; Morose, Willy; Collins, Sean E; Joseph, Patrice; Decome, Diessy; Ocheretina, Oksana; Galbaud, Stanislas; Hashiguchi, Lauren; Pierrot, Julma; Pape, Jean William

    2015-07-01

    In 2010, Haiti sustained a devastating earthquake that crippled the health-care infrastructure in the capital city, Port-au-Prince, and left 1.5 million people homeless. Subsequently, there was an increase in reported tuberculosis in the affected population. We conducted active tuberculosis case finding in a camp for internally displaced persons and a nearby slum. Community health workers screened for tuberculosis at the household level. People with persistent cough were referred to a physician. The National Tuberculosis Program continued its national tuberculosis reporting system. Even before the earthquake, Haiti had the highest tuberculosis incidence in the Americas. About half of the tuberculosis cases occur in the Port-au-Prince region. The number of reported tuberculosis cases in Haiti has increased after the earthquake, but data are too limited to determine if this is due to an increase in tuberculosis burden or to improved case detection. Compared to previous national estimates (230 per 100,000 population), undiagnosed tuberculosis was threefold higher in a camp for internally displaced persons (693 per 100,000) and fivefold higher in an urban slum (1165 per 100,000). With funding from the World Health Organization (WHO), active case finding is now being done systematically in slums and camps. Household-level screening for prolonged cough was effective in identifying patients with active tuberculosis in this study. Without accurate data, early detection of rising tuberculosis rates is challenging; data collection should be incorporated into pragmatic disease response programmes.

  13. Cost-effectiveness analysis of community active case finding and household contact investigation for tuberculosis case detection in urban Africa.

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    Juliet N Sekandi

    Full Text Available Case detection by passive case finding (PCF strategy alone is inadequate for detecting all tuberculosis (TB cases in high burden settings especially Sub-Saharan Africa. Alternative case detection strategies such as community Active Case Finding (ACF and Household Contact Investigations (HCI are effective but empirical evidence of their cost-effectiveness is sparse. The objective of this study was to determine whether adding ACF or HCI compared with standard PCF alone represent cost-effective alternative TB case detection strategies in urban Africa.A static decision modeling framework was used to examine the costs and effectiveness of three TB case detection strategies: PCF alone, PCF+ACF, and PCF+HCI. Probability and cost estimates were obtained from National TB program data, primary studies conducted in Uganda, published literature and expert opinions. The analysis was performed from the societal and provider perspectives over a 1.5 year time-frame. The main effectiveness measure was the number of true TB cases detected and the outcome was incremental cost-effectiveness ratios (ICERs expressed as cost in 2013 US$ per additional true TB case detected.Compared to PCF alone, the PCF+HCI strategy was cost-effective at US$443.62 per additional TB case detected. However, PCF+ACF was not cost-effective at US$1492.95 per additional TB case detected. Sensitivity analyses showed that PCF+ACF would be cost-effective if the prevalence of chronic cough in the population screened by ACF increased 10-fold from 4% to 40% and if the program costs for ACF were reduced by 50%.Under our baseline assumptions, the addition of HCI to an existing PCF program presented a more cost-effective strategy than the addition of ACF in the context of an African city. Therefore, implementation of household contact investigations as a part of the recommended TB control strategy should be prioritized.

  14. Cost-effectiveness analysis of community active case finding and household contact investigation for tuberculosis case detection in urban Africa.

    Science.gov (United States)

    Sekandi, Juliet N; Dobbin, Kevin; Oloya, James; Okwera, Alphonse; Whalen, Christopher C; Corso, Phaedra S

    2015-01-01

    Case detection by passive case finding (PCF) strategy alone is inadequate for detecting all tuberculosis (TB) cases in high burden settings especially Sub-Saharan Africa. Alternative case detection strategies such as community Active Case Finding (ACF) and Household Contact Investigations (HCI) are effective but empirical evidence of their cost-effectiveness is sparse. The objective of this study was to determine whether adding ACF or HCI compared with standard PCF alone represent cost-effective alternative TB case detection strategies in urban Africa. A static decision modeling framework was used to examine the costs and effectiveness of three TB case detection strategies: PCF alone, PCF+ACF, and PCF+HCI. Probability and cost estimates were obtained from National TB program data, primary studies conducted in Uganda, published literature and expert opinions. The analysis was performed from the societal and provider perspectives over a 1.5 year time-frame. The main effectiveness measure was the number of true TB cases detected and the outcome was incremental cost-effectiveness ratios (ICERs) expressed as cost in 2013 US$ per additional true TB case detected. Compared to PCF alone, the PCF+HCI strategy was cost-effective at US$443.62 per additional TB case detected. However, PCF+ACF was not cost-effective at US$1492.95 per additional TB case detected. Sensitivity analyses showed that PCF+ACF would be cost-effective if the prevalence of chronic cough in the population screened by ACF increased 10-fold from 4% to 40% and if the program costs for ACF were reduced by 50%. Under our baseline assumptions, the addition of HCI to an existing PCF program presented a more cost-effective strategy than the addition of ACF in the context of an African city. Therefore, implementation of household contact investigations as a part of the recommended TB control strategy should be prioritized.

  15. Pulmonary tuberculosis case detection in South Sudan

    African Journals Online (AJOL)

    introduction. Tuberculosis (TB) is a chronic inflammatory lung disease caused by Mycobacterium tuberculosis. Sick people with the. TB germs (or bacilli) transmit the germs into the air during coughing, sneezing, talking, or spitting. Inhaling a small number of the bacilli leads to infection [1]. When a person with active ...

  16. Crystal structures, metal activation, and DNA-binding properties of two-domain IdeR from Mycobacterium tuberculosis.

    Science.gov (United States)

    Wisedchaisri, Goragot; Chou, C James; Wu, Meiting; Roach, Claudia; Rice, Adrian E; Holmes, Randall K; Beeson, Craig; Hol, Wim G J

    2007-01-16

    The iron-dependent regulator IdeR is a key transcriptional regulator of iron uptake in Mycobacterium tuberculosis. In order to increase our insight into the role of the SH3-like third domain of this essential regulator, the metal-binding and DNA-binding properties of two-domain IdeR (2D-IdeR) whose SH3-like domain has been truncated were characterized. The equilibrium dissociation constants for Co2+ and Ni2+ activation of 2D-IdeR for binding to the fxbA operator and the DNA-binding affinities of 2D-IdeR in the presence of excess metal ions were estimated using fluorescence spectroscopy. 2D-IdeR binds to fxbA operator DNA with similar affinity as full-length IdeR in the presence of excess metal ion. However, the Ni2+ concentrations required to activate 2D-IdeR for DNA binding appear to be smaller than that for full-length IdeR while the concentration of Co2+ required for activation remains the same. We have determined the crystal structures of Ni2+-activated 2D-IdeR at 1.96 A resolution and its double dimer complex with the mbtA-mbtB operator DNA in two crystal forms at 2.4 A and 2.6 A, the highest resolutions for DNA complexes for any structures of iron-dependent regulator family members so far. The 2D-IdeR-DNA complex structures confirm the specificity of Ser37 and Pro39 for thymine bases and suggest preferential contacts of Gln43 to cytosine bases of the DNA. In addition, our 2D-IdeR structures reveal a remarkable property of the TEV cleavage sequence remaining after removal of the C-terminal His6. This C-terminal tail promotes crystal contacts by forming a beta-sheet with the corresponding tail of neighboring subunits in two unrelated structures of 2D-IdeR, one with and one without DNA. The contact-promoting properties of this C-terminal TEV cleavage sequence may be beneficial for crystallizing other proteins.

  17. Zoonotic Transmission of Tuberculosis Between Pastoralists and Their Livestock in South-East Ethiopia

    OpenAIRE

    Gumi, Balako; Schelling, Esther; Berg, Stefan; Firdessa, Rebuma; Erenso, Girume; Mekonnen, Wondale; Hailu, Elena; Melese, Ermias; Hussein, Jemal; Aseffa, Abraham; Zinsstag, Jakob

    2012-01-01

    Despite huge global efforts in tuberculosis (TB) control, pastoral areas remain under-investigated. During two years sputum and fine needle aspirate (FNA) specimens were collected from 260 Ethiopian pastoralists of Oromia and Somali Regional States with suspected pulmonary TB and from 32 cases with suspected TB lymphadenitis. In parallel, 207 suspected tuberculous lesions were collected from cattle, camels and goats at abattoirs. All specimens were processed and cultured for mycobacteria; sam...

  18. Imaging in extrapulmonary tuberculosis

    Directory of Open Access Journals (Sweden)

    Sanjay Gambhir

    2017-03-01

    Full Text Available Tuberculosis (TB remains a major global public health problem, with 1.5 million deaths annually worldwide. One in five cases of TB present as extrapulmonary TB (EPTB, posing major diagnostic and management challenges. Mycobacterium tuberculosis adapts to a quiescent physiological state and is notable for its complex interaction with the host, producing poorly understood disease states ranging from latent infection to active clinical disease. New tools in the diagnostic armamentarium are urgently required for the rapid diagnosis of TB and monitoring of TB treatments, and to gain new insights into pathogenesis. The typical and atypical imaging features of EPTB are reviewed herein, and the roles of several imaging modalities for the diagnosis and management of EPTB are discussed.

  19. Rapid diagnosis of M.tuberculosis meningitis by enumeration of cerebrospinal fluid antigen-specific T cells

    Science.gov (United States)

    Thomas, MM; Hinks, TSC; Raghuraman, S; Ramalingam, N; Ernst, M; Nau, R; Lange, C; Kösters, K; Gnanamuthu, C; John, GT; Marshall, B; Lalvani, A

    2009-01-01

    SUMMARY Setting Hospital in-patients with suspected tuberculous meningitis predominantly in India. Objective To determine whether interferon-γ-secreting Mycobacterium tuberculosis-antigen-specific T cells are present in the cerebrospinal fluid of patients with tuberculous meningitis, and to evaluate the feasibility of cerebrospinal fluid enzyme-linked immunospot for the diagnosis of active tuberculous meningitis. Design Prospective, blinded, hospital-based study. Results The overnight enzyme-linked immunospot assay detected Mycobacterium tuberculosis-antigen-specific interferon-γ-secreting T cells in cerebrospinal fluid from 9 out of 10 prospectively recruited patients with tuberculous meningitis, and 0 out of 7 control patients with meningitis of other aetiology. This corresponds to a diagnostic sensitivity of 90% (95%CI 56-100%) and specificity of 100% (95%CI 59-100%). Conclusion This pilot study demonstrates proof-of-principle for a new T cell-based diagnostic test for tuberculous meningitis which is rapid, sensitive and specific. PMID:18492332

  20. Incidence of tuberculosis among HIV-infected patients receiving highly active antiretroviral therapy in Europe and North America

    NARCIS (Netherlands)

    Costagliola, D; Dabis, F; Monforte, AD; de Wolf, F; Egger, M; Fatkenheuer, G; Gill, J; Hogg, R; Justice, A; Ledergerber, B; Lundgren, J; May, M; Phillips, A; Reiss, P; Sabin, C; Staszewski, S; Sterne, J; Weller, H.H.; May, M; Beckthold, B; Yip, B; Dauer, B; Fusco, J; Grabar, S; Lanoy, E; Junghans, C; Lavignolle, V.; van Leth, F; Pereira, E; Pezzotti, P; Phillips, A; Sabin, C; Schmeisser, N; Billaud, E; Boue, F; Duval, J.; Duvivier, C; Enel, P; Fournier, S; Gasnault, J; Gaud, C; Gilquin, J; Grabar, S; Khuong, MA; Lang, JM; Mary-Krause, M; Matheron, S; Meyohas, MC; Pialoux, G; Poizot-Martin, I.; Pradier, C; Rouveix, E; Salmon-Ceron, D; Sobel, A; Tattevin, P; Tissot-Dupont, H; Yasdanpanah, Y; Aronica, E; Tirard-Fleury, V.; Tortay, I.; Abgrall, S; Guiguet, M; Leneman, H; Lievre, L; Potard, V.; Saidi, S; Matheron, S; Vilde, JL; Leport, C; Yeni, P; Bouvet, E; Gaudebout, C; Crickx, B; Picard-Dahan, C; Weiss, L; Tisne-Dessus, D; Sicard, D; Salmon, D; Auperin, A; Viard, JP; Roudiere, L; Delfraissy, JF; Goujard, C; Lesprit, P; Jung, C; Meyohas, MC; Meynard, JL; Picard, O; Desplanque, N; Cadranel, J; Mayaud, C; Rozenbaum, W; Bricaire, F; Katlama, C; Herson, S; Simon, A; Decazes, JM; Molina, JM; Clauvel, JP; Gerard, L; Widal, GHLF; Sellier, P; Diemer, M; Dupont, C; Berthe, H; Saiag, P; Mortier, L; Mortier, E; Chandemerle, C; de Truchis, P; Bentata, M; Honore, P; Tassi, S; Jeantils, V.; Mechali, D; Taverne, B; Laurichesse, H; Gourdon, F; Lucht, F; Fresard, A; Faller, JP; Eglinger, P; Bazin, C; Verdon, R; Peyramond, D; Boibieux, A; Touraine, JL; Livrozet, JM; Trepo, C; Cotte, L; Ravaux, I.; Delmont, JP; Moreau, J; Gastaut, JA; Soubeyrand, J; Retornaz, F; Blanc, PA; Allegre, T; Galinier, A; Ruiz, JM; Lepeu, G; Granet-Brunello, P; Pelissier, L; Esterni, JP; Nezri, M; Cohen-Valensi, R; Laffeuillade, A; Chadapaud, S; Reynes, J; May, T; Rabaud, C; Raffi, F; Pugliese, P; Michelet, C; Arvieux, C; Caron, F; Borsa-Lebas, F; Lang, JM; Fraisse, P; Massip, P; Cuzin, L; Arlet-Suau, E; Legrand, MFT; Yasdanpanah, Y; Sobesky, M; Pradinaud, R; Guyon, F; Contant, M; Montroni, M; Scalise, G; Braschi, MC; Aviano, AR; Tirelli, U; Cinelli, R; Pastore, G; Ladisa, N; Minafra, G; Suter, F; Arici, C; Chiodo, F; Colangeli, V.; Fiorini, C; Coronado, O; Carosi, G; Cadeo, GP; Torti, C; Minardi, C; Bertelli, D; Rizzardini, G; Melzi, S; Manconi, PE; Catanzaro, PP; Cosco, L; Scerbo, A; Vecchiet, J; D'Alessandro, M; Santoro, D; Pusterla, L; Carnevale, G; Citterio, P; Vigano, P; Mena, M; Ghinelli, F; Sighinolfi, L; Leoncini, F; Mazzotta, F; Pozzi, M; Lo Caputo, S; Angarano, G; Grisorio, B; Saracino, A; Ferrara, S; Grima, P; Tundo, P; Pagano, G; Cassola, G; Alessandrini, A; Piscopo, R; Toti, M; Chigiotti, S; Soscia, F; Tacconi, L; Orani, A; Perini, P; Scasso, A; Vincenti, A; Chiodera, F; Castelli, P; Scalzini, A; Palvarini, L; Moroni, M; Lazzarin, A; Cargnel, A; Vigevani, GM; Caggese, L; Monforte, AD; Repetto, D; Galli, A; Merli, S; Pastecchia, C; Moioli, MC; Esposito, R; Mussini, C; Abrescia, N; Chirianni, A; Izzo, CM; Piazza, M; De Marco, M; Viglietti, R; Manzillo, E; Nappa, S; Colomba, A; Abbadessa, V.; Prestileo, T; Mancuso, S; Ferrari, C; Pizzaferri, P; Filice, G; Minoli, L; Bruno, R; Novati, S; Baldelli, F; Tinca, M; Petrelli, E; Cioppi, A; Alberici, F; Ruggieri, A; Menichetti, F; Martinelli, C; De Stefano, C; La Gala, A; Ballardini, G; Rizzo, E; Magnani, G; Ursitti, MA; Arlotti, M; Ortolani, P; Cauda, R; Dianzani, F; Ippolito, G; Antinori, A; Antonucci, G; D'Elia, S; Narciso, P; Petrosillo, N; Vullo, V.; De Luca, A; Bacarelli, A; Zaccarelli, M; Acinapura, R; De Longis, P; Brandi, A; Trotta, MP; Noto, P; Lichtner, M; Capobianchi, MR; Carletti, F; Girardi, E; Pezzotti, P; Rezza, G; Mura, MS; Mannazzu, M; Caramello, P; Di Perri, G; Soranzo, ML; Orofino, GC; Arnaudo, I.; Bonasso, M; Grossi, PA; Basilico, C; Poggio, A; Bottari, G; Raise, E; Ebo, F; De Lalla, F; Tositti, G; Resta, F; Loso, K; Lepri, AC; Battegay, M; Bernasconi, E; Boni, J; Bucher, H; Burgisser, P; Cattacin, S; Cavassini, M; Dubs, R; Egger, M; Elzi, L; Erb, P; Fantelli, K; Fischer, M; Flepp, M; Fontana, A; Francioli, P; Furrer, H; Gorgievski, M; Hirschel, B; Kaiser, L; Kind, C; Klimkait, T; Lauper, U; Ledergerber, B; Opravil, M; Paccaud, F; Pantaleo, G; Perrin, L; Piffaretti, JC; Rickenbach, M; Rudin, C; Schmid, P; Schupbach, J; Speck, R; Telenti, A; Trkola, A; Vernazza, P; Weber, R; Yerly, S; Bronsveld, W; Hillebrand-Haverkort, ME; Prins, JM; Bos, JC; Schattenkerk, JKME; Geerlings, SE; Godfried, MH; Lange, JMA; van Leth, FC; Lowe, SH; van der Meer, JTM; Nellen, FJB; Pogany, K; van der Poll, T; Reiss, P; Ruys, TA; Sankatsing, S; Steingrover, R; van Twillert, G; van der Valk, M; van Vonderen, MGA; Vrouenraets, SME; van Vugt, M; Wit, FWMN; Kuijpers, TW; Pajkrt, D; Scherpbier, HJ; van Eeden, A; ten Veen, JH; van Dam, PS; Roos, JC; Brinkman, K; Frissen, PHJ; Weigel, HM; Mulder, JW; van Gorp, ECM; Meenhorst, PL; Mairuhu, ATA; Ziekenhuis, S; Veenstra, J; Danner, SA; van Agtmael, MA; Claessen, FAP; Perenboom, RM; Rijkeboer, A; van Vonderen, M; Richter, C; van der Berg, J; van Leusen, R; Vriesendorp, R; Jeurissen, FJF; Kauffmann, RH; Koger, ELW; Bravenboer, B; ten Napel, CHH; Kootstra, GJ; Sprenger, HG; Miesen, WMAJ; Doedens, Rienus; Scholvinck, EH; ten Kate, RW; van Houte, DPF; Polee, M; Kroon, FP; Broek, van den; van Dissel, JT; Schippers, EF; Schreij, G; de Geest, SV; Verbon, A; Koopmans, PP; Keuter, M; Post, F; van der Ven, AJAM; van der Ende, Marchina E.; Gyssens, IC; van der Feltz, M; den Hollander, JG; de Marie, S; Nouwen, JL; Rijnders, BJA; de Vries, TEMS; Driessen, G; de Groot, R; Hartwig, N; Juttmann, J.; van de Heul, C; van Kasteren, MEE; Schneider, MME; Bonten, MJM; Borleffs, JCC; Ellerbroek, PM; Hoepelman, IM; Jaspers, CAJJ; Schouten, M.C.; Schurink, CAM; Geelen, SPM; Wolfs, TFW; Blok, WL; Tanis, AA; Groeneveld, PHP; Back, NKT; Bakker, MEG; Berkhout, B; Jurriaans, S; Cuijpers, T; Rietra, PJGM; Roozendaal, KJ; Pauw, W; van Zanten, AP; von Blomberg, BME; Savelkoul, P; Swanink, CMA; Franck, PFH; Lampe, AS; Hendriks, R; Schirm, J; Veenendaal, D; Storm, H; Weel, J; van Zeijl, H; Kroes, ACM; Claas, HCJ; Bruggeman, CAMVA; Goossens, VJ; Galama, JMD; Melchers, WJG; Poort, YAG; Doornum, GJJ; Niesters, MG; Osterhaus, ADME; Schutten, M; Buiting, AGM; Swaans, CAM; Boucher, CAB; Boel, E; Jansz, AF; Losso, M; Duran, A; Vetter, N; Karpov, A.; Vassilenko, A; Clumeck, N; De Wit, S; Poll, B; Colebunders, R; Machala, L; Rozsypal, H; Sedlacek, D; Nielsen, J; Lundgren, J; Benfield, T; Kirk, O; Gerstoft, J; Katzenstein, T; Hansen, ABE; Skinhoj, P; Pedersen, C; Zilmer, K; Katlama, C; Girard, PM; Viard, JP; Saint-Marc, T; Vanhems, P; Pradier, C; Dietrich, M; Manegold, C; van Lunzen, J; Stellbrink, HJ; Staszewski, S; Bickel, M; Goebel, FD; Fatkenheuer, G; Rockstroh, J; Schmidt, R; Kosmidis, J; Gargalianos, P; Sambatakou, H; Perdios, J; Panos, G; Filandras, A; Karabatsaki, E; Banhegyi, D; Mulcahy, F; Yust, I.; Turner, D; Burke, M; Pollack, S; Hassoun, G; Sthoeger, Z; Maayan, S; Chiesi, A; Esposito, R; Borghi, R; Arici, C; Pristera, R; Mazzotta, F; Gabbuti, A; Lichtner, M; Chirianni, A; Montesarchio, E; Iacomi, F; Lazzarin, A; Finazzi, R; Viksna, L; Chaplinskas, S; Hemmer, R; Staub, T; Reiss, P; Bruun, J; Maeland, A; Ormaasen, V.; Knysz, B; Gasiorowski, J; Horban, A; Prokopowicz, D; Wiercinska-Drapalo, A; Boron-Kaczmarska, A; Pynka, M; Beniowski, M; Mularska, E; Trocha, H; Antunes, F; Valadas, E; Mansinho, K; Matez, F; Duiculescu, D; Babes, V.; Streinu-Cercel, A; Vinogradova, E; Rakhmanova, A; Jevtovic, D; Mokras, M; Stanekova, D; Gonzalez-Lahoz, J; Sanchez-Conde, M; Garcia-Benayas, T; Martin-Carbonero, L; Soriano, Joan B.; Clotet, B; Jou, A; Conejero, J; Tural, C; Gatell, JM; Miro, JM; Blaxhult, A; Karlsson, A; Pehrson, P; Ledergerber, B; Weber, R; Francioli, P; Telenti, A; Hirschel, B; Soravia-Dunand, V.; Furrer, H; Kravchenko, E; Chentsova, N; Barton, S; Johnson, AM; Mercey, D; Phillips, A; Johnson, MA; Mocroft, A; Murphy, M; Weber, J; Scullard, G; Fisher, M; Brettle, R; Loveday, C; Clotet, B; Antunes, F; Blaxhult, A; Clumeck, N; Gatell, J; Horban, A; Johnson, A; Katlama, C; Ledergerber, B; Loveday, C; Phillips, A; Reiss, P; Vella, S; Gjorup, N; Kirk, O; Friis-Moeller, N; Mocroft, A; Cozzi-Lepri, A; Bannister, W; Mollerup, D; Podlevkareva, D; Olsen, CH; Kjaer, J; Raffanti, S; Dieterch, D; Justice, A; Becker, S; Scarsella, A; Fusco, G; Most, B; Balu, R; Rana, R; Beckerman, R; Ising, T; Fusco, J; Irek, R; Johnson, B; Hirani, A; DeJesus, E; Pierone, G; Lackey, P; Irek, C; Johnson, A; Burdick, J; Leon, S; Arch, J; Staszewski, S; Helm, EB; Carlebach, A; Muller, A; Haberl, A; Nisius, G; Lennemann, T; Rottmann, C; Muller, A; Haberl, A; Nisius, G; Lennemann, T; Rottmann, C; Wolf, T; Stephan, C; Bickel, M; Mosch, M; Gute, P; Locher, L; Lutz, T; Klauke, S; Knecht, G; Doerr, HW; Sturmer, M; Dauer, B; von Hentig, N; Jennings, B; Beylot, J; Chene, G; Dabis, F; Dupon, M; Longy-Boursier, M; Pellegrin, JL; Ragnaud, JM; Salamon, R; Dabis, F; Chene, G; Thiebaut, R; Lewden, C; Lawson-Ayayi, S; Dupon, M; Mercie, P; Moreau, JF; Moriat, P; Pellegrin, JL; Ragnaud, JM; Bernard, N; Lacoste, D; Malvy, D; Neau, D; Blaizeau, MJ; Decoin, M; Delveaux, S; Hannapier, C; Labarrere, S; Lavignolle-Aurillac, V.; Uwamaliya-Nziyumvira, B; Palmer, G; Touchard, D; Balestre, E; Alioum, A; Jacqmin-Gadda, H; Thiebaut, R; Beylot, J; Morlat, P; Bernard, N; Bonarek, M; Bonnet, F; Coadou, B; Gellie, P; Lacoste, D; Nouts, C; Dupon, M; Bocquentin, F; Dutronc, H; Lafarie, S; Longy-Boursier, M; Mercie, P; Aslan, A; Malvy, D; Pistonne, T; Thibaut, P; Vatan, R; Ragnaud, JM; Chambon, D; De La Taille, C; Cazorla, C; Neau, D; Ocho, A; Pellegrin, JL; Castera, L; Fleury, H; Lafon, ME; Masquelier, B; Pellegrin, E.; Breilh, D; Moreau, JF; Blanco, P; Loste, P; Caunegre, L; Bonnal, F; Farbos, S; Ferrand, M; Ceccaldi, J; Tchamgoue, S; De Witte, S; Buy, E; Alexander, C; Barrios, R; Braitstein, P; Brumme, Z; Chan, K; Cote, H; Gataric, N; Geller, J; Guillemi, S; Harrigan, K.; Harris, M; Hogg, R; Joy, R; Levy, A; Montaner, J; Montessori, V.; Palepu, A; Phillips, E; Phillips, P; Press, N; Tyndall, M; Wood, E; Yip, B; Ballinger, J; Bhagani, S; Breen, R; Byrne, P; Carroll, A; Cropley, Mark; Cuthbertson, Z; Drinkwater, T; Fernandez, T; Geretti, AM; Murphy, G; Ivens, D; Johnson, M; Kinloch-de Loes, S; Lipman, M; Madge, S; Prinz, B; Bell, DR; Shah, S; Swaden, L; Tyrer, M; Youle, M; Chaloner, C; Gumley, H; Holloway, J; Puradiredja, D; Sweeney, J; Tsintas, R; Bannister, W; Bansi, L; Cozzi-Lepri, A; Fox, Z; Lampe, F; Mocroft, A; Phillips, A; Sabin, C; Smith, C; Amoah, E; Clewley, G; Dann, L; Gregory, B; Jani, I.; Janossy, G; Kahan, M; Loveday, C; Thomas, M; Gill, MJ; Read, R; Fatkenheuer, G; Rockstroh, J; Schmeisser, V.; Voigt, K; Wasmuth, JC; Wohrmann, A

    2005-01-01

    Background. We obtained estimates of the incidence of tuberculosis (TB) among patients receiving HAART and identified determinants of the incidence. Methods. We analyzed the incidence of TB during the first 3 years after initiation of HAART among 17,142 treatment-naive, AIDS- free persons starting

  1. Activity of moxifloxacin and linezolid against Mycobacterium tuberculosis in combination with potentiator drugs verapamil, timcodar, colistin and SQ109

    NARCIS (Netherlands)

    Knegt, G.J. de; Meijden, A. van der; Vogel, C.P. de; Aarnoutse, R.E.; Steenwinkel, J.E. de

    2017-01-01

    Current treatment for tuberculosis (TB) is complicated by the emergence of multidrug resistant TB (MDR-TB). As a result, there is an urgent need for new powerful anti-TB regimens and novel strategies. In this study, we aimed to potentiate a moxifloxacin + linezolid backbone as treatment for MDR-TB

  2. Patients with active tuberculosis have increased expression of HIV coreceptors CXCR4 and CCR5 on CD4(+) T cells

    NARCIS (Netherlands)

    Juffermans, N. P.; Speelman, P.; Verbon, A.; Veenstra, J.; Jie, C.; van Deventer, S. J.; van der Poll, T.

    2001-01-01

    Expression of human immunodeficiency virus (HIV) coreceptors CXCR4 and CCR5 was found to be elevated on CD4(+) T cells (1) in blood samples obtained from patients with tuberculosis and (2) in blood samples obtained from healthy subjects and stimulated with mycobacterial lipoarabinomannan in vitro.

  3. State-wide hospital clinical laboratory plan for measuring cholinesterase activity for individuals suspected of exposure to nerve agent chemical weapons.

    Science.gov (United States)

    Wu, Alan H B; Smith, Andrew; McComb, Robert; Bowers, George N; Makowski, Gregory S; McKay, Charles A; Vena, Jason; McDonagh, John; Hopfer, Sidney; Sena, Salvatore F; Malkus, Herbert; Forte, Elaine; Kelly, Katherine

    2008-02-01

    Hospital laboratories currently lack the capacity to provide emergency determination of cholinesterase activity. We have developed a hospital-based 3-tiered system to test plasma for butyrylcholinesterase (BChE) activity and whole blood for red cell acetylcholinesterase (AChE) activity using available technology and personnel. Interagency communications, toxidrome definition, and patient triage will be coordinated by the Connecticut Department of Public Health and the Poison Control Center. Initial BChE data documents good precision between institutions (coefficient of variation chemical terrorism or large scale HazMat events.

  4. An Evaluation of Passive and Active Approaches to Improve Tuberculosis Notifications in Afghanistan.

    Directory of Open Access Journals (Sweden)

    A Sanaie

    Full Text Available In Afghanistan, improving TB case detection remains challenging. In 2014, only half of the estimated incident TB cases were notified, and notifications have decreased since peaking in 2007. Active case finding has been increasingly considered to improve TB case notifications. While access to health services has improved in Afghanistan, it remains poor and many people seeking health services won't receive proper care.From October 2011 through December 2012 we conducted three separate case finding strategies in six provinces of Afghanistan and measured impact on TB case notification. Systematically screening cough among attendees at 47 health facilities, active household contact investigation of smear-positive index TB patients, and active screening at 15 camps for internally displaced people were conducted. We collected both intervention yield and official quarterly notification data. Additional TB notifications were calculated by comparing numbers of cases notified during the intervention with those notified before the intervention, then adjusting for secular trends in notification.We screened 2,022,127 people for TB symptoms during the intervention, tested 59,838 with smear microscopy and detected 5,046 people with smear-positive TB. Most cases (81.7%, 4,125 were identified in health facilities while nearly 20% were found through active case finding. A 56% increase in smear-positive TB notifications was observed between the baseline and intervention periods among the 47 health facilities, where cases detected by all three strategies were notified.While most people with TB are likely to be identified through health facility screening, there are many people who remain without a proper diagnosis if outreach is not attempted. This is especially true in places like Afghanistan where access to general services is poor. Targeted active case finding can improve the number of people who are detected and treated for TB and can push towards the targets of

  5. Contact investigation in households of patients with tuberculosis in Hanoi, Vietnam: a prospective cohort study.

    Directory of Open Access Journals (Sweden)

    Gregory James Fox

    Full Text Available SETTING: Existing tuberculosis control strategies in Vietnam are based on symptomatic patients attending health services for investigation. This approach has not resulted in substantial reductions in the prevalence of tuberculosis disease, despite the National Tuberculosis Program achieving high treatment completion rates. Alternative approaches are being considered. OBJECTIVE: To determine the feasibility and yield of contact investigation in households of patients with smear positive pulmonary tuberculosis among household members of tuberculosis patients in Hanoi, Vietnam. METHODS: Household contacts of patients with smear positive pulmonary tuberculosis were recruited at four urban and rural District Tuberculosis Units in Hanoi. Clinical and radiological screening was conducted at baseline, six months and 12 months. Sputum microscopy and culture was performed in contacts suspected of having tuberculosis. MIRU-VNTR molecular testing was used to compare the strains of patients and their contacts with disease. RESULTS: Among 545 household contacts of 212 patients, four were diagnosed with tuberculosis at baseline (prevalence 734 cases per 100,000 persons, 95% CI 17-1451 and one was diagnosed with tuberculosis during the subsequent 12 months after initial screening (incidence 180 cases per 100,000 person-years, 95% CI 44-131. Two of these cases were culture positive for M. tuberculosis and both had identical or near-identical MIRU-VNTR strain types. CONCLUSION: Household contacts of patients with potentially infectious forms of tuberculosis have a high prevalence of disease. Household contact investigation is feasible in Vietnam. Further research is required to investigate its effectiveness.

  6. Identification of a novel class of small compounds with anti-tuberculosis activity by in silico structure-based drug screening.

    Science.gov (United States)

    Taira, Junichi; Morita, Koji; Kawashima, Shotaro; Umei, Tomohiro; Baba, Hiroki; Maruoka, Taira; Komatsu, Hideyuki; Sakamoto, Hiroshi; Sacchettini, James C; Aoki, Shunsuke

    2017-11-01

    The enzymes responsible for biotin biosynthesis in mycobacteria have been considered as potential drug targets owing to the important role in infection and cell survival that the biotin synthetic pathway plays in Mycobacterium tuberculosis. Among the enzymes that comprise mycobacterium biotin biosynthesis systems, 7,8-diaminopelargonic acid synthase (DAPAS) plays an essential role during the stationary phase in bacterial growth. In this study, compounds that inhibit mycobacterial DAPAS were screened in the virtual chemical library using an in silico structure-based drug screening (SBDS) technique, and the antimycobacterial activity of the selected compounds was validated experimentally. The DOCK-GOLD programs utilized by in silico SBDS facilitated the identification of a compound, referred to as KMD6, with potent inhibitory effects on the growth of model mycobacteria (M. smegmatis). The subsequent compound search, which was based on the structural features of KMD6, resulted in identification of three additional active compounds, designated as KMDs3, KMDs9 and KMDs10. The inhibitory effect of these compounds was comparable to that of isoniazid, which is a first-line antituberculosis drug. The high antimycobacterial activity of KMD6, KMDs9 and KMDs10 was maintained on the experiment with M. tuberculosis. Of the active compounds identified, KMDs9 would be a promising pharmacophore, owing to its long-term antimycobacterial effect and lack of cytotoxicity.

  7. MCL Plays an Anti-Inflammatory Role in Mycobacterium tuberculosis-Induced Immune Response by Inhibiting NF-κB and NLRP3 Inflammasome Activation

    Directory of Open Access Journals (Sweden)

    Qingwen Zhang

    2017-01-01

    Full Text Available Mycobacterium tuberculosis (Mtb remains a significant menace to global health as it induces granulomatous lung lesions and systemic inflammatory responses during active tuberculosis (TB. Micheliolide (MCL, a sesquiterpene lactone, was recently reported to have a function of relieving LPS-induced inflammatory response, but the regulative role of MCL on the immunopathology of TB still remains unknown. In this experiment, we examined the inhibitory effect of MCL on Mtb-induced inflammatory response in mouse macrophage-like cell line Raw264.7 by downregulating the activation of nuclear factor kappa B (NF-κB and NLRP3 inflammasome. Evidences showed that MCL decreased the secretion of Mtb-induced inflammatory cytokines (IL-1β and TNF-α in a dose-dependent manner. Meanwhile, MCL dramatically suppressed Mtb-induced activation of iNOS and COX2 as well as subsequent production of NO. Furthermore, MCL inhibited Mtb-induced phosphorylation of Akt (Ser 473 in Raw264.7. According to our results, MCL plays an important role in modulating Mtb-induced inflammatory response through PI3K/Akt/NF-κB pathway and subsequently downregulating the activation of NLRP3 inflammasome. Therefore, MCL may represent as a potential drug candidate in the adjuvant treatment of TB by regulating host immune response.

  8. Prevalence of latent and active tuberculosis among dairy farm workers exposed to cattle infected by Mycobacterium bovis.

    Directory of Open Access Journals (Sweden)

    Pedro Torres-Gonzalez

    Full Text Available BACKGROUND: Human tuberculosis caused by M. bovis is a zoonosis presently considered sporadic in developed countries, but remains a poorly studied problem in low and middle resource countries. The disease in humans is mainly attributed to unpasteurized dairy products consumption. However, transmission due to exposure of humans to infected animals has been also recognized. The prevalence of tuberculosis infection and associated risk factors have been insufficiently characterized among dairy farm workers (DFW exposed in settings with poor control of bovine tuberculosis. METHODOLOGY/PRINCIPAL FINDINGS: Tuberculin skin test (TST and Interferon-gamma release assay (IGRA were administered to 311 dairy farm and abattoir workers and their household contacts linked to a dairy production and livestock facility in Mexico. Sputa of individuals with respiratory symptoms and samples from routine cattle necropsies were cultured for M. bovis and resulting spoligotypes were compared. The overall prevalence of latent tuberculosis infection (LTBI was 76.2% (95% CI, 71.4-80.9% by TST and 58.5% (95% CI, 53.0-64.0% by IGRA. Occupational exposure was associated to TST (OR 2.72; 95% CI, 1.31-5.64 and IGRA (OR 2.38; 95% CI, 1.31-4.30 adjusting for relevant variables. Two subjects were diagnosed with pulmonary tuberculosis, both caused by M. bovis. In one case, the spoligotype was identical to a strain isolated from bovines. CONCLUSIONS: We documented a high prevalence of latent and pulmonary TB among workers exposed to cattle infected with M. bovis, and increased risk among those occupationally exposed in non-ventilated spaces. Interspecies transmission is frequent and represents an occupational hazard in this setting.

  9. Modern lineages of Mycobacterium tuberculosis in Addis Ababa ...

    African Journals Online (AJOL)

    Background: The genotyping of Mycobacterium tuberculosis strains is important to have unique insights into the dissemination dynamics and evolutionary genetics of this pathogen and for TB control as it allows the detection of suspected outbreaks and the tracing of transmission chains. Objective: To characterize M.

  10. A high-throughput screen against pantothenate synthetase (PanC identifies 3-biphenyl-4-cyanopyrrole-2-carboxylic acids as a new class of inhibitor with activity against Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Anuradha Kumar

    Full Text Available The enzyme pantothenate synthetase, PanC, is an attractive drug target in Mycobacterium tuberculosis. It is essential for the in vitro growth of M. tuberculosis and for survival of the bacteria in the mouse model of infection. PanC is absent from mammals. We developed an enzyme-based assay to identify inhibitors of PanC, optimized it for high-throughput screening, and tested a large and diverse library of compounds for activity. Two compounds belonging to the same chemical class of 3-biphenyl-4- cyanopyrrole-2-carboxylic acids had activity against the purified recombinant protein, and also inhibited growth of live M. tuberculosis in manner consistent with PanC inhibition. Thus we have identified a new class of PanC inhibitors with whole cell activity that can be further developed.

  11. Tuberculous dactylitis (spina ventosa with concomitant ipsilateral axillary scrofuloderma in an immunocompetent child: A rare presentation of skeletal tuberculosis

    Directory of Open Access Journals (Sweden)

    Bhaskar

    2013-01-01

    Full Text Available Tuberculous dactylitis is a distinctly uncommon, yet well recognized form of tuberculosis involving the small bones of the hand or foot. It occurs in young children in endemic areas under 5 years of age. Tuberculosis of the short tubular bones like phalanges, metacarpals or metatarsals is quite uncommon beyond 6 years of age, once the epiphyseal centers are well established. The radiographic features of cystic expansion have led to the name " Spina Ventosa" for tuberculous dactylitis of the short bones. Scrofuloderma is a mycobacterial infection affecting children and young adults, representing direct extension of tuberculosis into the skin from underlying structures e.g. lymph nodes. An 8-year-old malnourished girl had multiple axillary ulcers with lymphadenopathy. Tuberculous dactylitis with ipsilateral axillary scrofuloderma was suspected on clinical and radiological grounds. The suspicion was confirmed by histology and bacteriology. The patient responded to antitubercular drugs with progressive healing of the lesions without surgery. Concomitant presence of these dual lesions suggesting active disseminated tuberculosis in immune-competent child over 6 years is very rare and hardly reported.

  12. Tuberculous dactylitis (spina ventosa) with concomitant ipsilateral axillary scrofuloderma in an immunocompetent child: A rare presentation of skeletal tuberculosis.

    Science.gov (United States)

    Bhaskar; Khonglah, Tashi; Bareh, Jerryson

    2013-01-01

    Tuberculous dactylitis is a distinctly uncommon, yet well recognized form of tuberculosis involving the small bones of the hand or foot. It occurs in young children in endemic areas under 5 years of age. Tuberculosis of the short tubular bones like phalanges, metacarpals or metatarsals is quite uncommon beyond 6 years of age, once the epiphyseal centers are well established. The radiographic features of cystic expansion have led to the name "Spina Ventosa" for tuberculous dactylitis of the short bones. Scrofuloderma is a mycobacterial infection affecting children and young adults, representing direct extension of tuberculosis into the skin from underlying structures e.g. lymph nodes. An 8-year-old malnourished girl had multiple axillary ulcers with lymphadenopathy. Tuberculous dactylitis with ipsilateral axillary scrofuloderma was suspected on clinical and radiological grounds. The suspicion was confirmed by histology and bacteriology. The patient responded to antitubercular drugs with progressive healing of the lesions without surgery. Concomitant presence of these dual lesions suggesting active disseminated tuberculosis in immune-competent child over 6 years is very rare and hardly reported.

  13. Clinical management of concurrent diabetes and tuberculosis and the implications for patient services

    OpenAIRE

    Riza, Anca Lelia; Pearson, Fiona; Ugarte-Gil, Cesar; Alisjahbana, Bachti; van de Vijver, Steven; Panduru, Nicolae M; Hill, Philip C; Ruslami, Rovina; Moore, David; Aarnoutse, Rob; Critchley, Julia A; van Crevel, Reinout

    2014-01-01

    Diabetes triples the risk for active tuberculosis, thus the increasing burden of type 2 diabetes will help to sustain the present tuberculosis epidemic. Recommendations have been made for bidirectional screening, but evidence is scarce about the performance of specific tuberculosis tests in individuals with diabetes, specific diabetes tests in patients with tuberculosis, and screening and preventive therapy for latent tuberculosis infections in individuals with diabetes. Clinical management o...

  14. Lung cancer, brucellosis and tuberculosis: remarkable togetherness

    Directory of Open Access Journals (Sweden)

    Muhammed Emin Akkoyunlu

    2013-08-01

    Full Text Available A 68 years old male farmer referred with cough, expectorating sputum, intermittant fever, night sweats, fatigue and anorexia persisting for two weeks. There was a history of 80 packs each year of smoking and he was still an active smoker. Pneumonectomy was performed because of pulmonary epidermoid cancer and he received chemotherapy. He was diagnosed lung tuberculosis and using anti-tuberculous treatment for 4 months. He had a weight loss of 8 kg in last month. His body tempereature was 38.5 °C. Heart rate was 100/min. ESR was 51mm/h and CRP was 5.6 mg/ dL. There was no proliferation in blood and sputum cultures. Three sputum specimens were examined and AFB wasn’t detected. Fibronodular infiltration was seen in right lower zone of chest X-ray. In thorax CT, fibronodular densities were seen in lower l